In healthy controls, preactivation of muscles by exercise results in enhanced motor-evoked potential (MEP) responses to transcranial magnetic stimulation (TMS).

We tested the hypothesis that medicated, depressed patients would show reduced post-exercise MEP facilitation compared with controls.

Ten patients with DSM-IV depression (two male, eight female) and ten controls (three male, seven female) participated. MEPs were elicited at rest, then after exercising the contralateral abductor pollicis brevis muscle, using TMS of the primary motor cortex.

The mean MEP amplitude recorded after exercise (expressed as a percentage of baseline) was 210% in controls and 130% in patients. There was a significant difference in post-exercise MEP between patients and controls (P=0.03).

Post-exercise MEP facilitation was demonstrated in controls but not in patients. This supports the hypothesis that the modulation of cortical excitability may be impaired in depression.

Structural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes.

To investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression.

Thirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined.

An association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r’ = 0.31–0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group.

We found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression.

Early improvement with treatment is thought to be important in patients with first-episode schizophrenia, yet a valid definition is still outstanding.

To develop a valid definition of early improvement and test its predictive validity regarding response and remission.

We examined 188 in-patients with first-episode schizophrenia. Early improvement was defined as improvement in Positive and Negative Syndrome Scale (PANSS) total score at week 2, response as a 40% PANSS total score improvement at end-point, and remission according to consensus criteria.

Reasonable predictive validity of early improvement was found for a 46% PANSS total score improvement at week 2 and a 50% improvement for remission (area under the curve: response 0.707, remission 0.692). Estimated confidence intervals ranged from 26 to 62% PANSS reduction for response and remission.

Patients with a first episode of schizophrenia should improve by at least 30% in PANSS total score at week 2 to achieve response and remission.

People with schizophrenia may demonstrate cortical abnormalities, with gyri and sulci potentially being differentially affected.

To measure frontal and temporal sulcal cortical thickness, surface area and volume in the non-psychotic relatives of patients with schizophrenia as a potential vulnerability indicator for the disorder.

An automated parcellation method was used to measure the superior frontal, inferior frontal, cingulate, superior temporal and inferior temporal sulci in the relatives of patients (n=19) and controls (n=22).

Compared with controls, relatives had reversed hemispheric asymmetry in their cingulate sulcal thickness and a bilateral reduction in their superior temporal sulcal thickness.

Cingulate and superior temporal sulcal thickness abnormalities may reflect neural abnormalities associated with the genetic liability to schizophrenia. Cortical thinning in these regions suggests that liability genes affect the dendrites, synapses or myelination process during the neurodevelopment of the cortical mantle.

Familial co-occurrence of frontotemporal dementia and schizophrenia has never been investigated.

To test the hypothesis that frontotemporal dementia and schizophrenia might have a common aetiology in some families in which both syndromes coexist (mixed families).

The morbid risk for schizophrenia, calculated in first-degree relatives of 100 frontotemporal dementia probands, was compared with that calculated in first-degree relatives of 100 Alzheimer's disease probands. In mixed families, sequencing analysis of known frontotemporal dementia genes and detailed phenotype characterisation of individuals with frontotemporal dementia and schizophrenia were performed.

The morbid risk for schizophrenia was significantly higher in relatives of frontotemporal dementia probands (1.35, s.e. = 0.45) than in relatives of Alzheimer's disease probands (0.32, s.e. = 0.22). Ten mixed families were characterised. In three of them a frontotemporal dementia causal mutation was identified that was present in individuals with schizophrenia. Several specific clinical features were noted in people with schizophrenia and frontotemporal dementia in mixed families.

Co-occurrence of schizophrenia and frontotemporal dementia could indicate, in some families, a common aetiology for both conditions.

Treatment-resistant depression (TRD) is the most problematic outcome of depression in terms of functional impairment, suicidal thoughts and decline in physical health.

To investigate the genetic predictors of TRD using a genome-wide approach to contribute to the development of precision medicine.

A sample recruited by the European Group for the Study of Resistant Depression (GSRD) including 1148 patients with major depressive disorder (MDD) was characterised for the occurrence of TRD (lack of response to at least two adequate antidepressant treatments) and genotyped using the Infinium PsychArray. Three clinically relevant patient groups were considered: TRD, responders and non-responders to the first antidepressant trial, thus outcomes were based on comparisons of these groups. Genetic analyses were performed at the variant, gene and gene-set (i.e. functionally related genes) level. Additive regression models of the outcomes and relevant covariates were used in the GSRD participants and in a fixed-effect meta-analysis performed between GSRD, STAR*D (n = 1316) and GENDEP (n = 761) participants.

No individual polymorphism or gene was associated with TRD, although some suggestive signals showed enrichment in cytoskeleton regulation, transcription modulation and calcium signalling. Two gene sets (GO:0043949 and GO:0000183) were associated with TRD versus response and TRD versus response and non-response to the first treatment in the GSRD participants and in the meta-analysis, respectively (corrected P = 0.030 and P = 0.027).

The identified gene sets are involved in cyclic adenosine monophosphate mediated signal and chromatin silencing, two processes previously implicated in antidepressant action. They represent possible biomarkers to implement personalised antidepressant treatments and targets for new antidepressants.

D.S. has received grant/research support from GlaxoSmithKline and Lundbeck; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen and Lundbeck. S.M. has been a consultant or served on advisory boards for: AstraZeneca, Bristol-Myers Squibb, Forest, Johnson & Johnson, Leo, Lundbeck, Medelink, Neurim, Pierre Fabre, Richter. S.K. has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, Sepracor and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Organon, Schwabe, Sepracor, Servier, Janssen and Novartis; and has served on speakers' bureaus for AstraZeneca, Eli Lily, Lundbeck, Schwabe, Sepracor, Servier, Pierre Fabre, Janssen and Neuraxpharm. J.Z. has received grant/research support from Lundbeck, Servier, Brainsway and Pfizer, has served as a consultant or on advisory boards for Servier, Pfizer, Abbott, Lilly, Actelion, AstraZeneca and Roche and has served on speakers' bureaus for Lundbeck, Roch, Lilly, Servier, Pfizer and Abbott. J.M. is a member of the Board of the Lundbeck International Neuroscience Foundation and of Advisory Board of Servier. A.S. is or has been consultant/speaker for: Abbott, AbbVie, Angelini, Astra Zeneca, Clinical Data, Boehringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. C.M.L. receives research support from RGA UK Services Limited.

Needs for care in service users with schizophrenia are often defined by professionals and focus on basic needs for health and social care rather than broader existential issues.

To examine the perceptions of users and formal and informal carers of the needs of people with non-affective psychosis.

A qualitative study was conducted involving focus groups of service users and informal and formal carers in a major Brazilian city Results Existential needs were the most important theme for people with psychotic disorders. Informal and formal carers mainly regarded such needs as secondary to needs for health, housing, leisure and work. Carers usually reduced the existential questioning of the ill person to symptoms or the result of a privation such as lack or failure of medication and its consequences.

We require an approach to service users wherein respect and understanding are prized as the first needs from which all others will naturally follow. We also need to give greater priority to existential issues in validated schedules that measure needs in clinical work and research.

Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned.

To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.

Nationwide Swedish quasi-experimental, family-based study following cohorts born 1989–1993 (ntotal = 526 167, ncousins = 262 267, nsiblings = 216 424) between the ages of 15 and 21 years.

Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23–7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44–2.03). Similar pattern of effects was found for substance misuse.

There were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.