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Preview: Schizophrenia Bulletin - current issue

Schizophrenia Bulletin - current issue



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Cover

2016-10-04T06:17:00-07:00




Editorial_Board

2016-10-04T06:17:00-07:00




Subscriptions

2016-10-04T06:17:00-07:00




Contents_Page

2016-10-04T06:17:00-07:00







The Importance of Talk Therapy

2016-10-04T06:17:00-07:00







The Journey

2016-10-04T06:17:00-07:00




Somatic Comorbidity in Schizophrenia: Some Possible Biological Mechanisms Across the Life Span

2016-10-04T06:17:00-07:00

Schizophrenia is associated with decreased life expectancy (15–25 y) compared to the general population, with comorbid somatic diseases and in particular cardiovascular diseases being a major cause. Life style and medication probably account for much of the increased mortality risk due to somatic diseases in schizophrenia, but the evidence implicating biological pathways potentially affecting both body and brain is increasing. This includes overlapping genes between schizophrenia and somatic diseases, prenatal risk factors such as hypoxia and infections, and increased cardiovascular disease risk in drug-naïve patients at illness onset. Although environmental bias increases throughout the disease course, there are also some studies on chronic schizophrenia and postmortem brain samples that warrant further attention. In the following, we will attempt to move beyond environmental impact and explore some of the shared pathophysiological mechanisms potentially underlying both schizophrenia and somatic diseases.




Wendan Decoction for Schizophrenia

2016-10-04T06:17:00-07:00







Gesture Performance in Schizophrenia Predicts Functional Outcome After 6 Months

2016-10-04T06:17:00-07:00

The functional outcome of schizophrenia is heterogeneous and markers of the course are missing. Functional outcome is associated with social cognition and negative symptoms. Gesture performance and nonverbal social perception are critically impaired in schizophrenia. Here, we tested whether gesture performance or nonverbal social perception could predict functional outcome and the ability to adequately perform relevant skills of everyday function (functional capacity) after 6 months. In a naturalistic longitudinal study, 28 patients with schizophrenia completed tests of nonverbal communication at baseline and follow-up. In addition, functional outcome, social and occupational functioning, as well as functional capacity at follow-up were assessed. Gesture performance and nonverbal social perception at baseline predicted negative symptoms, functional outcome, and functional capacity at 6-month follow-up. Gesture performance predicted functional outcome beyond the baseline measure of functioning. Patients with gesture deficits at baseline had stable negative symptoms and experienced a decline in social functioning. While in patients without gesture deficits, negative symptom severity decreased and social functioning remained stable. Thus, a simple test of hand gesture performance at baseline may indicate favorable outcomes in short-term follow-up. The results further support the importance of nonverbal communication skills in subjects with schizophrenia.




Protein Interaction Networks Link Schizophrenia Risk Loci to Synaptic Function

2016-10-04T06:17:00-07:00

Schizophrenia is a severe and highly heritable psychiatric disorder affecting approximately 1% of the population. Genome-wide association studies have identified 108 independent genetic loci with genome-wide significance but their functional importance has yet to be elucidated. Here, we develop a novel strategy based on network analysis of protein–protein interactions (PPI) to infer biological function associated with variants most strongly linked to illness risk. We show that the schizophrenia loci are strongly linked to synaptic transmission (P FWE < .001) and ion transmembrane transport (P FWE = .03), but not to ontological categories previously found to be shared across psychiatric illnesses. We demonstrate that brain expression of risk-linked genes within the identified processes is strongly modulated during birth and identify a set of synaptic genes consistently changed across multiple brain regions of adult schizophrenia patients. These results suggest synaptic function as a developmentally determined schizophrenia process supported by the illness’s most associated genetic variants and their PPI networks. The implicated genes may be valuable targets for mechanistic experiments and future drug development approaches.




Defeatist Performance Beliefs, Negative Symptoms, and Functional Outcome in Schizophrenia: A Meta-analytic Review

2016-10-04T06:17:00-07:00

Negative symptoms are a strong predictor of poor functional outcome in people with schizophrenia. Unfortunately there are few effective interventions for either negative symptoms or functional outcome, despite the identification of potential mechanisms. Recent research, however, has elucidated a new potential mechanism for negative symptoms and poor functional outcome: defeatist performance beliefs (DPB), or negative thoughts about one’s ability to successfully perform goal-directed behavior that can prevent behavior initiation and engagement. We conducted 2 meta-analyses examining the relationship between DPB and both negative symptoms (n = 10 studies) and functional outcome (n = 8 studies) in people with schizophrenia. We found a small effect size for the relationship between DPB and negative symptoms, regardless of how negative symptoms were measured. We also found a small effect size for the relationship between DPB and functional outcome, which was significantly moderated by the method of assessing DPB and moderated by the sex composition of the study at a trend level. These findings highlight the potential of targeting DPB in psychosocial interventions for both negative symptoms and functional outcome.




Stress Sensitivity and Psychotic Experiences in 39 Low- and Middle-Income Countries

2016-10-04T06:17:00-07:00

Stress has a central role in most theories of psychosis etiology, but the relation between stress and psychosis has rarely been examined in large population-level data sets, particularly in low- and middle-income countries. We used data from 39 countries in the World Health Survey (n = 176 934) to test the hypothesis that stress sensitivity would be associated with psychotic experiences, using logistic regression analyses. Respondents in low-income countries reported higher stress sensitivity (P < .001) and prevalence of psychotic experiences (P < .001), compared to individuals in middle-income countries. Greater stress sensitivity was associated with increased odds for psychotic experiences, even when adjusted for co-occurring anxiety and depressive symptoms: adjusted odds ratio (95% CI) = 1.17 (1.15–1.19) per unit increase in stress sensitivity (range 2–10). This association was consistent and significant across nearly every country studied, and translated into a difference in psychotic experience prevalence ranging from 6.4% among those with the lowest levels of stress sensitivity up to 22.2% among those with the highest levels. These findings highlight the generalizability of the association between psychosis and stress sensitivity in the largest and most globally representative community-level sample to date, and support the targeting of stress sensitivity as a potential component of individual- and population-level interventions for psychosis.




Environmental Social Stress, Paranoia and Psychosis Liability: A Virtual Reality Study

2016-10-04T06:17:00-07:00

The impact of social environments on mental states is difficult to assess, limiting the understanding of which aspects of the social environment contribute to the onset of psychotic symptoms and how individual characteristics moderate this outcome. This study aimed to test sensitivity to environmental social stress as a mechanism of psychosis using Virtual Reality (VR) experiments. Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra high risk for psychosis, 42 siblings of patients with psychosis, and 53 controls walked 5 times in a virtual bar with different levels of environmental social stress. Virtual social stressors were population density, ethnic density and hostility. Paranoia about virtual humans and subjective distress in response to virtual social stress exposures were measured with State Social Paranoia Scale (SSPS) and self-rated momentary subjective distress (SUD), respectively. Pre-existing (subclinical) symptoms were assessed with the Community Assessment of Psychic Experiences (CAPE), Green Paranoid Thoughts Scale (GPTS) and the Social Interaction Anxiety Scale (SIAS). Paranoia and subjective distress increased with degree of social stress in the environment. Psychosis liability and pre-existing symptoms, in particular negative affect, positively impacted the level of paranoia and distress in response to social stress. These results provide experimental evidence that heightened sensitivity to environmental social stress may play an important role in the onset and course of psychosis.




Why Are Children in Urban Neighborhoods at Increased Risk for Psychotic Symptoms? Findings From a UK Longitudinal Cohort Study

2016-10-04T06:17:00-07:00

Background:

Urban upbringing is associated with a 2-fold adulthood psychosis risk, and this association replicates for childhood psychotic symptoms. No study has investigated whether specific features of urban neighborhoods increase children’s risk for psychotic symptoms, despite these early psychotic phenomena elevating risk for schizophrenia and other psychiatric disorders in adulthood.

Methods:

Analyses were conducted on over 2000 children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of UK-born twins. Neighborhood-level characteristics were assessed for each family via: a geodemographic discriminator indexing neighborhood-level deprivation, postal surveys of over 5000 residents living alongside the children, and in-home interviews with the children’s mothers. Children were interviewed about psychotic symptoms at age 12. Analyses were adjusted for important family-level confounders including socioeconomic status (SES), psychiatric history, and maternal psychosis.

Results:

Urban residency at age-5 (OR = 1.80, 95% CI = 1.16–2.77) and age-12 (OR = 1.76, 95% CI = 1.15–2.69) were both significantly associated with childhood psychotic symptoms, but not with age-12 anxiety, depression, or antisocial behavior. The association was not attributable to family SES, family psychiatric history, or maternal psychosis, each implicated in childhood mental health. Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders.

Conclusions:

Low social cohesion and crime victimization in the neighborhood partly explain why children in cities have an elevated risk of developing psychotic symptoms. Greater understanding of the mechanisms leading from neighborhood-level exposures to psychotic symptoms could help target interventions for emerging childhood psychotic symptoms.




A Psychometric Comparison of the Clinical Assessment Interview for Negative Symptoms and the Brief Negative Symptom Scale

2016-10-04T06:17:00-07:00

In 2005, the National Institute of Mental Health held a consensus development conference on negative symptoms of schizophrenia. Among the important conclusions of this meeting were that there are at least 5 commonly accepted domains of negative symptoms (blunted affect, alogia, avolition, anhedonia, asociality) and that new rating scales were needed to adequately assess these constructs. Two next-generation negative symptom scales resulted from this meeting: the Brief Negative Symptom Scale (BNSS) and Clinical Assessment Interview for Negative Symptoms (CAINS). Both measures are becoming widely used and studies have demonstrated good psychometric properties for each scale. The current study provides the first direct psychometric comparison of these scales. Participants included 65 outpatients diagnosed with schizophrenia or schizoaffective disorder who completed clinical interviews, questionnaires, and neuropsychological testing. Separate raters completed the BNSS and CAINS within the same week. Results indicated that both measures had good internal consistency, convergent validity, and discriminant validity. High correspondence was observed between CAINS and BNSS blunted affect and alogia items. Moderate convergence occurred for avolition and asociality items, and low convergence was seen among anhedonia items. Findings suggest that both scales have good psychometric properties, but that there are important distinctions among the items related to motivation and pleasure.




Diagnostic Stability of ICD/DSM First Episode Psychosis Diagnoses: Meta-analysis

2016-10-04T06:17:00-07:00

Background:

Validity of current International Classification of Disease/Diagnostic and Statistical Manual of Mental Disorders (ICD/DSM) first episode psychosis diagnoses is essential in clinical practice, research, training and public health.

Method:

We provide a meta-analytical estimate of prospective diagnostic stability and instability in ICD-10 or DSM-IV first episode diagnoses of functional psychoses. Independent extraction by multiple observers. Random effect meta-analysis conducted with the "metaprop," "metaninf," "metafunnel," "metabias," and "metareg" packages of STATA13.1. Moderators were tested with meta-regression analyses. Heterogeneity was assessed with the I 2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and Egger’s test.

Findings:

42 studies and 45 samples were included, for a total of 14 484 first episode patients and an average follow-up of 4.5 years. Prospective diagnostic stability ranked: schizophrenia 0.90 (95% CI 0.85–0.95), affective spectrum psychoses 0.84 (95% CI 0.79–0.89), schizoaffective disorder 0.72 (95% CI 0.61–0.73), substance-induced psychotic disorder 0.66 (95% CI 0.51–0.81), delusional disorder 0.59 (95% CI 0.47–0.71), acute and transient psychotic disorder/brief psychotic disorder 0.56 (95% CI 0.62–0.60), psychosis not otherwise specified 0.36 (95% CI 0.27–0.45, schizophreniform disorder 0.29 (95% CI 0.22–0.38). Diagnostic stability within schizophrenia spectrum psychoses was 0.93 (95% CI 0.89–0.97); changes to affective spectrum psychoses were 0.05 (95% CI 0.01–0.08). About 0.10 (95% CI 0.05–0.15) of affective spectrum psychoses changed to schizophrenia spectrum psychosis. Across the other psychotic diagnoses there was high diagnostic instability, mostly to schizophrenia.

Interpretation:

There is meta-analytical evidence for high prospective diagnostic stability in schizophrenia spectrum and affective spectrum psychoses, with no significant ICD/DSM differences. These results may inform the development of new treatment guidelines for early psychosis and impact drug licensing from regulatory agencies.




Cancer Immune Equilibrium and Schizophrenia Have Similar Interferon-{gamma}, Tumor Necrosis Factor-{alpha}, and Interleukin Expression: A Tumor Model of Schizophrenia

2016-10-04T06:17:00-07:00

For at least a century, a debate has continued as to whether cancer risk is reduced in schizophrenia. Genetic studies have also suggested the 2 conditions may share protein transcriptional pathways. The author predicted that if the pathophysiology of schizophrenia confers protection from cancer, then the immunology of schizophrenia should reflect a state of tumor suppression, ie, the opposite of tumor escape. To examine this possibility, the author performed a literature search for measurements of cytokines in drug-naïve first episode subjects with schizophrenia for comparison with cytokine expression in tumor escape vs tumor suppression. The comparison showed that instead of either tumor suppression or escape, schizophrenia appears to be in a state of tumor equilibrium. Based on this finding, the author hypothesized that the clinical presentation of schizophrenia may involve cell transformation similar to an early stage of cancer initiation or an attenuated tumorigenesis. While this condition could reflect the presence of an actual tumor such as an ovarian teratoma causing anti-NMDA receptor encephalitis, it would only explain a small percentage of cases. To find a more likely tumor model, the author then compared the cytokine profile of schizophrenia to individual cancers and found the best match was melanoma. To demonstrate the viability of the theory, the author compared the hallmarks, emerging hallmarks, and enabling characteristics of melanoma to schizophrenia and found that many findings in schizophrenia are understood if schizophrenia is a condition of attenuated tumorigenesis.




Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis

2016-10-04T06:17:00-07:00

Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2–20, n = 81–2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05–.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges’ g’s = 0.30–0.80, ORs = 1.47–1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1–2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets.




Mortality Risk Associated With Long-acting Injectable Antipsychotics: A Systematic Review and Meta-analyses of Randomized Controlled Trials

2016-10-04T06:17:00-07:00

Long-acting injectable (LAI) antipsychotics (LAI-APs) have several advantages over oral medications, but deaths reported in Japan during the early post-marketing phase vigilance period have raised safety concerns. We conducted a series of meta-analyses to assess whether LAI-APs affect the mortality of patients with schizophrenia. Three categorical meta-analyses of randomized controlled trials (RCTs) were performed to compare all-cause death (primary outcome) and death due to suicide: individual and pooled LAI-APs vs placebo, individual and pooled LAI-APs vs oral antipsychotics (OAPs), and head-to-head comparisons of LAI-APs. The risk ratios (RRs) and 95% CIs were calculated. We identified 52 RCTs (53 comparisons; total participants = 17 416, LAI-APs = 11 360, OAP = 3910, and placebo = 2146; mean study duration [wk]: LAI-APs vs placebo = 28.9, LAI-APs vs OAPs = 64.5). Neither pooled nor individual LAI-APs (aripiprazole, fluphenazine, olanzapine, paliperidone, and risperidone) differed from the placebo regarding the incidences of all-cause death (pooled LAI-APs: RR = 0.64, P = .37) and death due to suicide (pooled LAI-APs: RR = 0.98, P = .98). However, in a subgroup meta-analysis of only short-duration RCTs (≤13wk), pooled LAI-APs exhibited a trend toward lower incidence of all-cause death than placebo (RR = 0.29, P = .08). Pooled LAI-APs (aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol) did not differ from pooled OAPs regarding all-cause death (pooled LAI-APs: RR = 0.71, P = .30) and death due to suicide (pooled LAI-APs: RR = 0.94, P = .91). Individual LAI-APs and OAPs were associated with similar risks of death. Data for head-to-head comparisons of individual LAI-APs were insufficient. In conclusion, there was no significant difference between LAI-APs and placebo or OAPs regarding all-cause death and death due to suicide.




Globally Efficient Brain Organization and Treatment Response in Psychosis: A Connectomic Study of Gyrification

2016-10-04T06:17:00-07:00

Background:

Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis.

Methods:

Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding.

Results:

Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders.

Conclusions:

These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis.




A Randomized Controlled Trial of Clinician-Supported Problem-Solving Bibliotherapy for Family Caregivers of People With First-Episode Psychosis

2016-10-04T06:17:00-07:00

Family interventions for first-episode psychosis (FEP) are an integral component of treatment, with positive effects mainly on patients’ mental state and relapse rate. However, comparatively little attention has been paid to the effects of family interventions on caregivers’ stress coping and well-being, especially in non-Western countries. We aimed to test the effects of a 5-month clinician-supported problem-solving bibliotherapy (CSPSB) for Chinese family caregivers of people with FEP in improving family burden and carers’ problem-solving and caregiving experience, and in reducing psychotic symptoms and duration of re-hospitalizations, compared with those only received usual outpatient family support (UOFS). A randomized controlled trial was conducted across 2 early psychosis clinics in Hong Kong, where there might be inadequate usual family support services for FEP patients. A total of 116 caregivers were randomly selected, and after baseline measurement, randomly assigned to the CSPSB or UOFS. They were also assessed at 1-week and 6- and 12-month post-intervention. Intention-to-treat analyses were applied and indicated that the CSPSB group reported significantly greater improvements in family burden and caregiving experience, and reductions in severity of psychotic symptoms and duration of re-hospitalizations, than the UOFS group at 6- and 12-month follow-up. CSPSB produces moderate long-term benefits to caregivers and FEP patients, and is a low-cost adjunct to UOFS.




Motivational Context Modulates Prediction Error Response in Schizophrenia

2016-10-04T06:17:00-07:00

Background:

Recent findings demonstrate that patients with schizophrenia are worse at learning to predict rewards than losses, suggesting that motivational context modulates learning in this disease. However, these findings derive from studies in patients treated with antipsychotic medications, D2 receptor antagonists that may interfere with the neural systems that underlie motivation and learning. Thus, it remains unknown how motivational context affects learning in schizophrenia, separate from the effects of medication.

Methods:

To examine the impact of motivational context on learning in schizophrenia, we tested 16 unmedicated patients with schizophrenia and 23 matched controls on a probabilistic learning task while they underwent functional magnetic resonance imaging (fMRI) under 2 conditions: one in which they pursued rewards, and one in which they avoided losses. Computational models were used to derive trial-by-trial prediction error responses to feedback.

Results:

Patients performed worse than controls on the learning task overall, but there were no behavioral effects of condition. FMRI revealed an attenuated prediction error response in patients in the medial prefrontal cortex, striatum, and medial temporal lobe when learning to predict rewards, but not when learning to avoid losses.

Conclusions:

Patients with schizophrenia showed differences in learning-related brain activity when learning to predict rewards, but not when learning to avoid losses. Together with prior work, these results suggest that motivational deficits related to learning in schizophrenia are characteristic of the disease and not solely a result of antipsychotic treatment.




Mild Reinforcement Learning Deficits in Patients With First-Episode Psychosis

2016-10-04T06:17:00-07:00

Numerous studies have identified reinforcement learning (RL) deficits in schizophrenia. Most have focused on chronic patients with longstanding antipsychotic treatment, however, and studies of RL in early-illness patients have produced mixed results, particularly regarding gradual/procedural learning. No study has directly contrasted both rapid and gradual RL in first-episode psychosis (FEP) samples. We examined probabilistic RL in 34 FEP patients and 36 controls, using Go/NoGo (GNG) and Gain vs Loss-Avoidance (GLA) paradigms. Our results were mixed, with FEP patients exhibiting greater impairment in the ability to use positive, as opposed to negative, feedback to drive rapid RL on the GLA, but not the GNG. By contrast, patients and controls showed similar improvement across the acquisition. Finally, we found no significant between-group differences in the postacquisition expression of value-based preference in both tasks. Negative symptoms were modestly associated with RL measures, while the overall bias to engage in Go-responding correlated significantly with psychosis severity in FEP patients, consistent with striatal hyperdopaminergia. Taken together, FEP patients demonstrated more circumscribed RL impairments than previous studies have documented in chronic samples, possibly reflecting differential symptom profiles between first-episode and chronic samples. Our finding of relatively preserved gradual/procedural RL, in briefly medicated FEP patients, might suggest spared or restored basal ganglia function. Our findings of preserved abilities to use representations of expected value to guide decision making, and our mixed results regarding rapid RL, may reflect a lesser degree of prefrontal cortical functional impairment in FEP than in chronic samples. Further longitudinal research, in larger samples, is required.




Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naïve Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population

2016-10-04T06:17:00-07:00

Background:

Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied.

Aims:

To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls.

Method:

Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound.

Results:

Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls.

Conclusions:

PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls.




Cognitive Function in Individuals With Psychosis: Moderation by Adolescent Cannabis Use

2016-10-04T06:17:00-07:00

Prior cannabis use, compared to nonuse, is reported to be associated with less cognitive impairment in schizophrenia. The age of cannabis use and the persistent influence of cannabis use on cognitive function has not been examined across the psychosis dimension. Ninety-seven volunteers with psychosis (schizophrenia, schizoaffective, or bipolar psychosis) and 64 controls were recruited at the Dallas site of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Cannabis use history obtained in a semi-structured manner was used to categorize subjects into nonusers, adolescent-onset users, and late-onset users. The a priori hypothesis tested was that individuals with psychosis and a history of adolescent cannabis use (ACU) would have better global neuropsychological performance, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) battery, compared to those with psychosis and no cannabis use history. BACS Composite scores were significantly higher in individuals with psychosis with ACU compared to individuals with psychosis and no prior cannabis use. In subgroup analyses, ACU influenced global cognition in the schizophrenia/schizoaffective (SCZ) subgroup but not the bipolar psychosis subgroup. Exploratory analyses within the SCZ group, suggest that ACU was associated with better performance in specific domains compared to non-ACU groups. There are distinct associations between age of cannabis use and neuropsychological function across psychotic illnesses. Specifically, ACU is associated with better cognitive function in SCZ but not bipolar psychosis. This age-dependent and diagnosis-specific influence of cannabis may need to be factored into the design of future cognitive studies in SCZ.




A Meta-analytic Review of Auditory Event-Related Potential Components as Endophenotypes for Schizophrenia: Perspectives From First-Degree Relatives

2016-10-04T06:17:00-07:00

Introduction:

As endophenotypes bridge the gap between genetics and phenotypic disease expression, identifying reliable markers is important for fostering understanding of pathophysiology. The present aim was to conduct current meta-analyses of 3 key auditory event-related potential (ERP) components that have been held as potential endophenotypes for schizophrenia: P50, P300 amplitude and latency, and mismatch negativity (MMN), reflective of sensory gating, attention and classification speed, and perceptual discrimination ability, respectively. In order to assess endophenotype viability, these components were examined in unaffected relatives of patients with schizophrenia and healthy controls.

Methods:

Effect sizes (ES) were examined between relatives and controls for P50 suppression (10 studies, n = 360 relatives, 473 controls), P300 amplitude (20 studies, n = 868 relatives, 961 controls), P300 latency (17 studies, n = 674 relatives, 792 controls), and MMN (11 studies, n = 377 relatives, 552 controls).

Results:

Reliable differences in P50 suppression (ES = 0.86, P < .001), P300 amplitude (ES = –0.52, P < .001), and P300 latency (ES = 0.44, P < .05) were found between unaffected relatives and controls. A trend was found between relatives and controls for MMN (ES = 0.21, P = 0.06), and the use of extraneous channels was found to be a significant moderator (P = 0.01). When MMN was analyzed using frontocentral channel Fz, a significant difference was found (ES = 0.26, P < 0.01).

Discussion:

The results indicate that P50 suppression, P300 amplitude and P300 latency, and MMN may serve as viable endophenotypes for schizophrenia.




Predictive Motor Timing and the Cerebellar Vermis in Schizophrenia: An fMRI Study

2016-10-04T06:17:00-07:00

Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia.