Dementia with Lewy bodies (DLB) is increasingly recognized as a common cause of dementia in older people. However, its true frequency remains unclear, with previous studies reporting a prevalence range from zero to 22.8% of all dementia cases. This review aimed to establish the population prevalence and incidence for DLB and to compare this to its prevalence in secondary care settings.

A literature review of all relevant population and clinical studies was conducted using PubMed. Additional references from papers found during that process were added to this.

DLB accounted for 4.2% of all diagnosed dementias in the community. In secondary care this increased to 7.5%. The incidence of DLB was 3.8% of new dementia cases. There was a significant increase in DLB diagnoses when using the revised (2005) International Consensus Criteria (ICC) for DLB compared to the original (1996) criteria.

DLB currently accounts for around one in 25 dementia cases diagnosed in the community and one in 13 cases in secondary care. The significantly higher rates of DLB in secondary care may reflect enhanced diagnostic accuracy in specialist settings and/or the increased morbidity and carer burden of the DLB syndrome compared to other dementias. However, the true prevalence is likely to be much higher because DLB diagnoses are often missed, although there is evidence that new criteria aid case identification.

The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.

Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges’ g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses.

The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14–0.36, I 2 = 0%, 95% CI 0–58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00–12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size.

Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

Observations that older people who enjoy life more tend to live longer suggest that psychological well-being may be a potential resource for healthier ageing. We investigated whether psychological well-being was associated with incidence of physical frailty.

We used multinomial logistic regression to examine the prospective relationship between psychological well-being, assessed using the CASP-19, a questionnaire that assesses perceptions of control, autonomy, self-realization and pleasure, and incidence of physical frailty or pre-frailty, defined according to the Fried criteria (unintentional weight loss, weakness, self-reported exhaustion, slow walking speed and low physical activity), in 2557 men and women aged 60 to ⩾90 years from the English Longitudinal Study of Ageing (ELSA).

Men and women with higher levels of psychological well-being were less likely to become frail over the 4-year follow-up period. For a standard deviation higher score in psychological well-being at baseline, the relative risk ratio (RR) for incident frailty, adjusted for age, sex and baseline frailty status, was 0.46 [95% confidence interval (CI) 0.40–0.54]. There was a significant association between psychological well-being and risk of pre-frailty (RR 0.69, 95% CI 0.63–0.77). Examination of scores for hedonic (pleasure) and eudaimonic (control, autonomy and self-realization) well-being showed that higher scores on both were associated with decreased risk. Associations were partially attenuated by further adjustment for other potential confounding factors but persisted. Incidence of pre-frailty or frailty was associated with a decline in well-being, suggesting that the relationship is bidirectional.

Maintaining a stronger sense of psychological well-being in later life may protect against the development of physical frailty. Future research needs to establish the mechanisms underlying these findings.

The World Mental Health Survey Initiative (WMHSI) has advanced our understanding of mental disorders by providing data suitable for analysis across many countries. However, these data have not yet been fully explored from a cross-national lifespan perspective. In particular, there is a shortage of research on the relationship between mood and anxiety disorders and age across countries. In this study we used multigroup methods to model the distribution of 12-month DSM-IV/CIDI mood and anxiety disorders across the adult lifespan in relation to determinants of mental health in 10 European Union (EU) countries.

Logistic regression was used to model the odds of any mood or any anxiety disorder as a function of age, gender, marital status, urbanicity and employment using a multigroup approach (n = 35500). This allowed for the testing of specific lifespan hypotheses across participating countries.

No simple geographical pattern exists with which to describe the relationship between 12-month prevalence of mood and anxiety disorders and age. Of the adults sampled, very few aged ⩾80 years met DSM-IV diagnostic criteria for these disorders. The associations between these disorders and key sociodemographic variables were relatively homogeneous across countries after adjusting for age.

Further research is required to confirm that there are indeed stages in the lifespan where the reported prevalence of mental disorders is low, such as among younger adults in the East and older adults in the West. This project illustrates the difficulties in conducting research among different age groups simultaneously.

Telomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a biological marker of aging.

Participants were 3432 adults (mean age 52.9 years, range 32–79). Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Neuroticism was assessed using the 12-item neuroticism scale of the Revised Eysenck Personality Questionnaire (EPQ-R) at T2 and T3. TL was measured by a monochrome multiplex quantitative polymerase chain reaction (PCR) assay at T1, T2 and T3. A linear mixed model was used to assess whether neuroticism could predict TL prospectively after adjusting for age, sex, body mass index (BMI), frequency of sports, smoking status, presence of chronic diseases and level of education.

Neuroticism was a significant negative predictor of TL at follow-up (B = −0.004, p = 0.044) after adjusting for sex, age, baseline TL and various biological and lifestyle factors.

High neuroticism is significantly and prospectively associated with telomere attrition independent of lifestyle and other risk factors.

Observing incongruent actions interferes with ongoing action execution. This ‘interference effect’ is larger for observed biological actions than for non-biological actions. The current study used virtual reality to investigate the biological specificity of interference effects of action observation in autism spectrum conditions (ASC).

High-functioning adults with ASC and age- and IQ-matched healthy controls performed horizontal sinusoidal arm movements whilst observing arm movements conducted by a virtual reality agent with either human or robot form, which moved with either biological motion or at a constant velocity. In another condition, participants made the same arm movements while observing a real human. Observed arm movements were either congruent or incongruent with executed arm movements. An interference effect was calculated as the average variance in the incongruent action dimension during observation of incongruent compared with congruent movements.

Control participants exhibited an interference effect when observing real human and virtual human agent incongruent movements but not when observing virtual robot agent movements. Individuals with ASC differed from controls in that they showed no interference effects for real human, virtual human or virtual robot movements.

The current study demonstrates atypical interference effects in ASC.

Depression and anxiety are major causes of absence from work and underperformance in the workplace. Cognitive behavioural therapy (CBT) can be effective in treating such problems and online versions offer many practical advantages. The aim of the study was to investigate the effectiveness of a computerized CBT intervention (MoodGYM) in a workplace context.

The study was a phase III two-arm, parallel randomized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale (WSAS). Depression, anxiety, psychological functioning, costs and acceptability of the online process were also measured. Most data were collected online for 637 participants at baseline, 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline.

In both experimental and control groups depression scores improved over 6 weeks but attrition was high. There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS, nor for a difference in any of the secondary outcomes.

This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use, although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups.

Genomewide association studies (GWASs) on antidepressant efficacy have yielded modest results. A possible reason is that response is influenced by other factors, which possibly interact with genetic variation. We used a GWAS model to predict antidepressant response, by including predictors previously known to affect response, such as quality of life (QoL). We also evaluated the association between genes, previously implicated in gene–environment (G × E) interactions, and response using an enrichment analysis.

We examined a sample of 1426 depressed patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial: 774 responders, 652 non-responders and 418 865 single nucleotide polymorphisms (SNPs) were analysed. First, in a GWAS model, we investigated whether genetic variations interact with patients' levels of QoL to predict response, after controlling for demographic characteristics, severity and population stratification. Second, we conducted an enrichment analysis exploring whether candidate genes that have emerged from prior G × E interaction studies on depression are associated with treatment response.

The GWAS model, with QoL as a moderator, yielded one SNP (rs520210) associated with response in the NEDD4L gene (p = 3.64 × 10−8). In the Caucasian sample only, we observed a drop in significance for this SNP. The enrichment analysis showed that SNPs within serotonergic genes contained more significant markers that predicted response, compared with a random set of genes in the genome.

Our findings point to possible target genes, which are proposed for further independent replication. Our enrichment analysis provides further support, in a genomewide context, of the role of serotonergic genes in influencing antidepressant response.

Positron emission tomography and post-mortem studies of the number of somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptors in raphé nuclei have found both increases and decreases in depression. However, recent genetic studies suggest they may be increased in number and/or function. The current study examined the effect of buspirone on the electroencephalographic (EEG) centroid frequency, a putative index of somatodendritic 5-HT1A receptor functional status, in a cohort of medication-free depressed patients and controls.

A total of 15 depressed patients (nine male) and intelligence quotient (IQ)-, gender- and age-matched healthy controls had resting EEG recorded from 29 scalp electrodes prior to and 30, 60 and 90 min after oral buspirone (30 mg) administration. The effect of buspirone on somatodendritic 5-HT1A receptors was assessed by calculating the EEG centroid frequency between 6 and 10.5 Hz. The effect of buspirone on postsynaptic 5-HT1A receptors was assessed by measuring plasma growth hormone, prolactin and cortisol concentrations.

Analysis of variance revealed a significantly greater effect of buspirone on the EEG centroid frequency in patients compared with controls (F1,28 = 6.55, p = 0.016). There was no significant difference in the neuroendocrine responses between the two groups.

These findings are consistent with an increase in the functional status of somatodendritic, but not postsynaptic, 5-HT1A autoreceptors, in medication-free depressed patients in line with hypotheses based on genetic data. This increase in functional status would be hypothesized to lead to an increase in serotonergic negative feedback, and hence decreased release of 5-HT at raphé projection sites, in depressed patients.

Cardiovascular fitness influences many aspects of brain function. However, the relationship between cardiovascular fitness and suicidal behaviour is unknown. Therefore, we aimed to determine whether cardiovascular fitness at age 18 years is associated with future risk of suicide attempt/death.

We performed a population-based Swedish longitudinal cohort study of male conscripts with no previous or ongoing mental illness (n = 1 136 527). The conscription examination, which took place during 1968–2005, included the cycle ergonometric test and tests of cognitive performance. Future risk of suicide attempt/death over a 5- to 42-year follow-up period was calculated with Cox proportional hazards models controlling for several confounders including familial factors.

At least one suicide attempt was recorded for 12 563 men. Death by suicide without a prior attempt was recorded in 4814 additional individuals. In fully adjusted models low cardiovascular fitness was associated with increased risk for future attempt/death by suicide [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.64–1.94]. The HR changed only marginally after exclusion of persons who received in-patient care for depression (HR 1.76, 95% CI 1.61–1.94). Poor performance on both the cardiovascular fitness and cognitive tests was associated with a fivefold increased risk of suicide attempt or suicide death (HR 5.46, 95% CI 4.78–6.24).

Lower cardiovascular fitness at age 18 years was, after adjustment for a number of potential confounders, associated with an increased risk of attempt/death by suicide in adulthood. It remains to be clarified whether interventions designed to improve fitness in teens can influence the risk of suicidal behaviour later in life.

The development of depressive symptomatology is a recognized complication of treatment with the cytokine interferon-α (IFN-α) and has been seen as supporting inflammatory theories of the pathophysiology of major depression. Major depression has been associated with changes in glutamatergic activity and recent formulations of IFN-induced depression have implicated neurotoxic influences that could also lead to changes in glutamate function. The present study used magnetic resonance spectroscopy (MRS) to measure glutamate and its major metabolite glutamine in patients with hepatitis C who received treatment with pegylated IFN-α and ribavirin.

MRS measurements of glutamate and glutamine were taken from a 25 × 20 × 20 mm voxel including the pregenual anterior cingulate cortex in 12 patients before and after 4–6 weeks of treatment with IFN.

IFN treatment led to an increase in cortical levels of glutamine (p = 0.02) and a significant elevation in the ratio of glutamine to glutamate (p < 0.01). Furthermore, changes in glutamine level correlated significantly with ratings of depression and anxiety at the time of the second scan.

We conclude that treatment with IFN-α is associated with MRS-visible changes in glutamatergic metabolism. However, the changes seen differ from those reported in major depression, which suggests that the pathophysiology of IFN-induced depression may be distinct from that of major depression more generally.

Longitudinal studies reporting the association between cannabis use and developing depression provide mixed results. The objective of this study was to establish the extent to which different patterns of use of cannabis are associated with the development of depression using meta-analysis of longitudinal studies.

Peer-reviewed publications reporting the risk of developing depression in cannabis users were located using searches of EMBASE, Medline, PsychINFO and ISI Web of Science. Only longitudinal studies that controlled for depression at baseline were included. Data on several study characteristics, including measures of cannabis use, measures of depression and control variables, were extracted. Odds ratios (ORs) were extracted by age and length of follow-up.

After screening for 4764 articles, 57 articles were selected for full-text review, of which 14 were included in the quantitative analysis (total number of subjects = 76058). The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05–1.30]. The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21–2.16), compared with non-users or light users. Meta-regression revealed no significant differences in effect based on age of subjects and marginal difference in effect based on length of follow-up in the individual studies. There was large heterogeneity in the number and type of control variables in the different studies.

Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.

Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.

Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).

In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.

This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Available research has suggested that affiliation with prosocial peers reduces child and adolescent antisocial behavior. However, the etiologic mechanisms driving this association remain unclear. The current study sought to evaluate whether this association takes the form of a gene–environment interaction (G × E) in which prosocial peer affiliation acts to reduce the consequences of genetic risk for non-aggressive antisocial behavior during childhood.

Our sample consisted of 500 twin pairs aged 6–10 years from the Michigan State University Twin Registry (MSUTR).

The results robustly support moderation by prosocial peer affiliation. Genetic influences on non-aggressive antisocial behavior were observed to be several times larger in those with lower levels of prosocial peer affiliation than in those with higher levels of prosocial peer affiliation. This pattern of results persisted even after controlling for gene–environment correlations and deviant peer affiliation, and when restricting our analyses to those twins who shared all or nearly all of their friends.

Such findings not only suggest that prosocial peer affiliation moderates genetic influences on non-aggressive antisocial behaviors during childhood but also provide support for the theoretical notion that protective environmental experiences may exert their influence by promoting resilience to genetic risk.

Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene–environment correlation (r GE), wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive r GE by comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families.

Participants were 402 adoptive and 204 biological families. Familial environment was defined as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive r GE.

There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive r GE.

Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive r GE, where a general vulnerability toward externalizing psychopathology is passed down by the parents to the children.

The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD.

A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed.

Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r – 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results.

OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common.

Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961–1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory.

Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11–0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07–0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09–0.40) but father smoking was not (β = 0.02, 95% CI −0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03–0.49) or did not smoke (β = 0.30, 95% CI 0.04–0.57). By number of cigarettes, associations with hyperactivity were present for 10–19 and 20+ cigarettes per day among mothers.

In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.

The neurobiological underpinnings of attention deficit hyperactivity disorder (ADHD) are inconclusive. Activation abnormalities across brain regions in ADHD compared with healthy controls highlighted in task-based functional magnetic resonance imaging (fMRI) studies are heterogeneous. To identify a consistent pattern of neural dysfunction in ADHD, a meta-analysis of fMRI studies using Go/no-go, Stop and N-back tasks was undertaken.

Several databases were searched using the key words: ‘ADHD and fMRI’ and ‘ADHD and fMRI task’. In all, 20 studies met inclusion criteria comprising 334 patients with ADHD and 372 healthy controls and were split into N-back, Stop task and Go/no-go case–control groups. Using Signed Differential Mapping each batch was meta-analysed individually and meta-regression analyses were used to examine the effects of exposure to methylphenidate (MPH), length of MPH wash-out period, ADHD subtype, age and intelligence quotient (IQ) differences upon neural dysfunction in ADHD.

Across all tasks less activity in frontal lobe regions compared with controls was detected. Less exposure to treatment and lengthier wash-out times resulted in less left medial frontal cortex activation in N-back and Go/no-go studies. Higher percentage of combined-type ADHD resulted in less superior and inferior frontal gyrus activation. Different IQ scores between groups were linked to reduced right caudate activity in ADHD.

Consistent frontal deficits imply homogeneous cognitive strategies involved in ADHD behavioural control. Our findings suggest a link between fMRI results and the potentially normalizing effect of treatment and signify a need for segregated examination and contrast of differences in sample characteristics in future studies.

The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence.

We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs).

Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents.

The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children ‘grow out’ of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.