Depression is common in old age and is associated with risk of dementia, but its neuropathological correlates in the community are unknown.

To investigate for the first time in a population-representative sample of people with no dementia the association between depression observed during life and neurofibrillary tangles, diffuse and neuritic plaques, Lewy bodies, brain atrophy and cerebrovascular disease found in the brain at post-mortem.

Out of 456 donations to a population-based study, 153 brains were selected where donors had no dementia measured in life. Alzheimer and vascular pathology measures, Lewy bodies and neuronal loss were compared between those with (n = 36) and without (n = 117) depression ascertained using a fully structured diagnostic interview during life. Brain areas examined included frontal, parietal, temporal and occipital cortical areas as well as the entorhinal cortex, hippocampus and brain-stem monoaminergic nuclei.

Depression was significantly associated with the presence of subcortical Lewy bodies. No association was found between depression and cerebrovascular or Alzheimer pathology in cortical or subcortical areas, although depression was associated with neuronal loss in the hippocampus as well as in some of the subcortical structures investigated (nucleus basalis, substantia nigra, raphe nucleus).

Late-life depression was associated with subcortical and hippocampal neuronal loss but not with cerebrovascular or Alzheimer pathology.

Complaints about memory are common in older people but their relationship with underlying brain changes is controversial.

To investigate the relationship between subjective memory impairment and previous or subsequent changes in white matter lesions and brain volumes.

In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up.

Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms – associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) ∊4 allele and in those without baseline subjective memory impairment.

Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.

Little is known about outcomes after self-harm in East Asia.

To investigate mortality after self-harm in a Taiwanese population.

Between 2000 and 2003, 1083 individuals who self-harmed were identified through a population self-harm register in Nantou County, Taiwan, and followed until 2007 for date and cause of death on a national mortality database.

In total, 145 individuals died, 48 through suicide. The risks of all-cause and suicide mortality in the first year were 4.7% and 2.1% respectively, representing 8- and 131-fold age- and gender-standardised increases. Male gender and older age were independent risk factors for both suicide and non-suicide mortality. Use of more lethal methods in the index episode was associated with higher mortality but this was accounted for by gender.

Results in this sample support the recommendation that people with a history of recent self-harm should be a major target for suicide prevention programmes.

Irregular sleep–wake cycles and cognitive impairment are frequently observed in schizophrenia, however, how they interact remains unclear.

To investigate the repercussions of circadian rhythm characteristics on cognitive performance and psychopathology in individuals with schizophrenia.

Fourteen middle-aged individuals diagnosed with schizophrenia underwent continuous wrist actimetry monitoring in real-life settings for 3 weeks, and collected saliva samples to determine the onset of endogenous melatonin secretion as a circadian phase marker. Moreover, participants underwent multiple neuropsychological testing and clinical assessments throughout the study period.

Sleep–wake cycles in individuals with schizophrenia ranged from well entrained to highly disturbed rhythms with fragmented sleep epochs, together with delayed melatonin onsets and higher levels of daytime sleepiness. Participants with a normal rest–activity cycle (objectively determined by high relative amplitude of day/night activity) performed significantly better in frontal lobe function tasks. Stepwise regression analysis revealed that relative amplitude and age represented the best predictors for cognitive performance (Stroop colour–word interference task, Trail Making Test A and B, semantic verbal fluency task), whereas psychopathology (Positive and Negative Syndrome Scale) did not significantly correlate with either cognitive performance levels or the quality of sleep–wake cycles.

Consolidated circadian rhythms and sleep may be a prerequisite for adequate cognitive functioning in individuals with schizophrenia.

Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown.

To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis.

Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months.

The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions.

Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Recent studies have raised issues concerning the replicability of gene × environment (G × E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between abuse or maltreatment exposure and antisocial behaviour. This study attempted to replicate the findings in this area using a 30-year longitudinal study that has strong resemblance to the original research cohort.

To test the hypothesis that the presence of the low-activity MAOA genotype was associated with an increased response to abuse exposure.

Participants were 398 males from the Christchurch Health and Development Study who had complete data on: MAOA promoter region variable number tandem repeat genotype; antisocial behaviour to age 30; and exposure to childhood sexual and physical abuse.

Regression models were fitted to five antisocial behaviour outcomes (self-reported property offending; self-reported violent offending; convictions for property/violent offending; conduct problems; hostility) observed from age 16 to 30, using measures of childhood exposure to sexual and physical abuse. The analyses revealed consistent evidence of G × E interactions, with those having the low-activity MAOA variant and who were exposed to abuse in childhood being significantly more likely to report later offending, conduct problems and hostility. These interactions remained statistically significant after control for a range of potentially confounding factors. Findings for convictions data were somewhat weaker.

The present findings add to the evidence suggesting that there is a stable G × E interaction involving MAOA, abuse exposure and antisocial behaviour across the life course.

Mental illness is common among prisoners, but little evidence exists regarding changes in symptoms in custody over time.

To investigate the prevalence and predictors of psychiatric symptoms among prisoners during early custody.

In a prospective cohort study, 3079 prisoners were screened for mental illness within 3 days of reception. To establish baseline diagnoses and symptoms, 980 prisoners were interviewed; all remaining in custody were followed up 1 month and 2 months later.

Symptom prevalence was highest during the first week of custody. Prevalence showed a linear decline among men and convicted prisoners, but not women or remand prisoners. It decreased among prisoners with depression, but not among prisoners with other mental illnesses.

Overall, imprisonment did not exacerbate psychiatric symptoms, although differences in group responses were observed. Continued discussion regarding non-custodial alternatives for vulnerable groups and increased support for all during early custody are recommended.

Impaired neuropsychological function and differences in facial emotion processing are features of major depression. Some aspects of these functions may change during treatment and may be useful in assessing treatment response, even at an early stage of treatment.

To examine early and later changes in neuropsychological functioning and facial emotion processing as potential markers of treatment response in major depression.

In total, 68 newly admitted in-patients with a primary diagnosis of major depression and 50 healthy controls completed an assessment, including mood ratings, neuropsychological measures and facial emotion processing measures at three time points (baseline, 10–14 days and 6 weeks).

Pervasive neuropsychological impairment was evident at baseline in patients with depression compared with healthy controls. During 6 weeks of treatment, only simple reaction time, verbal working memory and the recognition of angry facial expressions showed differential change in those whose depression responded to treatment compared with treatment non-responders in the depression group. None of the measures showed a significant difference between treatment responders and non-responders at 10–14 days.

Despite significant impairment in neuropsychological functioning in the depression group, most measures failed to differentiate between treatment responders and non-responders at 10–14 days or at 6 weeks. Simple reaction time, verbal working memory and recognition of angry facial expressions may be useful in assessing response in severe depression but probably not at an early stage.

The pathophysiology of auditory verbal hallucinations remains poorly understood.

To characterise the time course of regional brain activity leading to auditory verbal hallucinations.

During functional magnetic resonance imaging, 11 patients with schizophrenia or schizoaffective disorder signalled auditory verbal hallucination events by pressing a button. To control for effects of motor behaviour, regional activity associated with hallucination events was scaled against corresponding activity arising from random button-presses produced by 10 patients who did not experience hallucinations.

Immediately prior to the hallucinations, motor-adjusted activity in the left inferior frontal gyrus was significantly greater than corresponding activity in the right inferior frontal gyrus. In contrast, motor-adjusted activity in a right posterior temporal region overshadowed corresponding activity in the left homologous temporal region. Robustly elevated motor-adjusted activity in the left temporal region associated with auditory verbal hallucinations was also detected, but only subsequent to hallucination events. At the earliest time shift studied, the correlation between left inferior frontal gyrus and right temporal activity was significantly higher for the hallucination group compared with non-hallucinating patients.

Findings suggest that heightened functional coupling between the left inferior frontal gyrus and right temporal regions leads to coactivation in these speech processing regions that is hallucinogenic. Delayed left temporal activation may reflect impaired corollary discharge contributing to source misattribution of resulting verbal images.

The neurobiological basis of personality is poorly understood. Frontotemporal lobar degeneration (FTLD) frequently presents with complex behavioural changes, and therefore potentially provides a disease model in which to investigate brain substrates of personality.

To assess neuroanatomical correlates of personality change in a cohort of individuals with FTLD using voxel-based morphometry (VBM).

Thirty consecutive individuals fulfilling consensus criteria for FTLD were assessed. Each participant's carer completed a Big Five Inventory (BFI) questionnaire on five key personality traits; for each trait, a change score was derived based on current compared with estimated premorbid characteristics. All participants underwent volumetric brain magnetic resonance imaging. A VBM analysis was implemented regressing change score for each trait against regional grey matter volume across the FTLD group.

The FTLD group showed a significant decline in extraversion, agreeableness, conscientiousness and openness and an increase in neuroticism. Change in particular personality traits was associated with overlapping profiles of grey matter loss in more anterior cortical areas and relative preservation of grey matter in more posterior areas; the most robust neuroanatomical correlate was identified for reduced conscientiousness in the region of the posterior superior temporal gyrus.

Quantitative measures of personality change in FTLD can be correlated with changes in regional grey matter. The neuroanatomical profiles for particular personality traits overlap brain circuits previously implicated in aspects of social cognition and suggest that dysfunction at the level of distributed cortical networks underpins personality change in FTLD.

Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder.

To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder.

Using a polygenic score analysis to test whether schizophrenia polygenic risk alleles, en masse, significantly discriminate between individuals with bipolar disorder with and without psychotic features. The primary sample included 1829 participants with bipolar disorder and the replication sample comprised 506 people with bipolar disorder.

The subset of participants with Research Diagnostic Criteria schizoaffective bipolar disorder (n = 277) were significantly discriminated from the remaining participants with bipolar disorder (n = 1552) in both the primary (P = 0.00059) and the replication data-sets (P = 0.0070). In contrast, those with psychotic bipolar disorder as a whole were not significantly different from those with non-psychotic bipolar disorder in either data-set.

Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia–bipolar disorder clinical spectrum: one that relates to expression of a ‘bipolar disorder-like’ phenotype and one that is associated with expression of ‘schizophrenia-like’ psychotic symptoms.

Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure – such as the proliferation of media exposure in an individual's social network – is also associated with eating disorders.

To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji.

We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n = 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE–Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors.

Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% CI 1.15–2.23 relating social network media exposure to upper-quartile EDE–Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association.

Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations.

In addition to the health burden caused by mental illnesses, these conditions contribute to economic disadvantage because of their impact on labour force participation.

To quantify the cost of lost savings and wealth to Australians aged 45–64 who retire from the labour force early because of depression or other mental illness.

Cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers and STINMOD, an income and savings microsimulation model.

People who are not part of the labour force because of depression or other mental illness have 78% (95% CI 92.2–37.1) and 93% (95% CI 98.4–70.5) less wealth accumulated respectively, compared with people of the same age, gender and education who are in the labour force with no chronic health condition. People who are out of the labour force as a result of depression or other mental illness are also more likely to have the wealth that they do have in cash assets, rather than higher-growth assets such as superannuation, home equity and other financial investments.

This lower accumulated wealth is likely to result in lower living standards for these individuals in the future. This will compound the impact of their condition on their health and quality of life, and put a large financial burden on the state as a result of the need to provide financial assistance for these individuals.

Prenatal loss, the death of a fetus/child through miscarriage or stillbirth, is associated with significant depression and anxiety, particularly in a subsequent pregnancy.

This study examined the degree to which symptoms of depression and anxiety associated with a previous loss persisted following a subsequent successful pregnancy.

Data were derived from the Avon Longitudinal Study of Parents and Children cohort, a longitudinal cohort study in the west of England that has followed mothers from pregnancy into the postnatal period. A total of 13 133 mothers reported on the number and conditions of previous perinatal losses and provided self-report measures of depression and anxiety at 18 and 32 weeks' gestation and at 8 weeks and 8, 21 and 33 months postnatally. Controls for pregnancy outcome and obstetric and psychosocial factors were included.

Generalised estimating equations indicated that the number of previous miscarriages/stillbirths significantly predicted symptoms of depression (β = 0.18, s.e. = 0.07, P<0.01) and anxiety (β = 0.14, s.e. = 0.05, P<0.01) in a subsequent pregnancy, independent of key psychosocial and obstetric factors. This association remained constant across the pre- and postnatal period, indicating that the impact of a previous prenatal loss did not diminish significantly following the birth of a healthy child.

Depression and anxiety associated with a previous prenatal loss shows a persisting pattern that continues after the birth of a subsequent (healthy) child. Interventions targeting women with previous prenatal loss may improve the health outcomes of women and their children.

Past episodes of depressive or anxiety disorders and subthreshold symptoms have both been reported to predict the occurrence of depressive or anxiety disorders. It is unclear to what extent the two factors interact or predict these disorders independently.

To examine the extent to which history, subthreshold symptoms and their combination predict the occurrence of depressive (major depressive disorder, dysthymia) or anxiety disorders (social phobia, panic disorder, agoraphobia, generalised anxiety disorder) over a 2-year period.

This was a prospective cohort study with 1167 participants: the Netherlands Study of Depression and Anxiety. Anxiety and depressive disorders were determined with the Composite International Diagnostic Interview, subthreshold symptoms were determined with the Inventory of Depressive Symptomatology–Self Report and the Beck Anxiety Inventory.

Occurrence of depressive disorder was best predicted by a combination of a history of depression and subthreshold symptoms, followed by either one alone. Occurrence of anxiety disorder was best predicted by both a combination of a history of anxiety disorder and subthreshold symptoms and a combination of a history of depression and subthreshold symptoms, followed by any subthreshold symptoms or a history of any disorder alone.

A history and subthreshold symptoms independently predicted the subsequent occurrence of depressive or anxiety disorder. Together these two characteristics provide reasonable discriminative value. Whereas anxiety predicted the occurrence of an anxiety disorder only, depression predicted the occurrence of both depressive and anxiety disorders.

Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).

To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants.

In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163).

Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype.

It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.