The past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field.

We undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health.

The HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to ‘HR criteria’ alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined ‘transition’ obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of ‘schizophrenia light progressing to schizophrenia’ is inadequate.

In the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable.

The self-referential memory (SRM) effect refers to the phenomenon that stimuli processed with reference to the self are better remembered than those referenced to others. Studies have shown that schizophrenia patients do not have this memorial advantage for self-referenced information. The current study investigated the electrophysiological mechanism of the abolished SRM effect in schizophrenia.

Twenty schizophrenia patients and 22 controls were recruited to complete an SRM task. We used a high-time resolution event-related potential (ERP) technique to analyze the electrophysiological differences between patients and controls during self- and other-reflection processing.

Behavior data indicated that healthy controls had a typical SRM bias that was absent in the schizophrenia patients. ERP comparison between groups showed that the schizophrenia patients presented smaller voltages in both self- and other-reflection conditions in the 160–260 ms (P2 component) and 800–1200 ms (positive slow wave) time windows over the pre/frontal cortex. Furthermore, the N2 amplitudes (270–380 ms) differed between self- and other-reflection conditions in patients but not in normal controls. More importantly, we found that the P3 amplitudes in the parietal cortex correlated significantly with the SRM bias score in the patients (r = –0.688).

These results provide comprehensive and direct electrophysiological evidence for self- and other-reflective dysfunction in schizophrenia patients and contribute to our understanding of the underlying neural substrates of the abolished SRM effect in schizophrenia.

Draft DSM-5 criteria for a mixed major depressive episode have been proposed, but their predictive validity has not yet been established. We hypothesized that such symptoms would be associated with poorer antidepressant treatment outcomes.

We examined outcomes among individuals with major depressive disorder participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, an effectiveness study conducted at primary and specialty care centers in the USA. Mixed features were derived from the six self-report items of the mania subscale of the Psychiatric Diagnosis Screening Questionnaire. Primary analyses examined the association between the presence of at least two of these in the 6 months before study entry, and remission across up to four sequential treatment trials, as well as adverse outcomes.

Of the 2397 subjects with a major depressive episode of at least 6 months' duration, 449 (18.7%) reported at least two mixed symptoms. The presence of such symptoms was associated with a greater likelihood of remission across up to four sequential treatments, which persisted after adjustment for potential confounding clinical and demographic variables (adjusted hazard ratio 1.16, 95% confidence interval 1.03–1.28). Two individual items, expansive mood and cheerfulness, were strongly associated with a greater likelihood of remission.

Proposed DSM-5 mixed state features were associated with a greater rather than a lesser likelihood of remission. While unexpected, this result suggests the potential utility of further investigation of depressive mixed states in major depression.

Testosterone may be a biological factor that protects males against eating disorders. Elevated prenatal testosterone exposure is linked to lower levels of disordered eating symptoms, but effects emerge only after mid-puberty. Whether circulating levels of testosterone account for decreased risk for disordered eating in boys after mid-puberty is currently unknown; however, animal data support this possibility. In rodents, prenatal testosterone's masculinizing effects on sex-differentiated behaviors emerge during puberty when circulating levels of testosterone increase and ‘activate’ the expression of masculinized phenotypes. This study investigated whether higher levels of circulating testosterone predict lower levels of disordered eating symptoms in adolescent boys, and in particular whether effects are associated with advancing pubertal maturation.

Participants were 213 male twins from the Michigan State University Twin Registry. The Minnesota Eating Behavior Survey and Eating Disorder Examination Questionnaire assessed several disordered eating symptoms. The Pubertal Development Scale assessed pubertal status. Afternoon saliva samples were assayed for testosterone using enzyme immunoassays.

Consistent with animal data, higher levels of circulating testosterone predicted lower levels of disordered eating symptoms in adolescent boys and effects emerged with advancing puberty. Results were not accounted for by several important covariates, including age, adiposity, or mood/anxiety symptoms.

Findings suggest that elevated circulating testosterone may be protective and underlie decreased risk for eating pathology in males during/after puberty, whereas lower levels of testosterone may increase risk and explain why some, albeit relatively few, males develop eating disorders.

The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.

Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges’ g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses.

The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14–0.36, I2 = 0%, 95% CI 0–58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00–12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size.

Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

To test the vascular depression hypothesis in the general population, we analyzed the association between current depression, medical history of depression, cognitive and somatic depressive symptom dimensions and measures of atherosclerosis [intima–media thickness (IMT) and carotid plaques].

We included a representative sample of 5000 participants from the Gutenberg Health Study (GHS). Depression was assessed by the nine-item Patient Health Questionnaire (PHQ-9), and IMT and carotid plaques were measured at both common carotid arteries using an edge detection system. Regression analyses were performed separately for participants with and without cardiovascular disease, adjusting for medical history, cardiovascular risk factors and psychotropic medication.

Contrary to hypotheses, we found no increased IMT for somatic symptoms of depression; the same was true for depression and cognitive symptoms in the fully adjusted model. Only a moderate relationship between medical history of depression and the presence of atherosclerotic plaques was maintained after correction.

The relationship between depression and atherosclerosis may be more complex than previously assumed. Although the vascular depression hypothesis was not supported, our results support the hypothesis that lasting depression leads to arteriosclerosis.

Intact sarcasm perception is a crucial component of social cognition and mentalizing (the ability to understand the mental state of oneself and others). In sarcasm, tone of voice is used to negate the literal meaning of an utterance. In particular, changes in pitch are used to distinguish between sincere and sarcastic utterances. Schizophrenia patients show well-replicated deficits in auditory function and functional connectivity (FC) within and between auditory cortical regions. In this study we investigated the contributions of auditory deficits to sarcasm perception in schizophrenia.

Auditory measures including pitch processing, auditory emotion recognition (AER) and sarcasm detection were obtained from 76 patients with schizophrenia/schizo-affective disorder and 72 controls. Resting-state FC (rsFC) was obtained from a subsample and was analyzed using seeds placed in both auditory cortex and meta-analysis-defined core-mentalizing regions relative to auditory performance.

Patients showed large effect-size deficits across auditory measures. Sarcasm deficits correlated significantly with general functioning and impaired pitch processing both across groups and within the patient group alone. Patients also showed reduced sensitivity to alterations in mean pitch and variability. For patients, sarcasm discrimination correlated exclusively with the level of rsFC within primary auditory regions whereas for controls, correlations were observed exclusively within core-mentalizing regions (the right posterior superior temporal gyrus, anterior superior temporal sulcus and insula, and left posterior medial temporal gyrus).

These findings confirm the contribution of auditory deficits to theory of mind (ToM) impairments in schizophrenia, and demonstrate that FC within auditory, but not core-mentalizing, regions is rate limiting with respect to sarcasm detection in schizophrenia.

Primary health care provides treatment for most patients with depression. Despite their importance for organizing services, long-term course of depression and risk factors for poor outcome in primary care are not well known.

In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 patients representing primary care patients in a Finnish city was screened for depression with the Primary Care Evaluation of Mental Disorders. SCID-I/P and SCID-II interviews were used to diagnose Axis I and II disorders. The 137 patients with DSM-IV depressive disorder were prospectively followed up at 3, 6, 18 and 60 months. Altogether, 82% of patients completed the 5-year follow-up, including 102 patients with a research diagnosis of major depressive disorder (MDD) at baseline. Duration of the index episode, recurrences, time spent in major depressive episodes (MDEs) and partial or full remission were examined with a life-chart.

Of the MDD patients, 70% reached full remission, in a median time of 20 months. One-third had at least one recurrence. The patients spent 34% of the follow-up time in MDEs, 24% in partial remission and 42% in full remission. Baseline severity of depression and substance use co-morbidity predicted time spent in MDEs.

This prospective, naturalistic, long-term study of a representative cohort of primary care patients with depression indicated slow or incomplete recovery and a commonly recurrent course, which need to be taken into account when developing primary care services. Severity of depressive symptoms and substance use co-morbidity should be systematically evaluated in planning treatment.

Alterations in gray matter (GM) are commonly observed in schizophrenia. Accumulating studies suggest that the brain changes associated with schizophrenia are distributed rather than focal, involving interconnected networks of areas as opposed to single regions. In the current study we aimed to explore GM volume (GMV) changes in a relatively large sample of treatment-naive first-episode schizophrenia (FES) patients using optimized voxel-based morphometry (VBM) and covariation analysis.

High-resolution T1-weighted images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first-episode drug-naive patients with schizophrenia and 86 age- and gender-matched healthy volunteers. Symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16 regions of interest (ROIs), selected on the basis of a previous meta-analysis. The relationships between GMVs in the ROIs were examined using an analysis of covariance (ANCOVA).

The VBM analysis revealed that first-episode patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis identified reductions in GMV in the left inferior frontal gyrus, bilateral hippocampus and right thalamus. The ANCOVA revealed different patterns of regional GMV correlations in patients and controls, including of inter- and intra-insula, inter-amygdala and insula–postcentral gyrus connections.

Schizophrenia involves regional reductions in GMV and changes in GMV covariance in the insula, amygdala and postcentral gyrus. These findings were evident at the onset of the disorder, before treatment, and therefore cannot be attributable to the effects of chronic illness progression or medication.

This study investigates possible circularity in mechanisms of change in participants of Master Your Mood (MYM), a cognitive-based, online intervention for young adults with depressive symptoms. A previous study showed that MYM effectively reduced depression and anxiety and strengthened mastery.

We randomized 244 participants with depressive symptoms into MYM or a wait-list control condition. We explored the circularity hypothesis by several analyses. Correlations were computed to determine the association between (change in) depression and anxiety. Path analysis mediation models were used to explore whether change in anxiety and mastery mediated the intervention effect on depression, whether depression and mastery mediated the effect on anxiety and whether depression and anxiety mediated the effect on mastery. We used linear regression to explore whether early changes in anxiety predicted later changes in depression, and whether early changes in depression predicted later changes in anxiety.

Co-morbidity between depression and anxiety was high (69.2%) and the association between depression and anxiety change was strong (r = 0.677, p < 0.01). Changes in anxiety and mastery mediated change in depression (mediation proportion 44%); changes in depression mediated change in anxiety (79%) and mastery (75%). We did not find an early change in anxiety predictive for a late change in depression, and vice versa.

This study appears to confirm the hypothesized circularity in the recovery process. We found high co-morbidity and strong correlation between depression and anxiety levels and bi-directional relationships between potential mediators and outcomes. Early anxiety change scores were not predictive of late depression change scores, and vice versa.

Most evidence in the UK on the effectiveness of brief therapy for depression concerns cognitive behaviour therapy (CBT). In a trial published in 2000, we showed that non-directive counselling and CBT were equally effective in general practice for patients with depression and mixed anxiety and depression. Our results were criticized for including patients not meeting diagnostic criteria for a depressive disorder. In this reanalysis we aimed to compare the effectiveness of the two therapies for patients with an ICD-10 depressive episode.

Patients with an ICD-10 depressive episode or mixed anxiety and depression were randomized to counselling, CBT or usual general practitioner (GP) care. Counsellors provided nondirective, interpersonal counselling following a manual that we developed based on the work of Carl Rogers. Cognitive behaviour therapists provided CBT also guided by a manual. Modelling was carried out using generalized estimating equations with the multiply imputed datasets. Outcomes were mean scores on the Beck Depression Inventory, Brief Symptom Inventory, and Social Adjustment Scale at 4 and 12 months.

A total of 134 participants were randomized to CBT, 126 to counselling and 67 to usual GP care. We undertook (1) an interaction analysis using all 316 patients who were assigned a diagnosis and (2) a head-to-head comparison using only those 130 (41%) participants who had an ICD-10 depressive episode at baseline. CBT and counselling were both superior to GP care at 4 months but not at 12 months. There was no difference in the effectiveness of the two psychological therapies.

We recommend that national clinical guidelines take our findings into consideration in recommending effective alternatives to CBT.

Violent criminal behaviour (VCB) runs strongly in families partly because of shared environmental factors. Can we clarify the environmental processes that contribute to similarity of risk for VCB in siblings?

We assessed VCB from the Swedish National Crime Register for the years 1973–2011 in siblings born 1950–1991. We examined by conditional logistic and Cox proportional hazard regression, respectively, whether resemblance for VCB in sibling pairs was influenced by their age difference and whether VCB was more strongly ‘transmitted’ from older→younger versus younger→older siblings.

In our best-fit logistic model, for each year of age difference in full sibling pairs, the risk for VCB in the sibling of a case versus control proband declined by 2.6% [95% confidence interval (CI) 2.2–3.0]. In our best-fit Cox model, the hazard rate for VCB in a sibling when the affected proband was older versus younger was 1.4, 2.1 and 2.9 respectively for a 1-, 5- and 10-year difference in siblings.

Controlling for genetic effects by examining only full siblings, sibling resemblance for risk for VCB was significantly greater in pairs closer versus more distant in age. Older siblings more strongly transmitted risk for VCB to their younger siblings than vice versa. These results strongly support the importance of familial–environmental influences on VCB and provide some insight into the possible mechanisms at work.

Depressive disorders are highly prevalent in adolescence and confer a heightened risk of recurrence in adulthood. Insight into the developmental neurocircuitry of depression could advance our understanding of depression and aid the development of effective treatment strategies. Whereas white-matter (WM) abnormalities are strongly implicated in adult depression, we still lack a firm understanding of WM architecture in adolescent depression. Using diffusion tensor imaging (DTI), we set out to investigate WM microstructure in a sample of clinically depressed adolescents relative to matched controls.

We employed tract-based spatial statistics (TBSS) to examine WM microstructure in 25 treatment-naive adolescents with clinical depression relative to 21 matched controls. Using TBSS, we examined fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used to control for multiple comparisons.

Our analysis revealed abnormal WM microstructure in clinically depressed adolescents. More specifically, whole-brain analysis revealed that patients had lower FA values in the body of the corpus callosum (CC), coupled with elevated RD and MD, and preserved AD. Conversely, region-of-interest analysis revealed that patients had higher FA values in the uncinate fasciculus (UF), coupled with elevated AD, reduced RD and preserved MD.

In line with neurocircuitry models of depression, our findings suggest that WM abnormalities within pathways facilitating cognitive and emotional functioning are involved in the pathophysiology of depression. Importantly, our findings show that these WM abnormalities are already present early in the course of the disorder.

Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts.

Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones.

We found that increases in emotional symptoms (exp βadj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp βadj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp βadj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp βadj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp βadj = 1.04, s.e. = 0.02, p = 0.05).

Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.

Increasing research effort is being dedicated to investigating the links between emotional processes and psychosis, despite the traditional demarcation between the two. Particular focus has alighted upon two specific anxious and depressive processes, worry and rumination, given the potential for links with aspects of delusions and auditory hallucinations. This study rigorously explored the nature of these links in the context of the daily life of people currently experiencing psychosis.

Experience sampling methodology (ESM) was used to assess the momentary links between worry and rumination on the one hand, and persecutory delusional ideation and auditory hallucinations on the other. Twenty-seven participants completed the 6-day experience sampling period, which required repeated self-reports on thought processes and experiences. Multilevel modelling was used to examine the links within the clustered data.

We found that antecedent worry and rumination predicted delusional and hallucinatory experience, and the distress they elicited. Using interaction terms, we have shown that the links with momentary symptom severity were moderated by participants' trait beliefs about worry/rumination, such that they were reduced when negative beliefs about worry/rumination (meta-cognitions) were high.

The current findings offer an ecologically valid insight into the influence of worry and rumination on the experience of psychotic symptoms, and highlight possible avenues for future intervention strategies.

This prospective cohort study explored the effects of prenatal and postpartum depression on breastfeeding and the effect of breastfeeding on postpartum depression.

The Edinburgh Postpartum Depression Scale (EPDS) was administered to 145 women at the first, second and third trimester, and at the neonatal period and 3 months postpartum. Self-report exclusive breastfeeding since birth was collected at birth and at 3, 6 and 12 months postpartum. Data analyses were performed using repeated-measures ANOVAs and logistic and multiple linear regressions.

Depression scores at the third trimester, but not at 3 months postpartum, were the best predictors of exclusive breastfeeding duration (β = −0.30, t = −2.08, p < 0.05). A significant decrease in depression scores was seen from childbirth to 3 months postpartum in women who maintained exclusive breastfeeding for ⩾3 months (F1,65 = 3.73, p < 0.10, ηp2 = 0.05).

These findings suggest that screening for depression symptoms during pregnancy can help to identify women at risk for early cessation of exclusive breastfeeding, and that exclusive breastfeeding may help to reduce symptoms of depression from childbirth to 3 months postpartum.