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Research round-up
Insight
Caia Image/Science Photo Library
Research round-up
For more on comorbidities in girls with ADHD see Pediatrics 2016, published online Sept 21. http://dx.doi.org/10.1542/ peds.2016–0430 For more on subcortical volumes in OCD see Am J Psychiatry 2016, published online Sept 9. http://dx.doi.org/10.1176/ appi.ajp.2016.16020201 For more on reporting antidepressant harms see Eur Neuropsychopharmacol 2016, published online Sept 19. http://dx.doi.org/10.1016/ j.euroneuro.2016.09.370 For more on serotonin, anxiety, and fear see Nature 2016; 537: 97–101. For more on preventing depressive disorders after traumatic brain injury see JAMA Psychiatry 2016, published online Sept 14. http://dx.doi.org/10.1001/ jamapsychiatry.2016.2189 For more on mental health in elderly people see Br J Psychiatry 2016, published online Sept 8 http://dx.doi.org/10.1192/ bjp.bp.115.180463
1018
Comorbidities in girls with ADHD
Reporting antidepressant harms
Tung and colleagues highlight the burden of psychiatric comorbidities in girls (mean age range 8·5–13·5 years) with attention-deficit/hyperactivity disorder (ADHD) in a meta-analysis. After adjusting for potential bias when appropriate, results indicated that relative to girls without ADHD, girls with ADHD were more likely to have oppositional defiant disorder (18 studies; odds ratio [OR] 5·61, 95% CI 3·17–10·48), conduct disorder (15 studies; 9·41, 5·63–15·73), anxiety (11 studies; 3·19, 1·81–5·65), or depression (12 studies; 4·21, 2·08–8·51). In girls with ADHD, the odds for externalising disorders (oppositional defiant disorder and conduct disorder) were higher compared with the odds for internalising disorders (anxiety and depression).
Suboptimal reporting of the safety of second-generation antidepressant medication in journal articles and US Food and Drug Administration (FDA) reviews is shown in a new metaanalysis by de Vries and colleagues. The authors included data from 133 trials of antidepressants for treating depression or anxiety disorders (31 296 individuals) in their study. Out of 133 trials included in the FDA reviews, 57 (43%) had data missing for serious adverse events. In addition, 61 (63%) of 97 published papers did not mention the occurrence of serious adverse events. A total of 21 published papers could be fully compared with FDA information; of these, only 6 (29%) provided complete reporting of serious adverse events and 9 (43%) reported a different number of serious adverse events compared with FDA data (in favour of the treatment in 7 of the papers).
Subcortical volumes in OCD With data from 25 institutes worldwide, the ENIGMA OCD Working Group have analysed brain imaging data for 1830 individuals (including 335 children) with obsessivecompulsive disorder (OCD), and compared them with images from 1759 control participants (including 287 children). In the meta-analysis, of the nine regions assessed, hippocampal volumes were lower in the adults with OCD than in controls (% difference: –2·802; p= 5·08 × 10–³), while pallidum volumes were higher in cases compared with controls (3·156; p = 1·60 × 10–³); mega-analysis supported these results. The differences in subcortical volumes were more marked in adults who were receiving medication than in control participants. In the paediatric cohort, no differences in subcortical volumes were apparent between cases and controls. Analysis of the paediatric unmedicated cohort indicated larger volumes in the thalamus than in control participants (% difference: 3·078; p = 2·09 × 10–³).
Serotonin, anxiety, and fear The potential role of serotonin (5-HT) in regulating fear and anxiety has been investigated in a mouse study by Marcinkiewcz and colleagues. Using a variety of methods, including neuronal labelling and footshock and fear-conditioning experiments in mice, researchers deduced that projections of 5-HT neurons in the dorsal raphe nucleus to the bed nucleus of the stria terminalis potentiated anxiety-like behaviour, which was inhibited by a 5-HT 2CR antagonist. Fluoxetine injection in test animals led to anxiety-like behaviour, which was decreased by chemogenetic inhibition of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis. Taking into account results from their various experiments, the authors proposed that, “acute fluoxetine engenders aversive behaviour by recruiting CRF neurons in the bed nucleus of the
stria terminalis that in turn inhibit putative GABAergic (anxiolytic and stress buffering) outputs from the bed nucleus of the stria terminalis to the ventral tegmental area and lateral hypothalamus.”
Preventing depressive disorders after TBI In a randomised clinical trial, Jorge and colleagues have assessed the efficacy of sertraline in the prevention of mood disorders in people who have had a traumatic brain injury (TBI). In the 24-week double-blind single centre (Iowa, USA) study, 46 participants with TBI were allocated to placebo and 48 to sertraline (100 mg per day). At 24 weeks follow-up, compared with placebo, the number needed to treat to prevent depressive disorder with sertraline was 5·9 (95% CI, 3·1–71·1; p=0·03). Although treatment was generally well tolerated, participants receiving sertraline were more likely to experience dry mouth (OR 7·2, 90% CI 1·9–27·6; p=0·01) or diarrhoea (2·3, 1·0–5·5; p=0·10) than individuals allocated to placebo.
Mental health in elderly people Results from the European MentDis_ ICF65+ study highlight the substantial burden of psychiatric disorders in people aged 65–84 years. Researchers included data for 3142 people from Spain, England, Italy, Germany, Israel, and Switzerland in their cross-sectional study. Overall, nearly half of the study population had experienced a mental disorder at some point over their lifetime (47·0%, 95% CI 42·8–51·3), with more than a third having experienced such a disorder in the previous 12 months (35·2%, 95% CI 31·0–39·5). Current mental disorders were present in nearly a quarter of the study population (23·3%, 95% CI 19·9–26·7).
Seema Kang
www.thelancet.com/psychiatry Vol 3 November 2016
Caia Image/Science Photo Library
Research round-up
For more on comorbidities in girls with ADHD see Pediatrics 2016, published online Sept 21. http://dx.doi.org/10.1542/ peds.2016–0430 For more on subcortical volumes in OCD see Am J Psychiatry 2016, published online Sept 9. http://dx.doi.org/10.1176/ appi.ajp.2016.16020201 For more on reporting antidepressant harms see Eur Neuropsychopharmacol 2016, published online Sept 19. http://dx.doi.org/10.1016/ j.euroneuro.2016.09.370 For more on serotonin, anxiety, and fear see Nature 2016; 537: 97–101. For more on preventing depressive disorders after traumatic brain injury see JAMA Psychiatry 2016, published online Sept 14. http://dx.doi.org/10.1001/ jamapsychiatry.2016.2189 For more on mental health in elderly people see Br J Psychiatry 2016, published online Sept 8 http://dx.doi.org/10.1192/ bjp.bp.115.180463
1018
Comorbidities in girls with ADHD
Reporting antidepressant harms
Tung and colleagues highlight the burden of psychiatric comorbidities in girls (mean age range 8·5–13·5 years) with attention-deficit/hyperactivity disorder (ADHD) in a meta-analysis. After adjusting for potential bias when appropriate, results indicated that relative to girls without ADHD, girls with ADHD were more likely to have oppositional defiant disorder (18 studies; odds ratio [OR] 5·61, 95% CI 3·17–10·48), conduct disorder (15 studies; 9·41, 5·63–15·73), anxiety (11 studies; 3·19, 1·81–5·65), or depression (12 studies; 4·21, 2·08–8·51). In girls with ADHD, the odds for externalising disorders (oppositional defiant disorder and conduct disorder) were higher compared with the odds for internalising disorders (anxiety and depression).
Suboptimal reporting of the safety of second-generation antidepressant medication in journal articles and US Food and Drug Administration (FDA) reviews is shown in a new metaanalysis by de Vries and colleagues. The authors included data from 133 trials of antidepressants for treating depression or anxiety disorders (31 296 individuals) in their study. Out of 133 trials included in the FDA reviews, 57 (43%) had data missing for serious adverse events. In addition, 61 (63%) of 97 published papers did not mention the occurrence of serious adverse events. A total of 21 published papers could be fully compared with FDA information; of these, only 6 (29%) provided complete reporting of serious adverse events and 9 (43%) reported a different number of serious adverse events compared with FDA data (in favour of the treatment in 7 of the papers).
Subcortical volumes in OCD With data from 25 institutes worldwide, the ENIGMA OCD Working Group have analysed brain imaging data for 1830 individuals (including 335 children) with obsessivecompulsive disorder (OCD), and compared them with images from 1759 control participants (including 287 children). In the meta-analysis, of the nine regions assessed, hippocampal volumes were lower in the adults with OCD than in controls (% difference: –2·802; p= 5·08 × 10–³), while pallidum volumes were higher in cases compared with controls (3·156; p = 1·60 × 10–³); mega-analysis supported these results. The differences in subcortical volumes were more marked in adults who were receiving medication than in control participants. In the paediatric cohort, no differences in subcortical volumes were apparent between cases and controls. Analysis of the paediatric unmedicated cohort indicated larger volumes in the thalamus than in control participants (% difference: 3·078; p = 2·09 × 10–³).
Serotonin, anxiety, and fear The potential role of serotonin (5-HT) in regulating fear and anxiety has been investigated in a mouse study by Marcinkiewcz and colleagues. Using a variety of methods, including neuronal labelling and footshock and fear-conditioning experiments in mice, researchers deduced that projections of 5-HT neurons in the dorsal raphe nucleus to the bed nucleus of the stria terminalis potentiated anxiety-like behaviour, which was inhibited by a 5-HT 2CR antagonist. Fluoxetine injection in test animals led to anxiety-like behaviour, which was decreased by chemogenetic inhibition of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis. Taking into account results from their various experiments, the authors proposed that, “acute fluoxetine engenders aversive behaviour by recruiting CRF neurons in the bed nucleus of the
stria terminalis that in turn inhibit putative GABAergic (anxiolytic and stress buffering) outputs from the bed nucleus of the stria terminalis to the ventral tegmental area and lateral hypothalamus.”
Preventing depressive disorders after TBI In a randomised clinical trial, Jorge and colleagues have assessed the efficacy of sertraline in the prevention of mood disorders in people who have had a traumatic brain injury (TBI). In the 24-week double-blind single centre (Iowa, USA) study, 46 participants with TBI were allocated to placebo and 48 to sertraline (100 mg per day). At 24 weeks follow-up, compared with placebo, the number needed to treat to prevent depressive disorder with sertraline was 5·9 (95% CI, 3·1–71·1; p=0·03). Although treatment was generally well tolerated, participants receiving sertraline were more likely to experience dry mouth (OR 7·2, 90% CI 1·9–27·6; p=0·01) or diarrhoea (2·3, 1·0–5·5; p=0·10) than individuals allocated to placebo.
Mental health in elderly people Results from the European MentDis_ ICF65+ study highlight the substantial burden of psychiatric disorders in people aged 65–84 years. Researchers included data for 3142 people from Spain, England, Italy, Germany, Israel, and Switzerland in their cross-sectional study. Overall, nearly half of the study population had experienced a mental disorder at some point over their lifetime (47·0%, 95% CI 42·8–51·3), with more than a third having experienced such a disorder in the previous 12 months (35·2%, 95% CI 31·0–39·5). Current mental disorders were present in nearly a quarter of the study population (23·3%, 95% CI 19·9–26·7).
Seema Kang
www.thelancet.com/psychiatry Vol 3 November 2016