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, I 2=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.

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.

Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic–pituitary–adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS.

A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day.

Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression.

Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.

Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo–pituitary–adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients.

Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients.

Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers.

Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.

Interpersonal sensitivity is a personality trait described as excessive awareness of both the behaviour and feelings of others. Although interpersonal sensitivity has been found to be one of the vulnerability factors to depression, there has been little interest in its relationship with the prodromal phase of psychosis. The aims of this study were to examine the level of interpersonal sensitivity in a sample of individuals with an at-risk mental state (ARMS) for psychosis and its relationship with other psychopathological features.

Method. Sixty-two individuals with an ARMS for psychosis and 39 control participants completed a series of self-report questionnaires, including the Interpersonal Sensitivity Measure (IPSM), the Prodromal Questionnaire (PQ), the Ways of Coping Questionnaire (WCQ) and the Depression and Anxiety Stress Scale (DASS).

Individuals with an ARMS reported higher interpersonal sensitivity compared to controls. Associations between interpersonal sensitivity, positive psychotic symptoms (i.e. paranoid ideation), avoidant coping and symptoms of depression, anxiety and stress were also found.

This study suggests that being ‘hypersensitive’ to interpersonal interactions is a psychological feature of the putatively prodromal phase of psychosis. The relationship between interpersonal sensitivity, attenuated positive psychotic symptoms, avoidant coping and negative emotional states may contribute to long-term deficits in social functioning. We illustrate the importance, when assessing a young client with a possible ARMS, of examining more subtle and subjective symptoms in addition to attenuated positive symptoms.

Global brain abnormalities such as brain volume loss and grey- and white-matter deficits are consistently reported in first-episode schizophrenia patients and may already be detectable in the very early stages of the illness. Whether these changes are dependent on medication use or related to intelligence quotient (IQ) is still debated.

Magnetic resonance imaging scans were obtained for 20 medication-naive patients with first-episode schizophrenia and 26 matched healthy subjects. Volume measures of total brain grey and white matter, third and lateral ventricles and cortical thickness/surface were obtained. Differences between the groups were investigated, taking into account the effect of intelligence.

Medication-naive patients showed statistically significant reductions in whole-brain volume and cerebral grey- and white-matter volume together with lateral ventricle enlargement compared to healthy subjects. IQ was significantly lower in patients compared to controls and was positively associated with brain and white-matter volume in the whole group. No significant differences in cortical thickness were found between the groups but medication-naive patients had a significantly smaller surface in the left superior temporal pole, Heschl's gyrus and insula compared to controls.

Our findings suggest that brain volume loss is present at illness onset, and can be explained by the reduced surface of the temporal and insular cortex. These abnormalities are not related to medication, but IQ.

Psychotic symptoms occur more frequently in the general population than psychotic disorder and index risk for psychopathology. Multiple studies have reported on the prevalence of these symptoms using self-report questionnaires or clinical interviews but there is a lack of consensus about the prevalence of psychotic symptoms among children and adolescents.

We conducted a systematic review of all published literature on psychotic symptom prevalence in two age groups, children aged 9–12 years and adolescents aged 13–18 years, searching through electronic databases PubMed, Ovid Medline, PsycINFO and EMBASE up to June 2011, and extracted prevalence rates.

We identified 19 population studies that reported on psychotic symptom prevalence among children and adolescents. The median prevalence of psychotic symptoms was 17% among children aged 9–12 years and 7.5% among adolescents aged 13–18 years.

Psychotic symptoms are relatively common in young people, especially in childhood. Prevalence is higher in younger (9–12 years) compared to older (13–18 years) children.

Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.

We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.

Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.

Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.

Auditory verbal hallucinations (AVH) in patients with borderline personality disorder (BPD) are frequently claimed to be brief, less severe and qualitatively different from those in schizophrenia, hence the term ‘pseudohallucinations’. AVH in BPD may be more similar to those experienced by healthy individuals, who experience AVH in a lower frequency and with a more positive content than AVH in schizophrenia. In this study the phenomenology of AVH in BPD patients was compared to that in schizophrenia and to AVH experienced by non-patients.

In a cross-sectional setting, the phenomenological characteristics of AVH in 38 BPD patients were compared to those in 51 patients with schizophrenia/schizoaffective disorder and to AVH of 66 non-patients, using the Psychotic Symptom Rating Scales (PSYRATS).

BPD patients experienced AVH for a mean duration of 18 years, with a mean frequency of at least daily lasting several minutes or more. The ensuing distress was high. No differences in the phenomenological characteristics of AVH were revealed among patients diagnosed with BPD and those with schizophrenia/schizoaffective disorder, except for ‘disruption of life’, which was higher in the latter group. Compared to non-patients experiencing AVH, BPD patients had higher scores on almost all items.

AVH in BPD patients are phenomenologically similar to those in schizophrenia, and different from those in healthy individuals. As AVH in patients with BPD fulfil the criteria of hallucinations proper, we prefer the term AVH over ‘pseudohallucinations’, so as to prevent trivialization and to promote adequate diagnosis and treatment.

DSM-IV-TR suggests that clinicians should assess clinically relevant personality traits that do not necessarily constitute a formal personality disorder (PD), and should note these traits on Axis II, but DSM-IV-TR does not provide a trait model to guide the clinician. Our goal was to provide a provisional trait model and a preliminary corresponding assessment instrument, in our roles as members of the DSM-5 Personality and Personality Disorders Workgroup and workgroup advisors.

An initial list of specific traits and domains (broader groups of traits) was derived from DSM-5 literature reviews and workgroup deliberations, with a focus on capturing maladaptive personality characteristics deemed clinically salient, including those related to the criteria for DSM-IV-TR PDs. The model and instrument were then developed iteratively using data from community samples of treatment-seeking participants. The analytic approach relied on tools of modern psychometrics (e.g. item response theory models).

A total of 25 reliably measured core elements of personality description emerged that, together, delineate five broad domains of maladaptive personality variation: negative affect, detachment, antagonism, disinhibition, and psychoticism.

We developed a maladaptive personality trait model and corresponding instrument as a step on the path toward helping users of DSM-5 assess traits that may or may not constitute a formal PD. The inventory we developed is reprinted in its entirety in the Supplementary online material, with the goal of encouraging additional refinement and development by other investigators prior to the finalization of DSM-5. Continuing discussion should focus on various options for integrating personality traits into DSM-5.

The high incidence of the metabolic syndrome in patients with psychosis is mainly attributed to antipsychotic treatment. However, it is also possible that psychological stress plays a role, inducing a chronic inflammatory process that may predispose to the development of metabolic abnormalities. We investigated the association between childhood maltreatment and inflammatory and metabolic biomarkers in subjects with first-episode psychosis and healthy controls.

Body mass index (BMI), weight and waist circumference were measured in 95 first-episode psychosis patients and 97 healthy controls. Inflammatory and metabolic markers were measured in a subsample of 28 patients and 45 controls. In all the subjects we collected information on childhood maltreatment and recent stressors.

Patients with childhood maltreatment had higher BMI [25.0 (s.e.=0.6) kg/m2] and C-reactive protein (CRP) levels [1.1 (s.e.=0.6) mg/dl] when compared with healthy controls [23.4 (s.e.=0.4) kg/m2, p=0.030 and 0.2 (s.e.=0.1) mg/dl, p=0.009, respectively]. In contrast, patients without childhood maltreatment were not significantly different from healthy controls for either BMI [24.7 (s.e.=0.6) kg/m2, p=0.07] or CRP levels [0.5 (s.e.=0.2) mg/dl, p=0.25]. After controlling for the effect of BMI, the difference in CRP levels across the three groups remained significant (F 2,58=3.6, p=0.035), suggesting that the increase in inflammation was not driven by an increase in adipose tissue.

Childhood maltreatment is associated with higher BMI, and increased CRP levels, in patients with a first-episode psychosis. Further studies need to confirm the mechanisms underlying the putative causal relationship between childhood maltreatment and higher BMI, and whether this is indeed mediated by increased inflammation.

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.

Individuals with bipolar disorder demonstrate abnormal social function. Neuroimaging studies in bipolar disorder have shown functional abnormalities in neural circuitry supporting face emotion processing, but have not examined face identity processing, a key component of social function. We aimed to elucidate functional abnormalities in neural circuitry supporting face emotion and face identity processing in bipolar disorder.

Twenty-seven individuals with bipolar disorder I currently euthymic and 27 healthy controls participated in an implicit face processing, block-design paradigm. Participants labeled color flashes that were superimposed on dynamically changing background faces comprising morphs either from neutral to prototypical emotion (happy, sad, angry and fearful) or from one identity to another identity depicting a neutral face. Whole-brain and amygdala region-of-interest (ROI) activities were compared between groups.

There was no significant between-group difference looking across both emerging face emotion and identity. During processing of all emerging emotions, euthymic individuals with bipolar disorder showed significantly greater amygdala activity. During facial identity and also happy face processing, euthymic individuals with bipolar disorder showed significantly greater amygdala and medial prefrontal cortical activity compared with controls.

This is the first study to examine neural circuitry supporting face identity and face emotion processing in bipolar disorder. Our findings of abnormally elevated activity in amygdala and medial prefrontal cortex (mPFC) during face identity and happy face emotion processing suggest functional abnormalities in key regions previously implicated in social processing. This may be of future importance toward examining the abnormal self-related processing, grandiosity and social dysfunction seen in bipolar disorder.

Rates of alcohol disorders peak in late adolescence and decrease substantially into the mid-20s. Our aim was to identify risk factors that predict alcohol problems that persist into the mid-20s.

Data are from the prospective, population-based Great Smoky Mountains Study (GSMS; n=1420), which followed children through late adolescence and into young adulthood. Alcohol persisters were defined as subjects with an alcohol disorder (abuse or dependence) in late adolescence (ages 19 and 21 years) that continued to meet criteria for an alcohol disorder at the mid-20s assessment.

The 3-month prevalence of having an alcohol disorder (abuse or dependence) decreased markedly from late adolescence into the mid-20s. A third of late adolescents with an alcohol disorder continued to meet criteria for an alcohol disorder in young adulthood (37 of 144 who met criteria in late adolescence). Risk factors for persister status included multiple alcohol abuse criteria during late adolescence but no alcohol dependence criteria. Risk factors for persister status also included associated features of alcohol dependence such as craving alcohol and drinking to unconsciousness. Persister status was also associated with depression, cannabis dependence and illicit substance use, but not with other psychiatric disorders. More than 90% of late adolescents with three or more of the risk factors identified met criteria for a young adult alcohol disorder.

Symptoms of alcohol abuse, not dependence, best predict long-term persistence of alcohol problems. The set of risk factors identified may be a useful screen for selective and indicated prevention efforts.

Improving the quality of mental health care requires integrating successful research interventions into ‘real-world’ practice settings. Coordinated Anxiety Learning and Management (CALM) is a treatment-delivery model for anxiety disorders encountered in primary care. CALM offers cognitive behavioral therapy (CBT), medication, or both; non-expert care managers assisting primary care clinicians with adherence promotion and medication optimization; computer-assisted CBT delivery; and outcome monitoring. This study describes incremental benefits, costs and net benefits of CALM versus usual care (UC).

The CALM randomized, controlled effectiveness trial was conducted in 17 primary care clinics in four US cities from 2006 to 2009. Of 1062 eligible patients, 1004 English- or Spanish-speaking patients aged 18–75 years with panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD) and/or post-traumatic stress disorder (PTSD) with or without major depression were randomized. Anxiety-free days (AFDs), quality-adjusted life years (QALYs) and expenditures for out-patient visits, emergency room (ER) visits, in-patient stays and psychiatric medications were estimated based on blinded telephone assessments at baseline, 6, 12 and 18 months.

Over 18 months, CALM participants, on average, experienced 57.1 more AFDs [95% confidence interval (CI) 31–83] and $245 additional medical expenses (95% CI $–733 to $1223). The mean incremental net benefit (INB) of CALM versus UC was positive when an AFD was valued ⩾$4. For QALYs based on the Short-Form Health Survey-12 (SF-12) and the EuroQol EQ-5D, the mean INB was positive at ⩾$5000.

Compared with UC, CALM provides significant benefits with modest increases in health-care expenditures.

Dysmorphic concern refers to an excessive preoccupation with a perceived or slight defect in physical appearance. It lies on a continuum of severity from no or minimal concerns to severe concerns over one's appearance. The present study examined the heritability of dysmorphic concerns in a large sample of twins.

Twins from the St Thomas UK twin registry completed a valid and reliable self-report measure of dysmorphic concerns, which also includes questions about perceived body odour and malfunction. Twin modelling methods (female twins only, n=3544) were employed to decompose the variance in the liability to dysmorphic concerns into additive genetic, shared and non-shared environmental factors.

Model-fitting analyses showed that genetic factors accounted for approximately 44% [95% confidence intervals (CI) 36–50%] of the variance in dysmorphic concerns, with non-shared environmental factors and measurement error accounting for the remaining variance (56%; 95% CI 50–63%). Shared environmental factors were negligible. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance.

Over-concern with a perceived or slight defect in physical appearance is a heritable trait, with non-shared environmental factors also playing an important role in its causation. The results are relevant for various psychiatric disorders characterized by excessive concerns in body appearance, odour or function, including but not limited to body dysmorphic disorder.

Previous studies on the relationship between blood pressure (BP) and psychological morbidity are conflicting. To resolve this confusing picture we examined the hypothesis that there is a non-linear relationship between panic and systolic BP (SBP) and explored the association of generalized anxiety symptoms with SBP.

We used data from the population-based Nord-Trøndelag health study (HUNT) in which all 92 936 individuals aged ⩾20 years residing in one Norwegian county were invited to participate. Panic was assessed using one item from the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS) and generalized anxiety with the remaining six items of this subscale. SBP was the mean of two measurements by an automatic device.

A total of 64 871 respondents had SBP recorded (70%). Both unadjusted (n=61 408) and adjusted analyses provided evidence for a non-linear relationship between panic and SBP, represented by a U-shaped curve with a minimum prevalence of panic at around 140 mmHg. The relationship was strengthened after adjustment for confounders, with the quadratic term significantly associated with panic (p=0.03). Generalized anxiety symptoms were associated only with low SBP.

The U-shaped relationship between SBP and panic provides a unifying explanation for the separate strands of published literature in this area. The results support the hypothesis that high BP and panic disorder could share brainstem autonomic and serotonergic abnormalities. By contrast, generalized anxiety symptoms were more common only at lower BPs, suggesting that any biological link between panic and high BP does not extend to generalized anxiety.

Associations between child maltreatment and adult violence, often termed the ‘cycle of violence’, are well documented. However, the nature of such links after appropriate control for confounding remains uncertain. We aimed to determine whether child maltreatment causes adult violent offending or whether suggested links are due to genetic or family environment confounding.

A total of 18 083 20- to 47-year-old twins from the Swedish population-based Study of Twin Adults: Genes and Environment (STAGE) participated. We linked information on self-reported child maltreatment with national register data on convictions for adult crime. We used a case-control design to elucidate associations among unrelated individuals and also conducted within-discordant twin pair analyses to estimate the influence of familial confounding on this association.

The odds ratio (OR), adjusted for age, sex and education, for violent offending in maltreated children grown up versus unrelated controls was 1.98 [95% confidence interval (CI) 1.52–2.57]. However, the association decreased to 1.18 (95% CI 0.62–2.25) when maltreated children were compared to their non-maltreated twins, suggesting substantial confounding by genetic or family environmental factors (within-twin OR <1.98) and a weak, non-significant causal effect (within-twin OR >1.00). Familial confounding was also pronounced for the association between child maltreatment and any offending.

Childhood maltreatment was found to be a weak causal risk factor for adult violent offending; hence, reducing maltreatment might decrease violent crime less than previously expected. Instead, considerable familial confounding of the link between child maltreatment and adult violent offending suggests that prevention strategies need to address overlapping genetic and/or family environmental liability for abusive and violent behavior.