Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.

Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.

Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).

Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.

To estimate the spectrum of familial risk for psychopathology in first-degree relatives of children with unabridged DSM-IV bipolar-I disorder (BP-I).

We conducted a blinded, controlled family study using structured diagnostic interviews of 157 children with BP-I probands (n=487 first-degree relatives), 162 attention deficit hyperactivity disorder (ADHD) (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives).

The morbid risk (MR) of BP-I disorder in relatives of BP-I probands (MR=0.18) was increased 4-fold [95% confidence interval (CI) 2.3–6.9, p<0.001] over the risk to relatives of control probands (MR=0.05) and 3.5-fold (95% CI 2.1–5.8, p<0.001) over the risk to relatives of ADHD probands (MR=0.06). In addition, relatives of children with BP-I disorder had high rates of psychosis, major depression, multiple anxiety disorders, substance use disorders, ADHD and antisocial disorders compared with relatives of control probands. Only the effect for antisocial disorders lost significance after accounted for by the corresponding diagnosis in the proband. Familial rates of ADHD did not differ between ADHD and BP-I probands.

Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I. Relatives of probands with BP-I were also at increased risk for other psychiatric disorders frequently associated with pediatric BP-I. These results support the validity of the diagnosis of BP-I in children as defined by DSM-IV. More work is needed to better understand the nature of the association between these disorders in probands and relatives.

Although a substantial body of research points to a link between psychological distress and inflammatory responses in middle-aged and older adults, particularly those with cardiovascular disease, the relationship between inflammation and distress in young, healthy individuals has not been established. This study was designed to investigate the cross-sectional association between psychological distress and inflammatory proteins in a young, healthy representative population of English adults.

Participants were 1338 individuals aged 16–34 years from the 2006 Health Survey for England (HSE). Blood samples to measure plasma fibrinogen and high sensitivity C-reactive protein (hsCRP), as well as measures of psychological distress (using the General Health Questionnaire 12-item scale, GHQ-12) and covariates, were collected during home visits. Linear regression was used to assess the relationship between psychological distress and fibrinogen and hsCRP.

Higher self-rated distress was positively associated with fibrinogen level in this young population, independently of age, sex, ethnicity, body mass index (BMI), high density lipoprotein (HDL) cholesterol, smoking, and alcohol and medication use (β=0.024, p<0.01). Psychological distress was not related to hsCRP.

Psychological distress may negatively impact inflammatory processes in young adulthood before the onset of chronic health problems such as hypertension and cardiovascular disease. Longitudinal research is needed to elucidate the relationship between distress and inflammation in young adults and its significance for later disease states.

Studies with healthy participants and patients with respiratory diseases suggest a relation between respiration and mood. The aim of the present analyses was to investigate whether emotionally challenged remitted depressed participants show higher respiration pattern variability (RPV) and whether this is related to mood, clinical outcome and increased default mode network connectivity.

To challenge participants, sad mood was induced with keywords of personal negative life events in individuals with remitted depression [recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls (HCs, n = 30) during functional magnetic resonance imaging. Respiration was measured by means of a built-in respiration belt. Additionally, questionnaires, a daily life assessment of mood and a 3 years follow-up were applied. For replication, we analysed RPV in an independent sample of 53 rMDD who underwent the same fMRI paradigm.

During sad mood, rMDD compared with HC showed greater RPV, with higher variability in pause duration and respiration frequency and lower expiration to inspiration ratio. Higher RPV was related to lower daily life mood and predicted higher depression scores as well as relapses during a 3-year follow-up period. Furthermore, in rMDD compared with HC higher main respiration frequency exhibited a more positive association with connectivity of the posterior cingulate cortex and the right parahippocampal gyrus.

The results suggest a relation between RPV, mood and depression on the behavioural and neural level. Based on our findings, we propose interventions focusing on respiration to be a promising additional tool in the treatment of depression.

Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance.

Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM.

The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients.

The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism–schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder.

In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis.

Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders.

Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.

Clinically ascertained reports suggest that boys and girls with attention deficit hyperactivity disorder (ADHD) may differ from each other in their vulnerability to substance use problems.

A total of 1545 Finnish adolescents were assessed for DSM-IV-based ADHD symptoms by their parents and classroom teachers using standardized rating scales at age 11–12 years. At age 14, substance use disorders and psychiatric co-morbidity were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism, providing DSM-III-R/DSM-IV diagnoses for Axis I disorders. At age 17.5, substance use was assessed by multi-item questionnaire.

Although baseline ADHD symptoms were less common among females, they were more predictive of adverse substance use outcomes once conduct disorder and previous substance use were controlled for. Only in females were baseline ADHD symptoms significant predictors of alcohol abuse and dependence and illicit drug use at age 14. At the age of 17.5, parents' reports of inattentiveness and hyperactivity were significant predictors for frequent alcohol use in both sexes, but they were more predictive of frequent alcohol and illicit drug use in girls. Impulsivity in teachers' ratings predicted frequent alcohol use and illicit drug use in boys. Parental reports of inattentiveness in their 11-/12-year-old daughters were a consistent predictor for illicit drug use across adolescence.

Inattentiveness and hyperactivity may be more predictive of alcohol use disorders and maladaptive patterns of alcohol and illicit drug use among girls than boys. The importance of these behavioural symptoms should be assessed further in the community, as they could jeopardize adolescents' successful transitioning into adult roles.

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients.

Altogether, 1552 out-patients, mean age 39.2±11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20–40/40–65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender.

Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV – Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97–5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26–2.60) in patients with pre-adult versus adult onset MDD.

Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Social anxiety disorder (SAD) is characterized by fear of social and performance situations. The consequence of scrutiny by others for the neural processing of performance feedback in SAD is unknown.

We used event-related functional magnetic resonance imaging to investigate brain activation to positive, negative, and uninformative performance feedback in patients diagnosed with SAD and age-, gender-, and education-matched healthy control subjects who performed a time estimation task during a social observation condition and a non-social control condition: while either being monitored or unmonitored by a body camera, subjects received performance feedback after performing a time estimation that they could not fully evaluate without external feedback.

We found that brain activation in ventral striatum (VS) and midcingulate cortex was modulated by an interaction of social context and feedback type. SAD patients showed a lack of social-context-dependent variation of feedback processing, while control participants showed an enhancement of brain responses specifically to positive feedback in VS during observation.

The present findings emphasize the importance of social-context processing in SAD by showing that scrutiny prevents appropriate reward-processing-related signatures in response to positive performances in SAD.

Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD.

Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task.

The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall.

The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.