Psychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders.

To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population.

We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene and carried out case–control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population.

We found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).

Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population.

No prospective studies have examined the role of C-reactive protein (CRP) in late-onset bipolar disorder.

We tested the hypothesis that elevated levels of CRP are associated cross-sectionally and prospectively with late-onset bipolar disorder, and that such an association possibly is causal.

We performed cross-sectional and prospective analyses with a median follow-up time of 5.9 years (interquartile range: 4.4– 7.6) in 78 809 individuals from the general population, and used genetic variants influencing CRP levels to perform a Mendelian randomisation study.

Elevated levels of CRP were associated both cross-sectionally and prospectively with late-onset bipolar disorder. When CRP was on a continuous scale, a doubling in CRP yielded an observational odds ratio for late-onset bipolar disorder of 1.28 (1.08–1.52) with a corresponding causal odds ratio of 4.66 (0.89–24.3).

Elevated CRP is associated with increased risk of late-onset bipolar disorder in the general population which was supported by the genetic analysis.

Little evidence exists on the treatment of traumatised refugees.

To estimate treatment effects of flexible cognitive–behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees.

Randomised controlled clinical trial with 2×2 factorial design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months.

A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression.

In a pragmatic clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees.

The substantial discrepancy between mentalising in experimental settings v. real-life social interactions hinders the understanding of the neural basis of real-life social cognition and of social impairments in psychiatric disorders.

To determine the neural mechanisms underlying naturalistic mentalising in individuals with and without autism spectrum disorder.

We investigated mentalising with a new video-based functional magnetic resonance imaging task in 20 individuals with autism spectrum disorder and 22 matched healthy controls.

Naturalistic mentalising implicated regions of the traditional mentalising network (medial prefrontal cortex, temporoparietal junction), and additionally the insula and amygdala. Moreover, amygdala activity predicted implicit mentalising performance on an independent behavioural task. Compared with controls, the autism spectrum disorder group did not show differences in neural activity within classical mentalising regions. They did, however, show reduced amygdala activity and a reduced correlation between amygdala activity and mentalising accuracy on the behavioural task, compared with controls.

These findings highlight the crucial role of the amygdala in making accurate implicit mental state inferences in typical development and in the social cognitive impairments of individuals with autism spectrum disorder.

The relationship between the duration of depressive symptoms and mortality remains poorly understood.

To examine whether the duration of depressive symptoms is associated with mortality risk.

Data (n = 9560) came from the English Longitudinal Study of Ageing (ELSA). We assessed depressive symptom duration as the sum of examinations with an eight-item Center for Epidemiologic Studies Depression Scale score of ⩾3; we ascertained mortality from linking our data to a national register.

Relative to those participants who never reported symptoms, the age- and gender-adjusted hazard ratios for elevated depressive symptoms over 1, 2, 3 and 4 examinations were 1.41 (95% CI 1.15–1.74), 1.80 (95% CI 1.44–2.26), 1.97 (95% CI 1.57–2.47) and 2.48 (95% CI 1.90–3.23), respectively (P for trend <0.001). This graded association can be explained largely by differences in physical activity, cognitive function, functional impairments and physical illness.

In this cohort of older adults, the duration of depressive symptoms was associated with mortality in a dose–response manner.

We previously reported that patients with early-stage bipolar disorder, but not healthy comparison controls, had body mass index (BMI)-related volume reductions in limbic brain areas, suggesting that the structural brain changes characteristic of bipolar disorder were more pronounced with increased weight.

To determine whether the most consistently reported neurochemical abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was also more prominent with higher BMI.

We used single-voxel proton magnetic resonance spectroscopy to measure hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1) and 28 healthy controls (mean BMI = 23.3).

In patients, but not healthy controls, linear regression demonstrated that higher BMI predicted greater Glx. Factorial ANCOVA showed a significant BMI×diagnosis interaction, confirming a distinct effect of weight on Glx in patients.

Together with our volumetric studies, these results suggest that higher BMI is associated with more pronounced structural and neurochemical limbic brain changes in bipolar disorder, even in early-stage patients with low obesity rates.

Accumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD).

To examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD.

Expression analyses were tested in 53 unmedicated people with MDD and 55 healthy controls. A two-stage genetic association analysis was performed in 3323 Han Chinese with or without MDD. Potential associations between CFH single nucleotide polymorphisms and age at MDD onset were evaluated.

CFH levels were significantly lower in the MDD group at both protein and mRNA levels (P = 0.009 and P = 0.014 respectively). A regulatory variant in the CFH gene, rs1061170, showed statistically significant genotypic and allelic differences between the MDD and control groups (genotypic P = 0.0005, allelic P = 0.0001). Kaplan–Meier survival analysis showed that age at onset of MDD was significantly associated with the C allele of rs1061170 (log rank statistic χ2 = 6.82, P = 0.009). The C-allele carriers had a younger age at onset of MDD (22.2 years, s.d. = 4.0) than those without the C allele (23.6 years, s.d. = 4.3).

CFH is likely to play an important role in the development of MDD. rs1061170 has an important effect on age at onset of MDD in Han Chinese and may therefore be related to early pathogenesis of MDD, although further study is needed.

The relationship between ethnic density and psychiatric disorder in postnatal women in the UK is unclear.

To examine the effect of own and overall ethnic density on postnatal depression (PND) and personality dysfunction.

Multilevel analysis of ethnically mixed community-level data gathered from a sample of 2262 mothers screened at 6 weeks postpartum for PND and personality dysfunction.

Living in areas of higher own ethnic density was protective against screening positive for PND in White women (z =–3.18, P = 0.001), even after adjusting for area level deprivation, maternal age, relationship status, screening positive for personality dysfunction, parity and geographical clustering (odds ratio (OR) 0.98 (95% CI 0.96–0.99); P = 0.002), whereas the effect on personality dysfunction (z =–2.42, P = 0.016) was no longer present once the effect of PND was taken into account (OR = 0.99 (95% CI 0.90–1.0); P = 0.13). No overall ethnic density effect was found for women screening positive for PND or personality dysfunction.

In White women, living in areas of higher own ethnic density was protective against developing PND.

To make informed choices, patients need information about negative as well as positive effects of treatments. There is little information about negative effects of psychological interventions.

To determine the prevalence of and risk factors for perceived negative effects of psychological treatment for common mental disorders.

Cross-sectional survey of people receiving psychological treatment from 184 services in England and Wales. Respondents were asked whether they had experienced lasting bad effects from the treatment they received.

Of 14 587 respondents, 763 (5.2%) reported experiencing lasting bad effects. People aged over 65 were less likely to report such effects and sexual and ethnic minorities were more likely to report them. People who were unsure what type of therapy they received were more likely to report negative effects (odds ratio (OR) = 1.51, 95% CI 1.22–1.87), and those that stated that they were given enough information about therapy before it started were less likely to report them (OR = 0.65, 95% CI 0.54–0.79).

One in 20 people responding to this survey reported lasting bad effects from psychological treatment. Clinicians should discuss the potential for both the positive and negative effects of therapy before it starts.

The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.

To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.

Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.

There were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).

Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder.

Delusional disorder has been the subject of very little investigation using brain imaging.

To examine potential structural and/or functional brain abnormalities in this disorder.

We used structural imaging (voxel-based morphometry, VBM) and functional imaging (during performance of the n-back task and whole-brain resting connectivity analysis) to examine 22 patients meeting DSM-IV criteria for delusional disorder and 44 matched healthy controls.

The patients showed grey matter reductions in the medial frontal/anterior cingulate cortex and bilateral insula on unmodulated (but not on modulated) VBM analysis, failure of de-activation in the medial frontal/anterior cingulate cortex during performance of the n-back task, and decreased resting-state connectivity in the bilateral insula.

The findings provide evidence of brain abnormality in the medial frontal/anterior cingulate cortex and insula in delusional disorder. A role for the former region in the pathogenesis of delusions is consistent with several other lines of evidence.

Negative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques.

To examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms.

A total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart.

When comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus.

Negative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

Light severely affects the occurrence of seasonal affective disorder (SAD).

To compare the prevalence of SAD in persons with severe visual impairment and persons with full sight, and in persons with severe visual impairment with or without light perception.

This cross-sectional study assessed the Global Seasonality Score (GSS) and the prevalence of SAD among 2781 persons with visual impairment and 4099 persons with full sight using the Seasonal Pattern Assessment Questionnaire (SPAQ).

Respondents with visual impairment had significantly higher GSS and prevalence of SAD compared with full sight controls, P<0.001. Light perception respondents were more vulnerable to seasonal change than both full sight and no light perception respondents.

The study showed a highly significant association between visual impairment and SPAQ-defined SAD parameters, supporting the hypothesis that decreased retinal light input plays a role in the pathogenesis of SAD.

Increased temporal and frontal slow-wave delta (1–4 Hz) and theta (4–7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity.

To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments.

Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity.

Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. control group. In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity.

Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis.

Little is known about predictors of recovery from bipolar depression.

We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression.

A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n = 141) or a brief psychoeducational intervention (n = 111). All analyses were by intention-to-treat.

Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression.

Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression.

Electroconvulsive therapy (ECT) is the most effective acute treatment for severe depression, but widely held concerns about memory problems may limit its use.

To find out whether repeated or maintenance courses of ECT cause cumulative cognitive deterioration.

Analysis of the results of 10 years of cognitive performance data collection from patients who have received ECT. The 199 patients had a total of 498 assessments, undertaken after a mean of 15.3 ECT sessions (range 0–186). A linear mixed-effect regression model was used, testing whether an increasing number of ECT sessions leads to deterioration in performance.

The total number of previous ECT sessions had no effect on cognitive performance. The major factors affecting performance were age, followed by the severity of depression at the time of testing and the number of days since the last ECT session.

Repeated courses of ECT do not lead to cumulative cognitive deficits. This message is reassuring for patients, carers and prescribers who are concerned about memory problems and confusion during ECT.

The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant.

To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance.

Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months.

Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity.

Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.