It has been well established that both genes and non-shared environment contribute substantially to the underlying aetiology of major depressive disorder (MDD). A comprehensive overview of genetic research in MDD is presented.

Papers were retrieved from PubMed up to December 2011, using many keywords including: depression, major depressive disorder, genetics, rare variants, gene–environment, whole genome, epigenetics, and specific candidate genes and variants. These were combined in a variety of permutations.

Linkage studies have yielded some promising chromosomal regions in MDD. However, there is a continued lack of consistency in association studies, in both candidate gene and genome-wide association studies (GWAS). Numerous factors may account for variable results including the use of different diagnostic approaches, small samples in early studies, population stratification, epigenetic phenomena, copy number variation (CNV), rare variation, and phenotypic and allelic heterogeneity. The conflicting results are also probably, in part, a consequence of environmental factors not being considered or controlled for.

Each research group has to identify what issues their sample may best address. We suggest that, where possible, more emphasis should be placed on the environment in molecular behavioural genetics to identify individuals at environmental high risk in addition to genetic high risk. Sequencing should be used to identify rare and alternative variation that may act as a risk factor, and a systems biology approach including gene–gene interactions and pathway analyses would be advantageous. GWAS may require even larger samples with reliably defined (sub)phenotypes.

Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample.

All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use.

The presence of anxiety disorders predicted shorter telomeres at follow-up (β = –0.073, t = –2.302, p = 0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (β = –0.077, t = –2.144, p = 0.032). No association was found between depressive disorders and shorter telomeres at follow-up (β = 0.010, t = 0.315, p = 0.753).

This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.

Sleep disturbances are persistent residual symptoms following remission of major depressive disorder (MDD) and are associated with an increased risk of MDD recurrence. The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD.

Participants were randomized to receive selective serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and Hypersomnia) were used to assess self-reported sleep quality.

Significant decreases in total insomnia (p < 0.0001) were observed, along with decreases in sleep onset, mid-nocturnal and early-morning insomnia (p's <0.002). Hypersomnia did not change significantly (p = 0.38). Changes in total, mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms. Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment (p = 0.0057). No significant moderating effect of any baseline sleep on change in depression severity was observed. There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item.

Exercise augmentation resulted in improvements in self-reported sleep quality in patients with non-remitted MDD. Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence, exercise augmentation may have an important role in the treatment of MDD.

Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence.

In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).

Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02–1.09, p = 0.002] but there was no association with depression (p = 0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97–1.09, p = 0.34) or depression (OR 1.02, 95% CI 0.95–1.09, p = 0.62) among smokers.

As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.

Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others.

Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping.

Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range.

Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases.

Preliminary research implicates threat-related attention biases in paediatric anxiety disorders. However, major questions exist concerning diagnostic specificity, effects of symptom-severity levels, and threat-stimulus exposure durations in attention paradigms. This study examines these issues in a large, community school-based sample.

A total of 2046 children (ages 6–12 years) were assessed using the Development and Well Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified based on presence or absence of ‘fear-related’ disorders, ‘distress-related’ disorders, and behavioural disorders. Two dot-probe tasks, which differed in stimulus exposure, assessed attention biases for happy-face and threat-face cues. The main analysis included 1774 children.

For attention bias scores, a three-way interaction emerged among face-cue emotional valence, diagnostic group, and internalizing symptom severity (F = 2.87, p < 0.05). This interaction reflected different associations between internalizing symptom severity and threat-related attention bias across diagnostic groups. In children with no diagnosis (n = 1411, mean difference = 11.03, s.e. = 3.47, df = 1, p < 0.001) and those with distress-related disorders (n = 66, mean difference = 10.63, s.e. = 5.24, df = 1, p < 0.05), high internalizing symptoms predicted vigilance towards threat. However, in children with fear-related disorders (n = 86, mean difference = −11.90, s.e. = 5.94, df = 1, p < 0.05), high internalizing symptoms predicted an opposite tendency, manifesting as greater bias away from threat. These associations did not emerge in the behaviour-disorder group (n = 211).

The association between internalizing symptoms and biased orienting varies with the nature of developmental psychopathology. Both the form and severity of psychopathology moderates threat-related attention biases in children.

Depression is a clinically relevant dimension, associated with both positive and negative symptoms, in patients with schizophrenia. However, in siblings it is unknown whether depression is associated with subclinical positive and negative symptoms.

Depressive symptoms and their association with positive and negative symptoms were examined in 813 healthy siblings of patients with a non-affective psychotic disorder, 822 patients and 527 healthy controls. Depressive episodes meeting DSM-IV-TR criteria (lifetime) and depressed mood (lifetime) were assessed with the Comprehensive Assessment of Symptoms and History (CASH) in all three groups. In the patient group, the severity of positive and negative psychosis symptoms was assessed with the CASH. In the siblings and healthy controls, the severity of subclinical psychosis symptoms was assessed with the Community Assessment of Psychic Experiences (CAPE).

Patients reported more lifetime depressed mood and more depressive episodes than both siblings and controls. Siblings had a higher chance of meeting lifetime depressive episodes than the controls; no significant differences in depressed mood were found between siblings and controls. In all three groups the number and duration of depressive symptoms were associated with (sub)clinical negative symptoms. In the patients and siblings the number of depressive symptoms was furthermore associated with (sub)clinical positive symptoms. Finally, lifetime depressed mood showed familial clustering but this clustering was absent for lifetime depressive episodes.

These findings suggest that a co-occurring genetic vulnerability for both depressive and psychotic symptomatology exists on a clinical and a subclinical level.

The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders.

Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls.

EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405).

Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia.

First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms.

Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention.

These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

Bullying victimization may be linked to psychosis but only self-report measures of victimization have been used so far. This study aimed (a) to investigate the differential associations of peer-nominated versus self-reported victim status with non-clinical psychotic experiences in a sample of young adolescents, and (b) to examine whether different types of self-reported victimization predict non-clinical psychotic experiences in these adolescents.

A combination of standard self-report and peer nomination procedures was used to assess victimization. The sample (n = 724) was divided into four groups (exclusively self-reported victims, self- and peer-reported victims, exclusively peer-reported victims, and non-victims) to test for a group effect on non-clinical psychotic experiences. The relationship between types of victimization and non-clinical psychotic experiences was examined by a regression analysis.

Self-reported victims, along with self- and peer-reported victims, scored higher than peer-reported victims and non-victims on non-clinical psychotic experiences. Self-reports of direct relational, indirect relational and physical victimization significantly improved the prediction of non-clinical psychotic experiences whereas verbal and possession-directed victimization had no significant predictive value.

The relationship between victimization and non-clinical psychotic experiences is only present for self-reported victimization, possibly indicative of an interpretation bias. The observed discrepancy between self-report and peer-report highlights the importance of implementing a combination of both measures for future research.

Individual variation in the clinical course of bipolar disorder may have prognostic and therapeutic implications but is poorly reflected in current classifications. We aimed to establish a typology of the individual clinical trajectories based on detailed prospective medium-term follow-up.

Latent class analysis (LCA) of nine characteristics of clinical course (time depressed, severity of depression, stability of depression, time manic, severity of mania, stability of mania, mixed symptoms, mania-to-depression and depression-to-mania phase switching) derived from life charts prospectively tracking the onsets and offsets of (hypo)manic, depressive, mixed and subsyndromal episodes in a representative sample of 176 patients with bipolar disorder.

The best-fitting model separated patients with bipolar disorder into large classes of episodic bipolar (47%) and depressive type (32%), moderately sized classes characterized by prolonged hypomanias (10%) and mixed episodes (5%) and five small classes with unusual course characteristics including mania-to-depression and depression-to-mania transitions and chronic mixed affective symptoms. This empirical typology is relatively independent of the distinction between bipolar disorder type I and type II. Lifetime co-morbidity of alcohol use disorders is characteristic of the episodic bipolar course type.

There is potential for a new typology of clinical course based on medium-term naturalistic follow-up of a representative clinical sample of patients with bipolar disorder. Predictive validity and stability over longer follow-up periods remain to be established.

While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD.

We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects (‘controls’) were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs.

The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years.

Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.

Initiation of cannabis use typically follows alcohol use, but the reverse order does occur and is more common for African-Americans (AAs) than European-Americans (EAs). The aim of this study was to test for differences in the order of initiation of cannabis and alcohol use between AA and EA women and to determine whether order and ethnicity contribute independently to risk for rapid progression to cannabis-related problems.

Data were drawn from structured psychiatric interviews of 4102 women (mean age = 21.6 years), 3787 from an all-female twin study and 315 from a high-risk family study; 18.1% self-identified as AA, 81.9% as EA. Ethnicity and order of initiation of cannabis and alcohol use were modeled as predictors of transition time from first use to onset of cannabis use disorder symptom(s) using Cox proportional hazards regression analyses.

AA women were nearly three times as likely as EA women to initiate cannabis use before alcohol use. Using cannabis before alcohol [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.08–1.93] and AA ethnicity (HR 1.59, 95% CI 1.13–2.24) were both associated with rapid progression from first use to cannabis symptom onset even after accounting for age at initiation and psychiatric risk factors.

The findings indicate that AA women are at greater risk for rapid development of cannabis-related problems than EA women and that this risk is even higher when cannabis use is initiated before alcohol use. Prevention programs should be tailored to the various patterns of cannabis use and relative contributions of risk factors to the development of cannabis-related problems in different ethnic groups.

Psychopathy and antisocial personality disorder (ASPD) are both characterized by impulsive, externalizing behaviors. Researchers have argued, however, that psychopathy is distinguished from ASPD by the presence of interpersonal–affective features that reflect an underlying deficit in emotional sensitivity. No study to date has tested for differential relations of these disorders with the brain's natural orienting response to sudden aversive events.

Electroencephalography was used to assess cortical reactivity to abrupt noise probes presented during the viewing of pleasant, neutral and unpleasant pictures in 140 incarcerated males diagnosed using the Psychopathy Checklist – Revised and DSM-IV criteria for ASPD. The primary dependent measure was the P3 event-related potential response to the noise probes.

Psychopaths showed significantly smaller amplitude of P3 response to noise probes across trials of all types compared with non-psychopaths. Follow-up analyses revealed that this overall reduction was attributable specifically to the affective–interpersonal features of psychopathy. By contrast, no group difference in general amplitude of probe P3 was evident for ASPD versus non-ASPD participants.

The findings demonstrate a reduced cortical orienting response to abrupt aversive stimuli in participants exhibiting features of psychopathy that are distinct from ASPD. The specificity of the observed effect fits with the idea that these distinctive features of psychopathy reflect a deficit in defensive reactivity, or mobilization of the brain's defensive system, in the context of threat cues.

A new diagnostic category, hoarding disorder (HD), has been proposed for inclusion in DSM-5. This study field-tested the validity, reliability and perceived acceptability of the proposed diagnostic criteria for HD.

Fifty unselected individuals with prominent hoarding behavior and 20 unselected, self-defined ‘collectors’ participated in thorough psychiatric assessments, involving home visits whenever possible. A semi-structured interview based on the proposed diagnostic criteria for HD was administered and scored by two independent raters. ‘True’ diagnoses were made by consensus according to the best-estimate diagnosis procedure. The percentage of true positive HD cases (sensitivity) and true negative HD cases (specificity) was calculated, along with inter-rater reliability for the diagnosis and each criterion. Participants were asked about their perceptions of the acceptability, utility and stigma associated with the new diagnosis.

Twenty-nine (58%) of the hoarding individuals and none of the collectors fulfilled diagnostic criteria for HD. The sensitivity, specificity and inter-rater reliability of the diagnosis, and of each individual criterion and the specifiers, were excellent. Most participants with HD (96%) felt that creating a new disorder would be very or somewhat acceptable, useful (96%) and not too stigmatizing (59%).

The proposed HD criteria are valid, reliable and perceived as acceptable and useful by the sufferers. Crucially, they seem to be sufficiently conservative and unlikely to overpathologize normative behavior. Minor changes in the wording of the criteria are suggested.

For too long there have been heated debates between those who believe that mental health care should be largely or solely provided from hospitals and those who adhere to the view that community care should fully replace hospitals. The aim of this study was to propose a conceptual model relevant for mental health service development in low-, medium- and high-resource settings worldwide.

We conducted a review of the relevant peer-reviewed evidence and a series of surveys including more than 170 individual experts with direct experience of mental health system change worldwide. We integrated data from these multiple sources to develop the balanced care model (BCM), framed in three sequential steps relevant to different resource settings.

Low-resource settings need to focus on improving the recognition and treatment of people with mental illnesses in primary care. Medium-resource settings in addition can develop ‘general adult mental health services’, namely (i) out-patient clinics, (ii) community mental health teams (CMHTs), (iii) acute in-patient services, (iv) community residential care and (v) work/occupation. High-resource settings, in addition to primary care and general adult mental health services, can also provide specialized services in these same five categories.

The BCM refers both to a balance between hospital and community care and to a balance between all of the service components (e.g. clinical teams) that are present in any system, whether this is in low-, medium- or high-resource settings. The BCM therefore indicates that a comprehensive mental health system includes both community- and hospital-based components of care.

Current trends in population aging affect both recipients and providers of informal family caregiving, as the pool of family caregivers is shrinking while demand is increasing. Epidemiological research has not yet examined the implications of these trends for burdens experienced by aging family caregivers.

Cross-sectional community surveys in 20 countries asked 13 892 respondents aged 50+ years about the objective (time, financial) and subjective (distress, embarrassment) burdens they experience in providing care to first-degree relatives with 12 broadly defined serious physical and mental conditions. Differential burden was examined by country income category, kinship status and type of condition.

Among the 26.9–42.5% respondents in high-, upper-middle-, and low-/lower-middle-income countries reporting serious relative health conditions, 35.7–42.5% reported burden. Of those, 25.2–29.0% spent time and 13.5–19.4% money, while 24.4–30.6% felt distress and 6.4–21.7% embarrassment. Mean caregiving hours per week in those giving any time were 16.6–23.6 (169.9–205.8 h/week per 100 people aged 50+ years). Burden in low-/lower-middle-income countries was 2- to 3-fold higher than in higher-income countries, with any financial burden averaging 14.3% of median family income in high-, 17.7% in upper-middle-, and 39.8% in low-/lower-middle-income countries. Higher burden was reported by women than men and for conditions of spouses and children than parents or siblings.

Uncompensated family caregiving is an important societal asset that offsets rising formal healthcare costs. However, the substantial burdens experienced by aging caregivers across multiple family health conditions and geographic regions threaten the continued integrity of their caregiving capacity. Initiatives supporting older family caregivers are consequently needed, especially in low-/lower-middle-income countries.

The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension ‘harm avoidance’ (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an ‘oversampling’ study design.

Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions.

5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in ‘self-directedness’.

This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high ‘self-directedness’ (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.