Major depression is associated with activation of the inflammatory response.

To examine C-reactive protein levels in depression and to determine the impact of selective serotonin reuptake inhibitor (SSRI) therapy.

Atwo-part study. In study 1, which used a between-subjects design, C-reactive protein was measured in 32 patients (20 currently depressed, 12 euthymic) with a history of DSM–IV major depression, all of whom were treated with an SSRI, and in a healthy comparison group (n=20). Study 2 employed a within-subject design: C-reactive protein was measured in 20 patients with major depression both before and after SSRI treatment.

In study 1, C-reactive protein levels did not differ between the group with depressive disorder (either currently depressed or euthymic) treated with SSRIs and the healthy group. In study 2 the protein levels dropped significantly following treatment with antidepressant medication.

Following SSRI treatment for major depression there is a significant drop in C-reactive protein concentrations whether or not the depression resolves. These findings indicate that antidepressants induce an anti-inflammatory response independent of antidepressant action.

Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.

We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.

We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.

Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1–27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5–30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11–2.21, P = 0.010).

Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.

Cerebrovascular changes and glucocorticoid mediated hippocampal atrophy are considered relevant for depression-related cognitive deficits, forming putative treatment targets.

This study examined the relative contribution of cortisol levels, brain atrophy and white matter hyperintensities to the persistence of cognitive deficits in older adults with depression.

Thirty-five people aged ⩾60 years with DSM–IV major depression and twenty-nine healthy comparison controls underwent magnetic resonance imaging (MRI) and were underwent magnetic resonance imaging (MRI) and were followed up for 18 months. We analysed the relationship between baseline salivary cortisol levels, whole brain, frontal lobe and hippocampal volumes, severity of white matter hyperintensities and follow-up cognitive function in both groups by testing the interaction between the groups and these biological measures on tests of memory, executive functions and processing speed in linear regression models.

Group differences in memory and executive function follow-up scores were associated with ratings of white matter hyperintensities, especially of the deep white matter and periventricular regions. Compared with healthy controls, participants with depression scoring within the third tertile of white matter hyperintensities dropped two and three standard deviations in executive function and memory scores respectively. No biological measure related to group differences in processing speed, and there were no significant interactions between group and cortisol levels, or volumetric MRI measures.

White matter hyperintensities, rather than cortisol levels or brain atrophy, are associated with continuing cognitive impairments in older adults with depression. The findings suggest that cerebrovascular disease rather than glucocorticoid-mediated brain damage are responsible for the persistence of cognitive deficits associated with depression in older age.

Bipolar disorder is complex and can be difficult to diagnose. It is often misdiagnosed as recurrent major depressive disorder.

We had three main aims. To estimate the proportion of primary care patients with a working diagnosis of unipolar depression who satisfy DSM–IV criteria for bipolar disorder. To test two screening instruments for bipolar disorder (the Hypomania Checklist (HCL–32) and Bipolar Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess whether individuals with major depressive disorder with subthreshold manic symptoms differ from those individuals with major depressive disorder but with no or little history of manic symptoms in terms of clinical course, psychosocial functioning and quality of life.

Two-phase screening study in primary care.

Three estimates of the prevalence of undiagnosed bipolar disorder were obtained: 21.6%, 9.6% and 3.3%. The HCL–32 and BSDS questionnaires had quite low positive predictive values (50.0 and 30.1% respectively). Participants with major depressive disorder and with a history of subthreshold manic symptoms differed from those participants with no or little history of manic symptoms on several clinical features and on measures of both psychosocial functioning and quality of life.

Between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder. The HCL–32 and BSDS screening questionnaires may be more useful for detecting broader definitions of bipolar disorder than DSM–IV-defined bipolar disorder. Subdiagnostic features of bipolar disorder are relatively common in primary care patients with unipolar depression and are associated with a more morbid course of illness. Future classifications of recurrent depression should include dimensional measures of bipolar symptoms.

Afro-Caribbean immigrants are reported to have a high rate of schizophrenia compared with other population groups.

In a prospective first contact study of schizophrenia in Jamaica in 1992, 335 patients were examined using the Present State Examination.

285 patients were evaluated as having a PSE ‘restrictive’ S + diagnosis of schizophrenia, and 32 as having a ‘broad’ S?, P, or O diagnosis of schizophrenia. With a population of 2.46 million, this represents a first-contact incidence rate for ‘restrictive’ schizophrenia of 1.16 per 10 000 population, and an age-corrected (15–54) incidence rate of 2.09 per 10 000.

Incidence rates for schizophrenia in Jamaica are lower than those reported in Afro-Caribbean immigrants in the UK and Holland, and within the reported range for other population groups worldwide.

Quantitative research about self-harm largely deals with self-poisoning, despite the high incidence of self-injury.

We compared patterns of hospital care and repetition associated with self-poisoning and self-injury.

Demographic and clinical data were collected in a multicentre, prospective cohort study, involving 10 498 consecutive episodes of self-harm at six English teaching hospitals.

Compared with those who self-poisoned, people who cut themselves were more likely to have self-harmed previously and to have received support from mental health services, but they were far less likely to be admitted to the general hospital or receive a psychosocial assessment. Although only 17% of people repeated self-harm during the 18 months of study, survival analysis that takes account of all episodes revealed a repetition rate of 33% in the year following an episode: 47% after episodes of self-cutting and 31% after self-poisoning (P<0.001). Of those who repeated, a third switched method of self-harm.

Hospital services offer less to people who have cut themselves, although they are far more likely to repeat, than to those who have self-poisoned. Attendance at hospital should result in psychosocial assessment of needs regardless of method of self-harm.

Controversy exists about the efficacy of psychotherapy for the mental health problems of sexually abused children.

To compare the relative efficacy of focused individual or group therapy in symptomatic sexually abused girls, and to monitor psychiatric symptoms for persistence or change.

A multi-centre psychotherapy outcome study recruited 71 sexually abused girls aged 6–14 years who were randomly assigned to focused individual psychotherapy (up to 30 sessions) or psychoeducational group therapy (up to 18 sessions). Changes over the course of the study were monitored.

Both treatment groups showed a substantial reduction in psychopathological symptoms and an improvement in functioning, but with no evident difference between individual and group therapy. However, individual therapy led to a greater improvement in manifestations of post-traumatic stress disorder (PTSD).

The beneficial effects on PTSD support the use of individual therapy. However, the small sample size and lack of a control group limit conclusions about changes attributable to treatment.

An age-related dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory.

To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM–III–R Major Depression.

Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI.

An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

Twenty per cent of patients with bipolar affective disorder suffer an illness that responds inadequately to treatment and has a poor outcome. Many patients, but not all, with bipolar disorder show white matter abnormalities on T2-weighted magnetic resonance imaging (MRI).

To explore the hypothesis that white matter abnormalities on MRI are seen more frequently in subjects whose illness has a poor outcome compared with those with a good outcome or controls.

Two groups of age- and gender-matched patients with bipolar disorder (14 with a good outcome and 15 with a poor outcome) and 15 controls, aged 20–65 years, were studied. Axial T2-weighted MRI scans were examined for the presence and severity of white matter abnormalities.

Significantly more poor outcome group members had deep subcortical punctate, but not periventricular, white matter hyperintensities than the good outcome group (P=0.035) or controls (P=0.003) and these abnormalities were of greater severity (P=0.030 and P < 0.014, respectively).

Subcortical white matter lesions are associated with poor outcome bipolar disorder.

Further treatment with clozapine is contraindicated in any patient who has previously experienced leucopenia or neutropenia during clozapine therapy.

To investigate the results of such a rechallenge in 53 patients.

An analysis was made of the demographic, haematological and outcome data of patients in the UK and Ireland who were rechallenged with clozapine following leucopenia or neutropenia during previous clozapine therapy.

Of 53 patients who were rechallenged, 20 (38%) experienced a further blood dyscrasia. In 17 of these 20 patients (85%) the second blood dyscrasia was more severe(P<0.001), in 12(60%) it lasted longer (P=0.0368) and in 17 (85%) it occurred more quickly on rechallenge (P<0.001). Of the original 53 patients, 55% (29 patients) are still receiving clozapine.

No clear risk factor for repeat blood dyscrasias was identified. Despite this, after risks and benefits have been considered, rechallenge may well be justified in some patients.