Cognitive Patterns and Conversion in a Representative Sample of Individuals at Risk for Psychosis.

ABSTRACT: Clinical high-risk (CHR) individuals belong to a heterogeneous group, of which only a few will cross the threshold for a clinical diagnosis. Cognitive disturbances are present in CHR subjects and may be indicative of transition. Our study aims to identify such deficits in a representative CHR for psychosis sample. Our sample comprised 92 CHR individuals and 54 controls from a representative cohort of the general population. They were followed up for a mean of 2.5 years, with 15 individuals converting to schizophrenia or other Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnoses. Neurocognitive assessment was performed with the University of Pennsylvania Computerized Neuropsychological Testing, and CHR status was assessed with the Structured Interview for Prodromal Syndromes (SIPS). Baseline scores were entered in a latent profile analysis model. Our study brought forward a four-class model on cognitive performance. One class displayed better performance, whereas the other three performed worse, all compared with controls. The class with lower executive function also had the highest score on disorganized communication (SIPS P5 = 1.36, p < 0.05), although unrelated to conversion. Among the low performers, the class significantly related to conversion (p = 0.023) had the highest score in decreased expression of emotion (SIPS N3 = 0.85, p < 0.05). Our study brings new and relevant data on non-help-seeking CHR individuals and the relationship between cognitive patterns and conversion. We have highlighted a specific cognitive signature, associated with negative symptoms, which represents a stable trait with presumed lower conversion to a psychiatric illness.

Relationship Between Symptomatic Dimensions and Global Functioning of Non-Help-Seeking Individuals at Risk for Psychosis.

This study aims to analyze the relationship between the symptomatic dimensions of psychosis and functioning of individuals at risk for psychosis (ultrahigh risk [UHR]) in a non-help-seeking UHR sample from the general population. The sample is the same as the one used in the Brazilian Subclinical Symptoms and Prodromal Psychosis cohort study. We applied questionnaires of functioning (Global Assessment of Functioning Scale) and symptomatic dimensions (Scale of Prodromal Symptoms). Next, we correlated the symptomatic dimensions with functioning. We found a significant relationship between avolition and uncommon thought content with poor functioning, whereas the remaining symptoms were not as relevant. Poor functioning was most related to avolition, a negative symptom, followed by unusual thought content, a positive symptom.

Lower phosphorylated glycogen synthase kinase-3B levels in platelets of patients with schizophrenia: increment by olanzapine treatment.

Glycogen synthase kinase-3B (GSK-3B) is involved with important neuronal processes such as cell survival, gene regulation, mood and cognitive performance. This enzyme is inactivated by phosphorylation at the phospho-Ser9 site. We compared GSK-3B levels in patients with schizophrenia to a health control group. The levels of phosphorylated and total GSK-3B in platelets of ten drug-free patients, ten long-term olanzapine treated patients and 20 healthy controls were determined by means of an enzyme immunoassay kit. In drug-free patients, GSK-3B levels were accessed again after 8 weeks on treatment with olanzapine. At baseline, drug-free patients presented lower phosphorylated and total GSK-3B levels than healthy controls (p < 0.05). After 8 weeks on olanzapine treatment, phosphorylated and total GSK-3B levels were significantly increased (p < 0.01). Reduced phospho-Ser9-GSK-3B in schizophrenia may disrupt signal-transduction pathways and influence crucial cellular processes, such as transcription, apoptosis, stress response and cell proliferation. Further studies should clarify whether the increment of GSK-3B phosphorylation by olanzapine is related to its antipsychotic effects.

Cannabis use influences disorganized symptoms severity but not transition in a cohort of non-help-seeking individuals at-risk for psychosis from São Paulo, Brazil.

BACKGROUND: Cannabis use is associated with an increased risk of developing a psychotic disorder. However, in individuals with at-risk mental states for psychosis (ARMS) this association is not clear, as well as the impact of cannabis use on symptom severity. The objective of this study was to evaluate the association of cannabis use patterns and ARMS risk status, transition to psychotic and psychiatric disorders, and psychopathology. METHOD: A sample of 109 ARMS and 197 control individuals was drawn from the general population. Lifetime, maximum and current amount of cannabis use were assessed with the South Westminster modified questionnaire. Participants were followed-up for a mean of 2.5 years and reassessed for transition to any psychiatric disorder. RESULTS: There were no differences between ARMS and controls regarding lifetime use, current amount of use, or maximum amount of cannabis use. There were also no differences between those who transitioned to a psychiatric disorder and those who did not regarding cannabis use variables. In ARMS individuals, cannabis use was significantly related to disorganization symptoms. CONCLUSION: The results of this study suggest that cannabis plays a role in the psychopathology of ARMS individuals, leading to more severe symptomatology.

Natural language processing in at-risk mental states: enhancing the assessment of thought disorders and psychotic traits with semantic dynamics and graph theory.

OBJECTIVE: Verbal communication has key information for mental health evaluation. Researchers have linked psychopathology phenomena to some of their counterparts in natural-language-processing (NLP). We study the characterization of subtle impairments presented in early stages of psychosis, developing new analysis techniques and a comprehensive map associating NLP features with the full range of clinical presentation. METHODS: We used NLP to assess elicited and free-speech of 60 individuals in at-risk-mental-states (ARMS) and 73 controls, screened from 4,500 quota-sampled Portuguese speaking citizens in Sao Paulo, Brazil. Psychotic symptoms were independently assessed with Structured-Interview-for-Psychosis-Risk-Syndromes (SIPS). Speech features (e.g.sentiments, semantic coherence), including novel ones, were correlated with psychotic traits (Spearman's-ρ) and ARMS status (general linear models and machine-learning ensembles). RESULTS: NLP features were informative inputs for classification, which presented 86% balanced accuracy. The NLP features brought forth (e.g. Semantic laminarity as 'perseveration', Semantic recurrence time as 'circumstantiality', average centrality in word repetition graphs) carried most information and also presented direct correlations with psychotic symptoms. Out of the standard measures, grammatical tagging (e.g. use of adjectives) was the most relevant. CONCLUSION: Subtle speech impairments can be grasped by sensitive methods and used for ARMS screening. We sketch a blueprint for speech-based evaluation, pairing features to standard thought disorder psychometric items.

Inequality and barriers in psychosis prevention: A systematic review on clinical high-risk for psychosis studies from developing countries.

Background: The clinical high-risk for psychosis (CHR) paradigm is one of the best studied preventive paradigms in psychiatry. However, most studies have been conducted in high-income countries. It is unclear if knowledge from such countries applies to low and middle-income countries (LAMIC), and if there are specific limitations hindering CHR research there. Our aim is to systematically review studies on CHR from LAMIC. Methods: A multistep PRISMA-compliant literature search was performed in PubMed and Web of Science for articles published until 1/03/2022, conducted in LAMIC, addressing the concept and correlates of CHR. Study characteristics as well as limitations were reported. Corresponding authors of the included studies were invited to answer an online poll. Quality assessment was done with the MMAT. Results: A total of 109 studies were included in the review: none from low-income countries, 8 from lower middle-income countries, and 101 from upper middle-income countries. The most frequent limitations were small sample size (47.9%), cross-sectional design (27.1%), and follow-up issues (20.8%). Mean quality of included studies was of 4.4. Out of the 43 corresponding authors, 12 (27.9%) completed the online poll. They cited further limitations as few financial resources (66.7%), no involvement of population (58.2%) and cultural barriers (41.7%). Seventy five percent researchers reported that CHR research should be conducted differently in LAMIC compared to high-income countries, due to structural and cultural issues. Stigma was mentioned in three out of five sections of the poll. Discussion: Results show the discrepancy of available evidence on CHR in LAMIC, given the shortage of resources in such countries. Future directions should aim to increase the knowledge on individuals at CHR in such settings, and to address stigma and cultural factors that may play a role in the pathways toward care in psychosis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316816, CRD42022316816.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis.

OBJECTIVES: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. METHODS: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. RESULTS: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). CONCLUSION: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features.

AIMS: Our study aimed to develop a machine learning ensemble to distinguish "at-risk mental states for psychosis" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings. METHODS: 58 non-help-seeking medication-naïve ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and "Subject's Overview" section was filmed (5-10 min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used. RESULTS: Final model reached 83 % of mean F1-score, and balanced accuracy of 85 %. Mean area under the curve for the receiver operator curve classifier was 93 %. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item). CONCLUSION: Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.

Motion energy analysis during speech tasks in medication-naïve individuals with at-risk mental states for psychosis.

Movement abnormalities are commonly observed in schizophrenia and at-risk mental states (ARMS) for psychosis. They are usually detected with clinical interviews, such that automated analysis would enhance assessment. Our aim was to use motion energy analysis (MEA) to assess movement during free-speech videos in ARMS and control individuals, and to investigate associations between movement metrics and negative and positive symptoms. Thirty-two medication-naïve ARMS and forty-six healthy control individuals were filmed during speech tasks. Footages were analyzed using MEA software, which assesses movement by differences in pixels frame-by-frame. Two regions of interest were defined-head and torso-and mean amplitude, frequency, and coefficient of variability of movements for them were obtained. These metrics were correlated with the Structured Interview for Prodromal Syndromes (SIPS) symptoms, and with the risk of conversion to psychosis-inferred with the SIPS risk calculator. ARMS individuals had significantly lower mean amplitude of head movement and higher coefficients of movement variability for both head and torso, compared to controls. Higher coefficient of variability was related to higher risk of conversion. Negative correlations were seen between frequency of movement and most SIPS negative symptoms. All positive symptoms were correlated with at least one movement variable. Movement abnormalities could be automatically detected in medication-naïve ARMS subjects by means of a motion energy analysis software. Significant associations of movement metrics with symptoms were found, supporting the importance of movement analysis in ARMS. This could be a potentially important tool for early diagnosis, intervention, and outcome prediction.

Use of a Bayesian Network Model to predict psychiatric illness in individuals with 'at risk mental states' from a general population cohort.

The 'at risk mental state' (ARMS) paradigm has been introduced in psychiatry to study prodromal phases of schizophrenia. With time it was seen that the ARMS state can also precede mental disorders other than schizophrenia, such as depression and anxiety. However, several problems hamper the paradigm's use in preventative medicine, such as varying transition rates across studies, the use of non-naturalistic samples, and the multifactorial nature of psychiatric disorders. To strengthen ARMS predictive power, there is a need for a holistic model incorporating-in an unbiased fashion-the small-effect factors that cause mental disorders. Bayesian networks, a probabilistic graphical model, was used in a populational cohort of 83 ARMS individuals to predict conversion to psychiatric illness. Nine predictors-including state, trait, biological and environmental factors-were inputted. Dopamine receptor 2 polymorphism, high private religiosity, and childhood trauma remained in the final model, which reached an 85.51% (SD = 0.1190) accuracy level in predicting conversion. This is the first time a robust model was produced with Bayesian networks to predict psychiatric illness among at risk individuals from the general population. This could be an important tool to strengthen predictive measures in psychiatry which should be replicated in larger samples to provide the model further learning.

Addressing Mood Disorder Diagnosis' Stigma With an Honest, Open, Proud (HOP)-Based Intervention: A Randomized Controlled Trial.

Introduction: The public stigma and self-stigma contribute to the dilemma of disclosing or not one's own mental illness diagnosis. Studies suggest that revealing it diminishes stress, besides helping with self-esteem. Honest, Open, Proud (HOP) is a group program that aids in the process of deciding on it, reducing its impact. Considering the relevance of this issue, the present study aimed to apply a HOP-based intervention in a group of patients diagnosed with mood disorders. Methods: A randomized controlled clinical trial was used, including 61 patients with mood disorders, of whom 31 were diagnosed with depression and 30 were diagnosed with bipolar disorder. They were randomly placed on the intervention (HOP) or the control group (unstructured psychoeducation). The evaluations occurred before (T0) and after (T1) the sessions. We administered eight scales, from which three presented relevant results: Coming Out with Mental Illness Scale (COMIS), Cognitive Appraisal of Stigma as a Stressor (CogApp), and Authenticity Scale. Results: The intervention groups (depression and bipolar) did not present a significant change regarding the decision to disclose their diagnostics. However, the depression group showed a decrease on the perception of stigma as a stressor (T0 = 0.50 vs. T1 = -1.45; p = 0.058). Improvements in post-intervention results were seen for both groups (depression and bipolar) on the Authenticity Scale-self-alienation subscale (T0 = 10.40 vs. T1 = 12.37, p = 0.058). Conclusion: Our HOP-based intervention appeared to be an important program to aid patients in facing stigma stress, showing positive effects, whether helping to diminish stress or to improve self-conscience, both of which have indirect effects on self-stigma. As it is a compact program, it can bring benefits when applying to public health institutions.

Childhood maltreatment in individuals at risk of psychosis: Results from the Brazilian SSAPP cohort.

BACKGROUND: Childhood maltreatment is a known risk factor for the development of mental disorders, such as psychotic symptoms. An extensive body of literature about childhood maltreatment and mental health has been developed in wealthy countries, but information about this connection is lacking in developing countries. AIMS: To explore a possible relationship between childhood maltreatment and ultra-high risk of psychosis in a non-help-seeking population in a low- and middle-income country. METHODS: A household survey was conducted in Sao Paulo, Brazil, involving over 2,500 individuals aged 18-30 years who were randomly selected from the general population. The participants underwent screening with the Prodromal Questionnaire. Ultra-high risk status was assessed using the Structured Interview for Prodromal Syndromes, and childhood maltreatment was assessed using the Childhood Trauma Questionnaire. The final sample comprised 87 ultra-high risk individuals and 115 controls. RESULTS: Childhood maltreatment was significantly more present among ultra-high risk individuals. In ultra-high risk individuals, physical and emotional neglect were inversely related to grandiosity symptoms, physical abuse was related to perceptual abnormalities and physical neglect was related to disorganized speech and thought. CONCLUSION: This is the first study to investigate the relationship between childhood maltreatment and ultra-high risk status and psychopathological features in a large Latin American sample. Further studies in this field are necessary to better understand the specific influence of various early life adversities on psychosis risk.

Hearing spirits? Religiosity in individuals at risk for psychosis-Results from the Brazilian SSAPP cohort.

In the last decades, biological and environmental factors related to psychosis were investigated in individuals at ultra-risk for psychosis (UHR) to predict conversion. Although religion relates to psychosis in a variety of ways, it is understudied in subclinical samples. Therefore, we assessed the interplay between religion and prodromal symptoms in 79 UHR and 110 control individuals. They were interviewed with the Duke University Religion Index and the Structured Interview for Prodromal Syndromes (SIPS). Organizational religious activity, a measure of how often someone attends churches/temples, was positively related to perceptual abnormalities/hallucinations (Spearman's rho = 0.262, p = 0.02). This relationship was replicated in a path analysis model (ß = 0.342, SE = 0.108, p = 0.002), as well as a link between organizational religious activity and lower ideational richness (ß = 0.401, SE = 0.105, p = 0.000) with no influence of sex, age, religious denomination, or socioeconomic class. Intrinsic religious activity was negatively correlated with suspiciousness (SIPS P2) (ß = -0.028, SE = 0.009, p = 0.002), and non-organizational religious activity was correlated with higher ideational richness (N5) (ß = -0.220, SE = 0.097, p = 0.023). We hypothesize that subjects with subclinical psychosis may possibly use churches and other religious organizations to cope with hallucinations. Indeed, Brazil is characterized by a religious syncretism and a strong influence of Spiritism in the popular culture. The mediumistic idea that some might be able to hear and/or see spirits is probably employed to explain subclinical hallucinations in the lay knowledge. Our results emphasize the importance of assessing religion and other region-specific aspects of various cultures when studying UHR individuals. This sort of assessment would enhance understanding of differences in conversion rates, and would help to transpose prevention programs from high-income countries to other settings.

Disclosing the diagnosis of schizophrenia: A pilot study of the 'Coming Out Proud' intervention.

BACKGROUND: Schizophrenia is one of the most stigmatized psychiatric disorders, and disclosing it is often a source of stress to individuals with the disorder. The Coming Out Proud (COP) group intervention is designed to reduce the stigma's negative impact and help participants decide if they want to disclose their disorder. AIMS: To assess the effect of the COP intervention in individuals with the diagnosis of schizophrenia. METHODS: A pilot study of 3 2-hour group lessons (6-12 participants) per week. Individuals were selected from three specialized outpatient services in São Paulo, Brazil; 46 people were willing to participate, 11 dropped out during the intervention and 4 were excluded due to low intelligence quotient (IQ), resulting in a final sample of 31 participants. Outcomes were assessed before ( T0/baseline) and after ( T1/directly) after the COP intervention, and at 3-week follow-up ( T2/3 weeks after T1). We applied eight scales, of which four scales are analyzed in this article (Coming Out with Mental Illness Scale (COMIS), Cognitive Appraisal of Stigma as a Stressor (CogApp), Self-Stigma of Mental Illness Scale-Short Form (SSMIS) and Perceived Devaluation-Discrimination Questionnaire (PDDQ)). RESULTS: People who completed the COP intervention showed a significant increase in the decision to disclose their diagnosis (22.5% in T0 vs 67.7% in T2). As to the perception of stigma as a stressor, mean values did not significantly differ after the intervention. Two results had marginal significance: self-stigma was reduced ( T0 = 3.10, SD = 1.70 vs T2 = 2.73, SD = 1.87; p = .063), while perceived discrimination increased ( T0 = 2.68, SD = .55 vs T2 = 2.93, SD = .75; p = .063). CONCLUSION: This study suggests that the COP group intervention facilitated participants' disclosure decisions. The results raise questions that require further analysis, taking sociocultural factors into account, as stigma is experienced differently across cultures.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Poverty, low education, and the expression of psychotic-like experiences in the general population of São Paulo, Brazil.

The aim of our study was to assess psychotic-like experiences in the general population aged 18-30 years old of the city of São Paulo, Brazil. A household survey was conducted with 1950 young-adults randomly drawn from the city's general population. The validated 92-item Portuguese version of the Prodromal Questionnaire (PQ) was used for face-to-face interviews. Latent class analysis was conducted. Mean age was of 24 years; 51.1% of the sample was of women. Mean total score on the PQ was 22.06 (SD=17.16). Considering a suggested cut-off of 14 in the positive subscale, 30.8% of individuals were above the threshold for ultra-high risk for psychosis detection. Latent class analysis resulted in a three classes clusterization. Class 1 (20%; n=390) had the highest overall PQ scores (mean=49.31,SD=10.783), class 2 (43%; n=835) had intermediate scores (mean=23.37,SD=6.56), and class 3 (37%; n=721) had the lowest scores (mean=5.81,SD=3.74). Class 1 had significantly more individuals with less education and significantly more individuals with lower socioeconomic class. Poverty and low education might be associated with the psychotic expression in the general population, amplifying their actions on the psychosis gradient in developing countries. The psychosis continuum might be constituted by three distinct quantitatively different classes.