So far, no comprehensive answer has emerged to the question of whether transcranial direct current stimulation (tDCS) can make a clinically useful contribution to the treatment of major depression. We aim to present a systematic review and meta-analysis of tDCS in the treatment of depression.

Medline and Embase were searched for open-label and randomized controlled trials of tDCS in depression using the expressions (‘transcranial direct current stimulation’ or ‘tDCS’) and (‘depression’ or ‘depressed’). Study data were extracted with a standardized data sheet. For randomized controlled trials, effect size (Hedges' g) was calculated and the relationships between study variables and effect size explored using meta-regression.

A total of 108 citations were screened and 10 studies included in the systematic review. Six randomized controlled trials were included in the meta-analysis, with a cumulative sample of 96 active and 80 sham tDCS courses. Active tDCS was found to be more effective than sham tDCS for the reduction of depression severity (Hedges' g=0.743, 95% confidence interval 0.21–1.27), although study results differed more than expected by chance (Q=15.52, df=6, p=0.017, I2=61.35). Meta-regression did not reveal any significant correlations.

Our study was limited by the small number of studies included, which often had small sample size. Future studies should use larger, if possible representative, health service patient samples, and optimized protocols to evaluate the efficacy of tDCS in the treatment of depression further.

Abnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors.

With the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of individuals with MDD. A systematic search identified 41 studies meeting our inclusion criteria.

There were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free samples compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume.

Individuals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities.

Experience Sampling Methodology (ESM) is ideally suited to test the predictions, and inform the development of contemporary cognitive models of depression. Yet there has been no systematic examination of ESM in depression research.

A search of databases (PsychARTICLES, PsycINFO, AMED, Ovid Medline and CINAHL) was conducted to identify studies published within the last 25 years investigating major depressive disorder (MDD) using ESM.

Altogether, 19 studies using ESM, or comparable methodologies, with clinically depressed individuals were identified and critically reviewed. The identified studies examined six aspects of MDD: methodological issues; positive and negative affect; cortisol secretion; antidepressant treatment; work performance; genetic risk factors.

Despite some methodological limitations of existing studies, ESM has made a significant contribution to our current understanding of depression by consolidating existing theories, uncovering new and clinically relevant findings and identifying questions for future research. This review concludes by introducing the possibility of using ESM as an intervention tool in clinical practice and proposing that ESM could be useful for furthering knowledge of the causes of MDD.

Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression.

A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change.

Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=−0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=−0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=−0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities.

The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.

Approximately 11% of schoolchildren are bullied on a regular basis. It has been argued that continuous exposure to stress is related to the development of psychotic symptoms. The current study sought to investigate whether being bullied in childhood is related to the development of psychotic symptoms.

A search of PubMed, PsycINFO and EMBASE was conducted. The reference lists of included papers were searched to identify other eligible papers. A meta-analysis was performed on a subgroup of studies.

We found four clinical and 10 general population studies that met inclusion criteria. The results of the clinical studies were mixed. However, the results of the non-clinical studies provided more consistent evidence that school bullying is related to the development of non-clinical psychotic symptoms. Stronger associations were found with increased frequency and severity and longer duration of being bullied. We performed a meta-analysis on seven population-based studies, yielding unadjusted and adjusted odds ratios (ORs) of 2.7 [95% confidence interval (CI) 2.1–3.6] and 2.3 (95% CI 1.5–3.4) respectively.

Although there is some evidence of an association between bullying and psychosis in clinical samples, the research is too sparse to draw any firm conclusions. However, population-based non-clinical studies support the role of bullying in the development of psychotic symptoms later in life. These findings are consistent with findings of an increased risk of psychotic symptoms among those exposed to other types of abuse.

Experts have proposed removing obsessive–compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.

Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).

Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive–compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.

On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.

Children whose parents die by, or attempt, suicide are believed to be at greater risk of suicidal behaviours and affective disorders. We systematically reviewed the literature on these associations and, using meta-analysis, estimated the strength of associations as well as investigated potential effect modifiers (parental and offspring gender, offspring age).

We comprehensively searched the literature (Medline, PsycINFO, EMBASE, Web of Science), finding 28 articles that met our inclusion criteria, 14 of which contributed to the meta-analysis. Crude odds ratio and adjusted odds ratio (aOR) were pooled using fixed-effects models.

Controlling for relevant confounders, offspring whose parents died by suicide were more likely than offspring of two living parents to die by suicide [aOR 1.94, 95% confidence interval (CI) 1.54–2.45] but there were heterogeneous findings in the two studies investigating the impact on offspring suicide attempt (aOR 1.31, 95% CI 0.73–2.35). Children whose parents attempted suicide were at increased risk of attempted suicide (aOR 1.95, 95% CI 1.48–2.57). Limited evidence indicated that exposure to parental death by suicide is associated with subsequent risk of affective disorders. Maternal suicidal behaviour and younger age at exposure were associated with larger effect estimates but there was no evidence that the association differed in sons versus daughters.

Parental suicidal behaviour is associated with increased risk of offspring suicidal behaviour. Findings suggest that maternal suicidal behaviour is a more potent risk factor than paternal, and that children are more vulnerable than adolescents and adults. However, there is no evidence of a stronger association in either male or female offspring.

Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews.

Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors.

We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference −1.02, 95% confidence interval (CI) −2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference −1.29, 95% CI −2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events.

Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.

Past research on the relationship between treatment delay and outcomes for first-episode psychosis has primarily focused on the role of duration of untreated psychosis (DUP) in predicting symptomatic outcomes up to 2 years. In the current study we examine the influence of both DUP and duration of untreated illness (DUI) on symptoms and functioning at 5 years follow-up while controlling for other early characteristics.

A total of 132 patients with first-episode psychosis and treated in an early intervention program were prospectively followed up for 5 years. Outcomes assessed included positive and negative symptoms, overall functioning, weeks on disability pension and weeks of full-time competitive employment.

While DUP showed a significant correlation with level of positive symptoms at follow-up, this was not independent of pre-morbid social adjustment. DUI emerged as a more robust independent predictor of negative symptoms, social and occupational functioning and use of a disability pension.

Delay between onset of non-specific symptoms and treatment may be a more important influence on long-term functioning for first-episode patients than DUP. This suggests the possible value of treating such signs and symptoms as early as possible regardless of the effectiveness of such interventions in reducing likelihood or severity of psychotic symptoms.

The base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown.

A systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes.

Six cohorts were identified with a 3–24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56%) was 3.5 times higher than for individuals without psychotic experiences (0.16%) and there was meta-analytic evidence of dose–response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction.

Subthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicated.

Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models.

We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model.

A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor.

The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.

Hallucinations have consistently been associated with traumatic experiences during childhood. This association appears strongest between physical and sexual abuse and auditory verbal hallucinations (AVH). It remains unclear whether traumatic experiences mainly colour the content of AVH or whether childhood trauma triggers the vulnerability to experience hallucinations in general. In order to investigate the association between hallucinations, childhood trauma and the emotional content of hallucinations, experienced trauma and phenomenology of AVH were investigated in non-psychotic individuals and in patients with a psychotic disorder who hear voices.

A total of 127 non-psychotic individuals with frequent AVH, 124 healthy controls and 100 psychotic patients with AVH were assessed for childhood trauma. Prevalence of childhood trauma was compared between groups and the relation between characteristics of voices, especially emotional valence of content, and childhood trauma was investigated.

Both non-psychotic individuals with AVH and patients with a psychotic disorder and AVH experienced more sexual and emotional abuse compared with the healthy controls. No difference in the prevalence of traumatic experiences could be observed between the two groups experiencing AVH. In addition, no type of childhood trauma could distinguish between positive or negative emotional valence of the voices and associated distress. No correlations were found between sexual abuse and emotional abuse and other AVH characteristics.

These results suggest that sexual and emotional trauma during childhood render a person more vulnerable to experience AVH in general, which can be either positive voices without associated distress or negative voices as part of a psychotic disorder.

The development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression.

One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting depressogenic cognitive processes (rumination, overgeneralization).

The addition of CNT to TAU significantly improved depressive symptoms at post-treatment [mean difference on the Hamilton Rating Scale for Depression (HAMD) 4.28, 95% confidence interval (CI) 1.29–7.26], 3- and 6-month follow-ups, and for rumination and overgeneralization post-treatment. There was no difference in the reduction of symptoms between CNT and RT (mean difference on the HAMD 1.98, 95% CI −1.14 to 5.11), although CNT significantly reduced rumination and overgeneralization relative to RT post-treatment, suggesting a specific benefit on these cognitive processes.

This study provides preliminary evidence that CNT guided self-help may be a useful addition to TAU in treating major depression in primary care, although the effect was not significantly different from an existing active treatment (RT) matched for structural and common factors. Because of its relative brevity and distinct format, it may have value as an additional innovative approach to increase the accessibility of treatment choices for depression.

Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design.

Adult female twins (n=536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program.

The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects.

Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.

Depression after myocardial infarction (MI) is associated with poor cardiovascular prognosis. There is some evidence that specifically depressive episodes that develop after the acute event are associated with poor cardiovascular prognosis. The aim of the present study was to evaluate whether an increase in the number of depressive symptoms after MI is associated with new cardiac events.

In 442 depressed and 325 non-depressed MI patients the Composite International Diagnostic Interview interview to assess post-MI depression was extended to evaluate the presence of the ICD-10 depressive symptoms just before and after the MI. The effect of an increase in number of depressive symptoms during the year following MI on new cardiac events up to 2.5 years post-MI was assessed with Cox regression analyses.

Each additional increase of one symptom was significantly associated with a 15% increased risk of new cardiac events, and this was stronger for non-depressed than for depressed patients. This association was independent of baseline cardiac disease severity. There was no interaction with the number of depressive symptoms pre-MI.

Our findings suggest that an increase in depressive symptoms after MI irrespective of the state of depression pre-MI explains why post-MI depression is associated with poor cardiovascular prognosis. Also increases in depressive symptoms after MI resulting in subthreshold depression should be evaluated as a prognostic marker. Whether potential mechanisms such as cardiac disease severity or inflammation underlie the association remains to be clarified.

Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes.

This cohort study recruited out-patients aged 18–75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n=398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n=387). Acute treatment was up to 14 weeks of citalopram (⩽60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology – Self-Rated (QIDS-SR16) ⩽5] or response (⩾50% reduction from baseline in QIDS-SR16) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ⩾11].

Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse.

Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.

Mental disorders are widely recognized to be associated with increased risk of all-cause mortality. However, the extent to which highest-risk groups for mortality overlap with those viewed with highest concern by mental health services is less clear. The aim of the study was to investigate clinical risk assessment ratings for suicide, violence and self-neglect in relation to all-cause mortality among people receiving secondary mental healthcare.

A total of 9234 subjects over the age of 15 years were identified from the South London and Maudsley Biomedical Research Centre Case Register who had received a second tier structured risk assessment in the course of their clinical care. A cohort analysis was carried out. Total scores for three risk assessment clusters (suicide, violence and self-neglect) were calculated and Cox regression models used to assess survival from first assessment.

A total of 234 deaths had occurred over an average 9.4-month follow-up period. Mortality was relatively high for the cohort overall in relation to national norms [standardized mortality ratio 3.23, 95% confidence interval (CI) 2.83–3.67] but not in relation to other mental health service users with similar diagnoses. Only the score for the self-neglect cluster predicted mortality [hazard ratio (HR) per unit increase 1.14, 95% CI 1.04–1.24] with null findings for assessed risk of suicide or violence (HRs per unit increase 1.00 and 1.06 respectively).

Level of clinician-appraised risk of self-neglect, but not of suicide or violence, predicted all-cause mortality among people receiving specific assessment of risk in a secondary mental health service.