Jonathan Cavanagh

Psychological autopsy studies of suicide: a systematic review.

BACKGROUND The psychological autopsy method offers the most direct technique currently available for examining the relationship between particular antecedents and suicide. This systematic review aimed to examine the results of studies of suicide that used a psychological autopsy method. METHOD A computer aided search of MEDLINE, BIDS ISI and PSYCHLIT, supplemented by reports known to the reviewers and reports identified from the reference lists of other retrieved reports. Two investigators systematically and independently examined all reports. Median proportions were determined and population attributable fractions were calculated, where possible, in cases of suicide and controls. RESULTS One hundred and fifty-four reports were identified, of which 76 met the criteria for inclusion; 54 were case series and 22 were case-control studies. The median proportion of cases with mental disorder was 91% (95 % CI 81-98%) in the case series. In the case-control studies the figure was 90% (88-95%) in the cases and 27% (14-48%) in the controls. Co-morbid mental disorder and substance abuse also preceded suicide in more cases (38%, 19-57%) than controls (6%, 0-13%). The population attributable fraction for mental disorder ranged from 47-74% in the seven studies in which it could be calculated. The effects of particular disorders and sociological variables have been insufficiently studied to draw clear conclusions. CONCLUSIONS The results indicated that mental disorder was the most strongly associated variable of those that have been studied. Further studies should focus on specific disorders and psychosocial factors. Suicide prevention strategies may be most effective if focused on the treatment of mental disorders.

Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis.

BACKGROUND Several magnetic resonance imaging (MRI) studies have identified structural abnormalities in association with bipolar disorder. The literature is, however, heterogeneous and there is remaining uncertainty about which brain areas are pivotal to the pathogenesis of the condition. AIMS To identify, appraise and summarise volumetric MRI studies of brain regions comparing bipolar disorder with an unrelated control group and individuals with schizophrenia. METHOD A systematic review and random-effects meta-analysis was carried out to identify key areas of structural abnormality in bipolar disorder and whether the pattern of affected areas separated bipolar disorder from schizophrenia. Significant heterogeneity was explored using meta-regression. RESULTS Participants with bipolar disorder are characterised by whole brain and prefrontal lobe volume reductions, and also by increases in the volume of the globus pallidus and lateral ventricles. In comparison with schizophrenia, bipolar disorder is associated with smaller lateral ventricular volume and enlarged amygdala volume. Heterogeneity was widespread and could be partly explained by clinical variables and year of publication, but generally not by differences in image acquisition. CONCLUSIONS There appear to be robust changes in brain volume in bipolar disorder compared with healthy volunteers, although most changes do not seem to be diagnostically specific. Age and duration of illness appear to be key issues in determining the magnitude of observed effect sizes.

A systematic review of manic and depressive prodromes.

BACKGROUND This paper explores whether individuals with a mood disorder can identify the nature and duration of depressive and manic prodromes. METHODS Seventy-three publications of prodromal symptoms in bipolar and unipolar disorders were identified by computer searches of seven databases (including MEDLINE and PsycLIT) supplemented by hand searches of journals. Seventeen studies (total sample=1191 subjects) met criteria for inclusion in a systematic review. RESULTS At least 80% of individuals with a mood disorder can identify one or more prodromal symptoms. There are limited data about unipolar disorders. In bipolar disorders, early symptoms of mania are identified more frequently than early symptoms of depression. The most robust early symptom of mania is sleep disturbance (median prevalence 77%). Early symptoms of depression are inconsistent. The mean length of manic prodromes (>20 days) was consistently reported to be longer than depressive prodromes (<19 days). However, depressive prodromes showed greater inter-individual variation (ranging from 2 to 365 days) in duration than manic prodromes (1-120 days). LIMITATIONS Few prospective studies of bipolar, and particularly unipolar disorders have been reported. CONCLUSIONS Early symptoms of relapse in affective disorders can be identified. Explanations of the apparent differences in the recognition and length of prodromes between mania and bipolar depression are explored. Further research on duration, sequence of symptom appearance and characteristics of prodromes is warranted to clarify the clinical usefulness of early symptom monitoring.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.

Depression: an inflammatory illness?

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Findings from preclinical and clinical studies suggest that psychiatric illnesses, particularly MDD, are associated with inflammatory processes. While it is unlikely that MDD is a primary ‘inflammatory’ disorder, there is now evidence to suggest that inflammation may play a subtle role in the pathophysiology of MDD. Most of the evidence that links inflammation to MDD comes from three observations: (a) one-third of those with major depression show elevated peripheral inflammatory biomarkers, even in the absence of a medical illness; (b) inflammatory illnesses are associated with greater rates of MDD; and (c) patients treated with cytokines are at greater risk of developing major depressive illness. We now know that the brain is not an immune privileged organ. Inflammatory mediators have been found to affect various substrates thought to be important in the aetiopathogenesis of MDD, including altered monoamine and glutamate neurotransmission, glucocorticoid receptor resistance and adult hippocampal neurogenesis. At a higher level, inflammation is thought to affect brain signalling patterns, cognition and the production of a constellation of symptoms, termed ‘sickness behaviour’. Inflammation may therefore play a role in the aetiology of depression, at least in a ‘cohort’ of vulnerable individuals. Inflammation may not only act as a precipitating factor that pushes a person into depression but also a perpetuating factor that may pose an obstacle to recovery. More importantly, inflammatory markers may aid in the diagnosis and prediction of treatment response, leading to the possibility of tailored treatments, thereby allowing stratification of what remains a heterogenous disorder.

Socio-economic status is associated with epigenetic differences in the pSoBid cohort

BACKGROUND Epigenetic programming and epigenetic mechanisms driven by environmental factors are thought to play an important role in human health and ageing. Global DNA methylation has been postulated as an epigenetic marker for epidemiological studies as it is reflective of changes in gene expression linked to disease. How epigenetic mechanisms are affected by psychological, sociological and biological determinants of health still remains unclear. The aim of this study was to investigate the relationship between socio-economic and lifestyle factors and epigenetic status, as measured by global DNA methylation content, in the pSoBid cohort, which is characterized by an extreme socio-economic and health gradient. METHODS DNA was extracted from peripheral blood leukocytes using the Maxwell® 16 System and Maxwell® 16 Blood DNA Purification kit (Promega, UK). Global DNA methylation was assessed using Methylamp™ Global DNA Methylation Quantification Ultra kit (Epigentek, USA). Associations between global DNA methylation and socio-economic and lifestyle factors were investigated in linear regression models. RESULTS Global DNA hypomethylation was observed in the most socio-economically deprived subjects. Job status demonstrated a similar relationship, with manual workers having 24% lower DNA methylation content than non-manual. Additionally, associations were found between global DNA methylation content and biomarkers of cardiovascular disease (CVD) and inflammation, including fibrinogen and interleukin-6 (IL-6), after adjustment for socio-economic factors. CONCLUSIONS This study has indicated an association between epigenetic status and socio-economic status (SES). This relationship has direct implications for population health and is reflected in further associations between global DNA methylation content and emerging biomarkers of CVD.

Guided self-help for functional (psychogenic) symptoms A randomized controlled efficacy trial

Objectives: Functional (psychogenic or somatoform) symptoms are common in neurology clinics. Cognitive-behavioral therapy (CBT) can be an effective treatment, but there are major obstacles to its provision in practice. We tested the hypothesis that adding CBT-based guided self-help (GSH) to the usual care (UC) received by patients improves outcomes. Methods: We conducted a randomized trial in 2 neurology services in the United Kingdom. Outpatients with functional symptoms (rated by the neurologist as “not at all” or only “somewhat” explained by organic disease) were randomly allocated to UC or UC plus GSH. GSH comprised a self-help manual and 4 half-hour guidance sessions. The primary outcome was self-rated health on a 5-point clinical global improvement scale (CGI) at 3 months. Secondary outcomes were measured at 3 and 6 months. Results: In this trial, 127 participants were enrolled, and primary outcome data were collected for 125. Participants allocated to GSH reported greater improvement on the primary outcome (adjusted common odds ratio on the CGI 2.36 [95% confidence interval 1.17–4.74; p = 0.016]). The absolute difference in proportion “better” or “much better” was 13% (number needed to treat was 8). At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning. Conclusions: CBT-based GSH is feasible to implement and efficacious. Further evaluation is indicated. Classification of evidence: This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health, as measured by the CGI, in patients with functional neurologic symptoms.

Accelerated Telomere Attrition Is Associated with Relative Household Income, Diet and Inflammation in the pSoBid Cohort

Background It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences. Methods A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters. Results The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6. Conclusions These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links.

Life events in suicide and undetermined death in south-east Scotland: a case-control study using the method of psychological autopsy.

Background: Adverse life events have been associated with increased risk of suicide. Mental disorders are also major risk factors for suicide. Matching cases and controls for mental disorder is thus appropriate in studies of suicide. This procedure was used to study the degree to which excess adversity was more common in cases who committed suicide as opposed to living controls matched for mental disorder. Methods: The study formed part of a retrospective case-control comparison of cases of suicide/undetermined death with living controls using psychological autopsy in south-east Scotland. Cases and controls were matched for age, sex and mental disorder. Informants were those closest to cases and controls. Cases and controls were assessed for life events using the Interview for Life Events. The subjects were 45 cases of suicide/undetermined death and 40 living controls. Results: Cases and controls did not differ significantly in severity of mental disorder. Adverse interpersonal events within the family (P=0.01) with an odds ratio (OR) of 9.0 (95% CI, 1.3–399) and adverse physical health-related events (OR 5.0, 95% CI 1.1–47, P=0.04) were significantly more common in cases than controls. Conclusions: Cases had significantly more adverse life events than controls overall. The categories accounting for these differences were interpersonal family adversity and physical ill-health. There were no significant differences in either the number or severity of ongoing difficulties between cases and controls. Recent adverse life events contribute to the increased risk of suicide even when age, sex and mental disorder are controlled for. Future research should examine interactions between social support and acute and chronic adversity.

Diurnal Variation of Adrenocortical Activity in Chronic Fatigue Syndrome

Baseline morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder and a control group of 15 weight-, age- and sex-matched healthy volunteers. Morning cortisol levels were non-significantly lower in CFS patients, while evening levels were non-significantly higher. ACTH concentrations were non-significantly higher in both the morning and evening. The diurnal change in cortisol levels was significantly less in CFS than in controls (p < 0.05). In CFS subjects, evening levels of cortisol correlated significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning. These results suggest that there is a relationship between adrenocortical function and disability in CFS, but do not reveal the causal connection.