Certain aspects of sleep co-occur with externalizing behaviours in youth, yet little is known about these associations in adults. The present study: (1) examines the associations between diurnal preference (morningness versus eveningness), sleep quality and externalizing behaviours; (2) explores the extent to which genetic and environmental influences are shared between or are unique to these phenotypes; (3) examines the extent to which genetic and environmental influences account for these associations.

Questionnaires assessing diurnal preference, sleep quality and externalizing behaviours were completed by 1556 young adult twins and siblings.

A preference for eveningness and poor sleep quality were associated with greater externalizing symptoms [r=0.28 (95% CI 0.23–0.33) and 0.34 (95% CI 0.28–0.39), respectively]. A total of 18% of the genetic influences on externalizing behaviours were shared with diurnal preference and sleep quality and an additional 14% were shared with sleep quality alone. Non-shared environmental influences common to the phenotypes were small (2%). The association between diurnal preference and externalizing behaviours was mostly explained by genetic influences [additive genetic influence (A)=80% (95% CI 0.56–1.01)], as was the association between sleep quality and externalizing behaviours [A=81% (95% CI 0.62–0.99)]. Non-shared environmental (E) influences accounted for the remaining variance for both associations [E=20% (95% CI −0.01 to 0.44) and 19% (95% CI 0.01–0.38), respectively].

A preference for eveningness and poor sleep quality are moderately associated with externalizing behaviours in young adults. There is a moderate amount of shared genetic influences between the phenotypes and genetic influences account for a large proportion of the association between sleep and externalizing behaviours. Further research could focus on identifying specific genetic polymorphisms common to both sleep and externalizing behaviours.

Cognitive-behavioral therapy (CBT) consisting of exposure and response prevention (EX/RP) is efficacious as a treatment for obsessive–compulsive disorder (OCD). However, about half of patients have a partial or poor response to EX/RP treatment. This study examined potential predictors and moderators of CBT augmentation of pharmacotherapy, to identify variables associated with a poorer response to OCD treatment.

Data were drawn from a large randomized controlled trial that compared the augmenting effects of EX/RP to stress management training (SMT; an active CBT control) among 108 participants receiving a therapeutic dose of a serotonin reuptake inhibitor (SRI). Stepwise regression was used to determine the model specification.

Pretreatment OCD severity and gender were significant moderators of outcome: severity affected SMT (but not EX/RP) outcome; and gender affected EX/RP (but not SMT) outcome. Adjusting for treatment type and pretreatment severity, significant predictors included greater co-morbidity, number of past SRI trials, and lower quality of life (QoL). Significant moderators, including their main-effects, and predictors accounted for 37.2% of the total variance in outcome, comparable to the impact of treatment type alone (R2=30.5%). These findings were replicated in the subgroup analysis of EX/RP alone (R2=55.2%).

This is the first randomized controlled study to examine moderators and predictors of CBT augmentation of SRI pharmacotherapy. Although effect sizes for individual predictors tended to be small, their combined effect was comparable to that of treatment. Thus, future research should examine whether monitoring for a combination of these risk factors and targeting them with multi-modular strategies can improve EX/RP outcome.

Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents).

A total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used latent profile analysis and ANOVA to identify and validate patterns of behavioral traits.

We distinguished three classes with medium to large effect sizes by mothers' and probands' drive for thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative differences. Class 1 (~33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 (~43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (~24%) included probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother–daughter symptom severity was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype.

A key finding is the importance of mother and daughter traits in the identification of temperament and personality patterns in families affected by AN. Mother–daughter pairs with severe ED and anxious/perfectionistic traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.

Parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms yield high estimates of heritability whereas self-ratings typically yield lower estimates. To understand why, the present study examined the etiological overlap between parent, teacher and self-ratings of ADHD symptoms in a population-based sample of 11–12-year-old twins.

Participants were from the Twins Early Development Study (TEDS). ADHD symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ) hyperactivity scale completed by parents, teachers and children. Structural equation modeling was used to examine genetic and environmental contributions to phenotypic variance/covariance.

The broad-sense heritability of ADHD symptoms was 82% for parent ratings, 60% for teacher ratings and 48% for self-ratings. Post-hoc analyses revealed significantly higher heritability for same-teacher than different-teacher ratings of ADHD (76% v. 49%). A common pathway model best explained the relationship between different informant ratings, with common genetic influences accounting for 84% of the covariance between parent, teacher and self-rated ADHD symptoms. The remaining variance was explained by rater-specific genetic and non-shared environmental influences.

Despite different heritabilities, there were shared genetic influences for parent, teacher and self-ratings of ADHD symptoms, indicating that different informants rated some of the same aspects of behavior. The low heritability estimated for self-ratings and different-teacher ratings may reflect increased measurement error when different informants rate each twin from a pair, and/or greater non-shared environmental influences. Future studies into the genetic influences on ADHD should incorporate informant data in addition to self-ratings to capture a pervasive, heritable component of ADHD symptomatology.

Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that ‘pessimism’-related emotion processing would characterize brain activity in major depression.

During functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences – pleasant, unpleasant and neutral – and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the ‘unknown’ expectation was compared with the ‘known’ expectation conditions.

While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations.

Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a ‘pessimistic’ attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

Language use is of increasing interest in the study of mental illness. Analytical approaches range from phenomenological and qualitative to formal computational quantitative methods. Practically, the approach may have utility in predicting clinical outcomes. We harnessed a real-world sample (blog entries) from groups with psychosis, strong beliefs, odd beliefs, illness, mental illness and/or social isolation to validate and extend laboratory findings about lexical differences between psychosis and control subjects.

We describe the results of two experiments using Linguistic Inquiry and Word Count software to assess word category frequencies. In experiment 1, we compared word use in psychosis and control subjects in the laboratory (23 per group), and related results to subject symptoms. In experiment 2, we examined lexical patterns in blog entries written by people with psychosis and eight comparison groups. In addition to between-group comparisons, we used factor analysis followed by clustering to discern the contributions of strong belief, odd belief and illness identity to lexical patterns.

Consistent with others’ work, we found that first-person pronouns, biological process words and negative emotion words were more frequent in psychosis language. We tested lexical differences between bloggers with psychosis and multiple relevant comparison groups. Clustering analysis revealed that word use frequencies did not group individuals with strong or odd beliefs, but instead grouped individuals with any illness (mental or physical).

Pairing of laboratory and real-world samples reveals that lexical markers previously identified as specific language changes in depression and psychosis are probably markers of illness in general.

Inflammation is a possible biological mechanism underlying the association between childhood maltreatment and psychosis. Previous investigations on this regard were mainly conducted on chronic schizophrenia and lacked control for confounders. We aim to investigate the role of familial liability, childhood maltreatment and recent stress in determining cytokine abnormalities at the onset of psychosis.

We recruited 114 first-episode psychosis (FEP) patients, 57 unaffected biological siblings of FEP patients, and 251 community-based controls. Plasma cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10 and TGF-β) were measured and differences across the groups analysed after adjusting for potential confounders.

FEP had a higher pro- and anti-inflammatory cytokine profile (IL-1β, IL-6, TNF-α, IL-10 and TGF-β), which was not observed in unaffected siblings. Siblings presented decreased IL-1β when compared with patients and controls. Childhood maltreatment was associated with higher levels of TGF-β in both patients and siblings when compared with controls. Physical childhood abuse was associated with increased levels of TGF-β in FEP patients but with decreased levels in controls. Other childhood maltreatment subtypes or recent stressors did not affect cytokine levels in any of the groups.

Normal or reduced cytokines in siblings represent possibly a protective factor and suggest that the identified inflammatory profile in FEP can be a real pathophysiological component of psychosis. Experience of childhood maltreatment may contribute as long-term immune priming for the TGF-β pathway, and increased levels of this cytokine in both patients and siblings exposed to childhood maltreatment point to a possible biological candidate of familial risk for psychosis.

Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.

A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.

In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).

This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

Anxiety disorders are highly prevalent in people with bipolar disorder, but it is not clear how many have anxiety disorders even at times when they are free of major mood episodes. We aimed to establish what proportion of euthymic individuals with bipolar disorder meet diagnostic criteria for anxiety disorders.

We performed a random-effects meta-analysis of prevalence rates of current DSM-III- and DSM-IV-defined anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder, specific phobia, obsessive–compulsive disorder, post-traumatic stress disorder, and anxiety disorder not otherwise specified) in euthymic adults with bipolar disorder in studies published by 31 December 2015.

Across 10 samples with 2120 individuals with bipolar disorder, 34.7% met diagnostic criteria for one or more anxiety disorders during euthymia [95% confidence interval (CI) 23.9–45.5%]. Direct comparison of 189 euthymic individuals with bipolar disorder and 17 109 population controls across three studies showed a 4.6-fold increase (risk ratio 4.60, 95% CI 2.37–8.92, p < 0.001) in prevalence of anxiety disorders in those with bipolar disorder.

These findings suggest that anxiety disorders are common in people with bipolar disorder even when their mood is adequately controlled. Euthymic people with bipolar disorder should be routinely assessed for anxiety disorders and anxiety-focused treatment should be initiated if indicated.

Schizophrenia patients show disturbances on a range of tasks that assess mentalizing or ‘Theory of Mind’ (ToM). However, these tasks are often developmentally inappropriate, make large demands on verbal abilities and explicit problem-solving skills, and involve after-the-fact reflection as opposed to spontaneous mentalizing.

To address these limitations, 55 clinically stable schizophrenia out-patients and 44 healthy controls completed a validated Animations Task designed to assess spontaneous attributions of social meaning to ambiguous abstract visual stimuli. In this paradigm, 12 animations depict two geometric shapes ‘interacting’ with each other in three conditions: (1) ToM interactions that elicit attributions of mental states to the agents, (2) Goal-Directed (GD) interactions that elicit attributions of simple actions, and (3) Random scenes in which no interaction occurs. Verbal descriptions of each animation are rated for the degree of Intentionality attributed to the agents and for accuracy.

Patients had lower Intentionality ratings than controls for ToM and GD scenes but the groups did not significantly differ for Random scenes. The descriptions of the patients less closely matched the situations intended by the developers of the task. Within the schizophrenia group, performance on the Animations Task showed minimal associations with clinical symptoms.

Patients demonstrated disturbances in the spontaneous attribution of mental states to abstract visual stimuli that normally evoke such attributions. Hence, in addition to previously established impairment on mentalizing tasks that require logical inferences about others' mental states, individuals with schizophrenia show disturbances in implicit aspects of mentalizing.

Decreased cortical thickness in frontal and temporal regions has been observed in individuals suffering from post-traumatic stress disorder (PTSD), compared to healthy controls and trauma-exposed participants without PTSD. In addition, individual differences, both functional and structural, in the anterior cingulate cortex (ACC) have been shown to predict symptom severity reduction. Although there is some evidence suggesting that activity in this region changes as a function of recovery, it remains unknown whether there are any structural correlates of recovery from PTSD.

Thirty participants suffering from moderate to severe PTSD underwent a magnetic resonance imaging (MRI) scan following an initial clinical assessment. A second assessment took place 6–9 months later. In addition, a subgroup of 25 participants completed a second MRI scan at that time. PTSD symptom severity changes over time were regressed against vertex-based cortical thickness.

We found that cortical thickness in the right subgenual ACC (sgACC) predicted symptom improvement. Moreover, cortical thickness within this region of the ACC, measured 6–9 months later (n = 25), was also correlated with the same measure of symptom improvement. By contrast, no relationship was found between change in cortical thickness in this area and current PTSD symptom levels or degree of recovery.

Our results suggest that sgACC thickness may be a stable marker of recovery potential in PTSD.

The benefits of peer support interventions (PSIs) for individuals with mental illness are not well known. The aim of this systematic review and meta-analysis was to assess the effectiveness of PSIs for individuals with mental illness for clinical, personal, and functional recovery outcomes.

Searches were conducted in PubMed, Embase, and PsycINFO (December 18, 2020). Included were randomized controlled trials (RCTs) comparing peer-delivered PSIs to control conditions. The quality of records was assessed using the Cochrane Collaboration Risk of Bias tool. Data were pooled for each outcome, using random-effects models.

After screening 3455 records, 30 RCTs were included in the systematic review and 28 were meta-analyzed (4152 individuals). Compared to control conditions, peer support was associated with small but significant post-test effect sizes for clinical recovery, g = 0.19, 95% CI (0.11–0.27), I2 = 10%, 95% CI (0–44), and personal recovery, g = 0.15, 95% CI (0.04–0.27), I2 = 43%, 95% CI (1–67), but not for functional recovery, g = 0.08, 95% CI (−0.02 to 0.18), I2 = 36%, 95% CI (0–61). Our findings should be considered with caution due to the modest quality of the included studies.

PSIs may be effective for the clinical and personal recovery of mental illness. Effects are modest, though consistent, suggesting potential efficacy for PSI across a wide range of mental disorders and intervention types.

Although the association between attention-deficit/hyperactivity disorder (ADHD) and drug use disorder (DUD) is well documented, it is unclear whether it is causal or results from familial confounding.

In this study we included all 551 164 individuals born in Sweden between 1991 and 1995 and used linked data from multiple nationwide registries to identify those with ADHD prior to age 15 years (1.71%). We used Cox proportional hazards models to investigate the future risk for DUD as a function of an ADHD registration and then compared the results from the entire population with the results from a co-relative design. Using the Swedish Multi-Generation Register, we identified all full-sibling, half-sibling and first-cousin pairs discordant for ADHD.

In the population sample, ADHD had a substantially increased risk for future DUD with a hazard ratio (HR) of 3.34 after accounting for gender and parental education. Examining discordant cousin pairs, discordant half-siblings and discordant siblings, those with ADHD had HRs for DUD of 3.09, 2.10 and 2.38 respectively. Controlling for the number of ADHD registrations, ADHD patients with and without stimulant treatment were similarly associated with later DUD risk.

ADHD diagnosed before 15 years of age was strongly related to future risk for DUD. The magnitude of this association was modestly reduced in relative pairs discordant for ADHD, suggesting that the ADHD–DUD association is partly causal and partly a result of familial confounding. We found no evidence to suggest that this association resulted from stimulant treatment.

Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.

This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.

Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).

Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.

In depression, non-remission, recurrence of depressive episodes after remission and conversion to bipolar disorder are crucial determinants of poor outcome. The present study aimed to determine the cumulative incidences and clinical predictors of these long-term outcomes after the first lifetime episode of depression.

A total of 301 in- or out-patients aged 18–70 years with a validated diagnosis of a single depressive episode were assessed from 2005 to 2007. At 5 years of follow-up, 262 patients were reassessed by means of the life chart method and diagnostic interviews from 2011 to 2013. Cumulative incidences and the influence of clinical variables on the rates of remission, recurrence and conversion to bipolar disorder, respectively, were estimated by survival analysis techniques.

Within 5 years, 83.3% obtained remission, 31.5% experienced recurrence of depression and 8.6% converted to bipolar disorder (6.3% within the first 2 years). Non-remission increased with younger age, co-morbid anxiety and suicidal ideations. Recurrence increased with severity and treatment resistance of the first depression, and conversion to bipolar disorder with treatment resistance, a family history of affective disorder and co-morbid alcohol or drug abuse.

The identified clinical characteristics of the first lifetime episode of depression should guide patients and clinicians for long-term individualized tailored treatment.

Prospective studies on the relationship between course of cannabis use and clinical outcome in patients with non-affective psychotic disorders are inconclusive. The current study examined whether (1) persistent, recently started, discontinued and non-cannabis-using patients with a psychotic disorder differed with regard to illness outcome at 3-year follow-up, and (2) whether timing of cannabis discontinuation was associated with course of clinical outcome.

This 3-year follow-up study was part of a multi-center study in the Netherlands and Belgium (Genetic Risk and Outcome of Psychosis; GROUP). We used mixed-model analyses to investigate the association between pattern of cannabis use and symptoms, global functioning and psychotic relapse.

In our sample of 678 patients, we found persistent users to have more positive and general symptoms, worse global functioning and more psychotic relapses compared with non-users and discontinued users [Positive and Negative Syndrome Scale (PANSS) positive, p < 0.001; PANSS general, p < 0.001; Global Assessment of Functioning (GAF) symptoms, p = 0.017; GAF disability, p < 0.001; relapses, p = 0.038]. Patients who started using cannabis after study onset were characterized by worse functioning at baseline and showed an increase in general symptoms (including depression and anxiety) at the 3-year follow-up (p = 0.005). Timing of cannabis discontinuation was not associated with clinical outcome.

These findings suggest that cannabis use in patients with a psychotic disorder has a long-lasting negative effect on illness outcome, particularly when persistent. Treatment should focus on discouraging cannabis use.