Dementia is currently incurable, irreversible and a major cause of disability for the world's older population. The association between mental health difficulties, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), and dementia has a long history within the civilian population. Despite the increased importance of this link within the military veteran population, who suffer a greater propensity of mental health difficulties and consist largely of over 65s, attention is only recently being paid to the salience of such an association for this group. This paper aims to explore the relationship between PTSD and MDD with dementia within the military veteran population.

A systematic review was conducted on articles from 1990 to July 2016 on MEDLINE, EMBASE, EBSCO and Web of Science electronic databases with an update conducted in February 2017.

Six empirical studies were identified from the review, the majority of which originated from the USA. Five of the studies asserted that veterans with a diagnosis of either PTSD or MDD are at a significantly greater risk of developing dementia than ‘healthy’ controls. The final study, conducted in Australia, found only a small, but non-significant, correlation between earlier MDD and future dementia, but no concurrent correlation.

While causality cannot be determined, it is likely that PTSD and depressive disorders are related to an increased risk of dementia in military veterans. Potential pathological explanations and risk factors are reviewed and the clinical and neuroscience implications of these findings are explored.

It is not clear whether relaxation therapies are more or less effective than cognitive and behavioural therapies in the treatment of anxiety. The aims of the present study were to examine the effects of relaxation techniques compared to cognitive and behavioural therapies in reducing anxiety symptoms, and whether they have comparable efficacy across disorders.

We conducted a meta-analysis of 50 studies (2801 patients) comparing relaxation training with cognitive and behavioural treatments of anxiety.

The overall effect size (ES) across all anxiety outcomes, with only one combined ES in each study, was g = −0.27 [95% confidence interval (CI) = −0.41 to −0.13], favouring cognitive and behavioural therapies (number needed to treat = 6.61). However, no significant difference between relaxation and cognitive and behavioural therapies was found for generalized anxiety disorder, panic disorder, social anxiety disorder and specific phobias (considering social anxiety and specific phobias separately). Heterogeneity was moderate (I2 = 52; 95% CI = 33–65). The ES was significantly associated with age (p < 0.001), hours of cognitive and/or behavioural therapy (p = 0.015), quality of intervention (p = 0.007), relaxation treatment format (p < 0.001) and type of disorder (p = 0.008), explaining an 82% of variance.

Relaxation seems to be less effective than cognitive and behavioural therapies in the treatment of post-traumatic stress disorder, and obsessive–compulsive disorder and it might also be less effective at 1-year follow-up for panic, but there is no evidence that it is less effective for other anxiety disorders.

Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a ‘natural’ experiment using spousal bereavement as a disease-independent mental stressor.

We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997–2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors.

In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37–2.63; aHR, 6–12 months: 1.38, 95% CI 1.34–1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes.

Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality.

Accumulating evidence links blood pressure variability (BPV) with white matter hyperintensities (WMH) and stroke. The longitudinal association between BPV with late onset depression (LOD) and cognitive decline remains unexplored.

Prospective cohort study of 2812 participant's age ⩾65 years (median age 72 years, 63.6% female) without dementia or stroke. Serial clinic visits assessed blood pressure, cognitive function, depression disorder, and depressive symptoms. A brain magnetic resonance imaging (MRI) substudy was performed in 1275 persons to examine possible associations with WMH.

The interaction between symptomatic LOD and systolic BPV was associated with cognitive decline on the Isaac Set Test [slope −4.45; 95% confidence interval (CI) −8.92 to −0.16, p = 0.04], Benton Visual Retention Test (slope −0.89; 95% CI −1.77 to −0.01, p = 0.049), Mini Mental State Examination (slope −1.08; 95% CI −1.86 to −0.30, p = 0.007) and Finger Tapping Test (slope −7.53; 95% CI −13.71 to −1.34, p = 0.017) but not Trail Making Test-A or -B/A. The MRI substudy demonstrated that systolic BPV was associated with cognitive decline via interactions with depression and total WMH volume, but this was not dependent on either deep or periventricular WMH volumes.

The findings show that the interaction between systolic BPV with symptomatic depression and WMH increases cognitive decline in persons ⩾65 years of age. Future work could extend these findings by examining systolic BPV in relation to cognitive decline and WMH in older populations with depression.

Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task.

We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not.

In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity.

Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.

In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.

Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.

Our findings show that 5-HT2AR activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

The neuropsychological origins of negative syndrome of schizophrenia remain elusive. Evidence from behavioural studies, which utilised emotion-inducing pictures to elicit motivated behaviour generally reported that that schizophrenia patients experienced similar affective experience as healthy individuals but failed to translate emotional salience to motivated behaviour, a phenomenon called emotion–behaviour decoupling. However, a few studies have examined emotion–behaviour decoupling in non-psychotic high-risk populations, who are relatively unaffected by medication effects.

In this study, we examined the nature and extent of emotion–behaviour decoupling in in three independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected relatives v. 45 controls; and 32 individuals with social anhedonia v. 32 controls). We administered an experimental task to examine their affective experience and its coupling with behaviour, using emotion-inducing slides, and allowed participants to alter stimulus exposure using button-pressing to seek pleasure or avoid aversion.

Schizophrenia patients reported similar affective experiences as their controls, while their unaffected relatives and individuals with high levels of social anhedonia exhibited attenuated affective experiences, in particular in the arousal aspect. Compared with their respective control groups, all of the three groups showed emotion–behaviour decoupling.

Our findings support that both genetically and behaviourally high-risk groups exhibit emotion–behaviour decoupling. The familial association apparently supports its role as a putative trait marker for schizophrenia.

Whilst preterm-born individuals have an increased risk of developing attention-deficit/hyperactivity disorder (ADHD), and are reported to have ADHD-like attention and arousal impairments, direct group comparisons are scarce.

We directly compared preterm-born adolescents (n = 186) to term-born adolescents with ADHD (n = 69), and term-born controls (n = 135), aged 11–23, on cognitive-performance, event-related potential and skin conductance level (SCL) measures associated with attention and arousal. The measures are from baseline and fast-incentive conditions of a four-choice reaction time task, previously shown to discriminate between the individuals with ADHD and controls. We aimed to establish whether preterm-born adolescents show: (a) identical cognitive-neurophysiological impairments to term-born adolescents with ADHD (b) possible additional impairments, and whether (c) the observed impairments correlate with ADHD symptom scores.

The preterm group, like the term-born ADHD group, showed increased mean reaction time (MRT) and reaction time variability (RTV) in the baseline condition, and attenuated contingent negative variation (CNV) amplitude (response preparation) in the fast-incentive condition. The preterm group, only, did not show significant within-group adjustments in P3 amplitude (attention allocation) and SCL (peripheral arousal). Dimensional analyses showed that ADHD symptoms scores correlated significantly with MRT, RTV and CNV amplitude only.

We find impairments in cognition and brain function in preterm-born adolescents that are linked to increased ADHD symptoms, as well as further impairments, in lack of malleability in neurophysiological processes. Our findings indicate that such impairments extend at least to adolescence. Future studies should extend these investigations into adulthood.

Downward trends in a number of adolescent risk behaviors including violence, crime, and drug use have been observed in the USA in recent years. It is unknown whether these are separate trends or whether they might relate to a general reduction in propensity to engage in such behaviors. Our objectives were to quantify trends in substance use disorders (SUDs) and delinquent behaviors over the 2003–2014 period and to determine whether they might reflect a single trend in an Externalizing-like trait.

We analyzed data from 12 to 17 year old participants from the National Survey on Drug Use and Health, a representative survey of the household dwelling population of the USA, across the 2003–2014 period (N = 210 599). Outcomes included past-year prevalence of six categories of substance use disorder and six categories of delinquent behavior.

Trend analysis suggested a net decline of 49% in mean number of SUDs and a 34% decline in delinquent behaviors over the 12-year period. Item Response Theory models were consistent with the interpretation that declines in each set of outcomes could be attributed to changes in mean levels of a latent, Externalizing-like trait.

Our findings suggest that declines in SUDs and some delinquent behaviors reflect a single trend related to an Externalizing-like trait. Identifying the factors contributing to this trend may facilitate continued improvement across a spectrum of adolescent risk behaviors.

We do not know how primary care treatment of depression varies by age across both psychotropic medication and psychological therapies.

Cohort study including 19 710 people aged 55+ with GP recorded depression diagnoses and 26 276 people with recorded depression symptoms during the period 2009–2013, from 373 General Practices in The Health Improvement Network (THIN) database in England. Main outcomes were initiation of treatment with anti-depressants, anxiolytics, hypnotics, anti-psychotic drugs, referrals to psychological therapies within 6 months of onset.

Treatment rates with antidepressants are high for those recorded with new depression diagnoses (87.1%) or symptoms of depression (58.7%). Treatment in those with depression diagnoses varies little by age. In those with depressive symptoms there was a J-shaped pattern with reduced antidepressant treatment in those in their 60s and 70s followed by increased treatment in the oldest age groups (85+ years), compared with those aged 55–59 years. Other psychotropic drug prescribing (hypnotics/anxiolytics, antipsychotics) all increase with increasing age. Recorded referrals for psychological therapies were low, and decreased steadily with increasing age, such that women aged 75–79 years with depression diagnoses had around six times lower odds of referral (OR 0.17, 95% CI 0.1–0.29) than those aged 55–59 years, and men aged 80–84 years had around seven times lower (OR 0.14, 95% CI 0.05–0.36).

The oldest age groups with new depression diagnoses and symptoms have fewer recorded referrals to psychological therapies, and higher psychotropic drug treatment rates in primary care. This suggests potential inequalities in access to psychological therapies.

To identify developmental sub-groups of depressive symptoms during the second decade of life, a critical period of brain development, using data from a prospective birth cohort. To test whether childhood intelligence and inflammatory markers are associated with subsequent persistent depressive symptoms.

IQ, a proxy for neurodevelopment, was measured at age 8 years. Interleukin 6 (IL-6) and C-reactive protein, typical inflammatory markers, were measured at age 9 years. Depressive symptoms were measured six times between 10 and 19 years using the short mood and feelings questionnaire (SMFQ), which were coded as binary variable and then used in latent class analysis to identify developmental sub-groups of depressive symptoms.

Longitudinal SMFQ data from 9156 participants yielded three distinct population sub-groups of depressive symptoms: no symptoms (81.2%); adolescent-onset symptoms (13.2%); persistent symptoms (5.6%). Lower IQ and higher IL-6 levels in childhood were independently associated with subsequent persistent depressive symptoms in a linear, dose–response fashion, but not with adolescent-onset symptoms. Compared with the group with no symptoms the adjusted odds ratio for persistent depressive symptoms per s.d. increase in IQ was 0.80 (95% CI, 0.68–0.95); that for IL-6 was 1.20 (95% CI, 1.03–1.39). Evidence for an association with IL-6 remained after controlling for initial severity of depressive symptoms at 10 years. There was no evidence that IL-6 moderated or mediated the IQ-persistent depressive symptom relationship.

The results indicate potentially important roles for two distinct biological processes, neurodevelopment and inflammation, in the aetiology of persistent depressive symptoms in young people.

Paranoia involves thoughts and beliefs about the harmful intent of others but the social consequences have been much less studied. We investigated whether paranoia predicts maladaptive social behaviour in terms of cooperative and punitive behaviour using experimental game theory paradigms, and examined whether reduced cooperation is best explained in terms of distrust as previous studies have claimed.

We recruited a large population sample (N = 2132) online. All participants completed the Green et al. Paranoid Thoughts Scale and (i) a Dictator Game and (ii) an Ultimatum Game, the former with an option for costly punishment. Following distrust-based accounts, we predicted highly paranoid people would make higher offers when the outcome depended on receiving a positive response from their partner (Ultimatum Game) but no difference when the partner's response was irrelevant (Dictator Game). We also predicted paranoia would increase punitive responses. Predictions were pre-registered in advance of data collection. Data and materials are open access.

Highly paranoid participants actually made lower offers than non-paranoid participants both in the Dictator Game and in the Ultimatum Game. Paranoia positively predicted punitive responses.

These findings suggest that distrust is not the best explanation for reduced cooperation in paranoia and alternative explanations, such as increased self-interest, may apply. However, the tendency to attribute harmful intent to partners was important in motivating punitive responses. These results highlight differing motivations underlying adverse social behaviour in paranoia and suggest that accounts based solely on the presenting features of paranoia may need to be rethought.

Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.

The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.

We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.

These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

Exposure to child maltreatment has been shown to increase lifetime risk for substance use disorders (SUD). However, this has not been systematically examined among race/ethnic groups, for whom rates of exposure to assaultive violence and SUD differ. This study examined variation by race/ethnicity and gender in associations of alcohol (AUD), cannabis (CUD), and tobacco (TUD) use disorders with three types of childhood interpersonal violence (cIPV): physical abuse, sexual abuse, and witnessing parental violence.

Data from the National Epidemiologic Survey of Alcohol-Related Conditions-III (N: 36 309), a US nationally representative sample, was utilized to examine associations of DSM-5 AUD, CUD and TUD with cIPV among men and women of five racial/ethnic groups. Models were adjusted for additional risk factors (e.g. parental substance use problems, participant's co-occurring SUD).

Independent contributions of childhood physical and sexual abuse to AUD, CUD, and TUD, and of witnessing parental violence to AUD and TUD were observed. Associations of cIPV and SUD were relatively similar across race/ethnicity and gender [Odds Ratios (ORs) ranged from 1.1 to 1.9], although associations of physical abuse with AUD and TUD were greater among males, associations of parental violence and AUD were greater among females, and associations of parental violence with AUD were greater among Hispanic women and American Indian men.

Given the paucity of research in this area, and the potential identification of modifiable risk factors to reduce the impact of childhood interpersonal violence on SUDs, further research and consideration of tailoring prevention and intervention efforts to different populations are warranted.

Pediatric traumatic brain injury (TBI) is a leading cause of long-term disability in children and adolescents worldwide. Amongst the wide array of consequences known to occur after pediatric TBI, behavioral impairments are among the most widespread and may particularly affect children who sustain injury early in the course of development. The aim of this study was to investigate the presence of internalizing and externalizing behavioral problems 6 months after preschool (i.e. 18–60 months old) mild TBI.

This work is part of a prospective, longitudinal cohort study of preschool TBI. Participants (N = 229) were recruited to one of three groups: children with mild TBI, typically developing children and orthopedic injured (OI) children. Mothers of children in all three groups completed the Child Behavior Checklist as a measure of behavioral outcomes 6-month post-injury. Demographics, injury-related characteristics, level of parental distress, and estimates of pre-injury behavioral problems were also documented.

The three groups did not differ on baseline characteristics (e.g. demographics and pre-injury behavioral problems for the mild TBI and OI groups) and level of parental distress. Mothers’ ratings of internalizing and externalizing behaviors were higher in the mild TBI group compared with the two control groups. Pre-injury behavioral problems and maternal distress were found to be significant predictors of outcome.

Our results show that even in its mildest form, preschool TBI may cause disruption to the immature brain serious enough to result in behavioral changes, which persist for several months post-injury.

The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.

Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).

Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).

The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.