Cognitive Performance and Long-Term Social Functioning in Psychotic Disorder: A Three-Year Follow-Up Study

ObjectiveStudies have linked cognitive functioning to everyday social functioning in psychotic disorders, but the nature of the relationships between cognition, social cognition, symptoms, and social functioning remains unestablished. Modelling the contributions of non-social and social cognitive ability in the prediction of social functioning may help in more clearly defining therapeutic targets to improve functioning.MethodIn a sample of 745 patients with a non-affective psychotic disorder, the associations between cognition and social cognition at baseline on the one hand, and self-reported social functioning three years later on the other, were analysed. First, case-control comparisons were conducted; associations were subsequently further explored in patients, investigating the potential mediating role of symptoms. Analyses were repeated in a subsample of 233 patients with recent-onset psychosis.ResultsInformation processing speed and immediate verbal memory were stronger associated with social functioning in patients than in healthy controls. Most cognition variables significantly predicted social functioning at follow-up, whereas social cognition was not associated with social functioning. Symptoms were robustly associated with follow-up social functioning, with negative symptoms fully mediating most associations between cognition and follow-up social functioning. Illness duration did not moderate the strength of the association between cognitive functioning and follow-up social functioning. No associations were found between (social) cognition and follow-up social functioning in patients with recent-onset psychosis.ConclusionsAlthough cognitive functioning is associated with later social functioning in psychotic disorder, its role in explaining social functioning outcome above negative symptoms appears only modest. In recent-onset psychosis, cognition may have a negligible role in predicting later social functioning. Moreover, social cognition tasks may not predict self-reported social functioning.     

Cannabis use and the risk of developing a psychotic disorder

We briefly review the evidence that cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychoses, by summarising longitudinal studies that: a) have examined relationships between cannabis use and the risk of psychosis or psychotic symptoms; and b) have controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. There is now reasonable evidence from longitudinal studies that regular cannabis use predicts an increased risk of schizophrenia and of reporting psychotic symptoms. These relationships have persisted after controlling for confounding variables such as personal characteristics and other drug use. The relationships did not seem to be explained by cannabis being used to self-medicate symptoms of psychosis. A contributory causal relationship is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter system with which the cannabinoid system interacts, as has been shown by animal studies and a human provocation study. We briefly explore the clinical and public health implications of the most plausible hypothesis, that cannabis use precipitates schizophrenia in persons who are vulnerable because of a personal or family history of schizophrenia.     

精神分裂症患者中的高泌乳素血症研究进展

高泌乳素血症在精神分裂症患者中发生率高,主要原因为抗精神病药物和精神分裂症本身的作用。精神分裂症患者服用抗精神病药物后泌乳素水平较快升高,长期服用后泌乳素水平可能趋向于稳定甚至降低,但仍高于正常值。高泌乳素血症会导致肥胖等诸多不良后果。而精神分裂症患者服用抗精神病药物后另一常见的副反应是代谢相关不良反应,越来越多的研究开始关注兼顾治疗高泌乳素血症及肥胖、糖脂代谢异常的方法。溴隐亭、阿立哌唑及芍药甘草汤等中药具有一定的降低泌乳素水平的作用,但使用有限制性,且不能改善抗精神病药物所致代谢相关的不良反应。二甲双胍除了能改善糖脂代谢紊乱,还具有潜在的降泌乳素作用,对于同时有代谢异常如肥胖、糖脂代谢异常及高泌乳素血症的患者来说可能具有双重治疗效果,但其降泌乳素的疗效和剂量需要进一步的大样本临床研究。     

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample

Background

There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.

Methods

We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.

Results

Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Conclusion

The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: 18F-Fallypride Positron Emission Tomography Study

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and ¹⁸F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ⁹-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ⁹-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in ¹⁸F-fallypride displacement. Voxel-based statistical maps, representing specific D_2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ⁹-THC administration, reflecting dopamine release. While Δ⁹-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ⁹-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ⁹-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.     

Calcium-Dependent Networks in Dopamine–Glutamate Interaction: The Role of Postsynaptic Scaffolding Proteins

Dopamine and glutamate systems are both involved in cognitive, behavioral, and motor processes. Dysfunction of dopamine–glutamate interplay has been suggested in several psychotic diseases, above all in schizophrenia, for which there exists a need for novel medications. Intracellular calcium-dependent transduction pathways are key determinants of dopamine–glutamate interactions, which take place mainly, albeit not exclusively, in the postsynaptic density (PSD), a highly specialized postsynaptic ultrastructure. Stimulation of dopamine and glutamate receptors modulates the gene expression and the function of specific PSD proteins, the “scaffolding” proteins (Homer, Shank, and PSD95), belonging to a complex Ca²⁺-regulated network that integrates and converges dopamine and glutamate signaling to appropriate nuclear targets. Dysfunction of scaffolding proteins leads to severe impairment of Ca²⁺-dependent signaling, which may underlie the dopamine–glutamate aberrations putatively implicated in the pathogenesis of psychotic disorders. Antipsychotic therapy has been demonstrated to directly and indirectly affect the neuronal Ca²⁺-dependent pathways through the modulation of PSD scaffolding proteins, such as Homer, therefore influencing both dopaminergic and glutamatergic functions and enforcing Ca²⁺-mediated long-term synaptic changes. In this review, we will discuss the role of PSD scaffolding proteins in routing Ca²⁺-dependent signals to the nucleus. In particular, we will address the implication of PSD scaffolding proteins in the intracellular connections between dopamine and glutamate pathways, which involve both Ca²⁺-dependent and Ca²⁺-independent mechanisms. Finally, we will discuss how new strategies for the treatment of psychosis aim at developing antipsychotics that may impact both glutamate and dopamine signaling, and what should be the possible role of PSD scaffolding proteins.     

Menstrual disorders associated with hyperprolactinemia

In hyperprolactinemia, menstrual disorders ranging from irregular bleeding, insufficient luteal phase, spanio-amenorrhea, to anovulatory cycles and amenorrhea, are frequent. Multiple mechanisms are involved in these disorders: hyperprolactinemia could act at the hypothalamic level on LHRH secretion and directly on LH and sex steroids secretion. Hyperprolactinemia could also act by impairing fertilization or implantation at the endometrial level.     

治疗帕金森病精神症状新药匹莫范色林

匹莫范色林(Pimavanserin)是一种新型的选择性5-羟色胺2A(5-HT2A)受体反向激动剂,用于治疗帕金森病患者伴发的错觉、幻觉、妄想等精神症状。临床试验研究表明,其疗效和安全性较现有药物具有明显优势,已于2016年4月29日被美国食品和药物管理局批准上市。本文将从匹莫范色林的药效、安全性、耐受性等方面进行综述,并对该药物的未来发展应用做了展望。     

Glutamatergic Postsynaptic Density Protein Dysfunctions in Synaptic Plasticity and Dendritic Spines Morphology: Relevance to Schizophrenia and Other Behavioral Disorders Pathophysiology,and Implications for Novel Therapeutic Approaches

Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic synapses, and made by scaffolding proteins, receptors, and effector proteins; it is considered a structural and functional crossroad where multiple neurotransmitter systems converge, including the dopaminergic, serotonergic, and glutamatergic ones, which are all implicated in the pathophysiology of psychosis. Decreased PSD-95 protein levels have been reported in postmortem brains of schizophrenia patients. Variants of Homer1, a key PSD protein for glutamate signaling, have been associated with schizophrenia symptoms severity and therapeutic response. Mutations in Shank gene have been recognized in autism spectrum disorder patients, as well as reported to be associated to behaviors reminiscent of schizophrenia symptoms when expressed in genetically engineered mice. Here, we provide a critical appraisal of PSD proteins role in the pathophysiology of schizophrenia and autism spectrum disorders. Then, we discuss how antipsychotics may affect PSD proteins in brain regions relevant to psychosis pathophysiology, possibly by controlling synaptic plasticity and dendritic spine rearrangements through the modulation of glutamate-related targets. We finally provide a framework that may explain how PSD proteins might be useful candidates to develop new therapeutic approaches for schizophrenia and related disorders in which there is a need for new biological treatments, especially against some symptom domains, such as negative symptoms, that are poorly affected by current antipsychotics.     

Cortical Morphology Differences in Subjects at Increased Vulnerability for Developing a Psychotic Disorder: A Comparison between Subjects with Ultra-High Risk and 22q11.2 Deletion Syndrome

IntroductionSubjects with 22q11.2 deletion syndrome (22q11DS) and subjects with ultra-high risk for psychosis (UHR) share a risk of approximately 30% to develop a psychotic disorder. Studying these groups helps identify biological markers of pathophysiological processes involved in the development of psychosis. Total cortical surface area (cSA), total cortical grey matter volume (cGMV), cortical thickness (CT), and local gyrification index (LGI) of the cortical structure have a distinct neurodevelopmental origin making them important target markers to study in relation to the development of psychosis.Results22q11DS subjects had lower total cSA and total cGMV compared to UHR and HC subjects. The 22q11DS subjects showed bilateral lower LGI in the i) prefrontal cortex, ii) precuneus, iii) precentral gyrus and iv) cuneus compared to UHR subjects. Additionally, lower LGI was found in the left i) fusiform gyrus and right i) pars opercularis, ii) superior, and iii) inferior temporal gyrus in 22q11DS subjects compared to HC. In comparison to 22q11DS subjects, the UHR subjects had lower CT of the insula. For both risk groups, positive symptom severity was negatively correlated to rostral middle frontal gyrus CT.ConclusionA shared negative correlation between positive symptom severity and rostral middle frontal gyrus CT in UHR and 22q11DS may be related to their increased vulnerability to develop a psychotic disorder. 22q11DS subjects were characterised by widespread lower degree of cortical gyrification linked to early and postnatal neurodevelopmental pathology. No implications for early neurodevelopmental pathology were found for the UHR subjects, although they did have distinctively lower insula CT which may have arisen from defective pruning processes during adolescence. Implications of these findings in relation to development of psychotic disorders are in need of further investigation in longitudinal studies.     

Hyperiodotyrosinemia-induced hyperprolactinemia and hyperaldosteronism

A 21-year-old goitrous hypothyroid Chinese woman had elevated serum iodotyrosines with a monoiodotyrosine level of 85.9 nmol/l (normal 0.49-0.89 nmol/l) and a diiodotyrosine level of 25.3 nmol/l (normal 0.023-0.53 nmol/l). She was amenorrheic with low luteinizing hormone and follicle-stimulating hormone levels at 5.8 and 2.8 U/l, respectively. The hypogonadotropic hypogonadism was due to an elevated prolactin level of 8.8 nmol/l. She also had a low potassium level of 3.2 mmol/l, and a high urinary aldosterone level of 158 nmol/day. The hyperprolactinemia, hypogonadotropic hypogonadism, hyperaldosteronism and hypokalemia subsided with the administration of bromocriptine 5 mg/day. However, bromocriptine accentuated the hyperiodotyrosinemia, and the patient remained hypothyroid. Levothyroxine therapy lowered the monoiodotyrosine and diiodotyrosine levels, ameliorated all her endocrinopathies, started her periods, and shrank the goiter. She probably had a deiodinase defect which permitted the discharge of accumulated iodotyrosines from the thyroid gland. Since iodotyrosines are tyrosine hydroxylase inhibitors, the hyperiodotyrosinemia causes dopamine synthesis inhibition, and induces the hyperprolactinemia and hyperaldosteronism.     

Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

Dopamine D4 Receptors: Beyond Schizophrenia

Dopamine D₄ receptors mediate a wide range of neuronal signal transduction cascades. Malfunctions of these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders, and their modification underlies the actions of many psychotropic drugs. Postmortem neuropathological and genetic studies provide inconclusive associations between D₄ receptors and schizophrenia. Clinical trials of partially selective lead D₄ antagonists have proved them to be ineffective against psychotic symptoms in patients diagnosed with schizophrenia. However, associations are emerging between D₄ receptors and other neuropsychiatric disorders, including attention-deficit hyperactivity disorder as well as specific personality traits such as novelty seeking. Preclinical studies indicate that D₄ receptors play a pivotal role in the cellular mechanisms of hyperactivity, impulsivity, and working memory. Accordingly, D₄ receptors have broader implications for human illnesses than has been suggested by early focus on psychotic illness as a clinical target, and selective D₄ agents may yield clinically useful drugs for several neuropsychiatric disorders that require improved treatments.     

Treating Depressive Symptoms in Psychosis: A Network Meta-Analysis on the Effects of Non-Verbal Therapies

AimsThe aim of this study was to examine whether non-verbal therapies are effective in treating depressive symptoms in psychotic disorders.Results10 RCTs were included, of which three were of high quality according to the CTAM. The direct evidence demonstrated a significant effect on the reduction in depressive symptoms relative to treatment as usual (TAU), in favor of overall non-verbal therapy (ES: -0.66, 95% C.I. = -0.88, -0.44) and music therapy (ES: -0.59, 95% C.I. = -0.85, -0.33). Combining both direct and indirect evidence, yoga therapy (ES: -0.79, 95% C.I. = -1.24, -0.35) had a significant effect on depressive symptoms, and occupational therapy (ES: 1.81, 95% C.I. = 0.81, 2.81) was less effective, relative to TAU. Exercise therapy did not show a significant effect on depressive symptoms in comparison to TAU (ES: -0.02 95% C.I. = -0.67, 0.62). Due to inconsistency of study evidence, the indirect effects should be interpreted cautiously.ConclusionsNon-verbal therapies appear to be effective in reducing depressive symptomatology in psychotic disorders, in particular music therapy and yoga therapy.     

Altered Transfer of Momentary Mental States (ATOMS) as the Basic Unit of Psychosis Liability in Interaction with Environment and Emotions

Psychotic disorders are thought to represent altered neural function. However, research has failed to map diagnostic categories to alterations in neural networks. It is proposed that the basic unit of psychotic psychopathology is the moment-to-moment expression of subtle anomalous experiences of subclinical psychosis, and particularly its tendency to persist from moment-to-moment in daily life, under the influence of familial, environmental, emotional and cognitive factors.In a general population twin sample (n = 579) and in a study of patients with psychotic disorder (n = 57), their non-psychotic siblings (n = 59) and unrelated controls (n = 75), the experience sampling paradigm (ESM; repetitive, random sampling of momentary mental states and context) was applied. We analysed, in a within-person prospective design, (i) transfer of momentary anomalous experience at time point (t–1) to time point (t) in daily life, and (ii) moderating effects of negative affect, positive affect, daily stressors, IQ and childhood trauma. Additionally, (iii) familial associations between persistence of momentary anomalous experience and psychotic symptomatology were investigated. Higher level of schizotypy in the twins (but not higher level of psychotic symptoms in patients) predicted more persistence of momentary anomalous experience in daily life, both within subjects and across relatives. Persistence of momentary anomalous experience was highest in patients, intermediate in their siblings and lowest in controls. In both studies, persistence of momentary anomalous experience was moderated by higher levels of negative affect, daily stressors and childhood trauma (only in twins), and by lower levels of positive affect. The study of alterations in the moment-to-moment transfer of subtle anomalous experience of psychosis, resulting in their persistence, helps to explain why psychotic and emotional dysregulation tend to cluster in a single phenotype such as schizophrenia, and how familial and environmental risks increase the risk of expression of psychosis from, first, subtle momentary anomalous experience to, second, observable clinical symptoms.     

Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

Background

It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention.

Methods/Design

The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency.

Discussion

This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.

Trial Registration

Current Controlled Trials ISRCTN29242879     

Neuropsychological Impairment in Prodromal,First-Episode,and Chronic Psychosis: Assessing RBANS Performance

BackgroundCognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis.MethodWe administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis.ResultsPerformance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis.ConclusionsCognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease.     

Combined Metaheuristic Algorithm and Radiomics Strategy for the Analysis of Neuroanatomical Structures in Schizophrenia and Schizoaffective Disorders

ObjectivesSchizophrenia (SZ) is the most chronic disabling psychotic brain disorder. It is characterized by delusions and auditory hallucinations, as well as impairments in memory. Schizoaffective (SA) signs are co-morbid with SZ and are characterized by symptoms of SZ and mood disorder. Various researches suggest that SZ and SA share a number of equally severe cognitive deficits, but the pathophysiology has not yet been addressed in a comprehensive way. In this work, the heterogeneity in whole brain, ventricle and cerebellum region from psychotic MR brain images is examined using Machine learning and radiomic features.Materials and methodsT1 weighted MR brain images are obtained from Schizconnect database for the analysis. The shape prior level set method is used to segment the ventricle and cerebellum structures. The radiomic features which include shape and texture are extracted from these regions to discriminate the SZ and SA subjects. The performance of these features is evaluated with Binary Particle Swarm Optimization (BPSO) based Fuzzy Support Vector Machine (FSVM) classifier.ResultsThe shape constrained Level Set method is able to better segment ventricles and cerebellum regions from the images. The significant features that are extracted from whole brain, ventricle and cerebellum are identified by the BPSO based FSVM. The combination of radiomic features extracted from cerebellum region achieved high classification accuracy (90.09%) using metaheuristic algorithm. The extracted features from cerebellum are correlated with PANSS score. The causal analysis shows that there is an association been the tissue texture variation in identifying the disease severity. The symmetry analysis shows that left brain mean area is larger than the right side area. In particular SA has low cerebellum area compared to SZ. The radiomic features such as Hermite, Laws and tensor extracted from the left cerebellum show a significant texture variation in all the considered subjects (p<0.0001).ConclusionsThe results are clinically relevant in discriminating the pattern change in the structure, hence this biomarker and frame work could be used for the severity study of psychotic disorders.