The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.

We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.

Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).

The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Substance use disorder is highly prevalent in people with psychiatric disorders, and known to impede the psychiatric treatment. Some studies show increased rates of service use, while others show a decrease. These conflicting results are further hampered by a lack of large-scale studies. The aim of this study was to investigate the association between substance use disorder and psychiatric service use in psychiatric patients.

The study was a prospective registry-based cohort study including patients with severe mental illness. The primary outcome was the number of hospitalisations, bed days and the number of psychiatric emergency department contacts. The association was calculated with incidence rate ratio with 95% confidence intervals.

The study included all psychiatric patients born since 1955. In total, 21 558 patients with schizophrenia (47.54% with substance use disorder), 80 778 patients with depression (28.78% with substance use disorder), 10 560 patients with bipolar affective disorder (40.08% with substance use disorder) and 69 252 patients with a personality disorder (39.18% with substance use disorder) were included. Patients with comorbid substance use disorder had significantly increased rates of hospitalisations, bed days and psychiatric emergency department contacts (p < 0.001) for the majority of the included substances, compared with patients without such disorders.

Substance use disorder was associated with an increased number of hospitalisations, bed days and increased number of psychiatric emergency department contacts for the majority of the included substances.

The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients.

In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups.

Patients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate.

TRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism – a glutamatergic mechanism would be a possible candidate.

Altered amygdala activation to fear-related stimuli has been proposed to be a potential neural correlate of heightened threat sensitivity in anxiety- and stress-related disorders. However, the role of stimulus awareness and disorder specificity remains widely unclear. Here we investigated amygdala responses to conscious and unconscious fearful faces in patients suffering from panic disorder (PD), generalized anxiety disorder (GAD), or post-traumatic stress disorder (PTSD) and in a large sample of healthy controls (HC).

During event-related functional magnetic resonance imaging participants (n = 120; 20 PD, 20 GAD, 20 PTSD, 60 HC) were confronted with briefly presented fearful faces, neutral faces, and non-faces in a backward masking paradigm. The design allowed for the analysis of trial-by-trial face detection performance and amygdala responses to fearful v. neutral faces.

All participants exhibited increased amygdala activation to fearful v. neutral faces during conscious trials. Specifically during unconscious face processing, the PTSD, compared with all other groups, showed higher right basolateral (BLA) amygdala activity to fearful v. neutral faces.

The present study shows that BLA amygdala hyperactivity during unconscious, but not conscious, processing of fearful faces differentiates PTSD from the investigated disorders. This finding suggests an automatic and specific neural hyper-responsivity to general fear cues in PTSD and supports the idea of categorical differences between PTSD and other anxiety-related disorders.

The intergenerational risk for mental illness is well established within diagnostic categories, but the risk is unlikely to respect diagnostic boundaries and may be reflected more broadly in early life vulnerabilities. We aimed to establish patterns of association between externalising and internalising vulnerabilities in early childhood and parental mental disorder across the full spectrum of diagnoses.

A cohort of Australian children (n = 69 116) entering the first year of school in 2009 were assessed using the Australian Early Development Census, providing measures of externalising and internalising vulnerability. Parental psychiatric diagnostic status was determined utilising record-linkage to administrative health datasets.

Parental mental illness, across diagnostic categories, was associated with all child externalising and internalising domains of vulnerability. There was little evidence to support interaction by parental or offspring sex.

These findings have important implications for informing early identification and intervention strategies in high-risk offspring and for research into the causes of mental illness. There may be benefits to focusing less on diagnostic categories in both cases.

Deaths from suicide, as recorded within the Northern Ireland Coroner's Office for the years 2005–2011 inclusive, were analysed in terms of standardised mortality ratios (SMRs), within Wards and Local Government Districts (LGDs). The aim of the study is to examine factors relating to the ecological context of the area within which the person resided at time of death. Area deprivation, religious composition and age structure are examined in terms of SMRs, while controlling for the number of individuals living within a designated area.

Random-intercept Poisson regression models were used in conjunction with empirical Bayes prediction to examine area effects.

Considerable variation occurs between the numbers of recorded deaths within each area. A strong association is shown between deprivation and the number of deaths by suicide within an area. There was considerable variation at the LGD level in terms of the number of deaths, but once the nested nature of Wards was taken into account and adjusted for level of deprivation, the variation between LGD was no longer statistically significant. When adjusted for the number of individuals within each age group, the number of deaths in the younger and middle-aged groups did not show a statistical difference (0.05 level), nor did the religious composition of the area in terms of the number of recorded deaths.

Based on SMRs, using empirical Bayes prediction, area effects were shown to be substantial, especially in urban locations where there are high rates of deprivation.

Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder.

Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms.

Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD).

Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.

Youths with obsessive–compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study.

A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control.

Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control.

This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.

Exposure to child maltreatment has been shown to increase lifetime risk for substance use disorders (SUD). However, this has not been systematically examined among race/ethnic groups, for whom rates of exposure to assaultive violence and SUD differ. This study examined variation by race/ethnicity and gender in associations of alcohol (AUD), cannabis (CUD), and tobacco (TUD) use disorders with three types of childhood interpersonal violence (cIPV): physical abuse, sexual abuse, and witnessing parental violence.

Data from the National Epidemiologic Survey of Alcohol-Related Conditions-III (N: 36 309), a US nationally representative sample, was utilized to examine associations of DSM-5 AUD, CUD and TUD with cIPV among men and women of five racial/ethnic groups. Models were adjusted for additional risk factors (e.g. parental substance use problems, participant's co-occurring SUD).

Independent contributions of childhood physical and sexual abuse to AUD, CUD, and TUD, and of witnessing parental violence to AUD and TUD were observed. Associations of cIPV and SUD were relatively similar across race/ethnicity and gender [Odds Ratios (ORs) ranged from 1.1 to 1.9], although associations of physical abuse with AUD and TUD were greater among males, associations of parental violence and AUD were greater among females, and associations of parental violence with AUD were greater among Hispanic women and American Indian men.

Given the paucity of research in this area, and the potential identification of modifiable risk factors to reduce the impact of childhood interpersonal violence on SUDs, further research and consideration of tailoring prevention and intervention efforts to different populations are warranted.

Sexual assault is a global concern with post-traumatic stress disorder (PTSD), one of the common sequelae. Early intervention can help prevent PTSD, making identification of those at high risk for the disorder a priority. Lack of representative sampling of both sexual assault survivors and sexual assaults in prior studies might have reduced the ability to develop accurate prediction models for early identification of high-risk sexual assault survivors.

Data come from 12 face-to-face, cross-sectional surveys of community-dwelling adults conducted in 11 countries. Analysis was based on the data from the 411 women from these surveys for whom sexual assault was the randomly selected lifetime traumatic event (TE). Seven classes of predictors were assessed: socio-demographics, characteristics of the assault, the respondent's retrospective perception that she could have prevented the assault, other prior lifetime TEs, exposure to childhood family adversities and prior mental disorders.

Prevalence of Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) PTSD associated with randomly selected sexual assaults was 20.2%. PTSD was more common for repeated than single-occurrence victimization and positively associated with prior TEs and childhood adversities. Respondent's perception that she could have prevented the assault interacted with history of mental disorder such that it reduced odds of PTSD, but only among women without prior disorders (odds ratio 0.2, 95% confidence interval 0.1–0.9). The final model estimated that 40.3% of women with PTSD would be found among the 10% with the highest predicted risk.

Whether counterfactual preventability cognitions are adaptive may depend on mental health history. Predictive modelling may be useful in targeting high-risk women for preventive interventions.

Neurocognitive deficits are often seen as core features of schizophrenia, and as primary determinants of poor functioning. Yet, our clinical observations suggest that individuals who score within the impaired range on standardized tests can reliably perform better in complex real-world situations, especially when performance is embedded within a positive socio-affective context.

We analyzed literature on the influence of non-neurocognitive factors on test performance in order to clarify their contributions.

We identified seven non-neurocognitive factors that significantly contribute to neurocognitive test performance: avolition, dysfunctional attitudes, effort, stress, negative emotions, asociality, and disorganized symptoms. We then proposed an alternative model based on dysfunctional (e.g. defeatist) attitudes and their consequences for motivation and sustained task engagement. We demonstrated that these factors account for substantial variance in negative symptoms, neurocognitive test performance, and functional outcomes. We then demonstrated that recovery-oriented cognitive therapy – which is derived from this alternative model and primarily targets dysfunctional beliefs – has been successful in the treatment of low functioning individuals with schizophrenia.

The contributions of neurocognitive impairments to poor real-world functioning in people with schizophrenia may be overstated in the literature, and may even be limited relative to non-neurocognitive factors. We offer suggestions for further research to more precisely quantify the contributions of attitudinal/motivation v. neurocognitive factors in schizophrenia.

Changes in positive and negative symptom profiles during acute psychotic episodes may be key drivers in the pathway to violence. Acute episodes are often preceded by fluctuations in affect before psychotic symptoms appear and affective symptoms may play a more important role in the pathway than previously recognised.

We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Positive and Negative Syndrome Scale. Information on violence was obtained using the McArthur Community Violence Instrument and Police National Computer.

The larger the shift in positive symptoms the more likely violence occurred in each 6-month period. However, shifts in angry affect were the main driving factor for positive symptom shifts associated with violence. Shifts in negative symptoms co-occurred with positive and conveyed protective effects, but these were overcome by co-occurring shifts in anger. Severe but stable delusions were independently associated with violence.

Intensification of angry affect during acute episodes of psychosis indicates the need for interventions to prevent violence and is a key driver of associated positive symptoms in the pathway to violence. Protective effects against violence exerted by negative symptoms are not clinically observable during symptom shifts because they are overcome by co-occurring anger.

The vulnerability hypothesis suggests that impairments after remission of depressive episodes reflect a pre-existing vulnerability, while the scar hypothesis proposes that depression leaves residual impairments that confer risk of subsequent episodes. We prospectively examined vulnerability and scar effects in mental and physical functioning in a representative Dutch population sample.

Three waves were used from the Netherlands Mental Health Survey and Incidence Study-2, a population-based study with a 6-years follow-up. Mental and physical functioning were assessed with the Medical Outcomes Study Short Form (SF-36). Major depressive disorder (MDD) was assessed with the Composite International Diagnostic Interview 3.0. Vulnerability effects were examined by comparing healthy controls (n = 2826) with individuals who developed a first-onset depressive episode during first follow-up but did not have a lifetime diagnosis of MDD at baseline (n = 181). Scarring effects were examined by comparing pre- and post-morbid functioning in individuals who developed a depressive episode after baseline that was remitted at the third wave (n = 108).

Both mental (B = −5.4, s.e. = 0.9, p < 0.001) and physical functioning (B = −8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who developed a first depressive episode after baseline compared with healthy controls. This effect was most pronounced in people who developed a severe episode. No firm evidence of scarring in mental or physical functioning was found. In unadjusted analyses, physical functioning was still lowered post-morbidly (B = −5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in adjusted analyses.

Functional impairments after remission of depression seem to reflect a pre-existing vulnerability rather than a scar.

Abnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis.

We performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life.

We detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life.

These findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.