Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range.

To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and panic disorder.

Fifty-six trials of second-generation antidepressants for the short-term treatment of an anxiety disorder were included. Baseline and change scores were extracted for placebo and treatment groups in each trial. Mixed effects meta-regression was used to investigate the effects of treatment group, baseline severity and their interaction.

Increased baseline severity did not predict greater improvement in drug groups compared with placebo groups. Standardised regression coefficients of the interaction term between baseline severity and treatment group were 0.04 (95% CI –0.13 to 0.20, P = 0.65) for GAD, –0.06 (95% CI –0.20 to 0.09, P = 0.43) for SAD, 0.04 (95% CI –0.07 to 0.16, P = 0.46) for OCD, 0.16 (95% CI –0.22 to 0.53, P = 0.37) for PTSD and 0.002 (95% CI –0.10 to 0.10, P = 0.96) for panic disorder. For OCD, baseline severity did predict improvement in both placebo and drug groups equally (β = 0.11, 95% CI 0.05 to 0.17, P = 0.001).

No relationship between baseline severity and drug–placebo difference was found for anxiety disorders. These results suggest that if the efficacy of antidepressants is considered clinically relevant, they may be prescribed to patients with anxiety regardless of symptom severity.

Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity.

To assess tDCS efficacy and to explore individual response predictors.

Systematic review and individual patient data meta-analysis.

Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38–4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22–4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12–0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS ‘doses' were, respectively, negatively and positively associated with tDCS efficacy.

The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose.

Stressful life events (SLEs) are associated with psychotic experiences. SLEs might act as an environmental risk factor, but may also share a genetic propensity with psychotic experiences.

To estimate the extent to which genetic and environmental factors influence the relationship between SLEs and psychotic experiences.

Self- and parent reports from a community-based twin sample (4830 16-year-old pairs) were analysed using structural equation model fitting.

SLEs correlated with positive psychotic experiences (r = 0.12–0.14, all P<0.001). Modest heritability was shown for psychotic experiences (25–57%) and dependent SLEs (32%). Genetic influences explained the majority of the modest covariation between dependent SLEs and paranoia and cognitive disorganisation (bivariate heritabilities 74–86%). The relationship between SLEs and hallucinations and grandiosity was explained by both genetic and common environmental effects.

Further to dependent SLEs being an environmental risk factor, individuals may have an underlying genetic propensity increasing their risk of dependent SLEs and positive psychotic experiences.

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.

To quantify the shared genetic variability between bipolar disorder and cognitive measures.

Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.

Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|–|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|–|1.00|), which remained significant after covarying for affective symptoms.

Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.

Attention-deficit hyperactivity disorder (ADHD) persists in around two-thirds of individuals in adolescence and early adulthood.

To examine the cognitive and neurophysiological processes underlying the persistence or remission of ADHD.

Follow-up data were obtained from 110 young people with childhood ADHD and 169 controls on cognitive, electroencephalogram frequency, event-related potential (ERP) and actigraph movement measures after 6 years.

ADHD persisters differed from remitters on preparation-vigilance measures (contingent negative variation, delta activity, reaction time variability and omission errors), IQ and actigraph count, but not on executive control measures of inhibition or working memory (nogo-P3 amplitudes, commission errors and digit span backwards).

Preparation-vigilance measures were markers of remission, improving concurrently with ADHD symptoms, whereas executive control measures were not sensitive to ADHD persistence/remission. For IQ, the present and previous results combined suggest a role in moderating ADHD outcome. These findings fit with previously identified aetiological separation of the cognitive impairments in ADHD. The strongest candidates for the development of non-pharmacological interventions involving cognitive training and neurofeedback are the preparation-vigilance processes that were markers of ADHD remission.

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.

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.

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.

Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders'.

To compare white matter integrity in patients with gambling disorder with healthy controls; to explore relationships between white matter integrity and disease severity in gambling disorder.

In total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics.

Gambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity.

Reduced corpus callosum fractional anisotropy is suggestive of disorganised/damaged tracts in patients with gambling disorder, and this may represent a trait/vulnerability marker for the disorder. Future research should explore these measures in a larger sample, ideally incorporating a range of imaging markers (for example functional MRI) and enrolling unaffected first-degree relatives of patients.

Higher daytime cortisol levels because of a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts.

To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method.

The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement.

Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected).

Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal–subcortical and frontal–limbic circuits.