For many years, the prevailing paradigm has stated that in each individual with schizophrenia (SZ) the genetic risk is due to a combination of many genetic variants, individually of small effect. Recent empirical data are prompting a re-evaluation of this polygenic, common disease–common variant (CDCV) model. Evidence includes a lack of the expected strong positive findings from genome-wide association studies and the concurrent discovery of many different mutations that individually strongly predispose to SZ and other psychiatric disorders. This has led some to adopt a mixed model wherein some cases are caused by polygenic mechanisms and some by single mutations. This model runs counter to a substantial body of theoretical literature that had supposedly conclusively rejected Mendelian inheritance with genetic heterogeneity. Here we ask how this discrepancy between theory and data arose and propose a rationalization of the recent evidence base.

In light of recent empirical findings, we reconsider the methods and conclusions of early theoretical analyses and the explicit assumptions underlying them.

We show that many of these assumptions can now be seen to be false and that the model of genetic heterogeneity is consistent with observed familial recurrence risks, endophenotype studies and other population-wide parameters.

We argue for a more biologically consilient mixed model that involves interactions between disease-causing and disease-modifying variants in each individual. We consider the implications of this model for moving SZ research beyond statistical associations to pathogenic mechanisms.

Psychiatric conditions in which symptoms arise involuntarily (‘diseases’) might be assumed to be more heritable than those in which choices are essential (behavioral disorders). We sought to determine whether psychiatric ‘diseases’ (Alzheimer's disease, schizophrenia, and mood and anxiety disorders) are more heritable than behavioral disorders (substance use disorders and anorexia nervosa).

We reviewed the literature for recent quantitative summaries of heritabilities. When these were unavailable, we calculated weighted mean heritabilities from twin studies meeting modern methological standards.

Heritability summary estimates were as follows: bipolar disorder (85%), schizophrenia (81%), Alzheimer's disease (75%), cocaine use disorder (72%), anorexia nervosa (60%), alcohol dependence (56%), sedative use disorder (51%), cannabis use disorder (48%), panic disorder (43%), stimulant use disorder (40%), major depressive disorder (37%), and generalized anxiety disorder (28%).

No systematic relationship exists between the disease-like character of a psychiatric disorder and its heritability; many behavioral disorders seem to be more heritable than conditions commonly construed as diseases. These results suggest an error in ‘common-sense’ assumptions about the etiology of psychiatric disorders. That is, among psychiatric disorders, there is no close relationship between the strength of genetic influences and the etiologic importance of volitional processes.

Research suggests that psychotic-like experiences (PLEs) in the general population are common, but can reflect either transitory or persistent developmental phenomena. Using a general adolescent population it was examined whether different developmental subtypes of PLEs exist and whether different trajectories of PLEs are associated with certain environmental risk factors, such as victimization and substance use.

Self-reported PLEs were collected from 409 adolescents (mean age 14 years 7 months) at four time points, each 6 months apart. General growth mixture modelling was utilized to identify classes of adolescents who followed distinct trajectories of PLEs across this period. Predictors of class membership included demographics, personality, victimization, depression, anxiety and substance use.

We identified the following three developmental subgroups of PLEs: (1) persistent; (2) increasing; (3) low. Adolescents on the persistent trajectory reported frequent victimization and consistent elevated scores in depression and anxiety. Adolescents on the increasing trajectory were engaging in cigarette use prior to any increases in PLEs and were engaging in cocaine, cannabis and other drug use as PLEs increased at later time points.

The findings suggest that different developmental subgroups of PLEs exist in adolescence and are differentially related to victimization and substance use.

An association between childhood maltreatment and subsequent alcohol abuse and/or dependence (AAD) has been found in multiple studies of females. Less is known about the association between childhood maltreatment and AAD among males, and the mechanisms that underlie this association in either gender. One explanation is that childhood maltreatment increases risk for AAD. An alternative explanation is that the same genetic or environmental factors that increase a child's risk for being maltreated also contribute to risk for AAD in adulthood.

Lifetime diagnosis of AAD was assessed using structured clinical interviews in a sample of 3527 male participants aged 19–56 years from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. The sources of childhood maltreatment–AAD association were estimated using both a matched case–control analysis of twin pairs discordant for childhood maltreatment and bivariate twin modeling.

Approximately 9% of participants reported childhood maltreatment, defined as serious neglect, molestation, or physical abuse occurring before the age of 15 years. Those who experienced childhood maltreatment were 1.74 times as likely to meet AAD criteria compared with males who did not experience childhood maltreatment. The childhood maltreatment–AAD association largely reflected environmental factors in common to members of twin pairs. Additional exploratory analyses provided evidence that AAD risk associated with childhood maltreatment was significantly attenuated after adjusting for measured family-level risk factors.

Males who experienced childhood maltreatment had an increased risk for AAD. Our results suggest that the childhood maltreatment–AAD association is attributable to broader environmental adversity shared between twins.

To identify sources of race/ethnic differences related to post-traumatic stress disorder (PTSD), we compared trauma exposure, risk for PTSD among those exposed to trauma, and treatment-seeking among Whites, Blacks, Hispanics and Asians in the US general population.

Data from structured diagnostic interviews with 34 653 adult respondents to the 2004–2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed.

The lifetime prevalence of PTSD was highest among Blacks (8.7%), intermediate among Hispanics and Whites (7.0% and 7.4%) and lowest among Asians (4.0%). Differences in risk for trauma varied by type of event. Whites were more likely than the other groups to have any trauma, to learn of a trauma to someone close, and to learn of an unexpected death, but Blacks and Hispanics had higher risk of child maltreatment, chiefly witnessing domestic violence, and Asians, Black men, and Hispanic women had higher risk of war-related events than Whites. Among those exposed to trauma, PTSD risk was slightly higher among Blacks [adjusted odds ratio (aOR) 1.22] and lower among Asians (aOR 0.67) compared with Whites, after adjustment for characteristics of trauma exposure. All minority groups were less likely to seek treatment for PTSD than Whites (aOR range: 0.39–0.61), and fewer than half of minorities with PTSD sought treatment (range: 32.7–42.0%).

When PTSD affects US race/ethnic minorities, it is usually untreated. Large disparities in treatment indicate a need for investment in accessible and culturally sensitive treatment options.

The prevalence of family childhood adversities (FCAs) and their joint effects on the first onset of subsequent mental disorders throughout the life course are rarely examined, especially in Asian communities.

Face-to-face household interviews of 5201 people aged 18–70 years in Beijing and Shanghai were conducted by a multi-stage household probability sampling method. The first onsets of four broad groups of mental disorders and six categories of FCAs were assessed using The World Mental Health Composite International Diagnostic Interview (WMH-CIDI). Joint effects of FCAs were analyzed by the best fitting of several competitive multivariate models.

FCAs were highly prevalent and inter-correlated. Half of them were in a family-dysfunction cluster. The best-fitting model included each of six types of FCA (with family-dysfunction FCAs being the strongest predictors), number of family-dysfunction FCAs, and number of other FCAs. Family-dysfunction FCAs had a significant subadditive association with subsequent disorders. Little specificity was found for the effects of particular FCAs with particular disorders. Predictive effects of FCAs reached the highest in ages 13–24 compared to ages 4–12 and ⩾25. Estimates of population-attributable risk proportions indicated that all FCAs together explained 38.5% of all first-onset disorders.

Chinese children were exposed to a broad spectrum of inter-related FCAs, as found in Western countries. FCAs related to family dysfunction were especially associated with subsequent mental disorders. Biological and/or environmental factors that mediate these long-term effects should be studied in prospective research on broad groups of FCAs.

Etiological theory and prior research with small or selected samples suggest that interpersonal violence clusters in families. However, the strength and pattern of this aggregation remains mostly unknown.

We investigated all convictions for violent crime in Sweden 1973–2004 among more than 12.5 million individuals in the nationwide Multi-Generation Register, and compared rates of violent convictions among relatives of violent individuals with relatives of matched, non-violent controls, using a nested case–control design.

We found strong familial aggregation of interpersonal violence among first-degree relatives [e.g. odds ratio (OR)sibling 4.3, 95% confidence interval (CI) 4.2–4.3], lower for more distant relatives (e.g. ORcousin 1.9, 95% CI 1.9–1.9). Risk patterns across biological and adoptive relations provided evidence for both genetic and environmental influences on the development of violent behavior. Familial risks were stronger among women, in higher socio-economic strata, and for early onset interpersonal violence. There were crime-specific effects (e.g. ORsibling for arson 22.4, 95% CI 12.2–41.2), suggesting both general and subtype-specific familial risk factors for violent behavior.

The observed familiality should be accounted for in criminological research, applied violence risk assessment, and prevention efforts.

Different theories of the link between socio-economic status (SES) and mental illness have been postulated. In particular, two theories of this association, social causation and social selection, differ in the implied causal pathway. The authors employ behavior genetic modeling to consider evidence for both social selection and social causation in the relationship between income variation and internalizing disorders.

Behavior genetic modeling was used to estimate the presence of gene–environment interaction (GxE, social causation) in the presence of gene–environment correlation (rGE, social selection). Participants were members of a sample of 719 twin pairs from the Midlife in the United States study. Four internalizing (INT) syndromes were assessed: major depression (MD); generalized anxiety disorder (GAD); panic attacks (PA); neuroticism (N). SES was measured with total family household income.

One factor best accounted for the variance shared between MD, GAD, PA and N. The etiology of variation in INT changed from high to low levels of income, with unique environmental factors playing a larger role in INT variation at lower levels of income. Across levels of income, rGE between income and INT was modest (low income ra=0.39 to high income ra=0.54), implying a selection process operating through genetic effects linking lower income with INT psychopathology.

Findings support social causation by suggesting that low income contributes significantly to environmental variation in INT. Modest support was found for social selection, but should be extended using longitudinal designs. Effective interventions for internalizing psychopathology may differ depending on income.

Mental capacity is an emerging ethical legal concept in psychiatric settings but its relation to clinical parameters remains uncertain. We sought to investigate the associations of regaining capacity to make treatment decisions following approximately 1 month of in-patient psychiatric treatment.

We followed up 115 consecutive patients admitted to a psychiatric hospital who were judged to lack capacity to make treatment decisions at the point of hospitalization. We were primarily interested in whether the diagnosis of schizophrenia and schizoaffective disorder associated with reduced chances of regaining capacity compared with other diagnoses and whether affective symptoms on admission associated with increased chances of regaining capacity. In addition, we examined how change in insight was associated with regaining capacity in schizophrenia, bipolar affective disorder (BPAD)-mania, and depression.

We found evidence that the category of ‘schizophrenia or schizoaffective disorder’ associated with not regaining capacity at 1 month compared with BPAD-mania [odds ratio (OR) 3.62, 95% confidence intervals (CI) 1.13–11.6] and depression (OR 5.35, 95% CI 1.47–9.55) and that affective symptoms on admission associated with regaining capacity (OR 1.23, 95% CI 1.02–1.48). In addition, using an interaction model, we found some evidence that gain in insight may not be a good indicator of regaining capacity in patients with depression compared with patients with schizophrenia and BPAD-mania.

We suggest that clinico-ethical studies using mental capacity provide a way of assessing the validity of nosological and other clinical concepts in psychiatry.

While anxiety has been associated with exaggerated emotional reactivity, depression has been associated with blunted, or context insensitive, emotional responding. Although anxiety and depressive disorders are frequently co-morbid, surprisingly little is known about emotional reactivity when the two disorders co-occur.

We utilized the emotion-modulated startle (EMS) paradigm to examine the effects of a concurrent depressive episode on emotional reactivity in young adults with anxiety disorders. Using an archival dataset from a multi-disciplinary project on risk factors in childhood-onset depression, we examined eye-blink startle reactions to late-onset auditory startle probes while participants viewed pictures with affectively pleasant, unpleasant and neutral content. EMS response patterns were analyzed in 33 individuals with a current anxiety (but no depressive) disorder, 24 individuals with a current anxiety disorder and co-morbid depressive episode and 96 healthy controls.

Control participants and those with a current anxiety disorder (but no depression) displayed normative linearity in startle responses, including potentiation by unpleasant pictures. By contrast, individuals with concurrent anxiety and depression displayed blunted EMS.

An anxiety disorder concurrent with a depressive episode is associated with reactivity that more closely resembles the pattern of emotional responding that is typical of depression (i.e. context insensitive) rather than the pattern that is typical for anxiety (i.e. exaggerated).

It is important for doctors and patients to know what factors help recovery from depression. Our objectives were to predict the probability of sustained recovery for patients presenting with mild to moderate depression in primary care and to devise a means of estimating this probability on an individual basis.

Participants in a randomized controlled trial were identified through general practitioners (GPs) around three academic centres in England. Participants were aged >18 years, with Hamilton Depression Rating Scale (HAMD) scores 12–19 inclusive, and at least one physical symptom on the Bradford Somatic Inventory (BSI). Baseline assessments included demographics, treatment preference, life events and difficulties and health and social care use. The outcome was sustained recovery, defined as HAMD score <8 at both 12 and 26 week follow-up. We produced a predictive model of outcome using logistic regression clustered by GP and created a probability tree to demonstrate estimated probability of recovery at the individual level.

Of 220 participants, 74% provided HAMD scores at 12 and 26 weeks. A total of 39 (24%) achieved sustained recovery, associated with being female, married/cohabiting, having a low BSI score and receiving preferred treatment. A linear predictor gives individual probabilities for sustained recovery given specific characteristics and probability trees illustrate the range of probabilities and their uncertainties for some important combinations of factors.

Sustained recovery from mild to moderate depression in primary care appears more likely for women, people who are married or cohabiting, have few somatic symptoms and receive their preferred treatment.

Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy.

A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks.

Participants with higher scores on the need for medical reassurance factor of the Panic–Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission.

This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Cognitive remediation is frequently based on computerized training methods that target different cognitive deficits. The aim of this article was to assess the efficacy of computer-assisted cognitive remediation (CACR) in schizophrenia and to determine whether CACR enables selective treatment of specific cognitive domains.

A meta-analysis was performed on 16 randomized controlled trials evaluating CACR. The effect sizes of differences between CACR and control groups were computed and classified according to the cognitive domain assessed. The possible influences of four potential moderator variables were examined: participants' age, treatment duration, weekly frequency, and control condition type. To test the domain-specific effect, the intended goal of each study was determined and the effect sizes were sorted accordingly. The effect sizes of the cognitive domains explicitly targeted by the interventions were then compared with those that were not.

CACR enhanced general cognition with a mean effect size of 0.38 [confidence interval (CI) 0.20–0.55]. A significant medium effect size of 0.64 (CI 0.29–0.99) was found for Social Cognition. Improvements were also significant in Verbal Memory, Working Memory, Attention/Vigilance and Speed of Processing with small effect sizes. Cognitive domains that were specifically targeted by the interventions did not yield higher effects than those that were not.

The results lend support to the efficacy of CACR with particular emphasis on Social Cognition. The difficulty in targeting specific domains suggests a ‘non-specific’ effect of CACR. These results are discussed in the light of the possible bias in remediation tasks due to computer interface design paradigms.

Depression and anxiety have been shown to be associated with obesity and underweight, but little is known about how the relationship varies across the life course, from adolescence through adulthood. We aimed to investigate the association between adolescent- and adult-onset affective symptoms and body mass index (BMI) change from age 15 to 53 years.

We used data from a British birth cohort born in 1946 and followed up ever since. The relationship between affective symptom profiles, distinguishing adolescent-onset and adult-onset symptoms, and BMI change from adolescence to age 53 years was investigated using multilevel models.

Women with adolescent-onset symptoms had lower mean BMI at age 15 years, faster rates of increase across adulthood, and higher BMI at age 53 years than those with no symptoms. Men with adolescent-onset symptoms had lower BMI at all ages from 15 to 53 years. The BMI trajectories of men and women with adult-onset symptoms did not differ from those with absence of symptoms at all ages.

The relationship between affective symptoms and change in BMI varies by sex and age at onset of symptoms. Adolescence may be an important period for the development of the association between affective symptoms and weight gain in girls. Intervention to prevent increases in BMI across adult life in women with adolescent-onset symptoms, even if they are not overweight at this age, should be considered.

Current theories and nosology assume that the self-evaluation (SE) of individuals with eating disorders (EDs) is unduly influenced by body shape and weight. However, experimental data supporting this link are scarce, and it is not specified which subdomains of SE might be affected.

We studied patients with anorexia nervosa (AN), bulimia nervosa (BN) and healthy controls (HC) with an affective priming (AP) procedure (Study 1) to unveil explicit and implicit associations between shape/weight and SE. We used weight/shape-related prime sentences, complemented by affectively congruent and incongruent target words from two SE domains. AP effects were assessed by event-related potentials (ERPs), reaction times (RTs) and subjective ratings. The ratings were also assessed (Study 2) in undergraduate restrained (RES) and unrestrained eaters (UNRES).

Study 1 demonstrated stronger AP effects in both ED groups compared to HC on RTs and subjective ratings. ERPs showed AP effects only in the BN group. Restrained eaters showed similar, albeit less pronounced, priming effects on subjective ratings.

ED patients associate shape/weight concerns with the non-appearance-related SE domains of interpersonal relationships and achievement/performance. These associations seem to be encoded deeper in BN patients relative to the other groups. Links between shape/weight and SE explain how body dissatisfaction impacts on self-esteem and mood in ED. The existence of similar associations in restrained eaters supports a continuum model according to which increasing associations between shape/weight and SE go along with increasing levels of ED symptoms.

Previous efforts to derive empirically based eating disorder (ED) typologies through latent structure modeling have been limited by the ethnic and cultural homogeneity of their study populations and their reliance on DSM-IV ED signs and symptoms as indicator variables.

Ethnic Fijian schoolgirls (n=523) responded to a self-report battery assessing ED symptoms, herbal purgative use, co-morbid psychopathology, clinical impairment, cultural orientation, and peer influences. Participants who endorsed self-induced vomiting or herbal purgative use in the past 28 days (n=222) were included in a latent profile analysis (LPA) to identify unique subgroups of bulimic symptomatology.

LPA identified a bulimia nervosa (BN)-like class (n=86) characterized by high rates of binge eating and self-induced vomiting, and a herbal purgative class (n=136) characterized primarily by the use of indigenous Fijian herbal purgatives. Both ED classes endorsed greater eating pathology and general psychopathology than non-purging participants, and the herbal purgative class endorsed greater clinical impairment than either the BN-like or non-purging participants. Cultural orientation did not differ between the two ED classes.

Including study populations typically under-represented in mental health research and broadening the scope of relevant signs and symptoms in latent structure models may increase the generalizability of ED nosological schemes to encompass greater cultural diversity.