DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia.

The essential role of the Reelin gene (RELN) during brain development makes it a prominent candidate in human epigenetic studies of Schizophrenia. Previous literature has reported differing levels of DNA methylation (DNAm) in patients with psychosis. Therefore, this study aimed to (1) examine and compare RELN DNAm levels in subjects at different stages of psychosis cross-sectionally, (2) analyse the effect of antipsychotics (AP) on DNAm, and (3) evaluate the effectiveness and applicability of RELN promoter DNAm as a possible biological-based marker for symptom severity in psychosis.. The study cohort consisted of 56 healthy controls, 87 ultra-high risk (UHR) individuals, 26 first-episode (FE) psychosis individuals and 30 chronic schizophrenia (CS) individuals. The Positive and Negative Syndrome Scale (PANSS) was used to assess Schizophrenia severity. After pyrosequencing selected CpG sites of peripheral blood, the Average mean DNAm levels were compared amongst the 4 subgroups. Our results showed differing levels of DNAm, with UHR having the lowest (7.72 ± 0.19) while the CS had the highest levels (HC: 8.78 ± 0.35; FE: 7.75 ± 0.37; CS: 8.82 ± 0.48). Significantly higher Average mean DNAm levels were found in CS subjects on AP (9.12 ± 0.61) compared to UHR without medication (UHR(-)) (7.39 ± 0.18). A significant association was also observed between the Average mean DNAm of FE and PANSS Negative symptom factor (R2 = 0.237, ß = -0.401, *p = 0.033). In conclusion, our findings suggested different levels of DNAm for subjects at different stages of psychosis. Those subjects that took AP have different DNAm levels. There were significant associations between FE DNAm and Negative PANSS scores. With more future experiments and on larger cohorts, there may be potential use of DNAm of the RELN gene as one of the genes for the biological-based marker for symptom severity in psychosis.

Social skills, negative symptoms and real-world functioning in individuals at ultra-high risk of psychosis.

BACKGROUND: Impairment in real-world social functioning is observed in individuals at Ultra-High Risk (UHR) of psychosis. Both social skills and negative symptoms appear to influence real-world functioning. This study aims to examine the psychometric properties of a social skills measure, the High-Risk Social Challenge task (HiSoC), and evaluate the relationship between social skills, negative symptoms, and real-world functioning in UHR individuals. METHODS: HiSoC data was analysed in 87 UHR individuals and 358 healthy controls. Exploratory factor analysis (EFA) was used to evaluate the factor structure of the HiSoC task. Convergent and divergent validity were assessed. Negative symptoms were assessed on the Positive and Negative Syndrome Scale (PANSS) and real-world functioning was indexed by the Global Assessment of Functioning (GAF). Commonality analysis was used to partition unique and shared variance of HiSoC and negative symptoms with real-world functioning. RESULTS: EFA yielded a three-factor structure of HiSoC consisting of Affect, Odd behaviour and language, and Social-interpersonal. The HiSoC task discriminated UHR and healthy controls (p < 0.001, Cohen's d = 0.437-0.598). Commonality analysis revealed that the unique variance of the social amotivation subdomain of negative symptoms was the strongest predictor of GAF (p < .001, R2 = .480). Shared variance of 3.7% between HiSoC Social-interpersonal and social amotivation was observed in relation to functioning. CONCLUSION: The HiSoC is a psychometrically valid task that is sensitive to identify social skill deficits in UHR. While social skills are related to functioning, experiential negative symptoms appear to be an important target for improving real-world functional outcomes.

Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia.

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). Exploratory Factor Analysis (EFA) was conducted to identify the factor structure of PANSS and validated with a meta-analysis (N = 16,171) of existing PANSS models. Temporal stability of the PANSS model and generalizability to individuals at ultra-high risk (UHR) of psychosis were evaluated. A five-factor solution best fit the PANSS data. These were the i) Positive, ii) Negative, iii) Cognitive/disorganization, iv) Depression/anxiety and v) Hostility factors. Convergence of PANSS symptom architecture between EFA model and meta-analysis was observed. Modest longitudinal reliability was observed. The schizophrenia derived PANSS factor model fit the UHR population, but not vice versa. We found that two other domains, Social Amotivation (SA) and Diminished Expression (DE), were nested within the negative symptoms factor. Here, we report one of the largest transethnic factorial structures of PANSS symptom domains (N = 19,682). Evidence reported here serves as crucial consolidation of a common PANSS structure that could aid in furthering our understanding of schizophrenia.

Grit protects medical students from burnout: a longitudinal study.

BACKGROUND: Burnout is a serious issue plaguing the medical profession with potential negative consequences on patient care. Burnout symptoms are observed as early as medical school. Based on a Job Demands-Resources model, this study aims to assess associations between specific job resources measured at the beginning of the first year of medical school with burnout symptoms occurring later in the first year. METHODS: The specific job resources of grit, tolerance for ambiguity, social support and gender were measured in Duke-NUS Medical School students at the start of Year 1. Students were then surveyed for burnout symptoms at approximately quarterly intervals throughout the year. Using high ratings of cynicism and exhaustion as the definition of burnout, we investigated the associations of the occurrence of burnout with student job resources using multivariable logistic regression analysis. RESULTS: Out of 59 students, 19 (32.2%) indicated evidence of burnout at some point across the first year of medical school. Stepwise multivariable logistic regression analysis identified grit as having a significant protective effect against experiencing burnout (Odds Ratio, 0.84; 95%CI 0.74 to 0.96). Using grit as a single predictor of burnout, area under the ROC curve was 0.76 (95%CI: 0.62 to 0.89). CONCLUSIONS: Grit was identified as a protective factor against later burnout, suggesting that less gritty students are more susceptible to burnout. The results indicate that grit is a robust character trait which can prognosticate burnout in medical students. These students would potentially benefit from enhanced efforts to develop grit as a personal job resource.

Quality of parental bonding is associated with symptom severity and functioning among individuals at ultra-high risk for psychosis.

Patients with schizophrenia tend to report having 'affectionless-controlling' mothers when the Parental Bonding Instrument (PBI) is used. However, there is limited research on the parenting styles received by individuals at ultra-high risk (UHR) for psychosis. Furthermore, previous PBI studies have suggested that a three-factor solution is more suitable than the original two-factors. This study aims to i) use a more sensitive measure of parental bonding by conducting an exploratory factor analysis (EFA), and (ii) to explore the association between parental bonding, symptom severity and functioning among the UHR. Data from 164 individuals at UHR and 510 healthy controls were collected. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). Functioning was measured using the Global Assessment of Functioning (GAF) and Social and Occupational Functioning Assessment Scale (SOFAS). Confirmatory factor analyses of existing factor structures and EFA of the PBI was conducted. Pearson's correlations and regressions were used to elucidate the associations between parenting factors and assessment scales. EFAs revealed a three-factor solution: 'care', 'authoritarianism', and 'overprotection'. UHR were 1.61 times more likely to report having affectionless-controlling mothers. UHR reported significantly lower maternal and paternal care, and higher maternal and paternal overprotection. Higher paternal overprotection was significantly associated with worse symptoms and functioning. Our findings replicate previous findings among individuals at UHR in an Asian setting, and suggest that affectionless-controlling or affectionless-authoritative-overprotective styles may be a poor fit for individuals at UHR.

Childhood adversities in people at ultra-high risk (UHR) for psychosis: a systematic review and meta-analysis.

Childhood adversities have been reported to be more common among individuals at ultra-high risk (UHR) for psychosis. This paper systematically reviewed and meta-analysed (i) the severity and prevalence of childhood adversities (childhood trauma exposure, bullying victimisation and parental separation or loss) among the UHR, and (ii) the association between adversities and transition to psychosis (TTP). PsycINFO, PubMed and Embase databases were searched for studies reporting childhood adversities among UHR individuals. Only published articles were included. Risk of bias was assessed using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (von Elm et al., 2007) and the tool developed by Hoy et al. (2012). Seventeen case-control, cross-sectional and longitudinal studies were included. UHR individuals experienced significantly more severe trauma than controls, regardless of trauma subtype. UHR were 5.5, 2.5 and 3.1 times as likely to report emotional abuse, physical abuse and bullying victimisation, respectively. There was no association with parental separation. However, childhood trauma was not significantly associated with TTP (follow-up periods: 6 months to 15 years), suggesting that trauma alone may not be a sufficient risk factor. Sexual abuse was associated with TTP but this may have been driven by a single large study. Potential confounders and low rates of TTP among UHR are limitations of this review. This is the first meta-analysis that quantitatively summarises the associations between childhood adversities and TTP among UHR, and between specific abuse subtypes and TTP. Specific recommendations have been made to increase the quality of future research. PROSPERO registration no. CRD42017054884.

Impact of distress related to attenuated psychotic symptoms in individuals at ultra high risk of psychosis: Findings from the Longitudinal Youth at Risk Study.

AIM: Recent studies have highlighted that attenuated psychotic symptoms (APS) are an important source of distress in ultra high risk (UHR) individuals and that this distress is related to transition to psychosis (TTP). This study examined distress associated with APS in UHR individuals and investigated its association with TTP. METHODS: The Comprehensive Assessment of At-Risk Mental State (CAARMS) was used to identify 173 UHR individuals, who were included as participants in the study. Distress related to APS was self-reported. Functioning was assessed on the Social and Occupational Functioning Assessment Scale. Associations between each of the 4 APS subscales in the CAARMS-non-bizarre ideas (NBI), perceptual abnormalities (PA), unusual thought content (UTC) and disorganized speech (DS)-with its distress level were examined. RESULTS: Of the 173 UHR participants, 154 (89%) reported distress related to one or more APS. NBI was rated to be the most distressing out of the 4 APS by the highest number of participants (32.9%) compared to UTC (12.1%), PA (24.9%) and DS (2.9%). Mean distress scores were significantly associated with CAARMS composite scores (P < .001). However, there was no significant relationship between distress scores and functioning. Both mean distress scores (OR = 1.034, P = .029) and functioning (OR = 0.892, P = .022) were significant predictors of transition to psychosis at 1 year of follow-up. CONCLUSIONS: This study provides additional evidence to link subjective distress experienced by UHR individuals to APS and to their subsequent clinical outcomes and has significant clinical implications.

Longitudinal Cognitive Changes in Young Individuals at Ultrahigh Risk for Psychosis.

Importance: Cognitive deficits are a key feature of risk for psychosis. Longitudinal changes in cognitive architecture may be associated with the social and occupational functioning in young people. Objectives: To examine longitudinal profiles of cognition in individuals at ultrahigh risk (UHR) for psychosis, compared with healthy controls, and to investigate the association of cognition with functioning. Design, Setting, and Participants: This study has a multiple-group prospective design completed in 24 months and was conducted from January 1, 2009, to November 11, 2012, as part of the Longitudinal Youth at-Risk Study conducted in Singapore. Participants either were recruited from psychiatric outpatient clinics, educational institutions, and community mental health agencies or self-referred. Follow-up assessments were performed every 6 months for 2 years or until conversion to psychosis. Individuals with medical causes for psychosis, current illicit substance use, or color blindness were excluded. Data analysis was conducted from June 2014 to May 2018. Main Outcomes and Measures: Neuropsychological, perceptual, and social cognitive tasks; semi-structured interviews, and the Structured Clinical Interview for DSM-IV Axis I disorders were administered every 6 months. The UHR status of nonconverters, converters, remitters, and nonremitters was monitored. Cognitive domain scores and functioning were investigated longitudinally. Results: In total, 384 healthy controls and 173 UHR individuals between ages 14 and 29 years were evaluated prospectively. Of the 384 healthy controls, 153 (39.8%) were female and 231 (60.2%) were male with a mean (SD) age of 21.69 (3.26) years. Of the 173 individuals at UHR for psychosis, 56 (32.4%) were female and 117 (67.6%) were male with a mean (SD) age of 21.27 (3.52) years). After 24 months of follow-up, 383 healthy controls (99.7%) and 122 individuals at UHR for psychosis (70.5%) remained. Baseline cognitive deficits were associated with psychosis conversion later (mean odds ratio [OR], 1.66; combined 95% CI, 1.08-2.83; P = .04) and nonremission of UHR status (mean OR, 1.67; combined 95% CI, 1.09-2.95; P = .04). Five cognitive components-social cognition, attention, verbal fluency, general cognitive function, and perception-were obtained from principal components analysis. Longitudinal component structure change was observed in general cognitive function (maximum vertical deviation = 0.59; χ2 = 8.03; P = .01). Group-by-time interaction on general cognitive function (F = 12.23; η2 = 0.047; P < .001) and perception (F = 8.33; η2 = 0.032; P < .001) was present. Changes in attention (F = 5.65; η2 = 0.013; P = .02) and general cognitive function (F = 7.18; η2 = 0.014; P = .01) accounted for longitudinal changes in social and occupational functioning. Conclusions and Relevance: Individuals in this study who met the UHR criteria appeared to demonstrate cognitive deficits, and those whose UHR status remitted were seen to recover cognitively. Cognition appeared as poor in nonremitters and appeared to be associated with poor functional outcome. This study suggests that cognitive dimensions are sensitive to the identification of young individuals at risk for psychosis and to the longitudinal course of those at highest risk.

The Impact of Medication Anticholinergic Burden on Cognitive Performance in People With Schizophrenia.

BACKGROUND: Cognitive deficits are prevalent in people with schizophrenia and associated with functional impairments. In addition to antipsychotics, pharmacotherapy in schizophrenia often includes other psychotropics, and some of these agents possess anticholinergic properties, which may impair cognition. The objective of this study was to explore the association between medication anticholinergic burden and cognition in schizophrenia. METHODS: Seven hundred five individuals with schizophrenia completed a neuropsychological battery comprising Judgment of Line Orientation Test, Wechsler Abbreviated Scale of Intelligence Matrix Reasoning, Continuous Performance Test-Identical Pairs Version, and the Brief Assessment of Cognition in Schizophrenia. Cognitive g and 3 cognitive factor scores that include executive function, memory/fluency, and speed of processing/vigilance, which were derived from a previously published analysis, were entered as cognitive variables. Anticholinergic burden was computed using 2 anticholinergic scales: Anticholinergic Burden Scale and Anticholinergic Drug Scale. Duration and severity of illness, antipsychotic dose, smoking status, age, and sex were included as covariates. RESULTS: Anticholinergic burden was associated with poorer cognitive performance in cognitive g, all 3 cognitive domains and most cognitive tasks in multivariate analyses. The associations were statistically significant, but the effect sizes were small (for Anticholinergic Burden Scale, Cohen f = 0.008; for Anticholinergic Drug Scale, Cohen f = 0.017). CONCLUSIONS: Although our results showed a statistically significant association between medications with anticholinergic properties and cognition in people with schizophrenia, the impact is of doubtful or minimal clinical significance.

Establishing the Brief Assessment of Cognition - Short form.

The study aims to identify and validate a parsimonious subset of tests in the commonly used Brief Assessment of Cognition in Schizophrenia (BACS) that allows the evaluation of global cognitive ability. Several permutations of subtests from the BACS were examined to identify the best subset of tests to compose the short form measure. The Brief Assessment of Cognition-Short Form (BAC-SF) was evaluated for convergent validity in healthy and psychiatric samples (N = 3718). Verbal Memory, Digit Sequencing, and Symbol Coding subtests were found to best summarize the variance of composite scores in both Asian and US Norming samples (r = 0.91) indicating that BAC-SF is an appropriate approximation of cognitive deficits. Test re-test reliability of the BAC-SF was adequate (Intraclass Correlation Coefficient (ICC) = 0.73) and showed sufficient separation between healthy controls and schizophrenia (Average Predictive Accuracy = 79.9%; replication = 76.5%). Findings indicate that the BAC-SF an could be used as a cognitive screener for large-scale clinical and epidemiological studies. The short form does not replace the need for comprehensive neuropsychological batteries purposed for detailed neuropsychological and clinical investigation of cognitive function. Further replication of the construct might be necessary in other clinical populations.

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis.

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

Impact of psychiatric comorbidity in individuals at Ultra High Risk of psychosis - Findings from the Longitudinal Youth at Risk Study (LYRIKS).

Recent studies have reported a high prevalence of psychiatric comorbidities in Ultra High Risk (UHR) for psychosis populations. This study examined the prevalence of comorbidity and its impact on symptoms, functioning, cognition and transition to psychosis in the Longitudinal Youth at Risk Study (LYRIKS) sample. The Comprehensive Assessment of At-Risk Mental State (CAARMS) was used to identify UHR individuals and 163 participants were included in the study. Comorbid disorders were identified using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Participants were evaluated on the CAARMS, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Beck Anxiety Inventory, Global Assessment of Functioning and Brief Assessment of Cognition in Schizophrenia. Clinical, functioning and cognitive characteristics by lifetime and current comorbidity groups were compared using multivariate tests. Independent predictors of comorbidity were identified through logistic regression. Chi-squared tests were used to compare comorbidity rates between those who had developed psychosis at one year and those who had not. We found that 131 UHR participants (80.4%) had a lifetime comorbidity while 82 (50.3%) had a current comorbidity with depressive disorders being the most common. UHR individuals with comorbidity had more severe symptoms, higher distress and lower functioning with no differences in general cognition. Lower functioning was associated with current comorbidity. Eleven participants (6.7%) had developed psychosis after one year and there were no differences in the comorbidity rates between those who developed psychosis and those who did not. Psychiatric comorbidities in the UHR group are associated with adverse clinical outcomes and warrant closer attention.

Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.

RATIONALE: Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids. OBJECTIVE: The objective of this study is to conduct a randomized controlled trial of adjunctive pregnenolone in schizophrenia. METHODS: Following a placebo lead-in, 120 participants were randomized to pregnenolone or placebo for 8 weeks (Institute for Mental Health, Singapore). Primary endpoints were changes in MATRICS Consensus Cognitive Battery (MCCB) composite scores (cognitive symptoms), UCSD Performance-based Skills Assessment-Brief (UPSA-B) composite scores (functional capacity), and Scale for Assessment of Negative Symptoms (SANS) total scores (negative symptoms). A modified intent-to-treat analysis approach was utilized. RESULTS: No significant changes compared to placebo were demonstrated in composite MCCB scores. In contrast, participants randomized to pregnenolone (n = 56) demonstrated greater improvements in functional capacity (UPSA-B composite changes) compared to placebo (n = 55), p = 0.03. Pregnenolone was also superior to placebo in the communication subscale of the UPSA-B (p < 0.001). Serum pregnenolone changes post-treatment were correlated with UPSA-B composite score changes in females (r s = 0.497, p < 0.042, n = 17) but not in males. Mean total SANS scores were very low at baseline and did not improve further post-treatment. Pregnenolone was well-tolerated. CONCLUSIONS: Pregnenolone improved functional capacity in participants with schizophrenia, but did not improve cognitive symptoms over an 8-week treatment period. Neurosteroid changes correlated with functional improvements in female participants. Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia.

The continuous performance test, identical pairs: norms, reliability and performance in healthy controls and patients with schizophrenia in Singapore.

AIM: To provide normative values for the healthy ethnic Chinese Singaporean population and a large sample of patients with schizophrenia for the Continuous Performance Task-Identical Pairs (CPT-IP). Participants Data were collected on 1011 healthy ethnic Chinese and 654 patients diagnosed with schizophrenia, all between 21 and 55 years of age. METHODS: Data were stratified by age and gender. The effects of age, gender and education were explored in patients and controls. Performance indices were assessed in their ability to predict group inclusion. Controls' performance was compared with that reported in a US sample. RESULTS: Performance was affected by age, sex, and education, with youth, male sex and higher education providing a performance advantage. Patients' performance was lower than controls' by more than 1 standard deviation, with the 3-digit d' score most significantly discriminating between controls and patients. The effects of socio-demographic factors on performance were in line with those conducted in the US and previously reported in the literature. CONCLUSIONS: This is the largest norming study ever conducted on the CPT-IP. It will enable investigators and clinicians to select appropriate indices to assess severity of cognitive decline and/or evaluate cognitive remediation therapy outcomes after taking into account age, gender and education factors.

The Longitudinal Youth at Risk Study (LYRIKS)--an Asian UHR perspective.

Numerous studies have been published on the psychosis prodrome and have explored a wide array of its many aspects. However, the set of risk factors identified by these various efforts is not homogenous across studies. This could be due to unique population factors or relatively small sample sizes. Only few studies were conducted on Asian populations, whose socio-cultural characteristics differ - in some cases remarkably - from those in western populations. Singapore is a highly dense city-state in South-east Asia, with low rates of substance abuse. The Longitudinal Youth at Risk Study (LYRIKS) commenced in Singapore in 2008, designed to comprehensively assess a group of ultra high risk (UHR) individuals and identify clinical, social, neuropsychological and biological risk factors unique to the local population. 173 UHR individuals were recruited from this single-site study over 4 years. Here, we detail aspects of the study methodology and report on the baseline social and clinical characteristics of the sample population. 78% of the UHR sample suffered from a psychiatric disorder, with Major Depressive Disorder present in more than half of the sample. The mean Global Assessment of Functioning (GAF) score was 57.4, which indicated a moderate level of impairment. Although the recruited sample did not differ significantly by social and clinical characteristics when compared to previously published reports, the conversion rate to psychosis was 3.5% (n=6) at 6 months. Follow-up measures are currently underway to assess longitudinal incidence of psychosis and impact of risk factors on cognition, functioning and remission.

Brief assessment of cognition in schizophrenia: normative data in an English-speaking ethnic Chinese sample.

There is a dearth of non-Western normative data for neuropsychological batteries designed to measure cognitive deficits in schizophrenia. Here, we provide normative data for English-speaking ethnic Chinese on the widely used Brief Assessment of Cognition in Schizophrenia acquired from 595 healthy community participants between ages 14 and 55. Means and standard deviations of subtests and composite scores were stratified by age group and sex. We also explored linear regression approaches to generate continuous norms adjusted for age, sex, and education. Notable differences in subtest performances were found against a Western comparison sample. Normative data established in the current sample are essential for clinical and research purposes as it serves as a reference source of cognition for ethnic Chinese.

Applicability of the MATRICS Consensus Cognitive Battery in Singapore.

The MATRICS Consensus Cognitive Battery (MCCB) was developed to provide a reliable, valid, and standard battery for clinical trials on cognitive enhancers in schizophrenia. In this study we tested the applicability of the MCCB to Singapore's English speakers. Healthy ethnic Chinese, Malay, and Indian English speakers (N = 171) of both genders were recruited within three age groups and three levels of education to match as closely as possible the US norming sample, and were administered the MCCB. Descriptive data, T scores, age, gender, education, and ethnicity effects on performance were explored and compared with the US norming study. Age, education, and ethnicity affected the battery's composite scores, with young and highly educated participants generally outperforming the old, less-educated ones. Male participants outperformed their female counterparts in two out of seven cognitive domains. Although generally lower when compared to the US norming sample, Singaporean scores reflected the same relationship with age, education, and gender, with the exception of a substantially worse performance in the social cognition domain. Differences among the ethnic groups in Singapore-and the poorer performance measured in these groups with respect to the US sample-call for the necessity of an extended norming study in Singapore.

Formulation of the age-education index: measuring age and education effects in neuropsychological performance.

The complex interplay of education, age, and cognitive performance on various neuropsychological tests is examined in the current study. New education indices were formulated and further investigated to reveal how age and education variances work together to account for performance on neuropsychological tests. Participants were 830 English-speaking ethnic Chinese. Neuropsychological measures such as Verbal Memory, Digit Sequencing, Token Motor Task, Semantic Fluency, Symbol Coding, Tower of London, Judgment of Line Orientation, and Matrix Reasoning of the Wechsler Adult Intelligence Scale were administered. Education was measured by total years of education and adjusted years of education, as well as ratios of both measures with age. Age and education were associated with neuropsychological performance. Adjusted years of education was associated with fluency and higher cognitive processes, while the ratio between adjusted years of education and age was associated with tasks implicating working memory. Changes in education modalities implicated tasks requiring language abilities. Education and age represent key neurodevelopmental milestones. In light of our findings, special consideration should to be given when neuropsychological assessments are carried out in cross-cultural contexts and in societies where educational systems and pedagogy tend to be complex.

Increased ratio of 2nd to 4th digit (2D:4D) in schizophrenia.

Sex differences in the onset, epidemiology, clinical presentation and neuropathology of schizophrenia suggest that sexual dimorphism in brain development may be relevant to pathogenesis. Sex hormones, in particular testosterone, are considered to be crucial in brain development, but few investigations have examined the potential role of prenatal testosterone in schizophrenia. In this study, we examined a retrospective marker of prenatal testosterone release - 2D:4D finger length ratio (2D:4D), the relative length of 2nd to 4th digit, in 64 Asian patients with schizophrenia and 64 sex-matched controls. No significant difference in mean finger lengths was present, however 2D:4D ratio was significantly different between patients and controls. The effect was primarily seen in males consistent with a 'less masculinised' pattern and hypotheses suggesting that schizophrenia may be associated with an abnormality in prenatal circulating testosterone.

Neural basis of generation of conclusions in elementary deduction.

In everyday life, people untrained in formal logic draw simple deductive inferences from linguistic material (i.e., elementary propositional deductions). Presently, we have limited information on the brain areas implicated when such conclusions are drawn. We used event-related fMRI to identify these brain areas. A set of multiple and independent criteria was derived from the two main theories in the field of reasoning to maximize the reliability of detection of areas in which activity is specifically associated with deductive inferences. Two left lateralized clusters of areas, one in frontal cortex (Brodmann Area 44 and 6) and one in parietal lobe (BA 40), satisfied all criteria; activation was present at the moment of inference, it was shared by both conditional ("if-based") and disjunctive ("or-based") inferences but was greater for disjunctive clauses. Identification of the reasoning network was corroborated by the observation that activity in these areas was greater the longer the reasoning time. Taken together with results from preceding studies, our findings suggest possible theoretically relevant dissociations between elementary propositional deductions and other types of deductive reasoning.