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D.C.O. is psychiatric commissioner on the Commission on Human Medicines and a member of the European Medicines Agency's Scientific Advisory Group on Psychiatry. He chaired the European Medicines Agency's review of the psychiatric use of valproate in pregnancy and women of childbearing potential.

Enhanced sensitivity to oestrogen signalling may drive increased risk for depressive symptoms when exposed to peripartum sex-steroid hormone fluctuations.

Testing if 116 pre-identified sex steroid-responsive transcripts that predicted perinatal depression (PND) translates to a pharmacological model of hormone-induced mood changes.

We generated longitudinal, genome-wide gene-expression and DNA-methylation data from 60 women exposed to a gonadotrophin-releasing hormone agonist (GnRHa) or placebo. We used linear mixed-effect models to assess differences between baseline and follow-up for gene expression and DNA methylation in the biphasic ovarian response to GnRHa.

Of the 116 PND-predictive transcripts, a significant (19%) overlap was observed with those differentially expressed post-GnRHa at both early and later follow-up, indicating sustained effects. Similarly, 49% of tested genes were differentially methylated post-GnRHa at the late follow-up. Within the GnRHa group, a large proportion of PND genes were significantly associated (gene expression; DNA methylation) with changes in depressive symptoms (28%; 66%), oestradiol levels (49%; 66%) and neocortex serotonin transporter binding (8%; 45%) between baseline and follow-up.

Our data bridge clinical PND biomarkers with a pharmacological model of sex hormone-induced mood changes and directly relate oestrogen-induced biological changes with depressive symptoms and associated serotonin-signalling changes. Our data highlight that individual variations in molecular sensitivity to oestrogen associate with susceptibility to hormone-induced mood changes and hold promise for candidate biomarkers.

V.G.F. received honorarium for being a speaker for H. Lundbeck A/S. E.B.B. receives research funding from Böhringer Ingelheim to investigate FKBP5 as a potential drug target for depression.

Contextually appropriate interventions delivered by primary maternal care providers (PMCPs) might be effective in reducing the treatment gap for perinatal depression.

To compare high-intensity treatment (HIT) with low-intensity treatment (LIT) for perinatal depression.

Cluster randomised clinical trial, conducted in Ibadan, Nigeria between 18 June 2013 and 11 December 2015 in 29 maternal care clinics allocated by computed-generated random sequence (15 HIT; 14 LIT). Interventions were delivered individually to antenatal women with DSM-IV (1994) major depression by trained PMCPs. LIT consisted of the basic psychosocial treatment specifications in the World Health Organization Mental Health Gap Action Programme – Intervention Guide. HIT comprised LIT plus eight weekly problem-solving therapy sessions with possible additional sessions determined by scores on the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome was remission of depression at 6 months postpartum (EPDS < 6).

There were 686 participants; 452 and 234 in HIT and LIT arms, respectively, with both groups similar at baseline. Follow-up assessments, completed on 85%, showed remission rates of 70% with HIT and 66% with LIT: risk difference 4% (95% CI −4.1%, 12.0%), adjusted odds ratio 1.12 (95% CI 0.73, 1.72). HIT was more effective for severe depression (odds ratio 2.29; 95% CI 1.01, 5.20; P = 0.047) and resulted in a higher rate of exclusive breastfeeding. Infant outcomes, cost-effectiveness and adverse events were similar.

Except among severely depressed perinatal women, we found no strong evidence to recommend high-intensity in preference to low-intensity psychological intervention in routine primary maternal care.

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A diagnosis of dissociative identity disorder (DID) is controversial and prone to under- and misdiagnosis. From the moment of seeking treatment for symptoms to the time of an accurate diagnosis of DID individuals received an average of four prior other diagnoses and spent 7 years, with reports of up to 12 years, in mental health services.

To investigate whether data-driven pattern recognition methodologies applied to structural brain images can provide biomarkers to aid DID diagnosis.

Structural brain images of 75 participants were included: 32 female individuals with DID and 43 matched healthy controls. Individuals with DID were recruited from psychiatry and psychotherapy out-patient clinics. Probabilistic pattern classifiers were trained to discriminate cohorts based on measures of brain morphology.

The pattern classifiers were able to accurately discriminate between individuals with DID and healthy controls with high sensitivity (72%) and specificity (74%) on the basis of brain structure. These findings provide evidence for a biological basis for distinguishing between DID-affected and healthy individuals.

We propose a pattern of neuroimaging biomarkers that could be used to inform the identification of individuals with DID from healthy controls at the individual level. This is important and clinically relevant because the DID diagnosis is controversial and individuals with DID are often misdiagnosed. Ultimately, the application of pattern recognition methodologies could prevent unnecessary suffering of individuals with DID because of an earlier accurate diagnosis, which will facilitate faster and targeted interventions.

The authors declare no competing financial interests.

Subsyndromal emotional symptoms in adolescence may represent precursors for full-blown emotional disorders in early adulthood. Understanding the neurobiological mechanisms that drive this development is essential for prevention.

Self-referential processing and emotion regulation are remodelled substantively during adolescence, therefore this study examined integration of key neural networks involved in these processes.

At baseline, clinical and resting-state functional magnetic resonance imaging data were collected for 88 adolescent girls (mean age 15 years), and 71 of these girls underwent repeat clinical assessment after 2 years. These 71 girls were then partitioned into two groups depending on the presence (ES+) or absence (ES−) of emotional symptoms, and differences in dynamic functional network connectivity were determined and correlated with clinical variables.

The two groups displayed a differential pattern of functional connectivity involving the left lateral prefrontal network (LPFN). Specifically, in the ES+ group this network displayed positive coupling with the right LPFN but negative coupling with the default mode network, and the inverse of this pattern was found in the ES− group. Furthermore, the coupling strengths between left and right LPFN at the irst time point predicted follow-up depression and state anxiety scores.

Our findings suggest that in adolescent girls, emotional symptoms may emerge as a result of impaired integration between networks involved in self-referential information processing and approach-avoidance behaviours. These impairments can compromise the pursuit of important goals and have an impact on emotion processing and finally may lead to the development of emotional disorders, such as anxiety and depression in adulthood.

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Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.

To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.

Participants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.

Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.

Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.

R.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.

Childhood adversity is a well-established risk factor for psychopathology; however, many who experience adversity do not go on to develop psychopathology. Poor self-concept and poor parental support are known risk factors for adolescent psychopathology, which may account for some of this mechanism.

To investigate candidate mediators in the relationship between childhood adversity and psychopathology.

We used data from the age 9 and 13 waves of the child-cohort of the Growing Up in Ireland study. We undertook mediation analysis by path decomposition of the relationship between childhood adversity and psychopathology (internalising and externalising problems) at age 13 and persistent psychopathology. Candidate mediators were self-concept, parent–child relationship and hobby participation at age 9.

Childhood adversity was reported by 28.2% of participants, and was significantly associated with internalising and externalising problems. Parent–child conflict mediated the relationship between childhood adversity and both age 13 and persistent psychopathology, accounting for 52.4% of the relationship between childhood adversity and persistent externalising problems (indirect odds ratio, 1.30; 95% CI 1.19–1.43) and 19.2% for persistent internalising problems (indirect odds ratio, 1.24; 95% CI 1.15–1.34). There was a small mediating effect of self-concept. Hobby participation and positive parent–child relationship did not mediate these relationships.

Parent–child conflict explains almost half the relationship between childhood adversity and persisting externalising problems in adolescence, and a fifth of the relationship with persisting internalising problems. This suggests parent–child conflict is a good target for interventions in childhood to prevent adolescent psychopathology.

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