The suppression of melatonin by light at 00.30 hours has been shown to be greater in winter than in summer in patients with seasonal affective disorder (SAD) but not in matched normal controls.

In this study 12 patients with SAD and 12 matched normal controls were exposed to morning light therapy in the winter. Melatonin profiles and sensitivity to light were measured before and after treatment.

The SAD but not the normal group showed a phase advance of melatonin rhythms in response to phototherapy. There was an association between phase position and phase shift in the SAD but not in the normal group.

There may be instability of circadian rhythms in SAD mediated by a high-amplitude phase response curve, rather than a fixed phase abnormality as had been previously suggested. This instability may be secondary to impaired serotoninergic function in the afferent pathways to the suprachiasmatic nuclei.

This paper highlights the role of the visual scan path as a physiological marker of information processing, while investigating positive symptomatology in schizophrenia.

The current literature is reviewed using computer search facilities (Medline).

Schizophrenics either scan or stare extensively, the latter related to negative symptoms. Schizophrenics particularly scan when viewing human faces.

Scan paths in schizophrenics are important when viewing meaningful stimuli such as human faces, because of the relationship between abnormal perception of stimuli and symptomatology in these subjects.

Health of the Nation Outcome Scales (HoNOS) were incorporated in a data set recording the routine clinical activities of a mental health team in Liverpool.

To evaluate the use of HoNOS in general adult psychiatry.

All consecutive patients who came in contact with the mental health team were administered HoNOS by the consultant psychiatrist. A cohort (n=204) of patients was identified over a period of 8 months. All patients (n=156) who had a repeat HoNOS after an interval of 6 months were included in the study.

There was an overall reduction in HoNOS scores after an interval of 6 months, more so among patients with psychotic and affective disorders. Patients scoring on other disorders showed no change on HoNOS. The measured change in clinical state based on the Clinical Global Impression scale was broadly consistent with HoNOS scores.

It was feasible to administer HoNOS during routine assessments, but HoNOS data were of limited value in care-planning in day-today clinical practice. The widespread adoption of HoNOS for use in routine clinical practice would be premature.

Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.

To investigate the potential association between clozapine and antibody deficiency.

Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.

Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).

Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.

S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.

Third rather than lateral ventriculomegaly may be a more specific finding in psychosis. The relevance of ventricular abnormality remains unclear.

To investigate the developmental correlates of ventricular enlargement.

Information on childhood development and magnetic resonance images in 1.5-mm contiguous sections were collected on 21 patients experiencing a first episode of psychosis.

Patients (n=21) had significantly less whole brain volume and enlarged third and lateral ventricles compared to controls (n=25). Third ventricle (r=0.48, P < 0.03) and lateral ventricle (r=0.65, P < 0.01) volumes correlated with developmental score. Patients with developmental delay had significantly larger third and lateral ventricles than those without.

Enlargement of both third and lateral ventricles is found in first-episode psychosis and is related to developmental delay in childhood. Insult to periventricular areas is relevant to the neurobiology of the disease. These findings support the view that schizophrenia involves disturbance of neurodevelopmental processes in some patients.

Internalised stigma in young people meeting criteria for at-risk mental states (ARMS) has been highlighted as an important issue, and it has been suggested that provision of cognitive therapy may increase such stigma.

To investigate the effects of cognitive therapy on internalised stigma using a secondary analysis of data from the EDIE-2 trial.

Participants meeting criteria for ARMS were recruited as part of a multisite randomised controlled trial of cognitive therapy for prevention and amelioration of psychosis. Participants were assessed at baseline and at 6, 12, 18 and 24 months using measures of psychotic experiences, symptoms and internalised stigma.

Negative appraisals of experiences were significantly reduced in the group assigned to cognitive therapy (estimated difference at 12 months was −1.36 (95% Cl −2.69 to −0.02), P = 0.047). There was no difference in social acceptability of experiences (estimated difference at 12 months was 0.46, 95% Cl −0.05 to 0.98, P = 0.079).

These findings suggest that, rather than increasing internalised stigma, cognitive therapy decreases negative appraisals of unusual experiences in young people at risk of psychosis; as such, it is a non-stigmatising intervention for this population.

Enhanced sensitivity to oestrogen signalling may drive increased risk for depressive symptoms when exposed to peripartum sex-steroid hormone fluctuations.

Testing if 116 pre-identified sex steroid-responsive transcripts that predicted perinatal depression (PND) translates to a pharmacological model of hormone-induced mood changes.

We generated longitudinal, genome-wide gene-expression and DNA-methylation data from 60 women exposed to a gonadotrophin-releasing hormone agonist (GnRHa) or placebo. We used linear mixed-effect models to assess differences between baseline and follow-up for gene expression and DNA methylation in the biphasic ovarian response to GnRHa.

Of the 116 PND-predictive transcripts, a significant (19%) overlap was observed with those differentially expressed post-GnRHa at both early and later follow-up, indicating sustained effects. Similarly, 49% of tested genes were differentially methylated post-GnRHa at the late follow-up. Within the GnRHa group, a large proportion of PND genes were significantly associated (gene expression; DNA methylation) with changes in depressive symptoms (28%; 66%), oestradiol levels (49%; 66%) and neocortex serotonin transporter binding (8%; 45%) between baseline and follow-up.

Our data bridge clinical PND biomarkers with a pharmacological model of sex hormone-induced mood changes and directly relate oestrogen-induced biological changes with depressive symptoms and associated serotonin-signalling changes. Our data highlight that individual variations in molecular sensitivity to oestrogen associate with susceptibility to hormone-induced mood changes and hold promise for candidate biomarkers.

V.G.F. received honorarium for being a speaker for H. Lundbeck A/S. E.B.B. receives research funding from Böhringer Ingelheim to investigate FKBP5 as a potential drug target for depression.