Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register

Background

Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.

Validation of the Chinese Version of the Schizophrenia Cognition Rating Scale

Objective The Schizophrenia Cognition Rating Scale (SCoRS) is an interview-based assessment tool for evaluating the cognitive deficit and daily functioning of patients with schizophrenia. Methods Sixty-eight patients with schizophrenia and 68 age- and sex-matched healthy individuals were recruited to validate the Chinese version of SCoRS in this study. All participants underwent cognitive assessment using the SCoRS, which was verified by the Brief Assessment of Cognition in Schizophrenia (BACS), and the UCSD Performance-based Skills Assessment, Brief Version (UPSA-B). Patients with schizophrenia were additionally assessed using the Positive and Negative Syndrome Scale (PANSS). Results SCoRS ratings reported by patients (SCoRS-S), those reported by the interviewer (SCoRS-I), and SCoRS global scores (SCoRS-G) showed significant correlation with all subscales of the BACS and the UPSA-B. On receiver operating characteristic curve analysis, SCoRS-S, SCoRS-I, and SCoRS-G significantly differentiated patients with schizophrenia from healthy controls. Moreover, SCoRS-S and SCoRS-I ratings showed positive correlation with the negative symptoms and general symptoms of PANSS. Conclusion The Chinese version of SCoRS showed good discriminant, concurrent, and external validity, suggesting that it is a useful and convenient tool for assessment of cognitive function among Mandarin-speaking patients with schizophrenia in clinical practice.     

Neurodegenerative Aspects in Vulnerability to Schizophrenia Spectrum Disorders

The neurodegenerative and neurotoxic aspects of schizophrenia and/or psychosis involve genetic, epigenetic, and neurotoxic propensities that impinge upon both the symptom domains and the biomarkers of the disorder, involving cellular apoptosis/excitotoxicity, increased reactive oxygen species formation, viral and bacterial infections, anoxic birth injury, maternal starvation, drugs of abuse, particularly cannabis, metabolic accidents, and other chemical agents that disrupt normal brain development or the integrity of brain tissues. Evidence for premorbid and prodromal psychotic phases, aspects of neuroimaging, dopamine, and psychosis vulnerability, and perinatal aspects provide substance for neurodegenerative influences. Not least, the agencies of antipsychotic contribute to the destructive spiral that disrupts normal structure and function. The etiopathogenesis of psychosis is distinguished also by disruptions of the normal functioning of the neurotrophins, in particular brain-derived neurotrophic factor, dyskinesic aspects, immune system disturbances, and metabolic aspects. Whether detrimental to neurodevelopment or tissue-destructive, or an acceleration of neurotoxic pathways, the notion of neurodegeneration in the pathophysiology of schizophrenia spectrum and psychotic disorders continues to gather momentum.     

Endophenotypes in Schizophrenia for the Perinatal Period: Criteria for Validation

Endophenotypes are disease-associated phenotypes that are thought to reflect the neurobiological or other mechanisms that underlie the more overt symptoms of a psychiatric illness. Endophenotypes have been critical in understanding the genetics, neurobiology, and treatment of schizophrenia. Because psychiatric illnesses have multiple causes, including both genetic and nongenetic risk factors, an endophenotype linked to one of the mechanisms may be expressed more frequently than the disease itself. However, in schizophrenia research, endophenotypes have almost exclusively been studied in older adolescents or adults who have entered or passed through the age of risk for the disorder. Yet, schizophrenia is a neurodevelopmental disorder where prenatal development starts a cascade of brain changes across the lifespan. Endophenotypes have only minimally been utilized to explore the perinatal development of vulnerability. One major impediment to the development of perinatally-useful endophenotypes has been the established validity criteria. For example, the criterion that the endophenotype be more frequently present in those with disease than those without is difficult to demonstrate when there can be a decades-long period between endophenotype measurement and the age of greatest risk for onset of the disorder. This article proposes changes to the endophenotype validity criteria appropriate to perinatal research and reviews how application of these modified criteria helped identify a perinatally-usable phenotype of risk for schizophrenia, P50 sensory gating, which was then used to propose a novel perinatal primary prevention intervention.Key words: infant, endophenotype, schizophrenia, sensory gating, biological markers     

Neural Basis of Speech-Gesture Mismatch Detection in Schizophrenia Spectrum Disorders

Patients with schizophrenia spectrum disorders (SSD) exhibit an aberrant perception and comprehension of abstract speech-gesture combinations associated with dysfunctional activation of the left inferior frontal gyrus (IFG). Recently, a significant deficit of speech-gesture mismatch detection was identified in SSD, but the underlying neural mechanisms have not yet been examined. A novel mismatch-detection fMRI paradigm was implemented manipulating speech-gesture abstractness (abstract/concrete) and relatedness (related/unrelated). During fMRI data acquisition, 42 SSD patients (schizophrenia, schizoaffective disorder, or other non-organic psychotic disorder [ICD-10: F20, F25, F28; DSM-IV: 295.X]) and 36 healthy controls were presented with short video clips of an actor reciting abstract or concrete sentences accompanied by either a semantically related or unrelated gesture. Participants indicated via button press whether they perceived each gesture as matching the speech content or not. Speech-gesture mismatch detection performance was significantly impaired in patients compared to controls. fMRI data analysis revealed that patients showed lower activation in bilateral frontal areas, including the IFG for all abstract > concrete speech-gesture pairs. In addition, they exhibited reduced engagement of the right supplementary motor area (SMA) and bilateral anterior cingulate cortices (ACC) for unrelated > related stimuli. We provide first evidence that impaired speech-gesture mismatch detection in SSD could be the result of dysfunctional activation of the SMA and ACC. Failure to activate the left IFG disrupts the integration of abstract speech-gesture combinations in particular. Future investigations should focus on brain stimulation of the SMA, ACC, and the IFG to improve communication and social functioning in SSD.     

Self-disorders and the Schizophrenia Spectrum: A Study of 100 First Hospital Admissions

Introduction: Self-disorders (SD) have been described as a core feature of schizophrenia both in classical and recent psychopathological literature. However, the specificity of SD for the schizophrenia spectrum disorders has never been demonstrated in a diagnostically heterogeneous sample, nor has the concurrent validity of SD been examined. Aim: (1) To examine the specificity of Examination of Anomalous Self-Experiences (EASE) measured SD to the schizophrenia spectrum disorder in first contact inpatients, (2) to explore the internal consistency and factorial structure of the EASE, (3) to assess the concurrent validity of SD by exploring correlations between SD and the canonical psychopathological dimensions of schizophrenia, (4) to explore relations of SD to intelligence, sociodemographic, and extrinsic illness characteristics. Methods: A total of 100 consecutive first admission patients underwent a comprehensive psychopathological examination and an assessment of SD with the EASE scale. The diagnostic distribution of the EASE scores was tested with ANOVA, whereas the relations between the EASE scores and other symptomatic dimensions of schizophrenia were tested with Spearman’s rho. A potential factorial structure and the internal consistency of the EASE scale were also examined. Results: SD aggregated significantly in the schizophrenia spectrum disorders, with no differences between schizophrenia and schizotypal disorders. EASE scores correlated moderately with canonical psychopathological dimensions of schizophrenia. Factor analysis of the EASE disclosed only one factor and the internal consistency of the EASE was excellent. Conclusions: SD aggregate selectively in the schizophrenia spectrum disorders, with similar levels in schizophrenia and schizotypy. The study lends validity to the view of SD as an experiential vulnerability phenotype of the schizophrenia spectrum disorders.     

Looking at the Schizophrenia Spectrum Through the Prism of Self-disorders: An Empirical Study

Nonpsychotic anomalies of subjective experience were emphasized in both classic literature and phenomenological psychiatry as essential clinical features of schizophrenia. However, only in recent years, their topicality with respect to the construct validity of the concept of the schizophrenia spectrum has been explicitly acknowledged, mainly as a consequence of the increasing focus on early detection and prevention of psychosis. The current study tested the hypothesis of a specific aggregation of self-disorders (SDs, various anomalies of self-awareness) in schizophrenia-spectrum conditions, comparing different diagnostic groups; 305 subjects, previously assessed in the Copenhagen Schizophrenia Linkage Study, were grouped into 4 experimental samples, according to their Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) main diagnosis: schizophrenia, (n = 29), schizotypal personality disorder (n = 61), other mental illness not belonging to the schizophrenia spectrum (n = 112), and no mental illness (n = 103). The effect of diagnostic grouping on the level of SDs was explored via general linear model and logistic regression. The diagnosis of schizophrenia and schizotypy predicted higher levels of SDs, and SDs scores were significantly different between spectrum and nonspectrum samples; the likelihood of experiencing SDs increased as well with the diagnostic severity. The findings support the assumption that SDs are a discriminant psychopathological feature of the schizophrenia spectrum and suggest their incorporation to strengthen its construct validity, with potential benefit for both early detection and pathogenetic research.     

Defining Psychosis: The Evolution of DSM-5 Schizophrenia Spectrum Disorders

Bereavement is a common experience in adults aged 60 and older. Loss of a loved one usually leads to acute grief characterized by yearning and longing, decreased interest in ongoing activities, and frequent thoughts of the deceased. For most, acute grief naturally evolves into a state of integrated grief, where the bereaved is able to reengage with everyday activities and find interest or pleasure. About 7 % of bereaved older adults, however, will develop the mental health condition of Complicated Grief (CG). In CG, the movement from acute to integrated grief is derailed, and grief symptoms remain severe and impairing. This article reviews recent publications on the diagnosis of CG, risk factors for the condition and evidenced-based treatments for CG. Greater attention to CG detection and treatment in older adults is needed.     

Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders

First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting “pseudospecificity.”Key words: cognition, general cognitive function, psychosis, planning, aripiprazole, risperidone     

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum

Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.     

Validation of the Autism Spectrum Screening Questionnaire in a Total Population Sample

There is a lack of instruments validated for screening of autism spectrum disorders (ASD) in general populations and primary care settings. The Autism Spectrum Screening Questionnaire (ASSQ) has previously been shown to have good screening properties in clinical settings. We used the ASSQ to screen a total population of 7–9 year-olds (N = 9430) for ASD in the Bergen Child Study. Parents and teachers filled in the ASSQ, and high-scorers were invited for clinical assessment, along with a large group of screen negative children. We found that the ASSQ was well suited as a general population screen. Combining parent and teacher ASSQ and using cut-off score of ≥17 provided the most efficient screen with sensitivity of 0.91 and specificity of 0.86.