DSM-5 Schizophrenia Research Articles

CPAN - A novel transdiagnostic dimensional approach to the assessment of psychotic disorders

IntroductionClassification of mental disorders evolved greatly over time, as DSM and ICD dominated both research and everyday practice in the past decades. DSM-5 was planned to represent biological features of psychiatric disorders and include results of genetic and imaging studies in the criteria. Unfortunately, this goal couldn’t be fulfilled, since, although there were promising results, evidence wasn’t strong enough to fully support the biological background of the currently used diagnostic categories. One possible explanation for this discrepancy is that biological disturbances don’t represent the somewhat artificial categorisation of these disorders. Many of the leading symptoms in psychotic disorders are nowadays considered as lying on a spectrum, such as autism, affective and psychotic spectrum disorders. Despite that, DSM-5 still describes schizophrenia, schizoaffective disorder and bipolar disorder as separate entities, however there can be major overlaps in the leading symptoms, moreover symptoms are not necessarily stable over time and can show fluctuations. It should be mentioned though that subgroups of schizophrenia in DSM-5 had been abolished and catatonia is considered as a trans-diagnostic specifier, moreover in ICD-11 certain symptoms can be added as symptoms specifiers to an existing diagnosis of primary psychotic disorder.ObjectivesOur aim was to establish a new trans-diagnostic, dimensional scale to assess the most important symptoms amongst patients with psychotic disorders. This scale is meant to represent the long-term clinical presentation and not a cross-sectional picture of a current state. We believe that long-term trajectories of these symptoms may be more connected to underlying biological features, such as genetic load (i.e. polygenic risk scores) and imaging results than the currently used diagnostic criteria. We think it is very important to create a tool, which is straightforward and short enough, so can be realistically used in everyday clinical work. This could provide important real-life data, which give us information about our patients from a different angle than the currently used diagnostic systems.MethodsWe have created the CPAN scale based on the current symptom specifiers of ICD-11 and the Clinician-Rated Dimensions of Psychosis Symptom Severity, which is an “emerging measure” for DSM-5 and also took into consideration our own clinical experience.ResultsThe new tool measures 4 symptoms (catatonia, psychosis, affective symptoms and negative symptoms) on a scale of 5 (0-4). We have also put in specifiers to be able to characterize patients more precisely, and output measures (suicidal risk, functionality) to open the way for further analysis.ConclusionsWe tried to establish a novel symptom scale to help assessing patients with psychotic symptoms in everyday clinical work. Our plan is to test the validity of CPAN in the near future.Disclosure of InterestNone Declared

Forensic psychiatry patients, services, and legislation in Nunavut and Greenland

Circumpolar regions face unique challenges in establishing and maintaining mental health care systems, including forensic psychiatry services. The scarcity of data and lack of evidence concerning the forensic psychiatry patient (FPP) populations of Nunavut and Greenland exacerbates the challenges of informing best practices and healthcare planning.By comparing the prevalence of forensic psychiatry patients, the mental health care services, and the legislation in these two relatively similar but unique regions, insight may be gained that can help inform healthcare planning.This cross-sectional study includes all forensic psychiatry in- and outpatients in one year from Nunavut (2018) and on February 29, 2020, in Greenland.The Greenland sample (n = 93) was nearly four times larger than the Nunavut sample (n = 15) at the population level. Despite considerable differences in forensic legislation and service supply, the forensic psychiatry patients in the two areas share several similarities. A total of 87% (n = 13) in the Nunavut sample were diagnosed with a DSM-5 schizophrenia spectrum disorder or other psychotic disorder. In Greenland, 82% (n = 76) were diagnosed with an ICD-10 F2 diagnosis (schizophrenia, schizotypal and delusional disorders). Approximately 2/3 of the patients in both populations were diagnosed with substance use disorder, and 60% of the Nunavut FPP received long-acting antipsychotic injections versus 62% in Greenland. Nearly half of the FPPs in both populations had never been convicted prior to entering the forensic psychiatry system; Nunavut 45% versus Greenland 47%. A substantial proportion of Greenlandic FPPs were outpatients compared to Nunavut (83% versus 47%).This study is an essential first step toward describing a Model of Care for forensic psychiatry patients in circumpolar regions; furthermore, the clinical similarities between the two populations provide support for future joint Arctic research and the inclusion of artic forensic patients in international studies.

Towards an integrative hope-dysfunctional beliefs perspective to personal recovery in schizophrenia: a path analysis

BackgroundEvidence shows that negative symptoms of schizophrenia and underlying dysfunctional cognition are related to persistently low functioning and quality of life. However, despite the abundance of existing recovery programs for people with schizophrenia, few have examined whether and how the widely-adopted hope-motivation recovery pathway and the deficit-oriented cognitive pathway might converge to influence functioning and quality of life.MethodsA cross-sectional, quantative survey recruited a convenient sample of adult outpatients with DSM-5 schizophrenia spectrum disorders and low social functioning (n = 124). Self-reported measurements included personal recovery (30-item Mental Health Recovery Measure), social functioning (8-item Social Functioning Questionnaire), hope (12-item Hope Scale), quality of life (28-item World Health Organization Quality of Life Scale-Abbreviated Version-Hong Kong), defeatist beliefs (15-item extracted from Dysfunctional Attitude Scale), and asocial beliefs (15-item extracted from Revised Social Anhedonia Scale). Correlation analysis and structural equation modelling was applied to investigate how the two pathways intertwined to predict social functioning and quality of life.ResultsAsocial beliefs and hope separately mediated two partial mediation pathways from defeatist beliefs to recovery outcomes (social functioning and personal recovery). Meanwhile, defeatist beliefs, social functioning, and personal recovery further predicted quality of life.ConclusionsThis is one of the very few studies that provides empirical evidence of a deficit-strength linkage in the recovery from schizophrenia. Remediation of dysfunctional beliefs and the injection of hope and successful experiences should be undertaken concurrently in recovery as they are associated with differential effects on enhancing social functioning and personal recovery, which then converge and contribute to a better quality of life.

Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study

BackgroundLittle is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD.MethodThe BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected.ResultsAmong 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone.ConclusionOur study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.

Do the negative symptoms of schizophrenia reflect reduced responsiveness to reward? Examination using a reward prediction error (RPE) task.

A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations. Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE. In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI. The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

The Impact of Baseline Anxiety on Drug Placebo Separation and Drug/Placebo Response in an Acute Schizophrenia Clinical Trial-A Post-hoc Analysis.

We sought to evaluate the impact of baseline anxiety levels on drug placebo separation and drug and placebo response in acutely psychotic schizophrenic subjects. In this post-hoc analysis, modified intent-to-treat Positive and Negative Syndrome Scale data were obtained from a phase 2, multi-center, 5 week, randomized, double-blind, placebo-controlled trial of KarXT in hospitalized adults with DSM-5 schizophrenia experiencing an acute exacerbation or relapse of symptoms. We investigated the impact of anxiety on drug placebo separation and drug and placebo response in 2 ways. In the first set of analyses, we dichotomized the data based on the absence or presence of anxiety symptoms. In the second set of analyses, we categorized subjects by levels of anxiety. All analyses were conducted using generalized linear models with normal distribution and identity link function. On average, subjects entering the trial were suffering from a moderate level of anxiety. Subjects with no baseline anxiety had a significant increase in placebo response, a decrease in drug response and did not separate drugs from placebo. With increasing levels of baseline anxiety, a larger drug placebo difference was observed. Our analyses identified that absence of anxiety at baseline was associated with a loss of signal at end of treatment between drug and placebo driven by a differential effect on placebo and treatment response. The effect observed was not related to the overall baseline symptom severity and was not mediated by improvement in anxiety itself. Interpretation of the results is caveated by the retrospective nature of the analyses.

Impulsive and aggressive traits and increased peripheral inflammatory status as psychobiological substrates of homicide behavior in schizophrenia

Background and objectivesAn association between inflammation and psychopathological domains of psychotic disorders is widely acknowledged; however, the involvement of inflammatory processes in the underlying pathophysiology of violent behavior in schizophrenia is yet to be elucidated. In this study, we aimed to address the differences in impulsive and aggressive traits as well as C-reactive protein (CRP) to albumin ratio (CAR) as a marker of inflammation between schizophrenia patients with a history of homicide and those without any history of interpersonal violence or criminal background. MethodsThe study population consisted of 80 male DSM-5 schizophrenia patients who were classified into two groups: homicidal (n=40) and non-violent (n=40). Impulsive and aggressive traits were evaluated with Barratt Impulsivity Scale-11 (BIS-11), and the Buss-Warren Aggression Questionnaire (BWAQ), respectively. For the calculation of CAR, the CRP and albumin levels were obtained from the file records of routine blood screenings performed in the month before the patients were included in the study. ResultsWhen adjusted for age, all subscale scores of the BIS-11 as well as BWAQ Total, Physical and Hostility scores were significantly higher in the homicidal group than in the control group. CRP and CAR were significantly higher, and albumin was significantly lower in the homicidal patients than the controls when adjusted for age, body-mass index and smoking status. Univariate and stepwise multivariate regression models indicated that BIS-11 Non-planning, BWAQ Total, BWAQ Hostility and CAR were independent predictors of belonging to the homicidal patient group, after stepwise adjustment for all potential confounders. ConclusionsOur findings suggest that certain impulsive and aggressive traits as well as CAR, as a proxy marker of peripheral inflammation, may contribute towards homicidal tendencies and may predict a specific predisposition towards lethal violence in schizophrenia. The study highlights inflammation as a potential biological correlate of a specific behavioral phenotype (homicide) in schizophrenia.

Cingulum bundle integrity in schizophrenia with auditory verbal hallucinations: A diffusion tensor imaging tractographic study.

Cingulum bundle (CB) is frequently implicated in schizophrenia; however, its role in specific symptoms of schizophrenia such as auditory verbal hallucinations (AVHs) is less explored. Few studies have reported association between reduced integrity of CB and severity of AVH. Using a symptom-based approach, this diffusion tensor imaging (DTI) tractographic study was aimed to assess and compare the integrity of CB in schizophrenia with AVH, schizophrenia without AVH and healthy controls. A total of 92 right-handed adult individuals (aged 18-50 yr) were recruited across three study groups. Those with Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of schizophrenia with AVH (group I; n=30) were compared to those with DSM-5 schizophrenia without lifetime AVH (group II; n=32) and healthy controls (group III; n=30; screened using Mini International Neuropsychiatric Interview version-7.0.0. and negative family history). Clinical assessments (groups I and II) included scale for assessment of positive symptoms, scale for assessment of negative symptoms, clinical global impression-schizophrenia and psychotic symptom rating scale. All participants underwent DTI, and quantitative tract-based measurements of fractional anisotropy (FA) were obtained for images using DTI studio version-3.0. All groups were comparable for age, gender, education and severity of illness. Group I had significantly lower FA values in the cingulate gyrus (CG) part of the left CB compared to groups II and III. No significant difference was found between groups II and III. The findings of this study suggest that the disruption in the left CB appears to be specific for AVH-positive schizophrenia. The finding is, however, preliminary subject to replication in future studies. Further investigations are needed to understand its relevance in the context of AVH-positive schizophrenia.

S105. DIGITAL BIOMARKERS FOR THE ASSESSMENT OF COGNITIVE, BEHAVIORAL AND FUNCTIONAL OUTCOMES IN INDIVIDUALS WITH SCHIZOPHRENIA

BackgroundAn individual’s mental health is best captured by considering the overall associations of biological, behavioral, and social functions that comprise the framework of individual experience. As such, accessing data on various health indicators concurrently can influence prediction of disease progression or change in response to treatment. Data generated passively by smartphones to measure human behavior has generated significant research interest and has increasingly been utilized in psychiatric disorders. In schizophrenia, passive and continuous assessment of how an individual uses their mobile device may give rise to clinically useful markers that can be used to improve treatment processes, adapt treatment choices, identify early risk for relapse to initiate clinical intervention, and develop new clinical models. A promising approach is to leverage current advances in mobile technology, data analytics and machine learning to enable automated and fast phenotyping of digital data. . In this context, the workflow for phenotyping (passive data collection → data storage and curation → trait extraction → machine learning/classification → models/apps for decision support) has to be carefully designed and efficiently executed to minimize resource usage and maximize utility. Digital phenotyping can be used in conjunction with standard care to reduce time to recognition and acknowledgement that worsening of a symptom needs to be addressed, to reduce time to receiving appropriate level of care, to increase ability to analyze and collect data from a variety of sources to improve mental health needs assessment and delivery of services, and to advance outcome measurement through comparison of passive and active data sets.AimThe aim of this pilot study is to test whether a smartphone digital phenotyping application can help detect early signs of treatment failure or response in individuals with chronic schizophrenia after discharge from hospital.Methods17 individuals with DSM-5 schizophrenia were provided with a smartphone and digital phenotyping app, MindStrong Health app, following discharge from an inpatient psychiatric facility. The participants were followed for 6 months with monthly rater administered evaluations assessing neurocognition (Brief Assessment of Cognition in Schizophrenia (BACS)), symptomatology (PANSS; CGI-S/I), quality of life (SF-36), healthcare utilization, alcohol/drug use, level of clinical insight and depression (Calgary Depression Rating Scale, CDSS). Digital phenotyping data included gestures (swipes, taps, other), orientation (the way the phone is pointing), acceleration (sudden movements of the phone), keystroke patterns with characters encoded, number of calls made, number of emails sent, number of text messages sent, and location information from the GPS. Predictive models were built using multiple machine learning techniques - random forest plots, linear regression and gradient boosting, to predict the target scores based on phone usage patterns.ResultsOf the 17 enrolled participants, 10 provided analyzable data (i.e., had at least 22 target days with data). There was a gradual reduction of passive data generation due to either non-use of the smart phone or due to non-recharging of the device. The mean PANSS score was 80.12 (14.56). BACS scores corresponding to motor speed (token motor task), verbal fluency (category instances, letter fluency), and attention and processing speed (symbol coding) were found to be highly correlated with a composite digital phenotyping marker while scores on the PANSS or CDSS were not.DiscussionThe study provides a basis for using smartphone-base mobile apps to use as an augmentation within clinical practice to gather further information on patients outside the clinic setting, focusing on their behavior in the ‘real world.’ In particular, the cognitive data derived from the digital device correlated well with rater administered traditional cognitive ratings. Collecting digital data can provide a much needed window into the lives of patients in between normally scheduled visits, while minimizing costs and inconvenience to the patient. Studies with larger sample sizes are required to assess relationships with relapse, rehospitalizations and treatment failure.

Aripiprazole Long-Acting Injection During First Episode Schizophrenia—An Exploratory Analysis

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18–26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive (p < 0.001) and negative (p < 0.001) symptoms and in general psychopathology (p < 0.001) and decrease in global severity (p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness.

T164. STRUCTURAL COVARIANCE IN DRUG-NAïVE FIRST EPISODE PSYCHOSIS: AN ULTRA-HIGH FIELD MRI STUDY

BackgroundStructural neuroimaging studies report disrupted morphological relationship in the grey matter volume (structural covariance) in patients with schizophrenia, indicating an impairment in functional and/or developmental plasticity. To our knowledge, no studies have examined the alterations in structural covariance across the entire brain in drug-naïve first episode psychosis. TOPSY (Tracking Outcomes of Psychosis) is one of the first studies intending to track the neurobiological trajectory using ultra-high field (7T) imaging starting from a drug-naïve first episode state. Here, we report the initial findings from the structural covariance of grey matter volume. To our knowledge, this is the first structural covariance analysis being reported using a 7T anatomical MRI acquisition.MethodsWe used ultra-high field (7 Tesla) MRI in 28 patients with FEP (satisfying criterion A of DSM-5 schizophrenia) and 18 controls, to estimate grey matter volume in a voxelwise manner. FEP and controls were matched for age, sex and parental socioeconomic status. Patients were recruited at an early intervention unit (PEPP, London Ontario) and had active psychotic symptoms at the time of scanning. Morphometric analysis was done using SPM12, after DARTEL based registration and segmentation but without spatial smoothing on 160 brain regions (6mm spheres) obtained using Dosenbach’s atlas. Correlation matrix for each group was constructed from 160*160 pearson correlation coefficients, followed by estimation of a bias matrix for each subject using jack-knife bias estimation. Bias values for each pair of nodes in an individual subject quantified the contribution of that subject to the overall within-group covariance. Higher positive values meant greater covariance between the two given nodes in that subject, relative to the rest of the group. These bias matrices can be considered equivalent to demeaned and normalised matrices of structural covariance. Structural covariance across all possible regional pairwise connections was tested using 2-tailed voxelwise T-test with FDR correction (p=0.05, 5% rate for false positives).ResultsPatients had a significant reduction in structural covariance affecting between right posterior insula and right precentral gyrus (within sensorimotor network, t=3.86, Hedge’s g = 1.15); between right posterior insula and left ventral prefrontal cortex (between sensorimotor and salience network, t=3.71, Hedge’s g = 1.10); and between right anterior cingulate cortex and right dorsal prefrontal cortex (between sensorimotor and default-mode network, t=3.10, Hedge’s g = 0.92). There were no pairwise connections with increased structural covariance among FEP subjects compared to healthy controls.DiscussionOur findings suggest that (1) structural covariance is disrupted even by the time of first-episode of psychosis; thus, the disruptions in morphological relationships reported in schizophrenia are not explicable by antipsychotic usage or illness duration (2) sensorimotor network regions show a predominant disruption in structural covariance, affecting morphological relationships with both salience and default mode regions. The functional and developmental plasticity of sensorimotor networks may be crucial for the early trajectory of psychosis.

T165. ULTRA-HIGH FIELD MORPHOMETRY IN DRUG-NAïVE FIRST EPISODE PSYCHOSIS

BackgroundStructural neuroimaging studies report distributed grey matter volume (GMV) deficits in drug-naïve first episode psychosis (FEP), though their relevance to symptom burden and cognitive deficits is currently unclear. When compared to studies in medicated patients and/or patients with established later-stage of psychosis, the GMV deficits reported have been limited in both spatial distribution and effect size, indicating the possibility of stage-specific progression during the clinical course of psychosis. TOPSY (Tracking Outcomes of Psychosis) is one of the first studies intending to track the neurobiological trajectory using ultra-high field (7T) imaging starting from a drug-naïve first episode state. Here, we report the initial findings from the voxel-based morphometry (VBM) of GMV. To our knowledge, this is the first VBM report from drug-naïve FEP subjects obtained using a 7T MRI acquisition.MethodsWe used ultra-high field (7 Tesla) MRI in 28 patients with FEP (satisfying criterion A of DSM-5 schizophrenia) and 18 controls, to evaluate differences in the grey matter. Volume in a voxelwise manner. FEP and controls were matched for age, sex and parental socioeconomic status. Patients were recruited at an early intervention unit (PEPP, London Ontario) and had active psychotic symptoms at the time of scanning. We also obtained abbreviated PANSS (8 items) scores to index the severity of psychosis. Analysis was done using SPM12, after DARTEL based registration and segmentation but without spatial smoothing. 2-tailed voxelwise T-test with FDR correction (p=0.05, 5% rate for false positives) was used. We used multiple regression analysis to predict the scores from processing speed measure (modified Symbol Substitution Test) and the severity of Delusions and Unusual Thought Content (P1 and G9), the 2 symptoms for which most subjects sought treatment in the first place.ResultsPatients had a significant reduction in GMV in left fusiform gyrus (Hedge’s g = 1.98, T= 6.7), and increased GMV in the right precuneus (Hedge’s g = 1.63, T= 5.5) and lingual cortex (Hedge’s g = 1.19, T= 4.0). We did not find any other areas of significant GMV change. Of these 3 circumscribed GMV changes, reduced fusiform GMV was found among FEP patients with lower processing speed (ß=0.45, p=0.04), higher severity of delusions (ß=-0.43, p=0.049) and unusual thought content (ß=-0.59, p=0.01). Increased precuneus GMV was found among FEP patients with higher severity of delusions (ß=0.62, p=0.008) and unusual thought content (ß=0.50, p=0.03). Right lingual changes were not related to the severity of delusions or processing speed scores.DiscussionOur findings suggest that (1) GMV deficits are minimal in drug-naïve FEP subjects, with large effect-size changes concentrated around face processing (fusiform) region (2) GMV increases co-occur with GMV reduction especially in those with most severe delusions and cognitive deficits indicating a role for compensatory plasticity. Subtle early brain structural changes appear to predict symptom burden and cognitive deficits at the time of first clinical presentation with psychosis. Focusing on treatments that manipulate the structure of fusiform cortex could potentially reduce the severity of some of the early symptoms in FEP.

Schizophrenia dissection by five anxiety and depressive subtype comorbidities: Clinical implications and evolutionary perspective

Twenty patients with DSM5 schizophrenia were comprehensively and formally assessed by an experienced psychiatrist. All subjects were assessed for: positive and negative psychotic symptoms; social anxiety; panic anxiety; obsessive compulsive disorder, atypical depression; major depression; suicide risk; and global assessment of functioning. Different profiles of clinical presentation and symptom evolution emerged for patients with schizophrenia who had co-morbid depression (15%), OCD (15%), panic or limited symptom attacks (55%) and social anxiety (5%). At least eighty percent of the sample had one or more of these co-morbidities. Summing up, the data support our previous finding that panic is highly prevalent in Schizophrenia with Auditory Hallucinations (>73% here, versus 100% before), and panic was paroxysmally concurrent with voice onset. Moreover, characteristic clinical findings may help point clinicians to five specific co-morbidity psychosis subtypes. Moreover, co-morbidity dissection of psychotic diagnoses recalls and parallels the historical psychopharmacologic dissection of non-psychotic anxiety and depressive subtypes diagnoses. Larger studies should further test and explore these preliminary findings.

Schizophrenia: An Overview.

Few changes were made to the diagnostic criteria for schizophrenia in DSM-5. Schizophrenia is a chronic mental illness with positive symptoms (delusions, hallucinations, disorganized speech and behavior), negative symptoms, and cognitive impairment. Discoveries in genetics, neuroimaging, and immune function continue to advance understanding of the etiologies for this elusive disease. The authors reviewed the current literature to give an overview. The topics include historical foundations, epidemiology, suicide risk, genomewide association studies, twin studies, neuroimaging, ventricular size, complement component 4 mediated synapse elimination, major histocompatibility complex markers, and associations seen in obstetrical complications, nutritional issues, prodromal and attenuated states, cannabis use, childhood trauma, immigration, and traumatic brain injury. Also reviewed are expressed emotions of caregivers and recidivism, conditions comorbid with obsessive-compulsive disorder, mood disorders, substance use, and finally some legal and ethical issues. These important developments in elucidating the disease mechanism will likely allow for the development of future novel treatment strategies.

Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions.

Diffusion tensor imaging (DTI) studies have provided evidence of widespread white matter (WM) abnormalities in schizophrenia. Although these abnormalities appear clinically significant, the relationship to specific clinical symptoms is limited and heterogeneous. This study examined the association between WM microstructure and the severity of the five main DSM-5 schizophrenia symptom dimensions. DTI was measured in forty patients with schizophrenia spectrum disorders. Using Tract-Based Spatial Statistics controlling for age, gender and antipsychotic dosage, our analyses revealed significant negative relationships between WM microstructure and two DSM-5 symptom dimensions: Whereas abnormal psychomotor behavior was particularly related to WM of motor tracts, negative symptoms were associated with WM microstructure of the prefrontal and right temporal lobes. However, we found no associations between WM microstructure and delusions, hallucinations or disorganized speech. These data highlight the relevance of characteristic WM disconnectivity patterns as markers for negative symptoms and abnormal psychomotor behavior in schizophrenia and provide evidence for relevant associations between brain structure and aberrant behavior.

Impact of DSM-5 changes on the diagnosis and acute treatment of schizophrenia.

To examine the consequences and validity of changes in Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnostic criteria for schizophrenia, eg, omission of subtypes, using a large dataset of double-blind, randomized, placebo-controlled schizophrenia trials. Data from 22 short-term efficacy registration trials of second generation antipsychotics for the treatment of acute psychotic episodes in patients with schizophrenia (N = 5233), submitted to the Dutch regulatory authority were analyzed. We examined whether patients in these pre-DSM-5 trials met the diagnostic criteria for schizophrenia according to DSM-5. Using linear regression, we examined differences in effect size between DSM-IV subtypes and between DSM-5 symptom dimensions. Over 99.5% of the patients met DSM-5 diagnostic criteria for schizophrenia and no differences in effect size were found between schizophrenia subtypes (P = .65). Symptom dimensions that respond best to treatment with second generation antipsychotics were hallucinations, delusions, disorganized speech, and mania (Hedge's g -0.23 to -0.31). Results of clinical trials in patients with pre-DSM-5 schizophrenia also apply to patients diagnosed with DSM-5 schizophrenia. Omission of the classic subtypes is justified as they are not predictive of response to treatment. The DSM-5 C-RDPSS scale adds valuable information to the categorical diagnosis of schizophrenia, which is relevant for antipsychotic response.

Schizophrenia in DSM-5: Assets and liabilities

Article history: Received 17 July 2013 Received in revised form 17 July 2013 Accepted 17 July 2013 Available online 8 September 2013 port and authoritative guidance to clinicians and researchers, as well as satisfy the needs of public agencies, the pharmaceutical industry, and, last but not the least, the general public for knowledge and understanding of the ‘state of the art’ concerning schizophrenia? The paradigm-transformative DSM-III, and subsequently ICD-10 and DSM-IV, were descendants of the Kraepelinian nosology of psychoses which postulated close relationships between clinical symptoms, the longitudinal course and outcome, and ultimately, brain pathology

Does change in definition of psychotic symptoms in diagnosis of schizophrenia in DSM-5 affect caseness?

Psychotic symptoms are a central element in the diagnosis of schizophrenia, although their precise definition has varied through the multiple iterations of DSM and the ICD. Schneiderian first-rank symptoms (FRS) have received a particularly prominent position in the diagnostic criteria of schizophrenia since ICD-9 and DSM-III. In the current iteration of DSM (DSM-IV-TR), whereas two characteristic symptoms are ordinarily required to meet criterion A, only a single symptom is necessary if the psychotic symptom happens to be a FRS, notably a bizarre delusion or auditory hallucination of a running commentary or ‘conversing voices’. Because of limited data in support of the special treatment of FRS, DSM-5 has made changes to criterion A, requiring that at least two psychotic symptoms be present in all cases with at least one of these symptoms being a delusion, hallucination, or disorganized speech. To assess the impact of these changes on the prevalence of schizophrenia, we examined a research dataset of 221 individuals with DSM-IV schizophrenia to study the prevalence and co-occurrence of various criterion A symptoms. Although bizarre delusions and/or Schneiderian hallucinations were present in 124 patients (56.1%), they were singly determinative of diagnosis in only one patient (0.46%). Additionally, only three of the 221 patients (1.4%) with DSM-IV schizophrenia did not have a delusion, hallucination, or disorganized speech. DSM-5 changes in criteria A should have a negligible effect on the prevalence of schizophrenia, with over 98% of individuals with DSM-IV schizophrenia continuing to receive a DSM-5 diagnosis of schizophrenia in this dataset.

Considering DSM-5: The Personal Experience of Schizophrenia in Relation to the DSM-IV-TR Criteria

Previous analyses have suggested that the personal experience of schizophrenia might be different from its depiction in the DSM-IV-TR. In this study, 17 people with schizophrenia or schizoaffective disorder were interviewed about their experiences of the DSM-IV-TR diagnostic criteria for schizophrenia. Descriptive phenomenological analysis was used to analyze the ways in which the personal experiences of the people in this study were similar to or different from the depiction of schizophrenia in the DSM-IV-TR. The personal experience of schizophrenia was similar in some way to each of the five diagnostic criteria for schizophrenia. Participants’ personal experiences also went beyond the DSM-IV-TR criteria. Specifically, participants described strong emotional reactions to their symptoms, including fear, sadness, embarrassment, and alienation. Also, participants described intense interest but severe disruptions in goal-directed behavior due to their hallucinations being engrossing, confusing, and distracting. Further, participants described not sharing their experiences in order to avoid social stigma. These findings suggest that the description of schizophrenia in DSM-5 may benefit from a change to DSM-IV-TR criteria to incorporate more of the personal experience of schizophrenia. Further research is needed to establish the representativeness, reliability, and validity of the qualitative findings described here.

Schizophrenia spectrum and other psychotic disorders

The DSM-5 list of diagnoses concerning schizophrenia spectrum and other psychotic disorders is expected to be revised and graduated from mild to severe. The proposed changes for the diagnosis of schizophrenia affect demands for characteristic symptoms, clarify relation to pervasive developmental disorders, and eliminate the classic subtypes of schizophrenia. A dimensional assessment will be measured on a 0-4 point scale. It is recommended that the concept of attenuated psychosis syndrome is further investigated. The propositions affecting characteristic symptoms of schizophrenia might increase diagnostic reliability and validity, but it is estimated to exclude about 2 % of patients currently diagnosed with DSM-IV schizophrenia from fulfilling criteria for DSM-5 schizophrenia. It might generate a problem for future young patients if the changes concerning demands on characteristic symptoms turn out to be more restrictive, leaving out a percentage of patients with psychotic symptoms from a diagnosis of schizophrenia; which in practice opens possibilities for intensive treatment options. On the other hand, not including attenuated psychosis syndrome at the present might protect patients from stigmatization and pharmacological treatment on poor indication. The introduction of dimensional assessments may make schizophrenia subtyping redundant and has the potential to enrich clinical practice and bridge communication between child and adolescent and adult psychiatry. The most recent guidelines for assessment and treatment of children and adolescents with schizophrenia are from 2001. They provide differentiated recommendations regarding diagnostics, assessment of symptoms and functioning and treatment strategies. There is an urgent need for updated guidelines in this field, especially concerning specific treatment guidelines.