Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.

We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.

At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.

These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD.

A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated.

Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity.

Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.

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.

Characteristics related to the areas where people live have been associated with suicide risk, although these might reflect aggregation into these communities of individuals with mental health or social problems. No studies have examined whether area characteristics during childhood are associated with subsequent suicide, or whether risk associated with individual characteristics varies according to childhood neighbourhood context.

We conducted a longitudinal study of 204 323 individuals born in Sweden in 1972 and 1977 with childhood data linked to suicide (n = 314; 0.15%) up to age 26–31 years. Multilevel modelling was used to examine: (i) whether school-, municipality- or county-level characteristics during childhood are associated with later suicide, independently of individual effects, and (ii) whether associations between individual characteristics and suicide vary according to school context (reflecting both peer group and neighbourhood effects).

Associations between suicide and most contextual measures, except for school-level gender composition, were explained by individual characteristics. There was some evidence of cross-level effects of individual- and school-level markers of ethnicity and deprivation on suicide risk, with qualitative interaction patterns. For example, having foreign-born parents increased the risk for individuals raised in areas where they were in a relative minority, but protected against suicide in areas where larger proportions of the population had foreign-born parents.

Characteristics that define individuals as being different from most people in their local environment as they grow up may increase suicide risk. If robustly replicated, these findings have potentially important implications for understanding the aetiology of suicide and informing social policy.

It has been previously demonstrated that a cognitive bias against disconfirmatory evidence (BADE) is associated with delusions. However, small samples of delusional patients, reliance on difference scores and choice of comparison groups may have hampered the reliability of these results. In the present study we aimed to improve on this methodology with a recent version of the BADE task, and compare larger groups of schizophrenia patients with/without delusions to obsessive–compulsive disorder (OCD) patients, a population with persistent and possibly bizarre beliefs without psychosis.

A component analysis was used to identify cognitive operations underlying the BADE task, and how they differ across four groups of participants: (1) high-delusional schizophrenia, (2) low-delusional schizophrenia, (3) OCD patients and (4) non-psychiatric controls.

As in past studies, two components emerged and were labelled ‘evidence integration’ (the degree to which disambiguating information has been integrated) and ‘conservatism’ (reduced willingness to provide high plausibility ratings when justified), and only evidence integration differed between severely delusional patients and the other groups, reflecting delusional subjects giving higher ratings for disconfirmed interpretations and lower ratings for confirmed interpretations.

These data support the finding that a reduced willingness to adjust beliefs when confronted with disconfirming evidence may be a cognitive underpinning of delusions specifically, rather than obsessive beliefs or other aspects of psychosis such as hallucinations, and illustrates a cognitive process that may underlie maintenance of delusions in the face of counter-evidence. This supports the possibility of the BADE operation being a useful target in cognitive-based therapies for delusions.

Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established.

The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate.

Widespread significant reductions of fractional anisotropy (FA) – including the cingulum, corpus callosum, superior and inferior longitudinal fascicule – were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = –0.49, p = 0.04) and higher depression severity (at a trend level: β = –0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = −0.28, p = 0.04; and β = −0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered.

Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.

For diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for major depressive disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, using a population cohort that shifts from low to elevated depression levels.

We assessed the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire; PHQ-9) and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n = 1289). We tested whether risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms.

All MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), whereas neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor.

The influence of risk factors varies substantially across DSM depression criterion symptoms. As symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum scores.

There is substantial variability in the degree of cognitive impairment among older depressed persons. Inconsistencies in previous findings may be due to differences in clinical and demographic characteristics across study samples. We assessed the influence of unipolar depression and severity of depression on cognitive performance in a population-based sample of elderly persons aged ⩾60 years.

Eighty-nine persons fulfilled ICD-10 criteria for unipolar depression (mild, n = 48; moderate, n = 38; severe, n = 3) after thorough screening for dementia (DSM-IV criteria), psychiatric co-morbidities and antidepressant pharmacotherapy. Participants (n = 2486) were administered an extensive cognitive test battery.

Moderate/severe unipolar depression was associated with poorer performance on tasks assessing processing speed, attention, executive function, verbal fluency, episodic memory and vocabulary. Mild depression was associated with poorer performance in processing speed, and few differences between mild and moderate/severe depression were observed. No association between depression and short-term memory, general knowledge or spatial ability was observed. Increasing age did not exacerbate the depression-related cognitive deficits, and the deficits remained largely unchanged after excluding persons in a preclinical phase of dementia. Furthermore, depression-related cognitive deficits were not associated with other pharmacological treatments that may affect cognitive performance.

Cognitive deficits in unipolar old-age depression involve a range of domains and the cognitive deficits seem to follow the spectrum of depression severity. The finding that mild depression was also associated with poorer cognitive functioning underscores the importance of detecting mild depression in elderly persons.

Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.

Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.

Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).

In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.

To investigate the risk of completed suicide in offspring during adolescence in relation to prior history of the same-sex parent's death by suicide and other causes.

A total of 500 adolescents who died by suicide at age 15–19 years between 1997 and 2007 were identified from the Taiwan Mortality Registration (TMR). For each case, 30 age- and time-matched controls were selected randomly from all adolescents registered in the Taiwan Birth Registry (TBR). A multivariate conditional logistic regression model was used to assess the risk of adolescent completed suicide in relation to their same-sex parent.

Adolescent suicide risk was positively associated with both paternal [odds ratio (OR) 5.38, 95% confidence interval (CI) 2.17–13.33] and maternal suicide (OR 6.59, 95% CI 1.82–23.91). The corresponding risk estimates associated with paternal and maternal deaths from non-suicidal causes were much lower, at 1.88 and 1.94 respectively. The risk of suicide in male adolescents was significantly associated with prior history of paternal death by suicide (OR 8.23, 95% CI 2.96–22.90) but not of maternal death by suicide (OR 3.50, 95% CI 0.41–30.13). On the other contrary, the risk of suicidal death in female adolescents was significantly associated with prior history of maternal suicide (OR 9.71, 95% CI 1.89–49.94) but not of paternal suicide (OR 2.42, 95% CI 0.30–19.57). However, these differences did not reach statistical significance.

Although limited by sample size, our study indicates that adolescent offspring suicidal death is associated with prior history of their same-sex parent's death by suicide.

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.

Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation.

A total of 1547 children (aged 6–12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data.

Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD.

Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.

Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.

This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.

Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.

Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Cannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms.

Clinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points – at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded.

Level of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up.

Effective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.

Recent community-based research has suggested that psychotic experiences act as markers of severity of psychopathology. There has, however, been a lack of clinic-based research. We wished to investigate, in a clinical sample of adolescents referred to a state-funded mental health service, the prevalence of (attenuated or frank) psychotic experiences and the relationship with (i) affective, anxiety and behavioural disorders, (ii) multimorbid psychopathology, (iii) global functioning, and (iv) suicidal behaviour.

The investigation was a clinical case–clinical control study using semi-structured research diagnostic psychiatric assessments in 108 patients newly referred to state adolescent mental health services.

Psychotic experiences were prevalent in a wide range of (non-psychotic) disorders but were strong markers of risk in particular for multimorbid psychopathology (Z = 3.44, p = 0.001). Young people with psychopathology who reported psychotic experiences demonstrated significantly poorer socio-occupational functioning than young people with psychopathology who did not report psychotic experiences, which was not explained by multimorbidity. Psychotic experiences were strong markers of risk for suicidal behaviour. Stratified analyses showed that there was a greatly increased odds of suicide attempts in patients with a major depressive disorder [odds ratio (OR) 8.89, 95% confidence interval (CI) 1.59–49.83], anxiety disorder (OR 15.4, 95% CI 1.85–127.94) or behavioural disorder (OR 3.13, 95% CI 1.11–8.79) who also had psychotic experiences compared with patients who did not report psychotic experiences.

Psychotic experiences (attenuated or frank) are an important but under-recognized marker of risk for severe psychopathology, including multimorbidity, poor functioning and suicidal behaviour in young people who present to mental health services.

The prevention of depression is a key public health policy priority. PredictD is the first risk algorithm for the prediction of the onset of major depression. Our aim in this study was to model the cost-effectiveness of PredictD in depression prevention in general practice (GP).

A decision analytical model was developed to determine the cost-effectiveness of two approaches, each of which was compared to treatment as usual (TAU) over 12 months: (1) the PredictD risk algorithm plus a low-intensity depression prevention programme; and (2) a universal prevention programme in which there was no initial identification of those at risk. The model simulates the incidence of depression and disease progression over 12 months and calculates the net monetary benefit (NMB) from the National Health Service (NHS) perspective.

Providing patients with PredictD and a depression prevention programme prevented 15 (17%) cases of depression in a cohort of 1000 patients over 12 months and had the highest probability of being the optimal choice at a willingness to pay (WTP) of £20 000 for a quality-adjusted life year (QALY). Universal prevention was strongly dominated by PredictD plus a depression prevention programme in that universal prevention resulted in less QALYs than PredictD plus prevention for a greater cost.

Using PredictD to identify primary-care patients at high risk of depression and providing them with a low-intensity prevention programme is potentially cost-effective at a WTP of £20 000 per QALY.

Individuals with major depressive disorder (MDD) tested in either the depressed (dMDD) or remitted phase (rMDD) recall fewer specific and more categorical autobiographical memories (AMs) compared to healthy controls (HCs). The current study aimed to replicate findings of AM overgenerality in dMDD or rMDD, and to elucidate differences in neurophysiological correlates of AM recall between these MDD samples and HCs.

Unmedicated participants who met criteria for the dMDD, rMDD or HC groups (n = 16/group) underwent functional magnetic resonance imaging (fMRI) while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from an assigned semantic category and counting the number of risers in a letter string.

The results showed fewer specific and more categorical AMs in both MDD samples versus HCs; dMDDs and rMDDs performed similarly on these measures. The neuroimaging results showed differences between groups in the dorsomedial prefrontal cortex (DMPFC), lateral orbitofrontal cortex (OFC), anterior insula, inferior temporal gyrus and parahippocampus/hippocampus during specific AM recall versus example generation. During specific AM recall cued by positively valenced words, group differences were evident in the DMPFC, middle temporal gyrus, parahippocampus/hippocampus and occipital gyrus, whereas differences during specific AM recall cued by negatively valenced words were evident in the DMPFC, superior temporal gyrus and hippocampus.

AM deficits exist in rMDDs, suggesting that these impairments constitute trait-like abnormalities in MDD. We also found distinct patterns of hemodynamic activity for each group as they recalled specific AMs, raising the possibility that each group used a partly unique strategy for self-referential focus during successful retrieval of specific memories.

Valuable trauma-related research may be hindered when the risks of asking participants about traumatic events are not carefully weighed against the benefits of their participation in the research.

The overall aim of our population-based survey was to improve the professional care of suicide-bereaved parents by identifying aspects of care that would be amenable to change. The study population included 666 suicide-bereaved and 377 matched (2:1) non-bereaved parents. In this article we describe the parents' perceptions of their contacts with us as well as their participation in the survey. We also present our ethical-protocol for epidemiological surveys in the aftermath of a traumatic loss.

We were able to contact 1410 of the 1423 eligible parents; eight of these parents expressed resentment towards the contact. Several participants and non-participants described their psychological suffering and received help because of the contact. A total of 666 suicide-bereaved and 377 non-bereaved parents returned the questionnaire. Just two out of the 1043 answered that they might, in the long term, be negatively affected by participation in the study; one was bereaved, the other was not. A significant minority of the parents reported being temporarily negatively affected at the end of their participation, most of them referring to feelings of sadness and painful memories. In parallel, positive experiences were widely expressed and most parents found the study valuable.

Our findings suggest, given that the study design is ethically sound, that suicide-bereaved parents should be included in research since the benefits clearly outweigh the risks.