Few studies have examined spontaneous remission from major depression. This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a year, and whether remission rates vary by disorder severity.

Wait-list controlled trials and observational cohort studies published up to 2010 with data describing remission from untreated depression at ⩽2-year follow-up were identified. Remission was defined as rescinded diagnoses or below threshold scores on standardized symptom measures. Nineteen studies were included in a regression model predicting the probability of 12-month remission from untreated depression, using logit transformed remission proportion as the dependent variable. Covariates included age, gender, study type and diagnostic measure.

Wait-listed compared to primary-care samples, studies with longer follow-up duration and older adult compared to adult samples were associated with lower probability of remission. Child and adolescent samples were associated with higher probability of remission. Based on adult samples recruited from primary-care settings, the model estimated that 23% of prevalent cases of untreated depression will remit within 3 months, 32% within 6 months and 53% within 12 months.

It is undesirable to expect 100% treatment coverage for depression, given many will remit before access to services is feasible. Data were drawn from consenting wait-list and primary-care samples, which potentially over-represented mild-to-moderate cases of depression. Considering reported rates of spontaneous remission, a short untreated period seems defensible for this subpopulation, where judged appropriate by the clinician. Conclusions may not apply to individuals with more severe depression.

Childhood adversity is a putative risk factor for schizophrenia, although evidence supporting this suggestion is inconsistent and controversial. The aim of this review was to pool and quality assess the current evidence pertaining to childhood adversity in people with schizophrenia compared to other psychiatric disorders and to non-psychiatric controls.

Included were case-control, cohort and cross-sectional studies. Medline, EMBASE and PsycINFO databases were searched. Study reporting was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and pooled evidence quality was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Twenty-five studies met inclusion criteria. Moderate to high quality evidence suggests increased rates of childhood adversity in schizophrenia compared to controls [odds ratio (OR) 3.60, p < 0.00001]. Increased childhood adversity was also reported in schizophrenia compared to anxiety disorders (OR 2.54, p = 0.007), although the effect was not significant in the subgroup analysis of five studies assessing only sexual abuse. No differences in rates of childhood adversity were found between schizophrenia and affective psychosis, depression and personality disorders whereas decreased rates of childhood adversity were found in schizophrenia relative to dissociative disorders and post-traumatic stress disorder (OR 0.03, p < 0.0001).

This is the first meta-analysis to report a medium to large effect of childhood adversity in people with schizophrenia and to assess specificity for schizophrenia. Further research is required that incorporates longitudinal design and other potentially causal variables to assess additive and/or interactive effects.

The foetal origins hypothesis suggests an association between low birth weight and later depression, yet evidence supporting this association has been inconsistent.

We systematically reviewed evidence for an association between low birth weight and adult depression or psychological distress in the general population by meta-analysis. We searched EMBASE, Medline, PsycINFO and ISI Web of Science for studies reporting observational data with low birth weight as the exposure and self- or clinician-rated depression or psychological distress measures as an outcome. Selective studies of exposures such as famine or outcomes such as severe illness only were excluded. Altogether,1454 studies were screened for relevance, 26 were included in the qualitative synthesis, 18 were included in the meta-analysis. A random effects meta-analysis method was used to obtain a pooled estimate of effect size.

The odds of depression or psychological distress was greater for those of low birth weight (<2500 g) compared to those of normal birth weight (>2500 g) or greater [odds ratio (OR) 1.15, 95% confidence intervals (CI) 1.00–1.32]. However, this association became non-significant after trim-and-fill correction for publication bias (OR 1.08, 95% CI 0.92–1.27). Using meta-regression, no differences in effect size were observed by gender, outcome measure of depression or psychological distress, or whether the effect size was adjusted for possible confounders.

We found evidence to support a weak association between low birth weight and later depression or psychological distress, which may be due to publication bias. It remains possible that the association may vary according to severity of symptoms or other factors.

Cognitive models have postulated that auditory hallucinations arise from the misattribution of internally generated cognitive events to external sources. Several experimental paradigms have been developed to assess this externalizing bias in clinical and non-clinical hallucination-prone samples, including source-monitoring, verbal self-monitoring and auditory signal detection tasks. This meta-analysis aims to synthesize the wealth of empirical findings from these experimental studies.

A database search was carried out for reports between January 1985 and March 2012. Additional studies were retrieved by contacting authors and screening references of eligible reports. Studies were considered eligible if they compared either (i) hallucinating and non-hallucinating patients with comparable diagnoses, or (ii) non-clinical hallucination-prone and non-prone participants using source-monitoring, verbal self-monitoring or signal detection tasks, or used correlational analyses to estimate comparable effects.

The analysis included 15 clinical (240 hallucinating patients and 249 non-hallucinating patients) and nine non-clinical studies (171 hallucination-prone and 177 non-prone participants; 57 participants in a correlation study). Moderate-to-large summary effects were observed in both the clinical and analogue samples. Robust and significant effects were observed in source-monitoring and signal detection studies, but not in self-monitoring studies, possibly due to the small numbers of eligible studies in this subgroup. The use of emotionally valenced stimuli led to effects of similar magnitude to the use of neutral stimuli.

The findings suggest that externalizing biases are important cognitive underpinnings of hallucinatory experiences. Clinical interventions targeting these biases should be explored as possible treatments for clients with distressing voices.

There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients.

Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined.

Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions.

Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.

Cortisol plays a multifaceted role in major depression disorder (MDD). Diurnal rhythms are disturbed, there is increased resistance to the feedback action of glucocorticoids, excess cortisol may induce MDD, basal levels may be higher and the post-awakening cortisol surge accentuated in those at risk for MDD. Does this suggest new avenues for studying MDD or its clinical management?

The relevant literature was reviewed.

Cortisol contributes to genetic variants for the risk for MDD and the way that environmental events amplify risk. The corticoids' influence begins prenatally, but continues into adulthood. The impact of cortisol at each phase depends not only on its interaction with other factors, such as psychological traits and genetic variants, but also on events that have, or have not, occurred previously.

This review suggests that the time is now right for serious consideration of the role of cortisol in a clinical context. Estimates of cortisol levels and the shape of the diurnal rhythm might well guide the understanding of subtypes of MDD and yield additional indicators for optimal treatment. Patients with disturbed cortisol rhythms might benefit from restitution of those rhythms; they may be distinct from those with more generally elevated levels, who might benefit from cortisol blockade. Higher levels of cortisol are a risk for subsequent depression. Should manipulation of cortisol or its receptors be considered as a preventive measure for some of those at very high risk of future MDD, or to reduce other cortisol-related consequences such as long-term cognitive decline?

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.

The literature describing the global prevalence of anxiety disorders is highly variable. A systematic review and meta-regression were undertaken to estimate the prevalence of anxiety disorders and to identify factors that may influence these estimates. The findings will inform the new Global Burden of Disease study.

A systematic review identified prevalence studies of anxiety disorders published between 1980 and 2009. Electronic databases, reference lists, review articles and monographs were searched and experts then contacted to identify missing studies. Substantive and methodological factors associated with inter-study variability were identified through meta-regression analyses and the global prevalence of anxiety disorders was calculated adjusting for study methodology.

The prevalence of anxiety disorders was obtained from 87 studies across 44 countries. Estimates of current prevalence ranged between 0.9% and 28.3% and past-year prevalence between 2.4% and 29.8%. Substantive factors including gender, age, culture, conflict and economic status, and urbanicity accounted for the greatest proportion of variability. Methodological factors in the final multivariate model (prevalence period, number of disorders and diagnostic instrument) explained an additional 13% of variance between studies. The global current prevalence of anxiety disorders adjusted for methodological differences was 7.3% (4.8–10.9%) and ranged from 5.3% (3.5–8.1%) in African cultures to 10.4% (7.0–15.5%) in Euro/Anglo cultures.

Anxiety disorders are common and the substantive and methodological factors identified here explain much of the variability in prevalence estimates. Specific attention should be paid to cultural differences in responses to survey instruments for anxiety disorders.

Risk factors that are associated with depression in the mother also negatively affect the child. This research sought to extend current knowledge by examining the duration and timing of maternal depression as a moderator of: (1) the impact of dependent interpersonal stress (DIS), such as partner conflict or low social support, and contextual risk (e.g. poverty) on child dysregulation; and (2) continuity in early child dysregulation.

Mother–child pairs (n = 12 152) who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) were examined between pregnancy and age 4 years. Data on maternal depression were collected five times between pregnancy and 33 months postpartum; on DIS and contextual risk three times between pregnancy and 33 months; and on child dysregulation at age 2 and 4 years.

Longitudinal latent class analysis identified a class of mothers (10%) who evinced a chronic level of depression between pregnancy and 33 months. For chronic-depressed versus non-depressed mothers, the results indicate that: (1) DIS predicted higher child dysregulation if experienced between pregnancy and age 2; (2) contextual risk had a differential effect on child dysregulation if experienced during pregnancy; and (3) children had higher continuity in dysregulation between age 2 and age 4.

Assessing the impact of the timing and duration of maternal depression, and different types of co-occurring risk factors, on child well-being is important. Maternal depression and associated DIS, in comparison to contextual risk, may be more responsive to intervention.

Summarizing the epidemiology of major depressive disorder (MDD) at a global level is complicated by significant heterogeneity in the data. The aim of this study is to present a global summary of the prevalence and incidence of MDD, accounting for sources of bias, and dealing with heterogeneity. Findings are informing MDD burden quantification in the Global Burden of Disease (GBD) 2010 Study.

A systematic review of prevalence and incidence of MDD was undertaken. Electronic databases Medline, PsycINFO and EMBASE were searched. Community-representative studies adhering to suitable diagnostic nomenclature were included. A meta-regression was conducted to explore sources of heterogeneity in prevalence and guide the stratification of data in a meta-analysis.

The literature search identified 116 prevalence and four incidence studies. Prevalence period, sex, year of study, depression subtype, survey instrument, age and region were significant determinants of prevalence, explaining 57.7% of the variability between studies. The global point prevalence of MDD, adjusting for methodological differences, was 4.7% (4.4–5.0%). The pooled annual incidence was 3.0% (2.4–3.8%), clearly at odds with the pooled prevalence estimates and the previously reported average duration of 30 weeks for an episode of MDD.

Our findings provide a comprehensive and up-to-date profile of the prevalence of MDD globally. Region and study methodology influenced the prevalence of MDD. This needs to be considered in the GBD 2010 study and in investigations into the ecological determinants of MDD. Good-quality estimates from low-/middle-income countries were sparse. More accurate data on incidence are also required.

Anxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI.

Subjects with MCI (n=268) were selected from the ‘Development of screening guidelines and criteria for pre-dementia Alzheimer's disease’ (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42) protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.

Depressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.3] and t-tau (OR 2.6, 95% CI 1.9–3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0–4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1–2.3; irritability: OR 2.2, 95% CI 1.5–3.3). Symptoms of depression and apathy were not related to any of the CSF markers.

In subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.

Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies.

Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review.

Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two- to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia.

Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a ‘sensitive period’ during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.

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.

Although aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial behavior have been shown to be differentially heritable, available studies have disagreed on the extent to which the genetic and environmental factors influencing AGG also influence RB. The current meta-analysis sought to clarify the extent of etiological overlap between AGG and RB.

Thirteen twin/sibling studies examining the covariation between AGG and RB were collected, of which 11 (with 12 independent samples) were ultimately included in the analyses (n=12923 twin/sibling pairs). Genetic and environmental correlations between AGG and RB served as study effect sizes. When squared, these correlations directly index the proportion of genetic and environmental overlap. Data were analyzed using mixed effect models.

Analyses revealed that genetic influences on AGG were largely, but not entirely, distinct from those on RB: only 38.4% of the genetic influences on AGG overlapped with those on RB. Similarly, only 10.2% of the non-shared environmental influences on AGG overlapped with those on RB. Although the conclusion that etiological influences on AGG are partially distinct from those on RB persisted across several potential moderators, the age of the sample and the informant used were found to moderate the extent of overlap.

The findings underscore the presence of meaningful etiological distinctions between AGG and RB, and imply that future conceptualizations of antisocial behavior should be organized (at least in part) around the dimensions of AGG and RB.