People with psychosis demonstrate impaired response inhibition on the Stop Signal Task (SST). It is less clear if this impairment extends to reflection impulsivity, a form of impulsivity that has been linked to substance use in non-psychotic samples.

We compared 49 patients with first-episode psychosis (FEP) and 30 healthy control participants on two forms of impulsivity measured using the Information Sampling Test (IST) and the SST, along with clinical and IQ assessments. We also compared those patients who used cannabis with those who had either given up or never used.

Patients with FEP had significantly greater impairment in response inhibition but not in reflection impulsivity compared with healthy controls. By contrast, patients who reported current cannabis use demonstrated greater reflection impulsivity than those that had either given up or never used, whereas there were no differences in response inhibition.

These data suggest that abnormal reflection impulsivity is associated with substance use in psychosis but not psychosis itself; the opposite relationship may hold for response inhibition.

Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children.

Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577).

ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score.

Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

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.

Recognition of communicative interactions is a complex social cognitive ability which is associated with a specific neural activity in healthy individuals. However, neural correlates of communicative interaction processing from whole-body motion have not been known in patients with schizophrenia (SCZ). Therefore, the current study aims to examine the neural activity associated with recognition of communicative interactions in SCZ by using displays of the dyadic interactions downgraded to minimalistic point-light presentations.

Twenty-six healthy controls (HC) and 25 SCZ were asked to judge whether two agents presented only by point-light displays were communicating or acting independently. Task-related activity and functional connectivity of brain structures were examined with General Linear Model and Generalized Psychophysiological Interaction approach, respectively.

HC were significantly more efficient in recognizing each type of action than SCZ. At the neural level, the activity of the right posterior superior temporal sulcus (pSTS) was observed to be higher in HC compared with SCZ for communicative v. individual action processing. Importantly, increased connectivity of the right pSTS with structures associated with mentalizing (left pSTS) and mirroring networks (left frontal areas) was observed in HC, but not in SCZ, during the presentation of social interactions.

Under-recruitment of the right pSTS, a structure known to have a pivotal role in social processing, may also be of importance for higher-order social cognitive deficits in SCZ. Furthermore, decreased task-related connectivity of the right pSTS may result in reduced use of additional sources of information (for instance motor resonance signals) during social cognitive processing in schizophrenia.

White matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset.

WM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years.

This young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants.

Our findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD – a group at particular risk of future hypo/manic episodes – suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies.

Elucidating individual aberrance is a critical first step toward precision medicine for heterogeneous disorders such as depression. The neuropathology of depression is related to abnormal inter-regional structural covariance indicating a brain maturational disruption. However, most studies focus on group-level structural covariance aberrance and ignore the interindividual heterogeneity. For that reason, we aimed to identify individualized structural covariance aberrance with the help of individualized differential structural covariance network (IDSCN) analysis.

T1-weighted anatomical images of 195 first-episode untreated patients with depression and matched healthy controls (n = 78) were acquired. We obtained IDSCN for each patient and identified subtypes of depression based on shared differential edges.

As a result, patients with depression demonstrated tremendous heterogeneity in the distribution of differential structural covariance edges. Despite this heterogeneity, altered edges within subcortical-cerebellum network were often shared by most of the patients. Two robust neuroanatomical subtypes were identified. Specifically, patients in subtype 1 often shared decreased motor network-related edges. Patients in subtype 2 often shared decreased subcortical-cerebellum network-related edges. Functional annotation further revealed that differential edges in subtype 2 were mainly implicated in reward/motivation-related functional terms.

In conclusion, we investigated individualized differential structural covariance and identified that decreased edges within subcortical-cerebellum network are often shared by patients with depression. The identified two subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of depression.

Aberrant salience may contribute to the development of schizophrenia symptoms via alterations in reward processing and motivation. However, tests of this hypothesis have yielded inconsistent results. These inconsistencies may reflect problems with the validity and specificity of measures of aberrant salience in schizophrenia. Therefore, we investigated relationships among measures of aberrant salience, reward, and motivation in schizophrenia and anxiety.

Individuals with schizophrenia (n = 30), anxiety (n = 33) or unaffected by mental disorder (n = 30) completed measures of aberrant salience [Aberrant Salience Inventory (ASI), Salience Attribution Test (SAT)], motivation (Effort Expenditure for Reward Task), and reinforcer sensitivity (Stimulus Chase Task).

Schizophrenia participants scored higher than anxiety (d = 0.71) and unaffected (d = 1.54) groups on the ASI and exhibited greater aberrant salience (d = 0.60) and lower adaptive salience (d = 0.98) than anxious participants on the SAT. There was no evidence of a correlation between measures of aberrant salience. Schizophrenia was associated with related deficits in motivated behaviour and maladaptive reward processing. However, these differences in reward processing did not correlate with aberrant salience measures.

The results suggest that key measures of aberrant salience have limited specificity and validity. These problems may account for inconsistent findings reported in the literature.

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.

Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network.

We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA).

We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers.

We found altered effective and structural connectivity within the ACC–thalamus network in SZ. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders.

In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies.

Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy.

Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed.

There is a well-established association between psychotic disorders and subsequent offending but the extent to which those who develop psychosis might have a prior history of offending is less clear. Little is known about whether the association between illness and offending exists in non-psychotic disorders. The aim of this study was to determine whether the association between mental disorder and offending is present prior to illness onset in psychotic and non-psychotic disorders.

In a nested case-control study, cases (n=101 890) with a first psychiatric contact during the period 1995 to 2006 were identified and matched by age and gender to population-based controls (n=2 236 195). Exposure was defined as prior criminal and violent offending.

Males with one offence had an incidence rate ratio (IRR) of 2.32 [95% confidence interval (CI) 2.26–2.40] for psychiatric admission whereas two or more convictions yielded an IRR of 4.97 (95% CI 4.83–5.11). For violent offending the associations were stronger and IRRs of 3.97 (95% CI 3.81–4.12) and 6.18 (95% CI 5.85–6.52) were found for one and several offences respectively. Estimates for females were of a similar magnitude. The pattern was consistent across most diagnostic subgroups, although some variability in effect sizes was seen, and persisted after adjustment for substance misuse and socio-economic status (SES).

A prior history of offending is present in almost one in five patients presenting to mental health services, which makes it an important issue for clinicians to consider when assessing current and future risks and vulnerabilities.

Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.

In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.

Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1–3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.

These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.