Few studies have focused on post-traumatic stress disorder (PTSD) remission in the population, none have modelled remission beyond age 54 years and none have explored in detail the correlates of remission from PTSD. This study examined trauma experience, symptom severity, co-morbidity, service use and time to PTSD remission in a large population sample.

Data came from respondents (n=8841) of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). A modified version of the World Health Organization's World Mental Health Composite International Diagnostic Interview (WMH-CIDI) was used to determine the presence and age of onset of DSM-IV PTSD and other mental and substance use disorders, type, age, and number of lifetime traumas, severity of re-experiencing, avoidance and hypervigilance symptoms and presence and timing of service use.

Projected lifetime remission rate was 92% and median time to remission was 14 years. Those who experienced childhood trauma, interpersonal violence, severe symptoms or a secondary anxiety or affective disorder were less likely to remit from PTSD and reported longer median times to remission compared to those with other trauma experiences, less severe symptoms or no co-morbidity.

Although most people in the population with PTSD eventually remit, a significant minority report symptoms decades after onset. Those who experience childhood trauma or interpersonal violence should be a high priority for intervention.

Psychological models of psychosis were examined using Experience Sampling Methods (ESM) to explore relationships between dimensions and appraisals of key symptoms and affect.

Individuals were signalled to complete ESM booklets 10 times per day for six consecutive days; 534 data points were obtained from 12 out-patients with psychosis.

Although only 3.6% of spontaneous thoughts were psychosis related, these predicted more negative and less positive affect. Delusions and hallucinations, when present, were rated at a moderate level of intensity, and intensity was associated with distress, interference and preoccupation. Symptom dimensions were related to each other, with weaker associations with delusional conviction, which, it is hypothesized, may represent a separate factor. Conviction and appraisals relating to insight and decentring (‘my problems are something to do with the way my mind works’) were highly variable. Decentring appraisals of delusions, but not insight, were associated with less distress. Appraisals about the power of voices were strong predictors of negative affect and symptom distress.

This study demonstrates that ESM is a useful methodology to capture ‘online’ variability in psychotic phenomenology and provides evidence supporting cognitive models, which posit that psychotic symptoms are multi-dimensional phenomena, shaped by appraisals that, in turn, predict their emotional and behavioural sequelae.

There may be biological plausibility to the notion that cannabis use and childhood trauma or maltreatment synergistically increase the risk for later development of psychotic symptoms. To replicate and further investigate this issue, prospective data from two independent population-based studies, the Greek National Perinatal Study (n=1636) and The Netherlands Mental Health Survey and Incidence Study (NEMESIS) (n=4842), were analyzed.

Two different data sets on cannabis use and childhood maltreatment were used. In a large Greek population-based cohort study, data on cannabis use at age 19 years and childhood maltreatment at 7 years were assessed. In addition, psychotic symptoms were assessed using the Community Assessment of Psychic Experiences (CAPE). In NEMESIS, the Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms at three different time points along with childhood maltreatment and lifetime cannabis use.

A significant adjusted interaction between childhood maltreatment and later cannabis use was evident in both samples, indicating that the psychosis-inducing effects of cannabis were stronger in individuals exposed to earlier sexual or physical mistreatment [Greek National Perinatal Study: test for interaction F(2, 1627)=4.18, p=0.02; NEMESIS: test for interaction χ2(3)=8.08, p=0.04].

Cross-sensitivity between childhood maltreatment and cannabis use may exist in pathways that shape the risk for expression of positive psychotic symptoms.

The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms.

We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD.

Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9–6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt.

This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.

In recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables.

Altogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR.

Remission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators.

These findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery.

Suicidal behavior is frequently associated with a history of childhood abuse yet it remains unclear precisely how early life adversity may increase suicide risk later in life. As such, our aim was to examine whether lifetime trajectories of disruptiveness and anxiousness trait dysregulation explain the association between childhood adversity and suicidal behavior; and moreover, to test the potential modifying effects of mental disorders on these associations.

A sample of 1776 individuals from a prospective school-based cohort followed longitudinally for over 22 years was investigated. We tested the influence of disruptiveness and anxiousness trajectories from age 6 to 12 years on the association between childhood adversity (i.e. sexual and physical abuse) and history of suicide attempts (SA) using logistic regression models. Both adolescent externalizing and internalizing Axis I disorders and gender were tested as potential modifiers of these associations.

Four distinct longitudinal trajectories were identified for both disruptiveness and anxiousness. The high disruptiveness trajectory accounted for the association between childhood adversity and SA, but only for females. The high anxiousness trajectory also explained the association between adversity and SA; however, in this case it was not sex but mental disorders that influenced the potency of the mediating effect. More specifically, anxiousness fully explained the effect of adversity on SA in the presence of externalizing disorders, whereas in the absence of these disorders, this effect was significantly attenuated.

This study provides evidence that both disruptiveness and anxiousness play an important role in explaining the relationship between childhood adversity and SA.

It has been proposed that the relationship between childhood trauma and hallucinations can be explained by dissociative processes. The present study examined whether the effect of childhood trauma on hallucination-proneness is mediated by dissociative tendencies. In addition, the influence of dissociative symptoms on a cognitive process believed to underlie hallucinatory experiences (i.e. reality discrimination; the capacity to discriminate between internal and external cognitive events) was also investigated.

Patients with schizophrenia spectrum disorders (n=45) and healthy controls (with no history of hallucinations; n=20) completed questionnaire measures of hallucination-proneness, dissociative tendencies and childhood trauma, as well as performing an auditory signal detection task.

Compared to both healthy and non-hallucinating clinical controls, hallucinating patients reported both significantly higher dissociative tendencies and childhood sexual abuse. Dissociation positively mediated the effect of childhood trauma on hallucination-proneness. This mediational role was particularly robust for sexual abuse over other types of trauma. Signal detection abnormalities were evident in hallucinating patients and patients with a history of hallucinations, but were not associated with pathological dissociative symptoms.

These results are consistent with dissociative accounts of the trauma-hallucinations link. Dissociation, however, does not affect reality discrimination. Future research should examine whether other cognitive processes associated with both dissociative states and hallucinations (e.g. deficits in cognitive inhibition) may explain the relationship between dissociation and hallucinatory experiences.

We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL).

Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ⩾70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes.

Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss.

Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment.

Stress questionnaires are included in many epidemiological cohort studies but the psychometric characteristics of these questionnaires are largely unknown. The aim of this study was to describe these characteristics for two short questionnaires measuring the lifetime and past year occurrence of stress: the List of Threatening Events (LTE) as a measure of acute stress and the Long-term Difficulties Inventory (LDI) as a measure of chronic stress.

This study was performed in a general population cohort consisting of 588 females (53.7%) and 506 males (46.3%), with a mean age of 53.5 years (s.d.=11.3 years). Respondents completed the LTE and the LDI for the past year, and for the age categories of 0–12, 13–18, 19–39, 40–60, and >60 years. They also completed questionnaires on perceived stress, psychological distress (the General Health Questionnaire, GHQ-12), anxiety and depression (the Symptom Checklist, SCL-8) and neuroticism (the Eysenck Personality Questionnaire – Revised Short Scale, EPQ-RSS-N). Approximately 2 years later, 976 respondents (89%) completed these questionnaires for a second time.

The stability of the retrospective reporting of long-term difficulties and life events was satisfactory: 0.7 for the lifetime LDI and 0.6 for the lifetime LTE scores. The construct validity of these lists is indicated by their positive associations with psychological distress, mental health problems and neuroticism.

This study in a large population-based sample shows that the LDI and LTE have sufficient validity and stability to include them in major epidemiological cohort studies.

Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall.

Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings.

Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD.

We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.

Several conceptual models have been considered for the assessment of personality pathology in DSM-5. This study sought to extend our previous findings to compare the long-term predictive validity of three such models: the Five-Factor Model (FFM), the Schedule for Nonadaptive and Adaptive Personality (SNAP), and DSM-IV personality disorders (PDs).

An inception cohort from the Collaborative Longitudinal Personality Disorder Study (CLPS) was followed for 10 years. Baseline data were used to predict long-term outcomes, including functioning, Axis I psychopathology, and medication use.

Each model was significantly valid, predicting a host of important clinical outcomes. Lower-order elements of the FFM system were not more valid than higher-order factors, and DSM-IV diagnostic categories were less valid than dimensional symptom counts. Approaches that integrate normative traits and personality pathology proved to be most predictive, as the SNAP, a system that integrates normal and pathological traits, generally showed the largest validity coefficients overall, and the DSM-IV PD syndromes and FFM traits tended to provide substantial incremental information relative to one another.

DSM-5 PD assessment should involve an integration of personality traits with characteristic features of PDs.

Addicts show both reward processing deficits and increased salience attribution to drug cues. However, no study to date has demonstrated that salience attribution to drug cues can directly modulate inferences of reward value to non-drug cues. Associative learning depends on salience: a more salient predictor of an outcome will ‘overshadow’ a less salient predictor of the same outcome. Similarly, blocking, a demonstration that learning depends on prediction error, can be influenced by the salience of the cues employed.

This study investigated whether salient drug cues might interact with neutral cues predicting financial reward in an associative learning task indexing blocking and overshadowing in satiated smokers (n=24), abstaining smokers (n=24) and non-smoking controls (n=24). Attentional bias towards drug cues, craving and expired CO were also indexed.

Abstaining smokers showed drug cue induced overshadowing, attributing higher reward value to drug cues than to neutral cues that were equally predictive of reward. Overshadowing was positively correlated with expired CO levels, which, in turn, were correlated with craving in abstainers. An automatic attentional bias towards cigarette cues was found in abstainers only.

These findings provide the first evidence that drug cues interact with reward processing in a drug dependent population.

While 20% of schizophrenia patients worldwide speak tonal languages (e.g. Mandarin), studies are limited to Western-language patients. Western-language patients show tonal deficits that are related to impaired emotional processing of speech. However, language processing is minimally affected. In contrast, in Mandarin, syllables are voiced in one of four tones, with word meaning varying accordingly. We hypothesized that Mandarin-speaking schizophrenia patients would show impairments in underlying basic auditory processing that, unlike in Western groups, would relate to deficits in word recognition and social outcomes.

Altogether, 22 Mandarin-speaking schizophrenia patients and 44 matched healthy participants were recruited from New York City. The auditory tasks were: (1) tone matching; (2) distorted tunes; (3) Chinese word discrimination; (4) Chinese word identification. Social outcomes were measured by marital status, employment and most recent employment status.

Patients showed deficits in tone-matching, distorted tunes, word discrimination and word identification versus controls (all p<0.0001). Impairments in tone-matching across groups correlated with both word identification (p<0.0001) and discrimination (p<0.0001). On social outcomes, tonally impaired patients had ‘lower-status’ jobs overall when compared with tonally intact patients (p<0.005) and controls (p<0.0001).

Our study is the first to investigate an interaction between neuropsychology and language among Mandarin-speaking schizophrenia patients. As predicted, patients were highly impaired in both tone and auditory word processing, with these two measures significantly correlated. Tonally impaired patients showed significantly worse employment-status function than tonally intact patients, suggesting a link between sensory impairment and employment status outcome. While neuropsychological deficits appear similar cross-culturally, their consequences may be language- and culture-dependent.

The aim of this study was to extend an earlier retrospective cohort study of schizophrenia via a prospective study to a follow-up of 34 years, with an emphasis on describing the life-course of the illness.

Subjects were 128 first-ever admissions for schizophrenia in 1963 to either of two mental hospital in Alberta, Canada. Follow-up continued until death or 1997. A symptom severity scale, with scores ranging from 0 (no symptoms) to 3 (hospitalized), was used to collect time-series data on each subject and create life-course curves. Indices were constructed to summarize the information in each curve. Information on social functioning was also collected.

Results were similar for men and women. The life-course curves showed marked variability of symptom severity across subjects and over time. The average score over the entire period of follow-up for the cohort indicated ‘moderate’ symptoms, and the change in average score from beginning to end of follow-up demonstrated a slight worsening of symptoms. The measures of social functioning indicated that only about one quarter of the patients had a good to excellent outcome.

The long-term course in schizophrenia is one of varying symptom severity, and for many patients, there is a poor overall outcome.

Non-medical use of prescription opioids represents a national public health concern of growing importance. Mood and anxiety disorders are highly associated with non-medical prescription opioid use. The authors examined longitudinal associations between non-medical prescription opioid use and opioid disorder due to non-medical opioid use and mood/anxiety disorders in a national sample, examining evidence for precipitation, self-medication and general shared vulnerability as pathways between disorders.

Data were drawn from face-to-face surveys of 34 653 adult participants in waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression models explored the temporal sequence and evidence for the hypothesized pathways.

Baseline lifetime non-medical prescription opioid use was associated with incidence of any mood disorder, major depressive disorder (MDD), bipolar disorder, any anxiety disorder and generalized anxiety disorder (GAD in wave 2, adjusted for baseline demographics, other substance use, and co-morbid mood/anxiety disorders). Lifetime opioid disorder was not associated with any incident mood/anxiety disorders. All baseline lifetime mood disorders and GAD were associated with incident non-medical prescription opioid use at follow-up, adjusted for demographics, co-morbid mood/anxiety disorders, and other substance use. Baseline lifetime mood disorders, MDD, dysthymia and panic disorder were associated with incident opioid disorder due to non-medical prescription opioid use at follow-up, adjusted for the same covariates.

These results suggest that precipitation, self-medication as well as shared vulnerability are all viable pathways between non-medical prescription opioid use and opioid disorder due to non-medical opioid use and mood/anxiety disorders.

Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder.

In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis.

Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders.

Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.

Tobacco smoking and poor mental health are both prevalent and detrimental health problems in young women. The temporal relationship between the two variables is unclear. We investigated the prospective bi-directional relationship between smoking and mental health over 13 years.

Participants were a randomly selected community sample of 10 012 young women with no experience of pregnancy, aged 18–23 years at baseline (1996) from the Australian Longitudinal Study on Women's Health. Follow-up surveys over 13 years were completed in 2000, 2003, 2006 and 2009, allowing for five waves of data. Measures included self-reported smoking and mental health measured by the Mental Health Index from the 36-item short-form health questionnaire and the 10-item Center for Epidemiologic Studies Depression Scale. Sociodemographic control variables included marital status, education level and employment status.

A strong cross-sectional dose–response relationship between smoking and poor mental health was found at each wave [odds ratio (OR) 1.41, 95% confidence intervals (CI) 1.17–1.70 to OR 2.27, 95% CI 1.82–2.81]. Longitudinal results showed that women who smoked had 1.21 (95% CI 1.06–1.39) to 1.62 (95% CI 1.24–2.11) times higher odds of having poor mental health at subsequent waves. Women with poor mental health had 1.12 (95% CI 1.17–1.20) to 2.11 (95% CI 1.68–2.65) times higher odds of smoking at subsequent waves. These results held after adjusting for mental health history and smoking history and sociodemographic factors. Correlation analysis and structural equation modelling results were consistent in showing that both directions of the relationship were statistically significant.

The association between poor mental health and smoking in young women appeared to be bi-directional.

Psychotic-like experiences (PLEs) in the general population are common, particularly in childhood, and may constitute part of a spectrum of normative development. Nevertheless, these experiences confer increased risk for later psychotic disorder, and are associated with poorer health and quality of life.

This study used factor analytic methods to determine the latent structure underlying PLEs, problem behaviours and personal competencies in the general child population, and used item response theory (IRT) to assess the psychometric properties of nine PLE items to determine which items best represented a latent psychotic-like construct (PSY). A total of 7966 children aged 9–11 years, constituting 95% of eligible children, completed self-report questionnaires.

Almost two-thirds of the children endorsed at least one PLE item. Structural analyses identified a unidimensional construct representing psychotic-like severity in the population, the full range of which was well sampled by the nine items. This construct was discriminable from (though correlated with) latent dimensions representing internalizing and externalizing problems. Items assessing visual and auditory hallucination-like experiences provided the most information about PSY; delusion-like experiences identified children at more severe levels of the construct.

Assessing PLEs during middle childhood is feasible and supplements information concerning internalizing and externalizing problems presented by children. The hallucination-like experiences constitute appropriate items to screen the population to identify children who may require further clinical assessment or monitoring. Longitudinal follow-up of the children is required to determine sensitivity and specificity of the PLE items for later psychotic illness.

The prevailing standard of care in the field involves background assumptions about the importance of prolonged use of antipsychotic medications for all schizophrenia (SZ) patients. However, do all SZ patients need antipsychotics indefinitely? Are there factors that help to identify which SZ patients can enter into prolonged periods of recovery without antipsychotics? This 20-year longitudinal research studied these issues.

A total of 139 early young psychotic patients from the Chicago Follow-up Study, including 70 patients with SZ syndromes and 69 with mood disorders, were assessed, prospectively, at the acute phase and then followed up six times over the next 20 years. Patients were assessed with standardized instruments for major symptoms, psychosocial functioning, personality, attitudinal variables, neurocognition and treatment.

At each follow-up, 30–40% of SZ patients were no longer on antipsychotics. Starting at the 4.5-year follow-ups and continuing thereafter, SZ patients not on antipsychotics for prolonged periods were significantly less likely to be psychotic and experienced more periods of recovery; they also had more favorable risk and protective factors. SZ patients off antipsychotics for prolonged periods did not relapse more frequently.

The data indicate that not all SZ patients need treatment with antipsychotics continuously throughout their lives. SZ patients not on antipsychotics for prolonged periods are a self-selected group with better internal resources associated with greater resiliency. They have better prognostic factors, better pre-morbid developmental achievements, less vulnerability to anxiety, better neurocognitive skills, less vulnerability to psychosis and experience more periods of recovery.

Candidate gene studies have been a key approach to the genetics of schizophrenia (SCZ). However, the results of these studies are confusing and no genes have been unequivocally implicated. The hypothesis-driven candidate gene literature can be appraised by comparison with the results of genome-wide association studies (GWAS).

We describe the characteristics of hypothesis-driven candidate gene studies from the SZGene database, and use pathway analysis to compare hypothesis-driven candidate genes with GWAS results from the International Schizophrenia Consortium (ISC).

SZGene contained 732 autosomal genes evaluated in 1374 studies. These genes had poor statistical power to detect genetic effects typical for human diseases, assessed only 3.7% of genes in the genome, and had low marker densities per gene. Most genes were assessed once or twice (76.9%), providing minimal ability to evaluate consensus across studies. The ISC studies had 89% power to detect a genetic effect typical for common human diseases and assessed 79% of known autosomal common genetic variation. Pathway analyses did not reveal enrichment of smaller ISC p values in hypothesis-driven candidate genes, nor did a comprehensive evaluation of meta-hypotheses driving candidate gene selection (SCZ as a disease of the synapse or neurodevelopment). The most studied hypothesis-driven candidate genes (COMT, DRD3, DRD2, HTR2A, NRG1, BDNF, DTNBP1 and SLC6A4) had no notable ISC results.

We did not find support for the idea that the hypothesis-driven candidate genes studied in the literature are enriched for the common genetic variation involved in the etiology of SCZ. Larger samples are required to evaluate this conclusion definitively.