Mary Ann Moon

Even without increased exercise or calorie restrictions, older white men and women at high risk for cardiovascular disease who followed a Mediterranean diet enriched with extra-virgin olive oil were 40% less likely to develop type 2 diabetes than those who were simply advised to reduce their fat intake, according to a report published online Jan. 6 in Annals of Internal Medicine.

Those on the olive oil–enriched Mediterranean diet also were less likely to develop diabetes than were those who followed a Mediterranean diet supplemented with nuts.

©Volosina/thinkstockphotos.com

None of the study’s three diets restricted caloric intake, nor did patients increase their physical activity. Thus, there was no appreciable weight loss or reduction in waist circumference in any of the three groups: The protective effect was attributed solely to the change in the overall dietary pattern, said Jordi Salas-Salvadó, M.D., Ph.D., of the Universitat Rovira i Virgili in Reus, Spain, and his associates.

"Of note, this dietary pattern is palatable and has a high potential for long-term sustainability, with obvious public health implications for primary prevention of diabetes," they added (Ann. Intern. Med. 2014 Jan. 6 [doi 10.7326/M13-1725]).

Dr. Salas-Salvadó and his colleagues compared three diets in a subset of 3,541 participants in the PREDIMED (Prevención con Dieta Mediterránea) clinical trial: men aged 55-80 years and women aged 60-80 years who had three or more cardiovascular risk factors such as smoking, hypertension, hypercholesterolemia, low LDL cholesterol, overweight or obesity, and family history of premature cardiovascular disease.

Those patients were randomly assigned to follow a Mediterranean diet supplemented with extra-virgin olive oil (EVOO) (1,154 patients), a Mediterranean diet supplemented with mixed walnuts, almonds, and hazelnuts (1,240 patients), or a diet advising reduced intake of all types of fat (1,147 control patients). The two intervention groups were given either free EVOO or free mixed nuts, and the control group was given nonfood gifts such as kitchenware.

The two intervention groups also received personal advice from dietitians regarding the use of EVOO or mixed nuts; increased intake of vegetables, fruits, legumes, and fish; switching from red or processed meat to white meat; avoiding butter, fast food, sweets, or sugar-sweetened drinks; increasing the use of sofrito sauce (tomatoes, garlic, onion, and spices simmered in olive oil) to add flavor to food; and reducing the consumption of alcohol except for red wine.

The two intervention groups met with dietitians every 3 months to receive information on Mediterranean foods, seasonal shopping lists, meal plans, and recipes, as well as personalized advice to enhance adherence. The control group also met with dietitians for sessions "with the same frequency and intensity," but with advice pertaining to a low-fat diet rather than a Mediterranean diet, Dr. Salas-Salvadó and his associates wrote.

At a median follow-up of 4.1 years (range, 2.5-5.7 years), rates of both nonadherence to the diet and withdrawal from the study were significantly higher in the control group than in either intervention group.

A total of 273 participants developed new-onset type 2 diabetes: 6.9% of patients following the Mediterranean diet plus EVOO, 7.4% of patients following the Mediterranean diet plus nuts, and 8.8% of the control group, the researchers reported.

After adjusting for smoking status, fasting glucose level, total energy intake level, and physical activity level, the hazard ratio for developing diabetes was 0.60 for the Mediterranean diet plus EVOO and 0.82 for the Mediterranean diet plus nuts, compared with the control group. That reflects a significant 40% reduction in risk for the first intervention group but a nonsignificant 18% reduction in risk for the second, the investigators said.

Those results were consistent across subgroups of patients defined by age, sex, comorbidities, family history of CVD, and degree of adiposity. The findings from sensitivity analyses also aligned with those of the main analysis: The relative risk for developing diabetes was 0.70 with the Mediterranean diet supplemented with EVOO and 0.82 for the Mediterranean diet supplemented with nuts.

The study was stronger than previous observational studies of this issue, the authors noted, because of its randomized design and statistical control of many potential confounding variables. It was limited, however, in that it assessed only a subgroup of participants in the PREDIMED clinical trial and because that trial did not have the development of diabetes as a primary endpoint. Moreover, the study involved only older white patients at high risk for CVD, "which limits the generalizability of our results to other age groups or ethnicities," Dr. Salas- Salvadó and his associates said.

The study was supported by the Spanish federal government, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Centero Nacional de Investigaciones Cardiovasculares, Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional, Ministerio de Ciencia e Innovación, Fundación Mapfre 2010, the Catalonia Department of Health, the European Federation, and the regional government of Navarra. Olive oil and mixed nuts were donated by the Fundación Patrimonio Comunal Olivarero and Hojiblanca SA, the California Walnut Commission, Borges SA, and Morella Nuts.

Even without increased exercise or calorie restrictions, older white men and women at high risk for cardiovascular disease who followed a Mediterranean diet enriched with extra-virgin olive oil were 40% less likely to develop type 2 diabetes than those who were simply advised to reduce their fat intake, according to a report published online Jan. 6 in Annals of Internal Medicine.

Those on the olive oil–enriched Mediterranean diet also were less likely to develop diabetes than were those who followed a Mediterranean diet supplemented with nuts.

©Volosina/thinkstockphotos.com

None of the study’s three diets restricted caloric intake, nor did patients increase their physical activity. Thus, there was no appreciable weight loss or reduction in waist circumference in any of the three groups: The protective effect was attributed solely to the change in the overall dietary pattern, said Jordi Salas-Salvadó, M.D., Ph.D., of the Universitat Rovira i Virgili in Reus, Spain, and his associates.

"Of note, this dietary pattern is palatable and has a high potential for long-term sustainability, with obvious public health implications for primary prevention of diabetes," they added (Ann. Intern. Med. 2014 Jan. 6 [doi 10.7326/M13-1725]).

Dr. Salas-Salvadó and his colleagues compared three diets in a subset of 3,541 participants in the PREDIMED (Prevención con Dieta Mediterránea) clinical trial: men aged 55-80 years and women aged 60-80 years who had three or more cardiovascular risk factors such as smoking, hypertension, hypercholesterolemia, low LDL cholesterol, overweight or obesity, and family history of premature cardiovascular disease.

Those patients were randomly assigned to follow a Mediterranean diet supplemented with extra-virgin olive oil (EVOO) (1,154 patients), a Mediterranean diet supplemented with mixed walnuts, almonds, and hazelnuts (1,240 patients), or a diet advising reduced intake of all types of fat (1,147 control patients). The two intervention groups were given either free EVOO or free mixed nuts, and the control group was given nonfood gifts such as kitchenware.

The two intervention groups also received personal advice from dietitians regarding the use of EVOO or mixed nuts; increased intake of vegetables, fruits, legumes, and fish; switching from red or processed meat to white meat; avoiding butter, fast food, sweets, or sugar-sweetened drinks; increasing the use of sofrito sauce (tomatoes, garlic, onion, and spices simmered in olive oil) to add flavor to food; and reducing the consumption of alcohol except for red wine.

The two intervention groups met with dietitians every 3 months to receive information on Mediterranean foods, seasonal shopping lists, meal plans, and recipes, as well as personalized advice to enhance adherence. The control group also met with dietitians for sessions "with the same frequency and intensity," but with advice pertaining to a low-fat diet rather than a Mediterranean diet, Dr. Salas-Salvadó and his associates wrote.

At a median follow-up of 4.1 years (range, 2.5-5.7 years), rates of both nonadherence to the diet and withdrawal from the study were significantly higher in the control group than in either intervention group.

A total of 273 participants developed new-onset type 2 diabetes: 6.9% of patients following the Mediterranean diet plus EVOO, 7.4% of patients following the Mediterranean diet plus nuts, and 8.8% of the control group, the researchers reported.

After adjusting for smoking status, fasting glucose level, total energy intake level, and physical activity level, the hazard ratio for developing diabetes was 0.60 for the Mediterranean diet plus EVOO and 0.82 for the Mediterranean diet plus nuts, compared with the control group. That reflects a significant 40% reduction in risk for the first intervention group but a nonsignificant 18% reduction in risk for the second, the investigators said.

Those results were consistent across subgroups of patients defined by age, sex, comorbidities, family history of CVD, and degree of adiposity. The findings from sensitivity analyses also aligned with those of the main analysis: The relative risk for developing diabetes was 0.70 with the Mediterranean diet supplemented with EVOO and 0.82 for the Mediterranean diet supplemented with nuts.

The study was stronger than previous observational studies of this issue, the authors noted, because of its randomized design and statistical control of many potential confounding variables. It was limited, however, in that it assessed only a subgroup of participants in the PREDIMED clinical trial and because that trial did not have the development of diabetes as a primary endpoint. Moreover, the study involved only older white patients at high risk for CVD, "which limits the generalizability of our results to other age groups or ethnicities," Dr. Salas- Salvadó and his associates said.

The study was supported by the Spanish federal government, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Centero Nacional de Investigaciones Cardiovasculares, Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional, Ministerio de Ciencia e Innovación, Fundación Mapfre 2010, the Catalonia Department of Health, the European Federation, and the regional government of Navarra. Olive oil and mixed nuts were donated by the Fundación Patrimonio Comunal Olivarero and Hojiblanca SA, the California Walnut Commission, Borges SA, and Morella Nuts.

Even without increased exercise or calorie restrictions, older white men and women at high risk for cardiovascular disease who followed a Mediterranean diet enriched with extra-virgin olive oil were 40% less likely to develop type 2 diabetes than those who were simply advised to reduce their fat intake, according to a report published online Jan. 6 in Annals of Internal Medicine.

Those on the olive oil–enriched Mediterranean diet also were less likely to develop diabetes than were those who followed a Mediterranean diet supplemented with nuts.

©Volosina/thinkstockphotos.com

None of the study’s three diets restricted caloric intake, nor did patients increase their physical activity. Thus, there was no appreciable weight loss or reduction in waist circumference in any of the three groups: The protective effect was attributed solely to the change in the overall dietary pattern, said Jordi Salas-Salvadó, M.D., Ph.D., of the Universitat Rovira i Virgili in Reus, Spain, and his associates.

"Of note, this dietary pattern is palatable and has a high potential for long-term sustainability, with obvious public health implications for primary prevention of diabetes," they added (Ann. Intern. Med. 2014 Jan. 6 [doi 10.7326/M13-1725]).

Dr. Salas-Salvadó and his colleagues compared three diets in a subset of 3,541 participants in the PREDIMED (Prevención con Dieta Mediterránea) clinical trial: men aged 55-80 years and women aged 60-80 years who had three or more cardiovascular risk factors such as smoking, hypertension, hypercholesterolemia, low LDL cholesterol, overweight or obesity, and family history of premature cardiovascular disease.

Those patients were randomly assigned to follow a Mediterranean diet supplemented with extra-virgin olive oil (EVOO) (1,154 patients), a Mediterranean diet supplemented with mixed walnuts, almonds, and hazelnuts (1,240 patients), or a diet advising reduced intake of all types of fat (1,147 control patients). The two intervention groups were given either free EVOO or free mixed nuts, and the control group was given nonfood gifts such as kitchenware.

The two intervention groups also received personal advice from dietitians regarding the use of EVOO or mixed nuts; increased intake of vegetables, fruits, legumes, and fish; switching from red or processed meat to white meat; avoiding butter, fast food, sweets, or sugar-sweetened drinks; increasing the use of sofrito sauce (tomatoes, garlic, onion, and spices simmered in olive oil) to add flavor to food; and reducing the consumption of alcohol except for red wine.

The two intervention groups met with dietitians every 3 months to receive information on Mediterranean foods, seasonal shopping lists, meal plans, and recipes, as well as personalized advice to enhance adherence. The control group also met with dietitians for sessions "with the same frequency and intensity," but with advice pertaining to a low-fat diet rather than a Mediterranean diet, Dr. Salas-Salvadó and his associates wrote.

At a median follow-up of 4.1 years (range, 2.5-5.7 years), rates of both nonadherence to the diet and withdrawal from the study were significantly higher in the control group than in either intervention group.

A total of 273 participants developed new-onset type 2 diabetes: 6.9% of patients following the Mediterranean diet plus EVOO, 7.4% of patients following the Mediterranean diet plus nuts, and 8.8% of the control group, the researchers reported.

After adjusting for smoking status, fasting glucose level, total energy intake level, and physical activity level, the hazard ratio for developing diabetes was 0.60 for the Mediterranean diet plus EVOO and 0.82 for the Mediterranean diet plus nuts, compared with the control group. That reflects a significant 40% reduction in risk for the first intervention group but a nonsignificant 18% reduction in risk for the second, the investigators said.

Those results were consistent across subgroups of patients defined by age, sex, comorbidities, family history of CVD, and degree of adiposity. The findings from sensitivity analyses also aligned with those of the main analysis: The relative risk for developing diabetes was 0.70 with the Mediterranean diet supplemented with EVOO and 0.82 for the Mediterranean diet supplemented with nuts.

The study was stronger than previous observational studies of this issue, the authors noted, because of its randomized design and statistical control of many potential confounding variables. It was limited, however, in that it assessed only a subgroup of participants in the PREDIMED clinical trial and because that trial did not have the development of diabetes as a primary endpoint. Moreover, the study involved only older white patients at high risk for CVD, "which limits the generalizability of our results to other age groups or ethnicities," Dr. Salas- Salvadó and his associates said.

The study was supported by the Spanish federal government, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Centero Nacional de Investigaciones Cardiovasculares, Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional, Ministerio de Ciencia e Innovación, Fundación Mapfre 2010, the Catalonia Department of Health, the European Federation, and the regional government of Navarra. Olive oil and mixed nuts were donated by the Fundación Patrimonio Comunal Olivarero and Hojiblanca SA, the California Walnut Commission, Borges SA, and Morella Nuts.

Primary care physicians avoid discussing sexual issues with adolescents at their annual visits, according to a report published online Dec. 30 in JAMA Pediatrics.

In a study analyzing audio-recorded yearly checkups between 49 pediatricians or family physicians and 253 of their adolescent patients, fully one-third of these visits included no mention at all of any topic touching on sexuality, including physical development, emotional development, STDs, pregnancy, sexual orientation, intercourse behaviors, other sexual behaviors, sexual abuse, or dating.

And even when such "discussions" did take place, they lasted an average of 36 seconds and rarely involved much input from the patients, said Stewart C. Alexander, Ph.D., of the department of medicine, Duke University Medical Center, Durham, N.C., and his associates.

These findings, taken together with other revealing results of what may be the first study to observe discussions of sexuality between physicians and adolescents, indicate that "physicians are missing opportunities to educate and counsel adolescent patients on healthy sexual behaviors and prevention of STDs [sexually transmitted diseases] and unplanned pregnancy."

The investigators assessed the frequency and duration of talk regarding sexual issues using data from Teen CHAT, a randomized trial that examined how health care providers talked to overweight adolescents about attaining a healthy weight. That trial began making audio recordings of annual health visits in 2009 and is ongoing.

For their analysis, Dr. Alexander and his colleagues assessed 253 recordings collected from annual visits at three academic and eight community-based primary care practices during a 4-year period. Participating physicians included 40 pediatricians and 9 family physicians.

All the patients were aged 12-17 years, and the mean age was 14.3 years. Just over half were girls; 47% were black, and 40% were white.

The physicians spent a mean of 22.4 minutes in the examination room with the adolescents. Talk regarding sexuality occurred in only 65% of visits and was initiated by the physician in every case; no patient ever brought up the topic, and many were reluctant to engage other than to answer specific questions with a "yes" or a "no."

When sexual issues were discussed, in 2% of visits, the physician spoke about sexual issues without attempting to engage the adolescent, and in another 2%, the physician spoke and the adolescent responded nonverbally. In 17%, adolescents made a mean of two yes or no responses. These "discussions" tended to last no more than 30 seconds.

To put this time frame in context, it takes more than 35 seconds just to read aloud the questions regarding sexual health that are suggested in American Academy of Pediatrics guidelines for adolescent health visits, without allowing any time for answers, the investigators noted (JAMA Ped. 2013 [doi:10.1001/jamapediatrics.2013.4338]).

Something approaching conversation about sexual issues occurred in only 35% of visits. In these cases, the adolescents made a mean of 7 statements to the physicians’ 14 statements over the course of 68 seconds.

Somewhat more complete conversations occurred in the remaining 8% of visits: the adolescents made a mean of 9 statements to the physicians’ 17 statements during interactions that averaged 103 seconds in 4% of visits, and the most talkative adolescents made a mean of 20 statements to the physicians’ 26 statements during 114-second interactions in 4% of visits.

Among the study’s other interesting findings:

• Asian physicians were nearly 90% less likely than those of other ethnicities "to have a sexuality talk of any length."

• When physicians specifically explained patient confidentiality, adolescents were four times more likely to discuss sexual issues during the visit. Unfortunately, physicians explained confidentiality in only 31% of the visits in this study.

• For every additional minute spent on the visit, there was a 6% increase in the likelihood that longer, more engaged conversation concerning sexual issues would take place.

• Black adolescents were nearly 60% more likely than those of other ethnicities to talk about sexual issues and nearly twice as likely to converse for longer than 30 seconds.

• Physicians were more likely to initiate discussions of sexual issues with girls than with boys, with black patients than with those of other ethnicities, and with older rather than younger adolescents.

Overall, the study findings indicate that physicians must be proactive in addressing sexual issues with adolescents and should spend more time discussing them. "Even if adolescents are reluctant to engage in sexuality talk, physicians initiating such a conversation sends a clear message to adolescents that sexuality is an appropriate and normal discussion topic at health maintenance visits, which may open the door for more extensive and detailed discussions during future visits," Dr. Alexander and his associates said.

This study may have been somewhat limited in that the patients tended to be overweight, given the nature of the Teen CHAT trial from which this study sample was drawn. However, there is no reason why physicians would speak differently to adolescents about sexual issues according to their weight, the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute. No relevant financial conflicts of interest were reported.

Primary care physicians avoid discussing sexual issues with adolescents at their annual visits, according to a report published online Dec. 30 in JAMA Pediatrics.

In a study analyzing audio-recorded yearly checkups between 49 pediatricians or family physicians and 253 of their adolescent patients, fully one-third of these visits included no mention at all of any topic touching on sexuality, including physical development, emotional development, STDs, pregnancy, sexual orientation, intercourse behaviors, other sexual behaviors, sexual abuse, or dating.

And even when such "discussions" did take place, they lasted an average of 36 seconds and rarely involved much input from the patients, said Stewart C. Alexander, Ph.D., of the department of medicine, Duke University Medical Center, Durham, N.C., and his associates.

These findings, taken together with other revealing results of what may be the first study to observe discussions of sexuality between physicians and adolescents, indicate that "physicians are missing opportunities to educate and counsel adolescent patients on healthy sexual behaviors and prevention of STDs [sexually transmitted diseases] and unplanned pregnancy."

The investigators assessed the frequency and duration of talk regarding sexual issues using data from Teen CHAT, a randomized trial that examined how health care providers talked to overweight adolescents about attaining a healthy weight. That trial began making audio recordings of annual health visits in 2009 and is ongoing.

For their analysis, Dr. Alexander and his colleagues assessed 253 recordings collected from annual visits at three academic and eight community-based primary care practices during a 4-year period. Participating physicians included 40 pediatricians and 9 family physicians.

All the patients were aged 12-17 years, and the mean age was 14.3 years. Just over half were girls; 47% were black, and 40% were white.

The physicians spent a mean of 22.4 minutes in the examination room with the adolescents. Talk regarding sexuality occurred in only 65% of visits and was initiated by the physician in every case; no patient ever brought up the topic, and many were reluctant to engage other than to answer specific questions with a "yes" or a "no."

When sexual issues were discussed, in 2% of visits, the physician spoke about sexual issues without attempting to engage the adolescent, and in another 2%, the physician spoke and the adolescent responded nonverbally. In 17%, adolescents made a mean of two yes or no responses. These "discussions" tended to last no more than 30 seconds.

To put this time frame in context, it takes more than 35 seconds just to read aloud the questions regarding sexual health that are suggested in American Academy of Pediatrics guidelines for adolescent health visits, without allowing any time for answers, the investigators noted (JAMA Ped. 2013 [doi:10.1001/jamapediatrics.2013.4338]).

Something approaching conversation about sexual issues occurred in only 35% of visits. In these cases, the adolescents made a mean of 7 statements to the physicians’ 14 statements over the course of 68 seconds.

Somewhat more complete conversations occurred in the remaining 8% of visits: the adolescents made a mean of 9 statements to the physicians’ 17 statements during interactions that averaged 103 seconds in 4% of visits, and the most talkative adolescents made a mean of 20 statements to the physicians’ 26 statements during 114-second interactions in 4% of visits.

Among the study’s other interesting findings:

• Asian physicians were nearly 90% less likely than those of other ethnicities "to have a sexuality talk of any length."

• When physicians specifically explained patient confidentiality, adolescents were four times more likely to discuss sexual issues during the visit. Unfortunately, physicians explained confidentiality in only 31% of the visits in this study.

• For every additional minute spent on the visit, there was a 6% increase in the likelihood that longer, more engaged conversation concerning sexual issues would take place.

• Black adolescents were nearly 60% more likely than those of other ethnicities to talk about sexual issues and nearly twice as likely to converse for longer than 30 seconds.

• Physicians were more likely to initiate discussions of sexual issues with girls than with boys, with black patients than with those of other ethnicities, and with older rather than younger adolescents.

Overall, the study findings indicate that physicians must be proactive in addressing sexual issues with adolescents and should spend more time discussing them. "Even if adolescents are reluctant to engage in sexuality talk, physicians initiating such a conversation sends a clear message to adolescents that sexuality is an appropriate and normal discussion topic at health maintenance visits, which may open the door for more extensive and detailed discussions during future visits," Dr. Alexander and his associates said.

This study may have been somewhat limited in that the patients tended to be overweight, given the nature of the Teen CHAT trial from which this study sample was drawn. However, there is no reason why physicians would speak differently to adolescents about sexual issues according to their weight, the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute. No relevant financial conflicts of interest were reported.

Primary care physicians avoid discussing sexual issues with adolescents at their annual visits, according to a report published online Dec. 30 in JAMA Pediatrics.

In a study analyzing audio-recorded yearly checkups between 49 pediatricians or family physicians and 253 of their adolescent patients, fully one-third of these visits included no mention at all of any topic touching on sexuality, including physical development, emotional development, STDs, pregnancy, sexual orientation, intercourse behaviors, other sexual behaviors, sexual abuse, or dating.

And even when such "discussions" did take place, they lasted an average of 36 seconds and rarely involved much input from the patients, said Stewart C. Alexander, Ph.D., of the department of medicine, Duke University Medical Center, Durham, N.C., and his associates.

These findings, taken together with other revealing results of what may be the first study to observe discussions of sexuality between physicians and adolescents, indicate that "physicians are missing opportunities to educate and counsel adolescent patients on healthy sexual behaviors and prevention of STDs [sexually transmitted diseases] and unplanned pregnancy."

The investigators assessed the frequency and duration of talk regarding sexual issues using data from Teen CHAT, a randomized trial that examined how health care providers talked to overweight adolescents about attaining a healthy weight. That trial began making audio recordings of annual health visits in 2009 and is ongoing.

For their analysis, Dr. Alexander and his colleagues assessed 253 recordings collected from annual visits at three academic and eight community-based primary care practices during a 4-year period. Participating physicians included 40 pediatricians and 9 family physicians.

All the patients were aged 12-17 years, and the mean age was 14.3 years. Just over half were girls; 47% were black, and 40% were white.

The physicians spent a mean of 22.4 minutes in the examination room with the adolescents. Talk regarding sexuality occurred in only 65% of visits and was initiated by the physician in every case; no patient ever brought up the topic, and many were reluctant to engage other than to answer specific questions with a "yes" or a "no."

When sexual issues were discussed, in 2% of visits, the physician spoke about sexual issues without attempting to engage the adolescent, and in another 2%, the physician spoke and the adolescent responded nonverbally. In 17%, adolescents made a mean of two yes or no responses. These "discussions" tended to last no more than 30 seconds.

To put this time frame in context, it takes more than 35 seconds just to read aloud the questions regarding sexual health that are suggested in American Academy of Pediatrics guidelines for adolescent health visits, without allowing any time for answers, the investigators noted (JAMA Ped. 2013 [doi:10.1001/jamapediatrics.2013.4338]).

Something approaching conversation about sexual issues occurred in only 35% of visits. In these cases, the adolescents made a mean of 7 statements to the physicians’ 14 statements over the course of 68 seconds.

Somewhat more complete conversations occurred in the remaining 8% of visits: the adolescents made a mean of 9 statements to the physicians’ 17 statements during interactions that averaged 103 seconds in 4% of visits, and the most talkative adolescents made a mean of 20 statements to the physicians’ 26 statements during 114-second interactions in 4% of visits.

Among the study’s other interesting findings:

• Asian physicians were nearly 90% less likely than those of other ethnicities "to have a sexuality talk of any length."

• When physicians specifically explained patient confidentiality, adolescents were four times more likely to discuss sexual issues during the visit. Unfortunately, physicians explained confidentiality in only 31% of the visits in this study.

• For every additional minute spent on the visit, there was a 6% increase in the likelihood that longer, more engaged conversation concerning sexual issues would take place.

• Black adolescents were nearly 60% more likely than those of other ethnicities to talk about sexual issues and nearly twice as likely to converse for longer than 30 seconds.

• Physicians were more likely to initiate discussions of sexual issues with girls than with boys, with black patients than with those of other ethnicities, and with older rather than younger adolescents.

Overall, the study findings indicate that physicians must be proactive in addressing sexual issues with adolescents and should spend more time discussing them. "Even if adolescents are reluctant to engage in sexuality talk, physicians initiating such a conversation sends a clear message to adolescents that sexuality is an appropriate and normal discussion topic at health maintenance visits, which may open the door for more extensive and detailed discussions during future visits," Dr. Alexander and his associates said.

This study may have been somewhat limited in that the patients tended to be overweight, given the nature of the Teen CHAT trial from which this study sample was drawn. However, there is no reason why physicians would speak differently to adolescents about sexual issues according to their weight, the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute. No relevant financial conflicts of interest were reported.

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

The three most important gaps in current understanding of psoriasis are the need to fully elucidate the genetic underpinnings of the disease, delineate in more detail its natural history and prognostic factors, and better characterize and treat its associated comorbidities, according to an article in the Journal of the American Academy of Dermatology.

The academy recently issued guidelines for the management of psoriasis and psoriatic arthritis, which included a section concerning the most prominent deficiencies in knowledge about the disease. In the current article (J. Am. Acad. Dermatol. 2014;70:146-67), the expert panel that wrote the guidelines now details some of those gaps and suggests how future research should address them.

Advances in genetic research have allowed considerable progress in our understanding of the pathogenesis of psoriasis, including the identification of genetic susceptibility regions and nucleotide polymorphisms that are significantly associated with immune pathways, skin barrier function, and epidermal proliferation. Future research should "explore whether the genetic basis of psoriasis stems from a primary defect in immunologic function, a defect in keratinocyte function, or a complex interaction of both," wrote Dr. Caitriona Ryan of the Psoriasis Research Center, Baylor University Medical Center, Dallas, and her associates on the expert panel.

In particular, genetic research should help elucidate the correlation between psoriasis genotype and phenotype, determining whether psoriasis and psoriatic arthritis are genetically distinct diseases, as well as the genetic differences underlying guttate, erythrodermic, inverse, palmoplantar, and pustular forms of the disease.

Immunologic studies are needed to define the roles of various inflammatory cells in patients’ skin and blood, and to assist the development of targeted immunotherapies that will correct immunologic dysfunction without causing adverse immunosuppression. Similarly, the role of angiogenesis and the vascular bed in the pathogenesis of psoriasis requires more research attention, because topical or systemic inhibition of this process appears to be beneficial.

Additionally, the environmental factors that predispose to the development of psoriasis or contribute to disease exacerbations are still poorly defined. Research into lifestyle factors and the role of bacterial and viral infections should be especially revealing, Dr. Ryan and her associates said.

Research to determine the prevalence and natural history of psoriasis across different populations also is critical. Robust, long-term, prospective epidemiology studies at the population level are key.

Several subpopulations of psoriasis patients also deserve special attention. There is a dearth of both clinical and basic scientific data on pediatric psoriasis, when children are the very patients most likely to suffer the adverse psychosocial effects of psoriasis and the most vulnerable to the adverse physical and developmental effects of treatments, the investigators noted.

Women who are pregnant or breastfeeding constitute another important subgroup of psoriasis patients. Studies are urgently needed to examine the effects of the disease itself and of its therapies on pregnancy outcomes. Similarly, the elderly are a subgroup of patients that requires special attention to adverse medication effects, because they have a high prevalence of comorbid conditions, greater use of concomitant medications, diminished renal function, and age-related changes in pharmacokinetics and pharmacodynamics.

Finally, future research must more closely examine several comorbidities now known to accompany psoriasis, including diabetes, obesity, the metabolic syndrome, and, most importantly, cardiovascular disease.

Severe psoriasis now should be considered an independent cardiovascular risk factor. "As physicians, it is our responsibility to counsel patients with psoriasis regarding the increased risk of cardiometabolic conditions and the need for lifestyle modifications, including smoking cessation, weight reduction, and regular screening for diabetes and hypertension," Dr. Ryan and her colleagues said.

Determining whether systemic treatment of psoriasis mitigates cardiometabolic risk, especially if it entails newer biologic agents, also is important, they added.

Psychological comorbidities should not be overlooked. Patients with psoriasis are known to have high rates of anxiety, depression, and alexithymia—the inability to recognize or discuss feelings or emotional states. Relaxation techniques, meditation, and cognitive-behavioral therapy have shown efficacy and need further assessment.

Sexual functioning also should be studied in greater detail, since psoriasis can have a significant impact on sexuality, particularly if the disease affects the genitals.

Dr. Ryan reported ties to Janssen-Cilag, Pfizer, Galderma, and Abbott, and her associates reported ties to numerous industry sources.

The three most important gaps in current understanding of psoriasis are the need to fully elucidate the genetic underpinnings of the disease, delineate in more detail its natural history and prognostic factors, and better characterize and treat its associated comorbidities, according to an article in the Journal of the American Academy of Dermatology.

The academy recently issued guidelines for the management of psoriasis and psoriatic arthritis, which included a section concerning the most prominent deficiencies in knowledge about the disease. In the current article (J. Am. Acad. Dermatol. 2014;70:146-67), the expert panel that wrote the guidelines now details some of those gaps and suggests how future research should address them.

Advances in genetic research have allowed considerable progress in our understanding of the pathogenesis of psoriasis, including the identification of genetic susceptibility regions and nucleotide polymorphisms that are significantly associated with immune pathways, skin barrier function, and epidermal proliferation. Future research should "explore whether the genetic basis of psoriasis stems from a primary defect in immunologic function, a defect in keratinocyte function, or a complex interaction of both," wrote Dr. Caitriona Ryan of the Psoriasis Research Center, Baylor University Medical Center, Dallas, and her associates on the expert panel.

In particular, genetic research should help elucidate the correlation between psoriasis genotype and phenotype, determining whether psoriasis and psoriatic arthritis are genetically distinct diseases, as well as the genetic differences underlying guttate, erythrodermic, inverse, palmoplantar, and pustular forms of the disease.

Immunologic studies are needed to define the roles of various inflammatory cells in patients’ skin and blood, and to assist the development of targeted immunotherapies that will correct immunologic dysfunction without causing adverse immunosuppression. Similarly, the role of angiogenesis and the vascular bed in the pathogenesis of psoriasis requires more research attention, because topical or systemic inhibition of this process appears to be beneficial.

Additionally, the environmental factors that predispose to the development of psoriasis or contribute to disease exacerbations are still poorly defined. Research into lifestyle factors and the role of bacterial and viral infections should be especially revealing, Dr. Ryan and her associates said.

Research to determine the prevalence and natural history of psoriasis across different populations also is critical. Robust, long-term, prospective epidemiology studies at the population level are key.

Several subpopulations of psoriasis patients also deserve special attention. There is a dearth of both clinical and basic scientific data on pediatric psoriasis, when children are the very patients most likely to suffer the adverse psychosocial effects of psoriasis and the most vulnerable to the adverse physical and developmental effects of treatments, the investigators noted.

Women who are pregnant or breastfeeding constitute another important subgroup of psoriasis patients. Studies are urgently needed to examine the effects of the disease itself and of its therapies on pregnancy outcomes. Similarly, the elderly are a subgroup of patients that requires special attention to adverse medication effects, because they have a high prevalence of comorbid conditions, greater use of concomitant medications, diminished renal function, and age-related changes in pharmacokinetics and pharmacodynamics.

Finally, future research must more closely examine several comorbidities now known to accompany psoriasis, including diabetes, obesity, the metabolic syndrome, and, most importantly, cardiovascular disease.

Severe psoriasis now should be considered an independent cardiovascular risk factor. "As physicians, it is our responsibility to counsel patients with psoriasis regarding the increased risk of cardiometabolic conditions and the need for lifestyle modifications, including smoking cessation, weight reduction, and regular screening for diabetes and hypertension," Dr. Ryan and her colleagues said.

Determining whether systemic treatment of psoriasis mitigates cardiometabolic risk, especially if it entails newer biologic agents, also is important, they added.

Psychological comorbidities should not be overlooked. Patients with psoriasis are known to have high rates of anxiety, depression, and alexithymia—the inability to recognize or discuss feelings or emotional states. Relaxation techniques, meditation, and cognitive-behavioral therapy have shown efficacy and need further assessment.

Sexual functioning also should be studied in greater detail, since psoriasis can have a significant impact on sexuality, particularly if the disease affects the genitals.

Dr. Ryan reported ties to Janssen-Cilag, Pfizer, Galderma, and Abbott, and her associates reported ties to numerous industry sources.

The three most important gaps in current understanding of psoriasis are the need to fully elucidate the genetic underpinnings of the disease, delineate in more detail its natural history and prognostic factors, and better characterize and treat its associated comorbidities, according to an article in the Journal of the American Academy of Dermatology.

The academy recently issued guidelines for the management of psoriasis and psoriatic arthritis, which included a section concerning the most prominent deficiencies in knowledge about the disease. In the current article (J. Am. Acad. Dermatol. 2014;70:146-67), the expert panel that wrote the guidelines now details some of those gaps and suggests how future research should address them.

Advances in genetic research have allowed considerable progress in our understanding of the pathogenesis of psoriasis, including the identification of genetic susceptibility regions and nucleotide polymorphisms that are significantly associated with immune pathways, skin barrier function, and epidermal proliferation. Future research should "explore whether the genetic basis of psoriasis stems from a primary defect in immunologic function, a defect in keratinocyte function, or a complex interaction of both," wrote Dr. Caitriona Ryan of the Psoriasis Research Center, Baylor University Medical Center, Dallas, and her associates on the expert panel.

In particular, genetic research should help elucidate the correlation between psoriasis genotype and phenotype, determining whether psoriasis and psoriatic arthritis are genetically distinct diseases, as well as the genetic differences underlying guttate, erythrodermic, inverse, palmoplantar, and pustular forms of the disease.

Immunologic studies are needed to define the roles of various inflammatory cells in patients’ skin and blood, and to assist the development of targeted immunotherapies that will correct immunologic dysfunction without causing adverse immunosuppression. Similarly, the role of angiogenesis and the vascular bed in the pathogenesis of psoriasis requires more research attention, because topical or systemic inhibition of this process appears to be beneficial.

Additionally, the environmental factors that predispose to the development of psoriasis or contribute to disease exacerbations are still poorly defined. Research into lifestyle factors and the role of bacterial and viral infections should be especially revealing, Dr. Ryan and her associates said.

Research to determine the prevalence and natural history of psoriasis across different populations also is critical. Robust, long-term, prospective epidemiology studies at the population level are key.

Several subpopulations of psoriasis patients also deserve special attention. There is a dearth of both clinical and basic scientific data on pediatric psoriasis, when children are the very patients most likely to suffer the adverse psychosocial effects of psoriasis and the most vulnerable to the adverse physical and developmental effects of treatments, the investigators noted.

Women who are pregnant or breastfeeding constitute another important subgroup of psoriasis patients. Studies are urgently needed to examine the effects of the disease itself and of its therapies on pregnancy outcomes. Similarly, the elderly are a subgroup of patients that requires special attention to adverse medication effects, because they have a high prevalence of comorbid conditions, greater use of concomitant medications, diminished renal function, and age-related changes in pharmacokinetics and pharmacodynamics.

Finally, future research must more closely examine several comorbidities now known to accompany psoriasis, including diabetes, obesity, the metabolic syndrome, and, most importantly, cardiovascular disease.

Severe psoriasis now should be considered an independent cardiovascular risk factor. "As physicians, it is our responsibility to counsel patients with psoriasis regarding the increased risk of cardiometabolic conditions and the need for lifestyle modifications, including smoking cessation, weight reduction, and regular screening for diabetes and hypertension," Dr. Ryan and her colleagues said.

Determining whether systemic treatment of psoriasis mitigates cardiometabolic risk, especially if it entails newer biologic agents, also is important, they added.

Psychological comorbidities should not be overlooked. Patients with psoriasis are known to have high rates of anxiety, depression, and alexithymia—the inability to recognize or discuss feelings or emotional states. Relaxation techniques, meditation, and cognitive-behavioral therapy have shown efficacy and need further assessment.

Sexual functioning also should be studied in greater detail, since psoriasis can have a significant impact on sexuality, particularly if the disease affects the genitals.

Dr. Ryan reported ties to Janssen-Cilag, Pfizer, Galderma, and Abbott, and her associates reported ties to numerous industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

A mother’s use of selective serotonin reuptake inhibitors during pregnancy doesn’t appear to raise the risk of autism spectrum disorders in her offspring, according to a report published online Dec. 18 in the New England Journal of Medicine.

In a cohort study of all 626,875 singleton live births that occurred in Denmark between 1996 and 2005, fetal exposure to maternal SSRI use did not significantly increase the risk that the child would be diagnosed as having an autism spectrum disorder during 5-14 years of follow-up, said Dr. Anders Hviid of the department of epidemiology research, Statens Serum Institut, Copenhagen, and his associates.

This large nationwide study had the statistical power to rule out all but a small increase in relative risk, they noted.

Creatas Images

Dr. Hviid and his colleagues undertook this study because a recent California case-control study reported that the risk of autism spectrum disorder increased by a factor of two among offspring of women who used antidepressants, particularly SSRIs, during pregnancy, and that this risk was increased by a factor of more than three if the woman used an SSRI during the first trimester (Arch. Gen. Psychiatry 2011;68:1104-12). Evidence from other studies also seemed to bolster this association.

In addition, a causal association is biologically plausible, because people with autism spectrum disorders are known to have increased levels of circulating serotonin, and because serotonin appears to play an important role in early brain development. "Manipulation of serotonin homeostasis can alter neuroanatomical and neurophysiological development and produce enduring behavioral changes in animal models," Dr. Hviid and his associates said.

The investigators analyzed data from the Danish national birth registry, national prescription registry, and national registry of psychiatric diagnoses to assess the 626,875 children, including those who were born to 6,068 mothers who used SSRIs during pregnancy. A total of 3,892 cases of autism spectrum disorder were diagnosed.

In an initial analysis, autism was strongly associated with maternal psychiatric diagnoses and with the use of drugs other than SSRIs during pregnancy. This suggested possible confounding by indication, meaning that any association found between SSRI use and autism might be due to the mother’s underlying psychiatric disorder rather than to the medication she took for it.

During 42,400 person-years of follow-up, there were 52 cases of autism spectrum disorder among the offspring of women who took SSRIs during pregnancy. "In unadjusted analyses, we did find a significantly increased risk of autism spectrum disorder in association with the use of SSRIs during pregnancy.

"In fully adjusted analyses, however, the risk was no longer significant. This was primarily due to adjustment for a number of psychiatric diagnoses [in the mother], which is consistent with the presence of confounding by indication in the unadjusted analysis," the investigators said (N. Engl. J. Med. 2013;369:2406-15 [doi:10.1056/NEJMoa1301449]).

In a further analysis, the researchers found that SSRI use before but not during pregnancy was associated with an increased risk of subsequent autism spectrum disorders in the offspring, similarly suggesting that any association arose from the mother’s underlying psychiatric disorder rather than from the medication.

A sensitivity analysis restricted to the 574,020 pregnancies for which complete information was available yielded the same results as the main analysis: SSRI use during pregnancy did not raise the risk of autism spectrum disorders in the offspring.

One of the strengths of this study was that it was large enough to include 52 cases of autism spectrum disorder, which is more than three times the number of cases assessed in previous studies of this issue.

However, this study was limited in that the prevalence of SSRI use during pregnancy was only 0.97% in this cohort, whereas the prevalence in the United States is estimated to be 5.6%. Similarly, the prevalence of autism spectrum disorders in this cohort was only 0.62%, while it is estimated to be 1.14% in the United States "Thus, our findings may not be generalizable to other countries," Dr. Hviid and his associates said.

This study was funded by the Danish Health and Medicines Authority. No financial conflicts of interest were reported.

A mother’s use of selective serotonin reuptake inhibitors during pregnancy doesn’t appear to raise the risk of autism spectrum disorders in her offspring, according to a report published online Dec. 18 in the New England Journal of Medicine.

In a cohort study of all 626,875 singleton live births that occurred in Denmark between 1996 and 2005, fetal exposure to maternal SSRI use did not significantly increase the risk that the child would be diagnosed as having an autism spectrum disorder during 5-14 years of follow-up, said Dr. Anders Hviid of the department of epidemiology research, Statens Serum Institut, Copenhagen, and his associates.

This large nationwide study had the statistical power to rule out all but a small increase in relative risk, they noted.

Creatas Images

Dr. Hviid and his colleagues undertook this study because a recent California case-control study reported that the risk of autism spectrum disorder increased by a factor of two among offspring of women who used antidepressants, particularly SSRIs, during pregnancy, and that this risk was increased by a factor of more than three if the woman used an SSRI during the first trimester (Arch. Gen. Psychiatry 2011;68:1104-12). Evidence from other studies also seemed to bolster this association.

In addition, a causal association is biologically plausible, because people with autism spectrum disorders are known to have increased levels of circulating serotonin, and because serotonin appears to play an important role in early brain development. "Manipulation of serotonin homeostasis can alter neuroanatomical and neurophysiological development and produce enduring behavioral changes in animal models," Dr. Hviid and his associates said.

The investigators analyzed data from the Danish national birth registry, national prescription registry, and national registry of psychiatric diagnoses to assess the 626,875 children, including those who were born to 6,068 mothers who used SSRIs during pregnancy. A total of 3,892 cases of autism spectrum disorder were diagnosed.

In an initial analysis, autism was strongly associated with maternal psychiatric diagnoses and with the use of drugs other than SSRIs during pregnancy. This suggested possible confounding by indication, meaning that any association found between SSRI use and autism might be due to the mother’s underlying psychiatric disorder rather than to the medication she took for it.

During 42,400 person-years of follow-up, there were 52 cases of autism spectrum disorder among the offspring of women who took SSRIs during pregnancy. "In unadjusted analyses, we did find a significantly increased risk of autism spectrum disorder in association with the use of SSRIs during pregnancy.

"In fully adjusted analyses, however, the risk was no longer significant. This was primarily due to adjustment for a number of psychiatric diagnoses [in the mother], which is consistent with the presence of confounding by indication in the unadjusted analysis," the investigators said (N. Engl. J. Med. 2013;369:2406-15 [doi:10.1056/NEJMoa1301449]).

In a further analysis, the researchers found that SSRI use before but not during pregnancy was associated with an increased risk of subsequent autism spectrum disorders in the offspring, similarly suggesting that any association arose from the mother’s underlying psychiatric disorder rather than from the medication.

A sensitivity analysis restricted to the 574,020 pregnancies for which complete information was available yielded the same results as the main analysis: SSRI use during pregnancy did not raise the risk of autism spectrum disorders in the offspring.

One of the strengths of this study was that it was large enough to include 52 cases of autism spectrum disorder, which is more than three times the number of cases assessed in previous studies of this issue.

However, this study was limited in that the prevalence of SSRI use during pregnancy was only 0.97% in this cohort, whereas the prevalence in the United States is estimated to be 5.6%. Similarly, the prevalence of autism spectrum disorders in this cohort was only 0.62%, while it is estimated to be 1.14% in the United States "Thus, our findings may not be generalizable to other countries," Dr. Hviid and his associates said.

This study was funded by the Danish Health and Medicines Authority. No financial conflicts of interest were reported.

A mother’s use of selective serotonin reuptake inhibitors during pregnancy doesn’t appear to raise the risk of autism spectrum disorders in her offspring, according to a report published online Dec. 18 in the New England Journal of Medicine.

In a cohort study of all 626,875 singleton live births that occurred in Denmark between 1996 and 2005, fetal exposure to maternal SSRI use did not significantly increase the risk that the child would be diagnosed as having an autism spectrum disorder during 5-14 years of follow-up, said Dr. Anders Hviid of the department of epidemiology research, Statens Serum Institut, Copenhagen, and his associates.

This large nationwide study had the statistical power to rule out all but a small increase in relative risk, they noted.

Creatas Images

Dr. Hviid and his colleagues undertook this study because a recent California case-control study reported that the risk of autism spectrum disorder increased by a factor of two among offspring of women who used antidepressants, particularly SSRIs, during pregnancy, and that this risk was increased by a factor of more than three if the woman used an SSRI during the first trimester (Arch. Gen. Psychiatry 2011;68:1104-12). Evidence from other studies also seemed to bolster this association.

In addition, a causal association is biologically plausible, because people with autism spectrum disorders are known to have increased levels of circulating serotonin, and because serotonin appears to play an important role in early brain development. "Manipulation of serotonin homeostasis can alter neuroanatomical and neurophysiological development and produce enduring behavioral changes in animal models," Dr. Hviid and his associates said.

The investigators analyzed data from the Danish national birth registry, national prescription registry, and national registry of psychiatric diagnoses to assess the 626,875 children, including those who were born to 6,068 mothers who used SSRIs during pregnancy. A total of 3,892 cases of autism spectrum disorder were diagnosed.

In an initial analysis, autism was strongly associated with maternal psychiatric diagnoses and with the use of drugs other than SSRIs during pregnancy. This suggested possible confounding by indication, meaning that any association found between SSRI use and autism might be due to the mother’s underlying psychiatric disorder rather than to the medication she took for it.

During 42,400 person-years of follow-up, there were 52 cases of autism spectrum disorder among the offspring of women who took SSRIs during pregnancy. "In unadjusted analyses, we did find a significantly increased risk of autism spectrum disorder in association with the use of SSRIs during pregnancy.

"In fully adjusted analyses, however, the risk was no longer significant. This was primarily due to adjustment for a number of psychiatric diagnoses [in the mother], which is consistent with the presence of confounding by indication in the unadjusted analysis," the investigators said (N. Engl. J. Med. 2013;369:2406-15 [doi:10.1056/NEJMoa1301449]).

In a further analysis, the researchers found that SSRI use before but not during pregnancy was associated with an increased risk of subsequent autism spectrum disorders in the offspring, similarly suggesting that any association arose from the mother’s underlying psychiatric disorder rather than from the medication.

A sensitivity analysis restricted to the 574,020 pregnancies for which complete information was available yielded the same results as the main analysis: SSRI use during pregnancy did not raise the risk of autism spectrum disorders in the offspring.

One of the strengths of this study was that it was large enough to include 52 cases of autism spectrum disorder, which is more than three times the number of cases assessed in previous studies of this issue.

However, this study was limited in that the prevalence of SSRI use during pregnancy was only 0.97% in this cohort, whereas the prevalence in the United States is estimated to be 5.6%. Similarly, the prevalence of autism spectrum disorders in this cohort was only 0.62%, while it is estimated to be 1.14% in the United States "Thus, our findings may not be generalizable to other countries," Dr. Hviid and his associates said.

This study was funded by the Danish Health and Medicines Authority. No financial conflicts of interest were reported.

Patients with multiple myeloma who were treated with lenalidomide are susceptible to new-onset or reactivated varicella zoster infection, according to a new report.

Prophylactic acyclovir appears to minimize this risk, said Dr. C. König of the department of hematology and oncology, University of Freiburg (Germany) Medical Center, and associates.

Patients with multiple myeloma are known to be susceptible to infections from the myeloma itself; underlying immunodeficiency; the intensive therapies they receive; age-related conditions such as frailty and immobility; and disease-related conditions such as renal dysfunction, pulmonary impairment, or damage to the alimentary mucosa. In addition, specific antimyeloma agents such as bortezomib are known to raise the risk of varicella zoster virus reactivation or infection.

However, the risk of varicella zoster infection after treatment with lenalidomide is unknown.

Dr. König and colleagues reviewed the medical records of 132 consecutive multiple myeloma patients treated with lenalidomide at their center during a 4-year period and found that 10 (7.6%) had varicella zoster infections. Six patients were infected during treatment with lenalidomide or shortly afterward, and the other four were infected months later.

Of the 10 patients, 7 were men and 3 were women. Their ages ranged from 46 to 81 years

Seven of these cases were typical varicella zoster infections. In addition, one patient had varicella zoster encephalitis, one had disseminated varicella zoster, and one had varicella zoster with conus-cauda syndrome (Ann. Hematol. 2013 [doi:10.1007/s00277-013-1951-6]).

In two patients, the infection was a reactivation of latent varicella zoster.

Given that varicella is a known complication of other antimyeloma agents and acyclovir prophylaxis usually prevents it, Dr. König and associates then introduced routine acyclovir prophylaxis for their multiple myeloma patients slated to receive lenalidomide.

During the next 18 months, they treated 40 more multiple myeloma patients with lenalidomide, but only 37 of these patients adhered to the recommended daily acyclovir prophylaxis. None of those 37 developed varicella zoster infection. However, extensive varicella zoster developed in all three who didn’t take prophylactic acyclovir.

If these findings are confirmed in other, prospective studies, acyclovir prophylaxis may become routine for patients with multiple myeloma who are treated with lenalidomide, the investigators said.

It will be important to monitor renal function in such patients, given that antivirals are known to raise the risk of nephrotoxicity, they noted.

This study was supported by German Cancer Aid (Deutsche Krebshilfe). No financial conflicts of interest were reported.

Patients with multiple myeloma who were treated with lenalidomide are susceptible to new-onset or reactivated varicella zoster infection, according to a new report.

Prophylactic acyclovir appears to minimize this risk, said Dr. C. König of the department of hematology and oncology, University of Freiburg (Germany) Medical Center, and associates.

Patients with multiple myeloma are known to be susceptible to infections from the myeloma itself; underlying immunodeficiency; the intensive therapies they receive; age-related conditions such as frailty and immobility; and disease-related conditions such as renal dysfunction, pulmonary impairment, or damage to the alimentary mucosa. In addition, specific antimyeloma agents such as bortezomib are known to raise the risk of varicella zoster virus reactivation or infection.

However, the risk of varicella zoster infection after treatment with lenalidomide is unknown.

Dr. König and colleagues reviewed the medical records of 132 consecutive multiple myeloma patients treated with lenalidomide at their center during a 4-year period and found that 10 (7.6%) had varicella zoster infections. Six patients were infected during treatment with lenalidomide or shortly afterward, and the other four were infected months later.

Of the 10 patients, 7 were men and 3 were women. Their ages ranged from 46 to 81 years

Seven of these cases were typical varicella zoster infections. In addition, one patient had varicella zoster encephalitis, one had disseminated varicella zoster, and one had varicella zoster with conus-cauda syndrome (Ann. Hematol. 2013 [doi:10.1007/s00277-013-1951-6]).

In two patients, the infection was a reactivation of latent varicella zoster.

Given that varicella is a known complication of other antimyeloma agents and acyclovir prophylaxis usually prevents it, Dr. König and associates then introduced routine acyclovir prophylaxis for their multiple myeloma patients slated to receive lenalidomide.

During the next 18 months, they treated 40 more multiple myeloma patients with lenalidomide, but only 37 of these patients adhered to the recommended daily acyclovir prophylaxis. None of those 37 developed varicella zoster infection. However, extensive varicella zoster developed in all three who didn’t take prophylactic acyclovir.

If these findings are confirmed in other, prospective studies, acyclovir prophylaxis may become routine for patients with multiple myeloma who are treated with lenalidomide, the investigators said.

It will be important to monitor renal function in such patients, given that antivirals are known to raise the risk of nephrotoxicity, they noted.

This study was supported by German Cancer Aid (Deutsche Krebshilfe). No financial conflicts of interest were reported.

Patients with multiple myeloma who were treated with lenalidomide are susceptible to new-onset or reactivated varicella zoster infection, according to a new report.

Prophylactic acyclovir appears to minimize this risk, said Dr. C. König of the department of hematology and oncology, University of Freiburg (Germany) Medical Center, and associates.

Patients with multiple myeloma are known to be susceptible to infections from the myeloma itself; underlying immunodeficiency; the intensive therapies they receive; age-related conditions such as frailty and immobility; and disease-related conditions such as renal dysfunction, pulmonary impairment, or damage to the alimentary mucosa. In addition, specific antimyeloma agents such as bortezomib are known to raise the risk of varicella zoster virus reactivation or infection.

However, the risk of varicella zoster infection after treatment with lenalidomide is unknown.

Dr. König and colleagues reviewed the medical records of 132 consecutive multiple myeloma patients treated with lenalidomide at their center during a 4-year period and found that 10 (7.6%) had varicella zoster infections. Six patients were infected during treatment with lenalidomide or shortly afterward, and the other four were infected months later.

Of the 10 patients, 7 were men and 3 were women. Their ages ranged from 46 to 81 years

Seven of these cases were typical varicella zoster infections. In addition, one patient had varicella zoster encephalitis, one had disseminated varicella zoster, and one had varicella zoster with conus-cauda syndrome (Ann. Hematol. 2013 [doi:10.1007/s00277-013-1951-6]).

In two patients, the infection was a reactivation of latent varicella zoster.

Given that varicella is a known complication of other antimyeloma agents and acyclovir prophylaxis usually prevents it, Dr. König and associates then introduced routine acyclovir prophylaxis for their multiple myeloma patients slated to receive lenalidomide.

During the next 18 months, they treated 40 more multiple myeloma patients with lenalidomide, but only 37 of these patients adhered to the recommended daily acyclovir prophylaxis. None of those 37 developed varicella zoster infection. However, extensive varicella zoster developed in all three who didn’t take prophylactic acyclovir.

If these findings are confirmed in other, prospective studies, acyclovir prophylaxis may become routine for patients with multiple myeloma who are treated with lenalidomide, the investigators said.

It will be important to monitor renal function in such patients, given that antivirals are known to raise the risk of nephrotoxicity, they noted.

This study was supported by German Cancer Aid (Deutsche Krebshilfe). No financial conflicts of interest were reported.

Older women are sedentary for approximately two-thirds of their waking hours, usually in bouts lasting about 30 minutes each punctuated by brief periods of activity, according to a report published Dec. 18 in JAMA.

Recent studies suggest a high volume of sedentary behavior may be a risk factor for adverse health outcomes. However, few data exist on how this behavior is patterned (for example, does most sedentary behavior occur in a few long bouts or in many short bouts?)

In a research letter to the editor, investigators presented data collected from 7,247 older women (mean age, 71 years) participating in an ancillary study of the Women’s Health Study who wore accelerometers for 1 week to track their physical activity. Overall, the women spent 65.5% of their waking hours – the equivalent of 9.7 hours per day – in sedentary behavior, said Eric J. Shiroma of Harvard School of Public Health, Boston, and his associates.

©gizos/iStockphoto.com

The mean number of sedentary intervals was 85.9/day, with a mean of 9 breaks per sedentary hour. Most sedentary time occurred in short rather than long intervals, with approximately one-third of the sedentary bouts lasting roughly 30 minutes, the researchers said (JAMA 2013;310:2562-3).

Accelerometers cannot convey whether the women were sitting, standing, or lying down during sedentary periods, but it is most likely that they were sitting. "If future studies confirm the health hazards of sedentary behavior and guidelines are warranted, these data may be useful to inform recommendations on how to improve such behavior," Mr. Shiroma and his associates said.

They noted that most participants in the Women’s Health Study were white and of higher socioeconomic status, so these findings may not apply to women of other backgrounds.

This study was supported by the National Institutes of Health. No relevant financial conflicts of interest were reported.

Older women are sedentary for approximately two-thirds of their waking hours, usually in bouts lasting about 30 minutes each punctuated by brief periods of activity, according to a report published Dec. 18 in JAMA.

Recent studies suggest a high volume of sedentary behavior may be a risk factor for adverse health outcomes. However, few data exist on how this behavior is patterned (for example, does most sedentary behavior occur in a few long bouts or in many short bouts?)

In a research letter to the editor, investigators presented data collected from 7,247 older women (mean age, 71 years) participating in an ancillary study of the Women’s Health Study who wore accelerometers for 1 week to track their physical activity. Overall, the women spent 65.5% of their waking hours – the equivalent of 9.7 hours per day – in sedentary behavior, said Eric J. Shiroma of Harvard School of Public Health, Boston, and his associates.

©gizos/iStockphoto.com

The mean number of sedentary intervals was 85.9/day, with a mean of 9 breaks per sedentary hour. Most sedentary time occurred in short rather than long intervals, with approximately one-third of the sedentary bouts lasting roughly 30 minutes, the researchers said (JAMA 2013;310:2562-3).

Accelerometers cannot convey whether the women were sitting, standing, or lying down during sedentary periods, but it is most likely that they were sitting. "If future studies confirm the health hazards of sedentary behavior and guidelines are warranted, these data may be useful to inform recommendations on how to improve such behavior," Mr. Shiroma and his associates said.

They noted that most participants in the Women’s Health Study were white and of higher socioeconomic status, so these findings may not apply to women of other backgrounds.

This study was supported by the National Institutes of Health. No relevant financial conflicts of interest were reported.

Older women are sedentary for approximately two-thirds of their waking hours, usually in bouts lasting about 30 minutes each punctuated by brief periods of activity, according to a report published Dec. 18 in JAMA.

Recent studies suggest a high volume of sedentary behavior may be a risk factor for adverse health outcomes. However, few data exist on how this behavior is patterned (for example, does most sedentary behavior occur in a few long bouts or in many short bouts?)

In a research letter to the editor, investigators presented data collected from 7,247 older women (mean age, 71 years) participating in an ancillary study of the Women’s Health Study who wore accelerometers for 1 week to track their physical activity. Overall, the women spent 65.5% of their waking hours – the equivalent of 9.7 hours per day – in sedentary behavior, said Eric J. Shiroma of Harvard School of Public Health, Boston, and his associates.

©gizos/iStockphoto.com

The mean number of sedentary intervals was 85.9/day, with a mean of 9 breaks per sedentary hour. Most sedentary time occurred in short rather than long intervals, with approximately one-third of the sedentary bouts lasting roughly 30 minutes, the researchers said (JAMA 2013;310:2562-3).

Accelerometers cannot convey whether the women were sitting, standing, or lying down during sedentary periods, but it is most likely that they were sitting. "If future studies confirm the health hazards of sedentary behavior and guidelines are warranted, these data may be useful to inform recommendations on how to improve such behavior," Mr. Shiroma and his associates said.

They noted that most participants in the Women’s Health Study were white and of higher socioeconomic status, so these findings may not apply to women of other backgrounds.

This study was supported by the National Institutes of Health. No relevant financial conflicts of interest were reported.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.