Most evidence suggesting an association between schizophrenia, antipsychotic medications and diabetes has been based on retrospective studies not controlled for important confounders.

To compare diabetogenic risk between antipsychotic medications; and to describe the limitations of current prospective data-sets.

Systematic review of prospective clinical data.

No difference in the incidence of glycaemic abnormalities between placebo cohorts and antipsychotic medication cohorts was identified. No significant difference between any of the antipsychotic medications studied in terms of their association with glycaemic abnormalities was identified. Treatment-related weight gain did not appear to increase the risk of developing diabetes.

Diabetogenic potential ascribed to atypical antipsychotic drugs, resulting from retrospective studies, may be incorrect. Cohort sizes and incomplete sampling must preclude any definitive conclusions. Long-term, large, comparative prospective trials are needed, along with agreement upon glucose measurement of choice.

International evidence on the cost and effects of interventions for reducing the global burden of depression remain scarce.

To estimate the population-level cost-effectiveness of evidence-based depression interventions and their contribution towards reducing current burden.

Primary-care-based depression interventions were modelled at the level of whole populations in 14 epidemiological subregions of the world. Total population-level costs (in international dollars or I) and effectiveness (disability adjusted life years (DALYs) averted) were combined to form average and incremental cost-effectiveness ratios.

Evaluated interventions have the potential to reduce the current burden of depression by 10–30%. Pharmacotherapy with older antidepressant drugs, with or without proactive collaborative care, are currently more cost-effective strategies than those using newer antidepressants, particularly in lower-income subregions.

Even in resource-poor regions, each DALYaverted by efficient depression treatments in primary care costs less than 1 year of average per capita income, making such interventions a cost-effective use of health resources. However, current levels of burden can only be reduced significantly if there is a substantial increase in treatment coverage.

Globalisation is the process by which traditional boundaries of cultures are changing. Industrialisation, urbanisation and influence of the media are influencing idioms of distress across cultures.

To discuss the role of globalisation, using the epidemiology, diagnosis, clinical presentation and treatment of depression across various cultures as an example.

Recent studies focusing on transcultural aspects of depression were reviewed and summarised.

Cultural, social and religious mores account for variations in the presentation of depression across cultures. Somatic symptoms are common presenting features throughout the world and may serve as cultural idioms of distress, but psychological symptoms can usually be found when probed. Feelings of guilt and suicide rates vary across cultures and depression may be underdiagnosed.

Training packages could enhance clinicians' cultural competency in multicultural settings. However, globalisation is likely to influence idioms of distress and pathways to care in ways that are difficult to predict.

There is a strong relationship between feeding problems in childhood and eating disorder in the mother. The mechanisms responsible for this relationship are not understood.

To elucidate family-environmental factors that could mediate this association.

A general population sample of children with feeding problems (n=35), other problems (shyness, fears or behavioural problems; n=58), or no problems (n=23) was identified. The mental state of their mothers was evaluated, including an assessment of current and past eating disorder. Video recordings were made in the families' homes of a mealtime and of the mothers and children participating in a standardised exploratory task.

Two family-environmental variables significantly distinguished the children with feeding problems from the other two groups: ‘mealtime disorganisation’ and ‘maternal strong control and disharmony’. Path analysis revealed the importance of these two environmental variables in mediating the association between child and maternal disturbance.

The degree of mealtime disorganisation and the level of maternal strong control and disharmony mediate the association between maternal eating disorder and child feeding disturbance.

There is growing evidence of a relationship between frontal neuroimaging and neuropsychological abnormalities and the physiopathology and course of late-onset major depression.

To assess acute antidepressant response in late-onset major depression in relation to baseline frontal perfusion ratios.

A 99mTc HMPAO single photon emission computed tomographic brain scan was performed in medication-free patients with late-onset major depression, who were then included in a 12-week antidepressant treatment regimen. Logistic regression was used to define a predictive model of non-remission.

Atotal of 47 patients completed the study 34 of whom were classed as remitters and 13 as non-remitters. The variable left anterior fronto-cerebellar perfusion ratio had a global predictive power of 87%. Analysing this variable together with the baseline variables age of onset and duration of index episode, the predictive power of the model rose to 94%.

Our study suggests that a specific frontal functioning could predict the acute antidepressant response in late-onset severe major depression.

In previous functional magnetic resonance imaging (fMRI) studies, participants with schizophrenia showed decreased language lateralisation, resulting from increased activation of the right hemisphere compared with controls.

To determine whether decreased lateralisation and increased right cerebral language activation constitute genetic predispositions for schizophrenia.

Language activation was measured using fMRI in 12 right-handed monozygotic twin pairs discordant for schizophrenia and 12 healthy right-handed monozygotic twin pairs who were matched for gender, age and education.

Language lateralisation was decreased in discordant twin pairs compared with the healthy twin pairs. The groups did not differ in activation of the language-related areas of the left hemisphere, but language-related activation in the right hemisphere was significantly higher in the discordant twin pairs than in the healthy pairs. Within the discordant twin pairs, language lateralisation was not significantly different between patients with schizophrenia and their co-twins.

Decreased language lateralisation may constitute a genetic predisposition for schizophrenia.

Dietary variations are known to predict the prevalence of physical illnesses such as diabetes and heart disease but the possible influence of diet on mental health has been neglected.

To explore dietary predictors of the outcome of schizophrenia and the prevalence of depression.

Ecological analysis of national dietary patterns in relation to international variations in outcome of schizophrenia and prevalence of depression.

A higher national dietary intake of refined sugar and dairy products predicted a worse 2-year outcome of schizophrenia. A high national prevalence of depression was predicted by a low dietary intake of fish and seafood.

The dietary predictors of outcome of schizophrenia and prevalence of depression are similar to those that predict illnesses such as coronary heart disease and diabetes, which are more common in people with mental health problems and in which nutritional approaches are widely recommended. Dietary intervention studies are indicated in schizophrenia and depression.

Earlier adoption studies have convincingly confirmed the importance of a genetic contribution to schizophrenia. The designs, however, did not incorporate observations of the rearing-family environment.

To test the hypothesis that genetic factors moderate susceptibility to environmentally mediated risks associated with rearing-family functioning.

A Finnish national sample of adopted-away offspring of mothers with schizophrenia-spectrum disorders was compared blindly with adoptees without this genetic risk. Adoptive rearing was assessed using family rating scales based upon extended family observations at initial assessment. Adoptees were independently re-diagnosed after a median interval of 12 years, with register follow-up after 21 years.

In adoptees at high genetic risk of schizophrenia, but not in those at low genetic risk, adoptive-family ratings were a significant predictor of schizophrenia-spectrum disorders in adoptees at long-term follow-up.

Adoptees at high genetic risk are significantly more sensitive to adverse v. ‘healthy’ rearing patterns in adoptive families than are adoptees at low genetic risk.

Evidence for structural hippocampal change in depression is limited despite reports of neuronal damage due to hypercortisolaemia and vascular pathology.

To compare hippocampal and white matter structural change in demographically matched controls and participants with early-onset and late-onset depression.

High-resolution volumetric magnetic resonance imaging (MRI) and rating of MRI hyperintensities.

A total of 51 people with depression and 39 control participants were included. Participants with late-onset depression had bilateral hippocampal atrophy compared with those with early-onset depression and controls. Hippocampal volumes did not differ between control participants and those with early-onset depression. Age of depression onset correlated (negatively) with hippocampal volume but lifetime duration of depression did not. Hyperintensity ratings did not differ between groups.

Results suggest that acquired biological factors are of greater importance in late-than in early-onset illness and that pathological processes other than exposure to hypercortisolaemia of depression underlie hippocampal atrophy in depression of late life.

In this retrospective analysis, we assessed the short-term risk of treatment-emergent diabetes (TED) among patients with schizophrenia during clinical trials of antipsychotic medications.

From a non-diabetic cohort of patients with schizophrenia (n=5013), the relationship between baseline non-fasting glucose measurement, presence at baseline of risk factors for diabetes, weight gain and therapy assignment on the risk of treatment-emergent diabetes were assessed.

At the baseline assessment, about a third of patients identified with TED during treatment had non-fasting glucose levels over 7.8 mmol/l and two-thirds had multiple diabetes risk factors. Both baseline non-fasting glucose level and the presence of multiple pre-existing diabetes risk factors appeared to have a major impact on the risk of developing diabetes.

Overall, risk factors for diabetes in patients with schizophrenia overlap those in the general population. The results also suggest that many patients identified with TED might have had pre-existing glycaemic abnormalities or a high baseline burden of diabetes risk factors.

Violence against women is increasingly recognised as an important issue in both research and social policy.

To assess the lifetime experience of physical and sexual violence among lone and partnered mothers and the association with psychiatric disorders.

Analysis of the Australian National Survey of Mental Health and Wellbeing. The representative sample included 2232 women with children who completed the Composite International Diagnostic Interview, a scale of psychological distress and sociodemographic measures.

Lone mothers were more likely to have psychiatric disorders (odds ratios between 2.4 and 3.4) and have experienced physical and sexual violence (odds ratios between 31 and 41) than partnered mothers. The measures of physical and sexual violence were better predictors of psychiatric disorders than either lone parent status or the sociodemographic measures.

Experience of physical and sexual violence accounted for much of the greater prevalence of psychiatric disorders among lone compared with partnered mothers.

Diabetes is more common in people with schizophrenia than in the general population.

To explore the possible reasons for the association between diabetes and schizophrenia.

Diet and other lifestyle factors in patients with schizophrenia were reviewed as risk factors for diabetes.

People with schizophrenia show features of the metabolic syndrome at the onset of illness, before treatment. They also eat a poor diet, take little exercise and have high rates of smoking. Food intake may be increased further by antipsychotic medication. Nutritional factors appear to have a key role in the development of diabetes in patients with schizophrenia and may also affect the outcome and severity of schizophrenia. A common pathway through which diet might contribute to the development of both diabetes and schizophrenia is proposed.

Lifestyle factors may influence outcomes in both diabetes and schizophrenia. Lifestyle interventions are the key to improving the long-term health of people with schizophrenia.

There is accumulating evidence of hypothalamic–pituitary–adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening has been described recently as a non-invasive test of the capacity of the HPA axis to respond to stress. The results of this test correlate closely with those of more invasive dynamic tests reported in the literature; furthermore, it can be undertaken in a naturalistic setting.

To assess the HPA axis using the salivary cortisol response to awakening in CFS.

We measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwards in 56 patients with CFS and 35 healthy volunteers.

Patients had a lower cortisol response to awakening, measured by the area under the curve.

This naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.

Hypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/ corticotrophin-releasing hormone (dex/ CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.

To test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.

Salivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.

Patients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.

The dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

Evidence suggests a reversal of the normal left-lateralised response to speech in schizophrenia.

To test the brain's response to emotional prosody in schizophrenia and bipolar disorder.

BOLD contrast functional magnetic resonance imaging of subjects while they passively listened or attended to sentences that differed in emotional prosody.

Patients with schizophrenia exhibited normal right-lateralisation of the passive response to ‘pure’ emotional prosody and relative left-lateralisation of the response to unfiltered emotional prosody. When attending to emotional prosody, patients with schizophrenia activated the left insula more than healthy controls. When listening passively, patients with bipolar disorder demonstrated less activation of the bilateral superior temporal gyri in response to pure emotional prosody, and greater activation of the left superior temporal gyrus in response to unfiltered emotional prosody. In both passive experiments, the patient groups activated different lateral temporal lobe regions.

Patients with schizophrenia and bipolar disorder may display some left-lateralisation of the normal right-lateralised temporal lobe response to emotional prosody.

Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.

Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.

Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.

People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.

The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

Command hallucinations are a distressing and high-risk group of symptoms that have long been recognised but little understood, with few effective treatments. In line with our recent research, we propose that the development of an effective cognitive therapy for command hallucinations (CTCH) would be enhanced by applying insights from social rank theory.

We tested the efficacy of CTCH in reducing beliefs about the power of voices and thereby compliance, in a single-blind, randomised controlled trial.

A total of 38 patients with command hallucinations, with which they had recently complied with serious consequences, were allocated randomly to CTCH or treatment as usual and followed up at 6 months and 12 months.

Large and significant reductions in compliance behaviour were obtained favouring the cognitive therapy group (effect size=1.1). Improvements were also observed in the CTCH but not the control group in degree of conviction in the power and superiority of the voices and the need to comply, and in levels of distress and depression. No change in voice topography (frequency, loudness, content) was observed. The differences were maintained at 12 months' follow-up.

The results support the efficacy of cognitive therapy for CTCH.

Low birth weight increases the risk of childhood behavioural problems, but it is not clear whether poor foetal growth has a long-term influence on susceptibility to depression.

To examine the relation between birth weight and risk of psychological distress and depression.

At age 16 years 5187 participants in the 1970 British Cohort Study completed the 12-item General Health Questionnaire to assess psychological distress. At age 26 years 8292 participants completed the Malaise Inventory to assess depression and provided information about a history of depression.

Women whose birth weight was 3 kg had an increased risk of depression at age 26 years (OR=1.3; 95% CI 1.0–1.5) compared with those who weighed > 3.5 kg. Birth weight was not associated with a reported history of depression or with risk of psychological distress at age 16 years. In men there were no associations between any measurement and the full range of birth weight but, compared with men of normal birth weight, those born weighing $2.5 kg were more likely to be psychologically distressed at age 16 years (OR=l.6, 95% CI 1.1–2.5) and to report a history of depression at age 26 years (OR=l.6, 95% CI 1.1–2.3).

Impaired neurodevelopment during foetal life may increase susceptibility to depression.

The initial phase of a trial of cognitive–behavioural therapy (CBT) for acutely ill patients with schizophrenia of recent onset showed that it speeded recovery.

To test the hypothesis that CBT in addition to treatment as usual (TAU) during the first or second acute episode of schizophrenia will confer clinical benefit over a follow-up period.

This was an 18-month follow-up of a multicentre prospective trial of CBT or supportive counselling administered as an adjunct to TAU, compared with TAU alone, for patients hospitalised for an acute episode of schizophrenia of recent onset. Primary outcomes were total and positive symptom scales, time to relapse and re-hospitalisation.

There were significant advantages for CBT and supportive counselling over TAU alone on symptom measures at 18 months but no group difference was seen for relapse or re-hospitalisation. There was a significant centre–treatment interaction, reflecting centre differences in the effect of introducing either treatment, but not in the comparison of CBT and supportive counselling. Medication dosage and compliance did not explain group differences.

Adjunctive psychological treatments can have a beneficial longterm effect on symptom reduction.