First-episode Schizophrenia Spectrum Disorders Research Articles

07-Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: A machine-learning study

Early diagnosis of schizophrenia might reduce the negative impact of the untreated disease. Progressive functional/structural changes were repeatedly detected using classical between-group statistics. However, these findings have been due to their low sensitivity and specificity not clinically useful. Machine learning methods are able to learn from the data and make predictions on the individual level, which might have a diagnostic potential. We performed a classification of patients with the first episode of schizophrenia (FES) and healthy controls (HC) from the resting state functional connectivity (rsFC) and fractional anisotropy (FA) using machine learning on 1:1 age and sex matched samples of 63/63 patients/HC (rsFC) and 77/77 (DTI). Support vector machine distinguished between patients and controls with an accuracy 73.0% (p = 0.001) (rsFC) and 62.34% (p = 0.005) (DTI). These results were not influenced by symptoms or medication. Our work shows that rsFC and FA might be used to classify patients with FES and HC on the individual level. The classification reflects ‘’trait” markers of FES, as the symptoms and medication had no significant effect. Additionally the results of the analysis of rsFC show the significance of anterior insula in the pathophysiology of FES.

Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders

Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders

Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder

Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)). Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity. Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.

Algorithm-based pharmacotherapy for first-episode schizophrenia involuntarily hospitalized: A retrospective analysis of real-world practice.

Little is known about the clinical outcomes of severely ill patients with first-episode schizophrenia spectrum disorders (FES) who are considered to lack the capacity to consent to clinical trials. We investigated the feasibility of an algorithm-based pharmacotherapy (ABP) and clinical outcomes of patients with FES involuntarily hospitalized and treated with ABP. We conducted a retrospective chart review of 160 patients admitted involuntarily between October 2012 and October 2015. Our algorithm aimed to delay olanzapine, standardize medications and suggest initiation of clozapine after failure (non-response or intolerability) of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at optimal dosage was 4 weeks or more. The physician adherence rate to ABP was 95%. Response and remission rates were 76.0% and 48.6% in the first adequate antipsychotic trial (Phase I, n = 146), 62.5% and 25.0% in the second adequate antipsychotic trial (Phase II, n = 32), and 16.7% and 0% in the third adequate antipsychotic trial (Phase III, n = 6). Response and remission rates in the clozapine trial (n = 9) increased to nearly the level of Phase I (66.7% and 44.4%). The treatment-resistance rate was 8.4% to 10.3%. These findings suggested the validity of ABP and initiation of clozapine for treatment-resistant psychotic symptoms for even severely ill involuntarily hospitalized patients with FES.

623. Classification of First-Episode Schizophrenia Spectrum Disorders and Controls from Whole Brain White Matter Fractional Anisotropy Using Machine Learning

623. Classification of First-Episode Schizophrenia Spectrum Disorders and Controls from Whole Brain White Matter Fractional Anisotropy Using Machine Learning

Classification of first-episode schizophrenia spectrum disorders and controls from whole brain white matter fractional anisotropy using machine learning

BackgroundSchizophrenia is a chronic disorder with an early onset and high disease burden in terms of life disability. Its early recognition may delay the resulting brain structural/functional alterations and improve treatment outcomes. Unlike conventional group-statistics, machine-learning techniques made it possible to classify patients and controls based on the disease patterns on an individual level. Diagnostic classification in first-episode schizophrenia to date was mostly performed on sMRI or fMRI data. DTI modalities have not gained comparable attention.MethodsWe performed the classification of 77 FES patients and 77 healthy controls matched by age and sex from fractional anisotropy data from using linear support-vector machine (SVM). We further analyzed the effect of medication and symptoms on the classification performance using standard statistical measures (t-test, linear regression) and machine learning (Kernel–Ridge regression).ResultsThe SVM distinguished between patients and controls with significant accuracy of 62.34% (P = 0.005). There was no association between the classification performance and medication nor symptoms. Group level statistical analysis yielded brain-wide significant differences in FA.ConclusionThe SVM in combination with brain white-matter fractional anisotropy might help differentiate FES from HC. The performance of our classification model was not associated with symptoms or medications and therefore reflects trait markers in the early course of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

SA33. In-Between Cognitive Domains Correlations in First-Episode Schizophrenia Spectrum Disorders

SA33. In-Between Cognitive Domains Correlations in First-Episode Schizophrenia Spectrum Disorders

Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations ofearly brain development.

Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score - the TMT-A score. No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis. To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.

The psychometric validity of the Center for Epidemiological Studies – Depression Scale (CES-D) in first episode schizophrenia spectrum

Depressive pathology is common in first-episode schizophrenia spectrum disorders (FES), and is frequently assessed using the Center for Epidemiological Studies – Depression Scale (CES-D), an instrument designed for use in community samples. Despite its widespread use, no prior study has examined the psychometric validity of the CES-D in assessing depressive pathology in FES. The aim of this study was to examine the psychometric validity of the CES-D in FES. This study involved secondary analysis of baseline data from a single blind, randomized controlled trial of vocational intervention for individuals with FES (N=91; age range: 15–25 years). Measures used were: CES-D, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Structured Clinical Interview for DSM-IV-TR (SCID-I/P). The CES-D strongly correlated with the depression subscale of the BPRS, and with the presence of full-threshold depressive disorder on the SCID-I/P. There was minimal overlap between the CES-D and SANS, with weak correlations emerging for avolition and anhedonia, and not for affective flattening, alogia, and attention. The CES-D cut-off of ≥23 produced high sensitivity and specificity values for determining full-threshold comorbid depressive disorder. Such findings indicate that the CES-D is effective for assessing and measuring depressive pathology in FES.

Factors Moderating the Relationship Between Childhood Trauma and Premorbid Adjustment in First-Episode Schizophrenia.

Childhood trauma is a recognised risk factor for schizophrenia. It has been proposed that childhood trauma interferes with normal neurodevelopment, thereby establishing a biological vulnerability to schizophrenia. Poor premorbid adjustment is frequently a precursor to schizophrenia, and may be a manifestation of neurodevelopmental compromise. We investigated the relationship between childhood trauma and premorbid adjustment in 77 patients with first-episode schizophrenia spectrum disorders. We also investigated possible mediating roles for other selected risk factors in the relationship. We found several significant correlations between different trauma types and both social and academic premorbid adjustment from childhood to late adolescence. There were no significant moderating effects for family history of schizophrenia or family history of psychiatric disorder. History of obstetric complications, substance abuse and poor motor coordination weakened some of the associations between childhood trauma and premorbid adjustment, while poor sequencing of motor acts strengthened the association. Our results confirm previous studies indicating an association between childhood trauma and premorbid adjustment. Results indicate a general rather than specific association, apparent with different types of trauma, and affecting both social and academic components of premorbid adjustment across childhood, early and late adolescence. Further, our results suggest a complex interplay of various risk factors, supporting the notion of different pathways to psychosis.

The Association between Anomalous Self-experiences, Self-esteem and Depressive Symptoms in First Episode Schizophrenia.

Background: Anomalous self-experiences (ASEs) aggregate in schizophrenia spectrum disorders, but the relationship between ASEs, and depression has been studied to a limited extent. Lower self-esteem has been shown to be associated with depression in early psychosis. Our hypothesis is that ASEs in early phases of schizophrenia are linked to lower levels of self-esteem, which in turn is associated with depression.Aim: The aim is to examine the relationship between ASEs, self-esteem and depression in first-episode schizophrenia spectrum disorders.Method: ASEs were assessed in 55 patients with first-episode schizophrenia by means of the Examination of anomalous Self-Experience (EASE) instrument. Assessment of depression was based on the Calgary Depression Scale for Schizophrenia (CDSS). Self-esteem was measured using the Rosenberg Self-Esteem Scale (RSES). Symptom severity was assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCI-PANSS). Substance misuse was measured with the Drug Use Disorder Identification Test (DUDIT), and alcohol use was measured with the Alcohol Use Disorder Identification Test (AUDIT). Data on childhood adjustment were collected using the Premorbid Adjustment Scale (PAS). Data on childhood trauma were collected using the Norwegian version of the Childhood Trauma Questionnaire, short form (CTQ-SF).Results: Analyses detected a significant association between current depression and ASEs as measured by the EASE in women, but not in men. The effect of ASEs on depression appeared to be mediated by self-esteem. No other characteristics associated with depression influenced the relationship between depression, self-esteem and ASEs.Conclusion: Evaluating ASEs can assist clinicians in understanding patients' experience of self-esteem and depressive symptoms. The complex interaction between ASEs, self-esteem, depression and suicidality could be a clinical target for the prevention of suicidality in this patient group.

The effect of comorbid depression on facial and prosody emotion recognition in first-episode schizophrenia spectrum

BackgroundComorbid depression is common in first-episode schizophrenia spectrum (FES) disorders. Both depression and FES are associated with significant deficits in facial and prosody emotion recognition performance. However, it remains unclear whether people with FES and comorbid depression, compared to those without comorbid depression, have overall poorer emotion recognition, or instead, a different pattern of emotion recognition deficits. The aim of this study was to compare facial and prosody emotion recognition performance between those with and without comorbid depression in FES. MethodsThis study involved secondary analysis of baseline data from a randomized controlled trial of vocational intervention for young people with first-episode psychosis (N=82; age range: 15–25 years). ResultsThose with comorbid depression (n=24) had more accurate recognition of sadness in faces compared to those without comorbid depression. Severity of depressive symptoms was also associated with more accurate recognition of sadness in faces. Such results did not recur for prosody emotion recognition. LimitationsIn addition to the cross-sectional design, limitations of this study include the absence of facial and prosodic recognition of neutral emotions. ConclusionsFindings indicate a mood congruent negative bias in facial emotion recognition in those with comorbid depression and FES, and provide support for cognitive theories of depression that emphasise the role of such biases in the development and maintenance of depression. Longitudinal research is needed to determine whether mood-congruent negative biases are implicated in the development and maintenance of depression in FES, or whether such biases are simply markers of depressed state.

P.3.a.005 - Diagnostic classification of patients with first-episode schizophrenia spectrum disorders from resting-fMRI

P.3.a.005 - Diagnostic classification of patients with first-episode schizophrenia spectrum disorders from resting-fMRI

Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders

ObjectiveA functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. MethodsUsing a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. ResultsThere was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. ConclusionsThe results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum.

Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study.

Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC). We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network. The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level. Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.

Impact of avolition and cognitive impairment on functional outcome in first-episode schizophrenia-spectrum disorder: a prospective one-year follow-up study

Previous research investigating the relationships between avolition, cognition and functioning in schizophrenia mostly focused on chronic samples and were cross-sectional in design. Impacts of avolition and cognition on longitudinal functional outcome in first-episode patients are under-studied. We assessed 114 Chinese aged 18–55years presenting with first-episode schizophrenia-spectrum disorder aiming to identify baseline predictors of 1-year functional outcome. Results showed that both avolition and global cognition independently predicted functioning, with avolition being the strongest predictor above and beyond cognition and other symptom dimensions. Our findings indicate the central role of in determining longitudinal functional status in the early illness stage.

Antipsychotic Prescribing Patterns in First-episode Schizophrenia: A Five-year Comparison.

ObjectiveEarly treatment choice is critical in first-episode schizophrenia-spectrum disorders. The purpose of this study was to describe prescribing trends of antipsychotics use in patients with first-episode schizophrenia in 2005 and 2010, respectively.MethodsWe reviewed the medical records of newly treated patients with schizophrenia from a university psychiatric hospital in 2005 (n=47) and 2010 (n=52). We defined patients as receiving a high antipsychotic dose if their ratio of prescribed daily dose (PDD) to defined daily dose (DDD) was greater than 1.5.ResultsThe rates of high-dose antipsychotic prescription were 61.7% and 53.8% in 2005 and 2010, respectively. The rates of antipsychotic polypharmacy were 34.6% in 2005 and 34.0% in 2010. The most common first-prescribed antipsychotics were (in descending order of prescription frequency) olanzapine, risperidone, aripiprazole, and haloperidol in 2005 and risperidone, quetiapine, paliperidone, and olanzapine in 2010. High-dose antipsychotics were significantly associated with antipsychotic poly-pharmacy (odds ratio=23.97; p<0.01). More individuals were treated with mood stabilizers in 2010 than in 2005 (p=0.003).ConclusionThe practice of prescribing high-dose antipsychotics and associated antipsychotic polypharmacy were common even for initial treatment of first-episode schizophrenia in 2005 and 2010. In 2010, the list of the most common first-prescribed antipsychotics changed, and the use of mood stabilizers increased in non-affective schizophrenia.

Altered Neural Correlate of the Self-Agency Experience in First-Episode Schizophrenia-Spectrum Patients: An fMRI Study

The phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia. To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35). A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA). (1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task. During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes.

Short term effectiveness of haloperidol versus risperidone in first-episode schizophrenia

Aim: The supposed superiority of second-generation antipsychotic medication over first-generation antipsychotic medication has been challenged recently by several studies. This naturalistic retrospective study aims to compare outcomes between patients admitted for the first time with first-episode schizophrenia-spectrum disorders who were started on either haloperidol or risperidone. Would choice of antipsychotic affect length of admission and three-month outcome? Methods: Seventy-seven patients from the Early Psychosis Intervention Programme at the Institute of Mental Health were included in this study. Length of stay was obtained from hospital electronic records. Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores at three months were used to assess severity of psychopathology and level of functioning respectively. A secondary analysis was also done to measure time to discontinuation for any reason. Results: There was a significant reduction in PANSS total, positive, negative and general psychopathology scores in both groups at three months, with the patients on risperidone showing a greater reduction in PANSS negative scores compared to the patients on haloperidol. However, there were no statistically significant differences between length of hospitalization and total PANSS score at three months between the two groups. Time to discontinuation was longer in the risperidone group compared to the haloperidol group. Conclusion: The findings of this study suggest that risperidone has a better effect on negative symptoms and is better tolerated, resulting in a longer time to discontinuation. Thus, starting a patient with first-episode schizophrenia-spectrum disorder on risperidone would result in a better short-term outcome as compared to starting the same patient on haloperidol.

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."