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Preview: Schizophrenia Bulletin - current issue

Schizophrenia Bulletin Current Issue





Published: Sat, 21 Oct 2017 00:00:00 GMT

Last Build Date: Sat, 21 Oct 2017 02:47:13 GMT

 



Contents_Page

2017-10-21




Cover

2017-10-21




Editorial_Board

2017-10-21




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2017-10-21




Developmental Differences Between Schizophrenia and Bipolar Disorder

2017-10-14

Abstract
Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein review studies with a focus on premorbid (adjustment and functionality) and early developmental milestones that include both SZ and BD patients. A search was performed in the PubMed electronic database, retrieving 619 abstracts; 30 were ultimately included in this systematic review. Eight prospective cohorts, 15 retrospective studies, and 7 studies based on national registries. Psychomotor developmental deviations and general adjustment problems characterize the childhood of subjects later diagnosed with SZ or BD; they are more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset, and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear risk trend for SZ and a U-shaped trend for BD. Social isolation and visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive developmental disorders increase the risk for both SZ and BD, more so in cases with normal intelligence. The predictive risk of each isolated developmental marker is low, but a significant percentage of subjects with SZ and a minority of adults with BD showed signs of premorbid abnormalities in childhood. The great limitation is still the lack of studies comparing SZ and BD that include psychotic and nonpsychotic bipolar cases separately. There are many cases, even in childhood/adolescent SZ, where no premorbid anomalies are found, and immunological disorders or other etiologies should be searched for. At least in cases with clear neurodevelopmental markers, rare genetic variants should be investigated.



Future of Days Past: Neurodevelopment and Schizophrenia

2017-10-11

Abstract
Since a proposal in 1986 that schizophrenia involved early neurodevelopmental deviations beginning in intrauterine life that showed varying expressivity as relevant neural systems matured, our understanding of the developmental components of the pathogenesis of schizophrenia has substantially evolved. This commentary highlights recent genetic and epigenetic evidence that prenatal development is a critical period for the expression of schizophrenia risk. Studies of gene expression have been fairly consistent in showing that genes implicated in schizophrenia show relatively greater expression during fetal than postnatal life. Consistent molecular evidence of early environmental perturbations contributing to risk has emerged from studies of epigenetic marks in the brain genome as potential environmental footprints and these also highlight the prenatal period. Analyses of gene expression in placenta dramatically identify the intrauterine environment as a direct point of impact of a component of schizophrenia genetic risk. Together, the enrichment of transcriptional and epigenetic associations with schizophrenia during fetal life suggest that both genetic and environmental risk for schizophrenia have a particular molecular impact on early development, possibly because of genetic biases in environmental sensitivity.



Studying Developmental Psychopathology Related to Psychotic Disorders—Challenges and Paradigms in Human Studies

2017-10-10

The neurodevelopmental nature of schizophrenia and associated disorders is a central component of most modern concepts of the pathophysiology of these illnesses1,2 and is the focus of this issue3–6 While psychosis typically manifests around adolescence and the current diagnostic criteria then usually only allow a diagnosis around this time, strong evidence shows that manifestation is preceded by prodromal high-risk states, often with an attenuated form of psychopathology then seen in full blown illness, which farther back in time are preceded by less specific prodromal states characterized by social withdrawal, depression, and impaired level of functioning,7 including motor function.8 It is also clear that people who later manifest with schizophrenia already show subtle broad abnormalities in social function and cognition as far back as the first year of life. Studying this broad array of abnormalities across the early life span is challenging, but also critically important because it is a prerequisite to understand disease mechanisms in their interaction with brain maturation and psychosocial development, an enterprise that far beyond the immediate scientific interest carries the hope of yielding markers useful for stratification and precision medicine in psychiatry.9 Arango et al.10 review this field in their lead article in this issue.



Animal Models of Developmental Neuropathology in Schizophrenia

2017-09-16

Schizophrenia is a heterogenous psychotic disorder of undetermined etiologies for which available treatments are limited. Recent advances in appreciating both genetic and environmental influences on risk for this disorder have raised tremendous hope for identifying actionable risk factors and correctable neuropathological processes. However, the development of preventive or therapeutic interventions requires model systems through which molecular hypotheses can be tested. This commentary is not intended as a broad consideration of the use of animal models in psychosis research, several of which have been published recently.1–3 Rather, we focus on a few examples that highlight how recent genetic and environmental advances, together with advances such as stem cell derived neural cells and the study of circuitry function in vivo, are shaping the use of animal models.



Developmental Interactive Framework for Psychotic Disorders

2017-09-14

Our training in psychiatry during the early 1960s was at a time of intense controversy regarding the origins of schizophrenia. Rather comprehensive explanatory theory for psychopathology was postulated at the level of genetics/biology or psychology or social theory. These perspectives competed for dominance more often than seeking integration although the biopsychosocial medical model, espoused by Engel,1 integrated these perspectives in a general systems framework. At that time the Danish adoption studies confirmed that inherited genes conveyed familial risk for schizophrenia, but were often interpreted as not only establishing schizophrenia as a genetic disease but also as falsifying psychological and social theories of etiology.2 At the time of our early research concerning schizophrenia, there was the view that a careful diagnosis based on stringent criteria would identify persons with a disease entity that sharply reduced the heterogeneity observed in development and course of illness in cohorts based on a broad concept of schizophrenia. Schneider viewed symptoms of first rank as distinguished nuclear schizophrenia and Langfeldt separated true from pseudo schizophrenia with criteria including first rank symptoms. The view that a broad concept of schizophrenia without stringent criteria in the United States led to over-inclusion, and hence heterogeneity, suggested a solution partly based on first rank symptoms.



30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis

2017-09-14

Abstract
At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it over-reached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms.



New Research Strategy for Measuring Pre- and Postnatal Metal Dysregulation in Psychotic Disorders

2017-08-31

Abstract
While previous studies have found evidence for detrimental effects of metals on neurodevelopment, the long-term effects on mental health remain unclear. The objective was to explore the effect of early metal exposure on risk of psychotic disorder and on symptom severity following illness onset. Through the use of validated tooth-biomarkers, we estimated pre- and postnatal exposure levels of essential elements (copper, magnesium, manganese, and zinc) and elements associated with neurotoxicity (lead, arsenic, lithium, and tin). We found consistently higher levels of lithium in patients compared to controls. Higher levels of magnesium and lower levels of zinc were associated with more severe psychopathology over 20 years after metal exposure. The results show promise for the use of teeth biomarkers in examining early environmental risk for psychosis and underscore the relevance of studying metal exposure during critical neurodevelopmental periods.



Convergence and Divergence of Brain Network Dysfunction in Deficit and Non-deficit Schizophrenia

2017-07-20

Abstract
Deficit schizophrenia (DS), characterized by primary and enduring negative symptoms, has been considered as a pathophysiologically distinct schizophrenic subgroup. Neuroimaging characteristics of DS, especially functional brain network architecture, remain largely unknown. Resting-state functional magnetic resonance imaging and graph theory approaches were employed to investigate the topological organization of whole-brain functional networks of 114 male participants including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local efficiency (Eloc) than the HC group, implying the reduction of local specialization of brain information processing (reduced functional segregation). The DS, but not NDS group, exhibited enhanced parallel information transfer (enhanced functional integration) as determined by smaller characteristic path length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented significant correlations with Brief Psychiatric Rating Scale (BPRS) total score in the DS group. At the nodal level, both the NDS and DS groups showed higher functional connectivity in the inferior frontal gyrus and hippocampus, and lower connectivity in the visual areas and striatum than the controls. The DS group exhibited higher nodal connectivity in the right inferior temporal gyrus than the NDS and HC group. The diminished expression of Scale for the Assessment of Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity of right putamen, while asociality/amotivation positively correlated with right hippocampus across whole patients. We highlighted the convergence and divergence of brain functional network dysfunctions in patients with DS and NDS, which provides crucial insights into pathophysiological mechanisms of the 2 schizophrenic subtypes.



Barbara Fish and a Short History of the Neurodevelopmental Hypothesis of Schizophrenia

2017-07-14

Abstract
The neurodevelopmental hypothesis of schizophrenia has become a paradigm broadly accepted in today’s research in schizophrenia and its spectrum. This article traces the historical development of the neurodevelopmental hypothesis of schizophrenia up until the time of its explicit formulation in 1987, by Weinberger and by Murray and Lewis, with a main focus on the seminal contribution of Barbara Fish to its conception and elaboration.



Dissociation of Brain Activation in Autism and Schizotypal Personality Disorder During Social Judgments

2017-06-21

Abstract
Background
There are overlaps between autism and schizophrenia but these are particularly pronounced, especially in social domains, for higher functioning individuals with autism spectrum disorders (ASD) or schizotypal personality disorder (SPD). It is not known whether these overlapping social deficits result from shared or distinct brain mechanisms. We therefore compared social cognition in ASD and SPD using functional magnetic resonance imaging (fMRI).
Methods
Twenty-one individuals with SPD, 28 with ASD and 33 controls were compared with respect to clinical symptoms using the Positive and Negative Syndrome Scale; social cognition, using a social judgment task and Ekman 60 faces task; and brain activation using an fMRI task of social judgment.
Results
The ASD and SPD groups showed few differences in symptoms or social cognition. However, fMRI showed that, compared to ASD, the SPD group showed significantly greater activation during social compared to gender judgments in the amygdala and 3 clusters: right posterior cerebellum, extending into fusiform and inferior temporal gyri; left posterior cerebellum; and left intraparietal sulcus extending through medial portions of the temporal gyri into the fusiform gyrus (all P < .05 family-wise error corrected). Control activations lay between the ASD and SPD groups.
Conclusions
Although social cognitive deficits in ASD and SPD appear superficially similar they are the result of different brain mechanisms. These findings have implications for therapeutic interventions targeted at social dysfunction in these conditions.






Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population

2017-06-06

Abstract
Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16–75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern.



Intranasal Oxytocin May Improve High-Level Social Cognition in Schizophrenia, But Not Social Cognition or Neurocognition in General: A Multilevel Bayesian Meta-analysis

2017-06-06

Abstract
While there is growing interest in the potential for intranasal oxytocin (IN-OT) to improve social cognition and neurocognition (ie, nonsocial cognition) in schizophrenia, the extant literature has been mixed. Here, we perform a Bayesian meta-analysis of the efficacy of IN-OT to improve areas of social and neurocognition in schizophrenia. A systematic search of original research publications identified randomized controlled trials (RCTs) of IN-OT as a treatment for social and neurocognitive deficits in schizophrenia for inclusion. Standardized mean differences (SMD) and corresponding variances were used in multilevel Bayesian models to obtain meta-analytic effect-size estimates. Across a total of 12 studies (N = 273), IN-OT did not improve social cognition (SMD = 0.07, 95% credible interval [CI] = [−0.06, 0.17]) or neurocognition (SMD = 0.12, 95% CI = [−0.12, 0.34]). There was moderate between study heterogeneity for social cognition outcomes (τs= 0.12). Moderator analyses revealed that IN-OT had a significantly larger effect on high-level social cognition (ie, mentalizing and theory of mind) compared to low-level social cognition (ie, social cue perception) (b = 0.19, 95% CI = [0.05, 0.33]). When restricting our analysis to outcomes for high-level social cognition, there was a significant effect of IN-OT (SMD = 0.20, 95 % CI = [0.05, 0.33]) but the effect was not robust to sensitivity analyses. The present analysis indicates that IN-OT may have selective effects on high-level social cognition, which provides a more focused target for future studies of IN-OT.



Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis

2017-05-30

Abstract
Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects.






Genome-Wide Association Study of Psychosis Proneness in the Finnish Population

2017-05-19

Abstract
The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman’s Schizotypia scales), and Schizoidia scale. Genome-wide genetic data was available for ~9.84 million SNPs. Heritability estimates ranged from 16% to 27%. Phenotypic, genetic and environmental correlations ranged from 0.04–0.43, 0.25–0.73, and 0.12–0.43, respectively. Univariate GWAs tests revealed an intronic SNP (rs12449097) at the TMC7 gene (16p12.3) that significantly associated (P = 3.485 × 10–8) with the hypomanic scale. Bivariate GWAs tests including the hypomanic and physical anhedonia scales suggested a further borderline significant SNP (rs188320715; P-value = 5.261 × 10–8, ~572 kb downstream the ARID1B gene at 6q25.3). Gene-based tests highlighted 20 additional genes of which 5 had previously been associated to schizophrenia and/or bipolar disorder: CSMD1, CCDC141, SLC1A2, CACNA1C, and SNAP25. Altogether the findings explained from 3.7% to 14.1% of the corresponding trait heritability. In conclusion, this study provides preliminary genomic evidence suggesting that qualitatively similar biological factors may underlie different psychosis proneness measures, some of which could further predispose to schizophrenia and bipolar disorder.



Ethnic Minority Status, Age-at-Immigration and Psychosis Risk in Rural Environments: Evidence From the SEPEA Study

2017-05-17

Abstract
Objective
Several ethnic minority groups experience elevated rates of first-episode psychosis (FEP), but most studies have been conducted in urban settings. We investigated whether incidence varied by ethnicity, generation status, and age-at-immigration in a diverse, mixed rural, and urban setting.
Method
We identified 687 people, 16–35 years, with an ICD-10 diagnosis of FEP, presenting to Early Intervention Psychosis services in the East of England over 2 million person-years. We used multilevel Poisson regression to examine incidence variation by ethnicity, rural–urban setting, generation status, and age-at-immigration, adjusting for several confounders including age, sex, socioeconomic status, population density, and deprivation.
Results
People of black African (incidence rate ratio: 4.06; 95% confidence interval [CI]: 2.63–6.25), black Caribbean (4.63; 95% CI: 2.38–8.98) and Pakistani (2.31; 95% CI: 1.35–3.94) origins were at greatest FEP risk relative to the white British population, after multivariable adjustment. Non-British white migrants were not at increased FEP risk (1.00; 95% CI: 0.77–1.32). These patterns were independently present in rural and urban settings. For first-generation migrants, migration during childhood conferred greatest risk of psychotic disorders (2.20; 95% CI: 1.33–3.62).
Conclusions
Elevated psychosis risk in several visible minority groups could not be explained by differences in postmigratory socioeconomic disadvantage. These patterns were observed across rural and urban areas of our catchment, suggesting that elevated psychosis risk for some ethnic minority groups is not a result of selection processes influencing rural–urban living. Timing of exposure to migration during childhood, an important social and neurodevelopmental window, may also elevate risk.



Using Directed Acyclic Graphs in Epidemiological Research in Psychosis: An Analysis of the Role of Bullying in Psychosis

2017-05-17

Abstract
Modern psychiatric epidemiology researches complex interactions between multiple variables in large datasets. This creates difficulties for causal inference. We argue for the use of probabilistic models represented by directed acyclic graphs (DAGs). These capture the dependence structure of multiple variables and, used appropriately, allow more robust conclusions about the direction of causation. We analyzed British national survey data to assess putative mediators of the association between bullying victimization and persecutory ideation. We compared results using DAGs and the Karlson–Holm–Breen (KHB) logistic regression commands in STATA. We analyzed data from the 2007 English National Survey of Psychiatric Morbidity, using the equivalent 2000 survey in an instant replication. Additional details of methods and results are provided in the supplementary material. DAG analysis revealed a richer structure of relationships than could be inferred using the KHB logistic regression commands. Thus, bullying had direct effects on worry, persecutory ideation, mood instability, and drug use. Depression, sleep and anxiety lay downstream, and therefore did not mediate the link between bullying and persecutory ideation. Mediation by worry and mood instability could not be definitively ascertained. Bullying led to hallucinations indirectly, via persecutory ideation and depression. DAG analysis of the 2000 dataset suggested the technique generates stable results. While causality cannot be fully determined from cross-sectional data, DAGs indicate the relationships providing the best fit. They thereby advance investigation of the complex interactions seen in psychiatry, including the mechanisms underpinning psychiatric symptoms. It may consequently be used to optimize the choice of intervention targets.



Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia

2017-05-17

Abstract
Background
Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown.
Methods
89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups.
Results
Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices.
Conclusion
These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia.



Twelve-Month Health Care Use and Mortality in Commercially Insured Young People With Incident Psychosis in the United States

2017-04-07

Abstract
Objective
To assess 12-month mortality and patterns of outpatient and inpatient treatment among young people experiencing an incident episode of psychosis in the United States.
Method
Prospective observational analysis of a population-based cohort of commercially insured individuals aged 16–30 receiving a first observed (index) diagnosis of psychosis in 2008–2009. Data come from the US Department of Health and Human Services’ Multi-Payer Claims Database Pilot. Outcomes are all-cause mortality identified via the Social Security Administration’s full Death Master File; and inpatient, outpatient, and psychopharmacologic treatment based on health insurance claims data. Outcomes are assessed for the year after the index diagnosis.
Results
Twelve-month mortality after the index psychosis diagnosis was 1968 per 100000 under our most conservative assumptions, some 24 times greater than in the general US population aged 16–30; and up to 7372 per 100000, some 89 times the corresponding general population rate. In the year after index, 61% of the cohort filled no antipsychotic prescriptions and 41% received no individual psychotherapy. Nearly two-thirds (62%) of the cohort had at least one hospitalization and/or one emergency department visit during the initial year of care.
Conclusions
The hugely elevated mortality observed here underscores that young people experiencing psychosis warrant intensive clinical attention—yet we found low rates of pharmacotherapy and limited use of psychosocial treatment. These patterns reinforce the importance of providing coordinated, proactive treatment for young people with psychosis in US community settings.



Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development

2017-03-11

Abstract
Background
Several nonpsychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the etiology of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by correlated genetic risk factors.
Methods
Polygenic risk scores (PRS), reflecting an individual’s genetic risk for schizophrenia, were constructed for 2588 children from the Netherlands Twin Register (NTR) and 6127 from the Avon Longitudinal Study of Parents And Children (ALSPAC). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13, and 15 years in the 2 cohorts. Results were then meta-analyzed, and a meta-regression analysis was performed to test differences in effects sizes over, age and disorders.
Results
Schizophrenia PRS were associated with childhood and adolescent psychopathology. Meta-regression analysis showed differences in the associations over disorders, with the strongest association with childhood and adolescent depression and a weaker association for ODD/CD at age 7. The associations increased with age and this increase was steepest for ADHD and ODD/CD. Genetic correlations varied between 0.10 and 0.25.
Conclusion
By optimally using longitudinal data across diagnoses in a multivariate meta-analysis this study sheds light on the development of childhood disorders into severe adult psychiatric disorders. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology.



Task-Related Functional Connectivity Analysis of Emotion Discrimination in a Family Study of Schizophrenia

2017-02-16

Abstract
Poor emotion recognition is a core deficit in schizophrenia and is associated with poor functional outcome. Functional magnetic resonance imaging (fMRI) multivariate analysis methods were used to elucidate the neural underpinnings of face and emotion processing associated with both genetic liability and disease-specific effects. Schizophrenia patients, relatives, and controls completed a task that included 4 facial emotion discrimination conditions and an age discrimination condition during fMRI. Three functional networks were derived from the data: the first involved in visual attention and response generation, the second a default mode network (DMN), and a third involved in face and emotion processing. No differences in activation were found between groups for the visual attention and response generation network, suggesting that basic processes were intact. Both schizophrenia patients and relatives showed evidence for hyperdeactivation in the DMN compared to controls, with relatives being intermediate, suggesting a genetic liability effect. Both disease-specific and genetic liability effects were found for the face processing network, which included the amygdala. Patients exhibited lower coordinated network activity compared to controls and relatives across all facial discrimination conditions. Additionally, in relation to the other emotion discrimination conditions, a heightened coordinated response during fear and anger discrimination was observed in schizophrenia compared to other conditions, whereas relatives demonstrated heightened coordinated activity for anger discrimination only relative to other emotion conditions. With regards to brain functioning, this study found that schizophrenia is associated with abnormal processing of threat-related information, and that in part may be associated with the genetic risk for the disorder, suggesting that the facial and emotion processing network could be targeted for intervention.



A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia

2017-02-13

Abstract
Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement.



Neural Mechanisms Underlying Affective Theory of Mind in Violent Antisocial Personality Disorder and/or Schizophrenia

2017-02-11

Abstract
Among violent offenders with schizophrenia, there are 2 sub-groups, one with and one without, conduct disorder (CD) and antisocial personality disorder (ASPD), who differ as to treatment response and alterations of brain structure. The present study aimed to determine whether the 2 groups also differ in Theory of Mind and neural activations subsuming this task. Five groups of men were compared: 3 groups of violent offenders—schizophrenia plus CD/ASPD, schizophrenia with no history of antisocial behavior prior to illness onset, and CD/ASPD with no severe mental illness—and 2 groups of non-offenders, one with schizophrenia and one without (H). Participants completed diagnostic interviews, the Psychopathy Checklist Screening Version Interview, the Interpersonal Reactivity Index, authorized access to clinical and criminal files, and underwent functional magnetic resonance imaging while completing an adapted version of the Reading-the-Mind-in-the-Eyes Task (RMET). Relative to H, nonviolent and violent men with schizophrenia and not CD/ASPD performed more poorly on the RMET, while violent offenders with CD/ASPD, both those with and without schizophrenia, performed similarly. The 2 groups of violent offenders with CD/ASPD, both those with and without schizophrenia, relative to the other groups, displayed higher levels of activation in a network of prefrontal and temporal-parietal regions and reduced activation in the amygdala. Relative to men without CD/ASPD, both groups of violent offenders with CD/ASPD displayed a distinct pattern of neural responses during emotional/mental state attribution pointing to distinct and comparatively successful processing of social information.



Clinical, Cognitive, and Neuroimaging Evidence of a Neurodevelopmental Continuum in Offspring of Probands With Schizophrenia and Bipolar Disorder

2017-02-09

Abstract
Background
Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders.
Aims
To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth.
Methods
One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6–17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders.
Results
Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders.
Conclusions
Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.



Severely Schizophrenic and Successful? Yes, It’s Possible!

2016-08-24

My name is Donald Carroll. I am 47 years old, and I have suffered with severe schizophrenia (or schizo-affective disorder) since I was 28 years old. I suffer constant auditory and visual hallucinations, but I have also experienced hallucinations of touch, taste, and even smell. I experience a myriad of other uncomfortable sensations in my brain, many of them very difficult to explain. I have sought relief from the symptoms of my illness for nearly 17 years, to no avail. I have worked with many doctors over the years, and I have tried all of the anti-psychotic medications known to man. I have been subjected to electro-shock therapy on several occasions, hospitalized several times or more, all with absolutely no success as regards finding a medication or treatment that could suppress my hallucinations such that I could function much better overall, and suffer less.