Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.

We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.

Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = −2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = −2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01–0.001) and those born outside the UK (p values<0.05).

Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression.

Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD.

In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns.

These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.

To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia.

Female twins (n=1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx.

Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance.

Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors.

One third of referrals from primary to secondary care are for medically unexplained symptoms (MUS). We aimed to determine the association of depression and anxiety disorders with high use of specialist services by patients with MUS. We did this by comparing their prevalence in patients who had been repeatedly referred with symptoms for which they had received repeated specialist diagnoses of MUS with that in two control groups. We also determined the adequacy of treatment received.

A case-control study in five general practices in Edinburgh, UK. Data collection was by case note review and questionnaire. Cases were 193 adults with three or more referrals over 5 years, at least two of which resulted in a diagnosis of MUS. Controls were: (a) patients referred only once over 5 years (n=152); (b) patients with three or more referrals for symptoms always diagnosed as medically explained (n=162).

In total, 93 (48%) of the cases met our criteria for current depression, anxiety or panic disorders. This compared with 38 (25%) and 52 (35.2%) of the control groups; odds ratios (95% confidence intervals) of 2.6 (1.6–4.1) and 1.6 (1.01–2.4), respectively. Almost half (44%) of the cases with current depression or anxiety had not received recent minimum effective therapy.

Depression, anxiety and panic disorders are common in patients repeatedly referred to hospital with MUS. Improving the recognition and treatment of these disorders in these patients has the potential to provide better, more appropriate and more cost-effective medical care.

Studies in Western countries have repeatedly shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in China?

Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression and regression coefficients by linear or Poisson regression.

Any form of CSA was significantly associated with recurrent MD [OR 3.26, 95% confidence interval (CI) 1.95–5.45]. This association strengthened with increasing CSA severity: non-genital (OR 2.47, 95% CI 1.17–5.23), genital (OR 2.77, 95% CI 1.32–5.83) and intercourse (OR 13.35, 95% CI 1.83–97.42). The association between any form of CSA and MD remained significant after accounting for parental history of depression, childhood emotional neglect (CEN), childhood physical abuse (CPA) and parent–child relationship. Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes and an increased risk for generalized anxiety disorder (GAD; OR 1.92, 95% CI 1.39–2.66) and dysthymia (OR 2.16, 95% CI 1.52–3.09).

In Chinese women CSA is strongly associated with MD and this association increases with greater severity of CSA. Depressed women with CSA have an earlier age of onset, longer depressive episodes and increased co-morbidity with GAD and dysthymia. Although reporting biases cannot be ruled out, our results are consistent with the hypothesis that, as in Western countries, CSA substantially increases the risk for MD in China.

Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear.

This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted.

Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day.

A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.

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.

An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes.

We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress–adversity, emotional–behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation.

Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs.

The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

The anxiety disorders are robust correlates/predictors of suicidal ideation, but it is unclear whether (a) the anxiety disorders are specifically associated with suicidal ideation or (b) the association is due to co-morbidity with depression and other disorders. One means of modeling co-morbidity is through the personality traits neuroticism/negative emotionality (N/NE) and extraversion/positive emotionality (E/PE), which account for substantial shared variance among the internalizing disorders. The current study examines the association between the internalizing disorders and suicidal ideation, after controlling for co-morbidity via N/NE and E/PE.

The sample consisted of 327 psychiatric out-patients. Multiple self-report and interview measures were collected for internalizing disorders [depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety, panic and specific phobia] and suicidal ideation, as well as self-report measures for N/NE and E/PE. A model was hypothesized in which each disorder and suicidal ideation was regressed on N/NE, and depression and social anxiety were regressed on E/PE. Structural equation modeling (SEM) was used to examine the unique association of suicidality with each disorder, beyond shared variance with N/NE and E/PE.

The hypothesized model was an acceptable fit to the data. Although zero-order analyses indicated that suicidal ideation was moderately to strongly correlated with all of the disorders, only depression and PTSD remained significantly associated with suicidal ideation in the SEM analyses.

In a latent variable model that accounts for measurement error and a broad source of co-morbidity, only depression and PTSD were uniquely associated with suicidal ideation; panic, GAD, social anxiety and specific phobia were not.

Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years.

The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis.

At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively).

Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.