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.

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.

Previous studies suggest that alcohol-use disorder severity, defined by the number of criteria met, provides a more informative phenotype than dichotomized DSM-IV diagnostic measures of alcohol use disorders. Therefore, this study examined whether alcohol-use disorder severity predicted first-incident depressive disorders, an association that has never been found for the presence or absence of an alcohol use disorder in the general population.

In a national sample of persons who had never experienced a major depressive disorder (MDD), dysthymia, manic or hypomanic episode (n=27 571), we examined whether a version of DSM-5 alcohol-use disorder severity (a count of three abuse and all seven dependence criteria) linearly predicted first-incident depressive disorders (MDD or dysthymia) after 3-year follow-up. Wald tests were used to assess whether more complicated models defined the relationship more accurately.

First-incidence of depressive disorders varied across alcohol-use disorder severity and was 4.20% in persons meeting no alcohol-use disorder criteria versus 44.47% in persons meeting all 10 criteria. Alcohol-use disorder severity significantly predicted first-incidence of depressive disorders in a linear fashion (odds ratio 1.14, 95% CI 1.06–1.22), even after adjustment for sociodemographics, smoking status and predisposing factors for depressive disorders, such as general vulnerability factors, psychiatric co-morbidity and subthreshold depressive disorders. This linear model explained the relationship just as well as more complicated models.

Alcohol-use disorder severity was a significant linear predictor of first-incident depressive disorders after 3-year follow-up and may be useful in identifying a high-risk group for depressive disorders that could be targeted by prevention strategies.

The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.

We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.

Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d −0.20 to −0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.

Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

Non-suicidal self-injury (NSSI) is the deliberate and direct injuring of body tissue without suicidal intent for purposes not socially sanctioned. Few studies have examined the correlates of NSSI among young adults. This study aimed to identify predictors of lifetime and past-year NSSI, and describe motives for NSSI and disclosure of NSSI to others.

Interviews were conducted annually with 1081 students enrolled in the College Life Study, a prospective longitudinal study conducted at a large public mid-Atlantic university. NSSI characteristics were assessed at Year 4. Demographic and predictor variables were assessed during Years 1 to 4. Multivariate logistic regression models were used to identify correlates of lifetime NSSI and predictors of past-year NSSI.

The prevalence of past-year and lifetime NSSI was 2% and 7% respectively (>70% were female for both lifetime and past-year NSSI). Seven percent of NSSI cases self-injured once, whereas almost half self-injured six or more times. Independent predictors of past-year NSSI were maternal depression, non-heterosexual orientation, affective dysregulation and depression. Independent predictors of lifetime NSSI were depression, non-heterosexual orientation, paternal depression and female sex. One in six participants with NSSI had attempted suicide by young adulthood. The three most commonly reported motives for NSSI were mental distress, coping and situational stressors. Most (89%) told someone about their NSSI, most commonly a friend (68%).

This study identified unique predictors of NSSI, which should help to elucidate its etiology and has implications for early identification and interventions.

Mortality, including suicide and accidents, is elevated in self-harm populations. Although risk factors for suicide following self-harm are often investigated, rarely have those for accidents been studied. Our aim was to compare risk factors for suicide and accidents.

A prospective cohort (n=30 202) from the Multicentre Study of Self-harm in England, 2000–2007, was followed up to 2010 using national death registers. Risk factors for suicide (intentional self-harm and undetermined intent) and accidents (narcotic poisoning, non-narcotic poisoning, and non-poisoning) following the last hospital presentation for self-harm were estimated using Cox models.

During follow-up, 1833 individuals died, 378 (20.6%) by suicide and 242 (13.2%) by accidents. Independent predictors of both suicide and accidents were: male gender, age ⩾35 years (except accidental narcotic poisoning) and psychiatric treatment (except accidental narcotic poisoning). Factors differentiating suicide from accident risk were previous self-harm, last method of self-harm (twofold increased risks for cutting and violent self-injury versus self-poisoning) and mental health problems. A risk factor specific to accidental narcotic poisoning was recreational/illicit drug problems, and a risk factor specific to accidental non-narcotic poisoning and non-poisoning accidents was alcohol involvement with self-harm.

The similarity of risk factors for suicide and accidents indicates common experiences of socio-economic disadvantage, life problems and psychopathology resulting in a variety of self-destructive behaviour. Of factors associated with the accidental death groups, those for non-narcotic poisoning and other accidents were most similar to suicide; differences seemed to be related to criteria coroners use in reaching verdicts. Our findings support the idea of a continuum of premature death.

Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not.

Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement.

Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13.

These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

The gene encoding the regulator of G-protein signaling subtype 4 (RGS4), located on chromosome 1q23-3, has been proposed as a possible susceptibility gene for schizophrenia and has been specifically linked to prefrontal cortical structural and functional integrity.

The effects of four core single nucleotide polymorphisms (SNPs) within the RGS4 gene on oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts.

The risk allele of RGS4SNP18 was found to be associated with two variables of antisaccade performance, increased error rate and variation in the correct antisaccade latency. By contrast, the same allele and also the risk allele of RGS4SNP4 led to an improvement in smooth eye pursuit performance (increased gain). Structural equation modeling confirmed that the combined gene variation of RGS4SNP4 and RGS4SNP18 was a significant predictor of antisaccade but not smooth eye pursuit performance.

These results provide evidence for a specific effect of schizophrenia-related RGS4 genotype variations to prefrontal dysfunction measured by oculomotor indices of performance in normal individuals, further validating the hypothesis that RGS4 is related to prefrontal dysfunction in schizophrenia.

This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females (by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis.

A large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework – a multi-site research project examining incident cases of psychosis in Italy's Veneto region.

Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal caregivers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.

These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care.

Although some evidence suggests that borderline personality disorder (BPD) is primarily a disorder of the emotion regulation system, findings remain inconsistent. One potential explanation for this is the moderating role of dissociation.

In this study, 33 female subjects with BPD and 26 healthy controls (HC; matched by education level and nicotine intake) were presented idiographic aversive, standard unpleasant and neutral scripts. Modulation of startle reflex and electrodermal responses (skin conductance level; SCL) were measured during imagery of emotional and neutral scripts. Additionally, self-reports of emotional experience (valence and arousal) and present-state dissociation were assessed.

Patients with BPD showed elevated levels of dissociative experiences during testing. Present-state dissociation mediated group differences in SCL and startle response between the HC and BPD groups.

These results suggest that careful attention must be paid to the moderating effect of dissociative symptoms on the psychophysiological responses of BPD patients. Furthermore, the findings have important implications for the assessment and treatment of BPD, including the need to carefully assess BPD patients for dissociative symptoms and to incorporate the treatment of dissociation.

This study examines the structure of the Personality Belief Questionnaire (PBQ), a self-report instrument designed to assess dysfunctional beliefs associated with personality pathology, as proposed by the cognitive theory of personality dysfunction.

The PBQ was examined using exploratory factor analysis (EFA) with responses from 438 depressed out-patients, and confirmatory factor analysis (CFA) with responses from 683 treatment-seeking psychiatric out-patients. All participants were assessed for personality disorder (PD) using a standard clinical interview. The validity of the resulting factor structure was assessed in the combined sample (n=1121) by examining PBQ scores for patients with and without PD diagnoses.

Exploratory and confirmatory analyses converged to indicate that the PBQ is best described by seven empirically identified factors: six assess dysfunctional beliefs associated with forms of personality pathology recognized in DSM-IV. Validity analyses revealed that those diagnosed with a PD evidenced a higher average score on all factors, relative to those without these disorders. Subsets of patients diagnosed with specific DSM-IV PDs scored higher, on average, on the factor associated with their respective diagnosis, relative to all other factors.

The pattern of results has implications for the conceptualization of personality pathology. To our knowledge, no formal diagnostic or assessment system has yet systematically incorporated the role of dysfunctional beliefs into its description of personality pathology. The identification of dysfunctional beliefs may not only aid in case conceptualization but also may provide unique targets for psychological treatment. Recommendations for future personality pathology assessment systems are provided.

We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL).

Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ⩾70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes.

Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss.

Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment.

The rubber hand illusion (RHI) has been widely used to investigate the bodily self in healthy individuals. The aim of the present study was to extend the use of the RHI to examine the bodily self in eating disorders (EDs).

The RHI and self-report measures of ED psychopathology [the Eating Disorder Inventory – 3 (EDI-3) subscales of Drive for Thinness, Bulimia, Body Dissatisfaction, Interoceptive Deficits, and Emotional Dysregulation; the 21-item Depression, Anxiety and Stress Scale (DASS-21); and the Self-Objectification Questionnaire (SOQ)] were administered to 78 individuals with an ED and 61 healthy controls.

Individuals with an ED experienced the RHI significantly more strongly than healthy controls on both perceptual (i.e. proprioceptive drift) and subjective (i.e. self-report questionnaire) measures. Furthermore, both the subjective experience of the RHI and associated proprioceptive biases were correlated with ED psychopathology. Approximately 23% of the variance for embodiment of the fake hand was accounted for by ED psychopathology, with interoceptive deficits and self-objectification significant predictors of embodiment.

These results indicate that the bodily self is more plastic in people with an ED. These findings may shed light on both aetiological and maintenance factors involved in EDs, particularly visual processing of the body, interoceptive deficits, and self-objectification.

Evidence for an effect of work stressors on common mental disorders (CMD) has increased over the past decade. However, studies have not considered whether the effects of work stressors on CMD remain after taking co-occurring non-work stressors into account.

Data were from the 2007 Adult Psychiatric Morbidity Survey, a national population survey of participants ⩾16 years living in private households in England. This paper analyses data from employed working age participants (N=3383: 1804 males; 1579 females). ICD-10 diagnoses for depressive episode, generalized anxiety disorder, obsessive compulsive disorder, agoraphobia, social phobia, panic or mixed anxiety and depression in the past week were derived using a structured diagnostic interview. Questionnaires assessed self-reported work stressors and non-work stressors.

The effects of work stressors on CMD were not explained by co-existing non-work stressors. We found independent effects of work and non-work stressors on CMD. Job stress, whether conceptualized as job strain or effort–reward imbalance, together with lower levels of social support at work, recent stressful life events, domestic violence, caring responsibilities, lower levels of non-work social support, debt and poor housing quality were all independently associated with CMD. Social support at home and debt did not influence the effect of work stressors on CMD.

Non-work stressors do not appear to make people more susceptible to work stressors; both contribute to CMD. Tackling workplace stress is likely to benefit employee psychological health even if the employee's home life is stressful but interventions incorporating non-work stressors may also be effective.

Loneliness has a significant influence on both physical and mental health. Few studies have investigated the possible associations of loneliness with mortality risk, impact on men and women and whether this impact concerns the situation of being alone (social isolation), experiencing loneliness (feeling lonely) or both. The current study investigated whether social isolation and feelings of loneliness in older men and women were associated with increased mortality risk, controlling for depression and other potentially confounding factors.

In our prospective cohort study of 4004 older persons aged 65–84 years with a 10-year follow-up of mortality data a Cox proportional hazard regression analysis was used to test whether social isolation factors and feelings of loneliness predicted an increased risk of mortality, controlling for psychiatric disorders and medical conditions, cognitive functioning, functional status and sociodemographic factors.

At 10 years follow-up, significantly more men than women with feelings of loneliness at baseline had died. After adjustment for explanatory variables including social isolation, the mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence interval (CI) 1.04–1.63] in men and 1.04 (95% CI 0.90–1.24) in women. No higher risk of mortality was found for social isolation.

Feelings of loneliness rather than social isolation factors were found to be a major risk factor for increasing mortality in older men. Developing a better understanding of the nature of this association may help us to improve quality of life and longevity, especially in older men.

In primary care frequent attenders with medically unexplained symptoms (MUS) pose a clinical and health resource challenge. We sought to understand these presentations in terms of the doctor–patient relationship, specifically to test the hypothesis that such patients have insecure emotional attachment.

We undertook a cohort follow-up study of 410 patients with MUS. Baseline questionnaires assessed adult attachment style, psychological distress, beliefs about the symptom, non-specific somatic symptoms, and physical function. A telephone interview following consultation assessed health worry, general practitioner (GP) management and satisfaction with consultation. The main outcome was annual GP consultation rate.

Of consecutive attenders, 18% had an MUS. This group had a high mean consultation frequency of 5.24 [95% confidence interval (CI) 4.79–5.69] over the follow-up year. The prevalence of insecure attachment was 28 (95% CI 23–33) %. A significant association was found between insecure attachment style and frequent attendance, even after adjustment for sociodemographic characteristics, presence of chronic physical illness and baseline physical function [odds ratio (OR) 1.96 (95% CI 1.05–3.67)]. The association was particularly strong in those patients who believed that there was a physical cause for their initial MUS [OR 9.52 (95% CI 2.67–33.93)]. A possible model for the relationship between attachment style and frequent attendance is presented.

Patients with MUS who attend frequently have insecure adult attachment styles, and their high consultation rate may therefore be conceptualized as pathological care-seeking behaviour linked to their insecure attachment. Understanding frequent attendance as pathological help seeking driven by difficulties in relating to caregiving figures may help doctors to manage their frequently attending patients in a different way.

One aim of personalized medicine is to determine which treatment is to be preferred for an individual patient, given all patient information available. Particularly in mental health, however, there is a lack of a single objective, reliable measure of outcome that is sensitive to crucial individual differences among patients.

We examined the feasibility of quantifying the total clinical value provided by a treatment (measured by both harms and benefits) in a single metric. An expert panel was asked to compare 100 pairs of patients, one from each treatment group, who had participated in a randomized clinical trial (RCT) involving interpersonal psychotherapy (IPT) and escitalopram, selecting the patient with the preferred outcome considering both benefits and harms.

From these results, an integrated preference score (IPS) was derived, such that the differences between any two patients' IPSs would predict the clinicians' preferences. This IPS was then computed for all patients in the RCT. A second set of 100 pairs was rated by the panel. Their preferences were highly correlated with the IPS differences (r=0.84). Finally, the IPS was used as the outcome measure comparing IPT and escitalopram. The 95% confidence interval (CI) for the effect size comparing treatments indicated clinical equivalence of the treatments.

A metric that combines benefits and harms of treatments could increase the value of RCTs by making clearer which treatments are preferable and, ultimately, for whom. Such methods result in more precise estimation of effect sizes, without increasing the required sample size.

The aim of the study was to present nationally representative data on the lifetime independent association between attention deficit hyperactivity disorder (ADHD) and psychiatric co-morbidity, correlates, quality of life and treatment seeking in the USA.

Data were derived from a large national sample of the US population. Face-to-face surveys of more than 34 000 adults aged 18 years and older residing in households were conducted during the 2004–2005 period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version.

ADHD was associated independently of the effects of other psychiatric co-morbidity with increased risk of bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, specific phobia, and narcissistic, histrionic, borderline, antisocial and schizotypal personality disorders. A lifetime history of ADHD was also associated with increased risk of engaging in behaviors reflecting lack of planning and deficient inhibitory control, with high rates of adverse events, lower perceived health, social support and higher perceived stress. Fewer than half of individuals with ADHD had ever sought treatment, and about one-quarter had ever received medication. The average age of first treatment contact was 18.40 years.

ADHD is common and associated with a broad range of psychiatric disorders, impulsive behaviors, greater number of traumas, lower quality of life, perceived social support and social functioning, even after adjusting for additional co-morbidity. When treatment is sought, it is often in late adolescence or early adulthood, suggesting the need to improve diagnosis and treatment of ADHD.