Processing speed in first episode of psychosis and first-degree relatives: A candidate endophenotype of spectrum schizophrenia disorders.

OBJECTIVE: The processing speed (PS) is highly impacted in individuals experiencing their first episode of psychosis (FEP). Conducting family studies can help to determine whether PS can serve as an endophenotype of schizophrenia spectrum disorders (SSDs), offering valuable insights into the prevention and diagnosis of SSDs. METHOD: A comprehensive cognitive battery, encompassing tests for PS, verbal memory, visual memory, working memory, executive functions, motor dexterity, and attention, was administered to a sample consisting of 133 FEP patients, 146 parents, 98 siblings, and 202 healthy controls (HCs). Univariate analyses (analysis of covariance [ANCOVA]) were conducted to compare the different cognitive domains between groups, utilizing sex, age, and years of education as covariates and Bonferroni corrections. Effect sizes (ESs) were calculated for estimating the magnitude of differences between groups. RESULTS: Group comparisons revealed significant differences in all cognitive domains. PS was the most impaired function in patients. Parents and siblings had intermediate PS performance between FEP patients and HC. Large ES were observed in PS between FEP versus siblings, FEP versus controls, parents versus controls, and parents versus siblings. CONCLUSIONS: Despite not meeting all the necessary criteria, the PS observed in FEP patients and their first-degree relatives suggests its potential as a promising endophenotype of SSDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychotic Disorder after Left Posterior Cerebral Artery Stroke-An Atypical Event

Introduction: Stroke survivors usually present physical and neuropsychiatric complications. Post-stroke psychosis (PSPsy) is a particularly neglected sequel despite its disruptive nature. Objectives: To present a case of early emerging neuropsychiatric symptoms following a left posterior cerebral artery (PCA) stroke. To review and discuss PSPsy clinical manifestations, pathophysiology, and clinical outcomes. Clinical Case: A previously autonomous 68-year-old woman with vascular risk factors and depressive disorder presented to the emergency department with a 5-day history of disorientation, motor aphasia, and right hypoesthesia. Computer tomography revealed a left PCA stroke. She was started on acetylsalicylic acid and rosuvastatin and discharged the next day. Afterward, the patient developed a depressive mood, emotional lability, periods of confusion, delusions of persecution, guilt and unworthiness, auditory hallucinations, and suicide ideation. She was admitted to a psychiatric hospital and started on risperidone with a good response, being discharged after 15 days with the resolution of psychiatric symptoms. Conclusions: PSPsy is more common after right hemisphere lesions and usually develops after some months. Nevertheless, our patient presented PSPsy following an ischemic event of the left PCA, with neuropsychiatric symptomatology dominating the clinic since the beginning. The involvement of the retrosplenial cortex or its connections was likely important for this atypical presentation. Due to the lack of guidelines on approaching PSPsy, most patients are treated with the same strategies used for non-stroke patients. A better comprehension of the anatomical basis underlining the symptomatology in these patients could deepen the understanding of psychosis and psychotic disorders. (AU)

Neuropsychiatric Features of Fregoli Syndrome: An Individual Patient Meta-Analysis.

OBJECTIVE: Fregoli syndrome is a rare delusion characterized by the belief that familiar people are presenting themselves disguised as others to the affected person. Theories of delusional misidentification have suggested secondary ("organic") underlying mechanisms; however, the pathoetiology of Fregoli syndrome has not been systematically evaluated. The investigators aimed to compare the neuropsychiatric features of Fregoli syndrome in primary and secondary psychoses. METHODS: A systematic review and patient-level meta-analysis were conducted. Five databases were searched, ultimately yielding 83 studies that met selection criteria. Demographic characteristics, diagnosis, delusional content, neuropsychiatric features, investigations, and treatment information were extracted. Random-effects models were calculated, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total of 119 patients with Fregoli syndrome were identified: 62 patients (52%) with primary psychosis, 50 (42%) with secondary psychosis, and seven (6%) with an unclear etiology. Patients with secondary psychosis were less likely than patients with primary psychosis to experience persecutory features (OR=0.26, 95% CI=0.10, 0.67; p=0.0057). Moreover, patients with secondary psychosis were more likely to experience Fregoli syndrome during a first episode of psychosis (OR=11.00, 95% CI=2.45, 49.39; p=0.0017). Right-sided brain lesions were more prominent than left-sided brain lesions in the total sample (χ2=5.0, df=1, p=0.025) and in the secondary psychosis subgroup (χ2=4.26, df=1, p=0.039). CONCLUSIONS: This is the first meta-analysis to investigate Fregoli syndrome. An estimated 42% of the reported cases involved a secondary etiology. These findings provide clinicians with a better understanding of the symptomatology of Fregoli syndrome and have potential to be applied in future research and clinical practice.

El trastorno del lenguaje de las personas con esquizofrenia y su relación con la gravedad y la funcionalidad / The language disorder of people with schizophrenia and its relationship with severity and functionality

RESUMEN: Objetivo: estudiar las características del lenguaje en pacientes que padecen esquizofrenia u otros trastornos psicóticos. Método: 55 pacientes diagnosticados de esquizofrenia (50) y trastorno esquizoafectivo (5). Se aplica la escala TLC de Andreasen, la escala EEAG para la funcionalidad, la CGI para la gravedad. Se recogen datos sociodemográficos. Resultados: Las medias son: edad: 61,47 años, internamiento: 19,47 años, CGI: 5,8, EEAG: 32,5. La subescala de desconexión de la TLC puntúa de media: 8,43, y la de Subproducción verbal: 1,2. La desconexión correlaciona negativamente con EEAG, y positivamente con CGI. La Subproducción verbal correlaciona con CGI. Conclusiones: Los participantes presentan un grado de gravedad elevado y de funcionalidad bajo. Presentan alteraciones importantes del lenguaje, particularmente de pobreza del habla, pero también de desconexión verbal. Con puntuaciones que varían de leve a moderado. Ambas subescalas correlacionan con gravedad. Además, la desconexión es mayor en los pacientes con peor funcionalidad. La alteración del lenguaje en esquizofrenia está relacionada con la gravedad y la funcionalidad, lo cual tiene importantes consecuencias en la vida de las personas que padecen esta enfermedad.

ABSTRACT Objective: to study the characteristics of language in patients suffering from schizophrenia or other psychotic disorders. Method: 55 patients diagnosed with schizophrenia (50) and schizoaffective disorder (5). The Andreasen TLC scale, the EEAG scale for functionality and the CGI for gravity are applied. Sociodemographic data are collected. Results: Mean age: 61.47 years, mean years hospitalized: 19.47 years, CGI: 5.8, EEAG: 32.5. The TLC disconnection subscale scores on average: 8.43, and the Verbal Underproduction: 1.2. Disconnection correlates negatively with EEAG, and positively with CGI. Verbal underproduction correlates with CGI. Conclusions: The participants present a high degree of severity and low functionality. They present significant language alterations, poor speech, and verbal disconnection. With scores ranging from mild to moderate. Both subscales correlate with severity. In addition, the Disconnection is greater in patients with worse functionality. Language impairment in schizophrenia is related to severity and functionality, which has important consequences in the lives of people with this disease.

Neural mechanisms of motor dysfunction in individuals at clinical high-risk for psychosis: Evidence for impairments in motor activation.

Motor abnormalities are a core feature of psychotic disorders observed from the premorbid period through chronic illness, suggesting motor dysfunction may reflect the pathophysiology of psychosis. Electrophysiology research in schizophrenia suggests impaired motor activation and preparation may underlie these motor abnormalities. Despite behavioral studies suggesting similar motor dysfunction in those at clinical high-risk (CHR) for psychosis, there have been no studies examining neural mechanisms of motor dysfunction in the CHR period, where research can inform pathophysiological and risk models. The present study used the lateralized readiness potential (LRP), an event-related potential index of motor activation and preparation, to examine mechanisms of motor dysfunction in 42 CHR and 41 control participants (N = 83, 56% female). Response competition was manipulated to determine whether deficits are secondary to cognitive control impairments or reflect primary motor deficits. Behaviorally, CHR participants exhibited overall slower responses than controls. Further, relative to controls, CHR participants showed reduced activation of correct but not incorrect responses, reflected in blunted LRP amplitude under weak response competition and no difference in amplitude associated with the incorrect response under strong response competition. This pattern of results suggests individuals at CHR for psychosis exhibit primary motor deficits in activating and preparing behavioral responses and are contrary to a deficit in cognitive control. Further, blunted LRP amplitude was associated with worsening of negative symptoms at 12-month follow-up. Together, these findings are consistent with LRP studies in psychosis and implicate motor activation deficits as potential mechanisms of motor dysfunction in the high-risk period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample.

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

Antipsychotic-Associated Weight Gain and Clinical Improvement Under Clozapine Treatment.

BACKGROUND: Antipsychotic-associated weight gain is a common adverse effect with several negative outcomes in the clinical evolution of patients, which might also affect patients' self-identity from physical appearance and imply treatment discontinuation. However, recent research has drawn attention to an unexpected clinical improvement associated with weight gain, mostly in patients under treatment with clozapine or olanzapine. METHODS: Twenty-three treatment-resistant psychosis patients initiating clozapine were evaluated. Longitudinal psychopathological assessment through the Positive and Negative Syndrome Scale (PANSS) and anthropometric evaluation were performed at baseline, week 8, and 18. RESULTS: Body mass index (BMI) change during clozapine treatment was associated with clinical improvement measured with PANSS total score at week 8 (P = 0.021) while showed a trend at week 18 (P = 0.058). The PANSS general score was also associated with weight gain at week 8 (P = 0.022), whereas negative subscale score showed a trend at week 8 (P = 0.088) and was associated between week 8 and 18 (P = 0.018). Sex differences applied at week 8 for PANSS total score, where clinical improvement was significantly associated with BMI in male subjects (P = 0.024). We also stratified for time to initiate clozapine, finding significant associations in negative symptom at week 8 (P = 0.023) and week 18 (P = 0.003) for subjects, which started clozapine after 3 years of illness. CONCLUSIONS: Our results suggest that in subjects initiating clozapine, clinical improvement is associated with BMI increase, mostly in negative symptom and in patients after 3 years of antipsychotic use. Our findings were already described in the preantipsychotic era, suggesting some pathophysiological mechanism underlying both conditions.

Cardiometabolic health risks, lifestyle behaviours and quality of life in people diagnosed with early psychosis - A cross-sectional study.

WHAT IS KNOWN ON THE SUBJECT?: People diagnosed with schizophrenia have poor cardiometabolic health, with elevated 10-year cardiovascular disease risk (CVD-R) scores and low quality of life (QOL). There is a lack of understanding about CVD-R scores in people diagnosed with early psychosis and no studies have quantified CVD-R using the QRISK® 3 calculator in this client group. Establishing potential relationships between modifiable lifestyle behaviours/treatment characteristics with CVD-R or QOL may identify targets for early intervention. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first study to quantify the individual 10-year CVD-R of people diagnosed with early psychosis utilising the QRISK® 3 calculator. This is also the first study to investigate relationships between QOL and CVD-R and lifestyle factors in a cohort of Thai people diagnosed with early psychosis. We observed low levels of physical health-related QOL and high levels of CVR-R despite participants reporting relatively positive lifestyle behaviours. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The cardiometabolic health state of this client group warrants as much attention as for those with an enduring severe mental illness; early preventative interventions are warranted. It may be useful to routinely quantify the CVD-R of people diagnosed with early psychosis using the QRISK® 3 calculator, even in the absence of immediate concerns about lifestyle behaviours. Mental health nurses should utilise evidence-based approaches such as increasing activity levels, dietary counselling and behaviour change interventions to mitigate poor physical health in this client group. ABSTRACT: Introduction People diagnosed with schizophrenia have poor cardiometabolic health, with elevated 10-year cardiovascular disease risk (CVD-R) scores and poor quality of life (QOL). There is lack of understanding of these issues in early psychosis. Aims To quantify CVD-R in people diagnosed with early psychosis and profile their obesity prevalence, lifestyle behaviours and QOL. Secondary aim was to explore associations between lifestyle behaviours/treatment characteristics and CVD-R/QOL. Method Baseline data from 81 RCT participants were used to profile cardiometabolic health risks (QRISK® 3, BMI and waist circumference). Participants self-reported lifestyle behaviours and QOL. Relationships between modifiable treatment/lifestyle factors and QOL/CVD-R were explored. Results Participants' relative risk for CVD over 10 years was 1.93 times higher than healthy counterparts; 39% also had an obese BMI and physical QOL was poor. No significant associations were observed between CVD-R or QOL with treatment characteristics and lifestyle factors. Discussion Despite positive lifestyle behaviours, participants had elevated CVD-R scores and poor physical health-related QOL. Quantifying CVD-R with QRISK® 3 may highlight the need for health promotion interventions. Implications for practice Mental health professionals should be aware that elevated CVD-R exists in the context of relatively healthy lifestyle behaviours and utilise evidence-based interventions to address these issues.

Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography.

BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.

Neural Indicator of Altered Mismatch Detection Predicts Atypical Cognitive-Perceptual Experiences in Psychotic Psychopathology.

BACKGROUND: Atypical auditory processing (AAP) in psychotic psychopathology is evident in early (N1), mid-latency (P2/N2/mismatch negativity), and late (P3) neural responses. The influence of attention on AAP, and how temporal stages of AAP are associated with phenomenology of psychotic psychopathology are not well understood. METHODS: We used a directed attention oddball task to characterize stages of AAP in psychosis and to examine the influence of selective attention. Ninety patients with schizophrenia (SCZ), 53 patients with bipolar disorder (BP), 90 healthy controls and 72 first-degree relatives of SCZ (SREL) were studied. We used principal components analysis to decompose average-reference 64-channel subject-level ERPs. RESULTS: Altered attentional modulation was evident in SCZ at early (N1 factor) and late (P3 factor) stages of AAP, but not at mid-latency P2 factor. Irrespective of condition, N1 and P3 were reduced in SCZ, which predicted greater psychopathology and schizotypal personality traits. Diminished mid-latency mismatch detection (P2 factor) was evident in SCZ, BP, and SREL and was associated with greater positive symptoms of psychosis as well as self-reported atypical cognitive-perceptual experiences. CONCLUSIONS: Attentional modulation of early N1, and later P3 neural responses was atypical in patients, but the degree of attentional modulation did not relate to symptom severity or schizotypal traits. Our findings suggest the link between mid-latency mismatch detection and atypical cognitive/perceptual experiences is not driven by attentional deficits alone and point to the promise of mid-latency mismatch detection as a candidate endophenotype and intervention target.

Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

Dynamic Interplay Between Insight and Persistent Negative Symptoms in First Episode of Psychosis: A Longitudinal Study.

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms.

An Event-Related Potential Investigation of Early Visual Processing Deficits During Face Perception in Youth at Clinical High Risk for Psychosis.

Impairments in early visual face perception are well documented in patients with schizophrenia. Specifically, event-related potential (ERP) research in patients with schizophrenia has demonstrated deficits in early sensory processing of stimulus properties (P1 component) and the structural encoding of faces (N170 component). However, it is not well understood if similar impairments are present in individuals at clinical high risk (CHR) for psychosis (ie, those in the putative prodromal stage of the illness). Thus, it is unknown if face perception deficits are the result of illness onset or are present in the high-risk period for the illness. The present study used the ERP technique to examine neural activation when viewing facial emotion expressions and objects in 44 CHR and 47 control adolescents and young adults (N = 91). P1 amplitude was similar across groups, indicating that early sensory processing impairments did not substantially contribute to face perception deficits in CHR youth. CHR youth exhibited reduced N170 amplitude compared to controls when viewing faces but not objects, implicating a specific deficit in the structural encoding of faces rather than a general perceptual deficit. Further, whereas controls demonstrated the expected face-selective N170 effect (ie, larger amplitude for faces than objects), CHR youth did not, which suggests that facial emotion expressions do not elicit the expected preferential perceptual processing for critical social information in individuals at CHR for psychosis. Together, these findings provide valuable information regarding the specific impairments contributing to face perception deficits in the high-risk period where treatment stands to aid in preventing illness progression.

Autistic Symptoms and Social Functioning in Psychosis: A Network Approach.

Psychotic and autistic symptoms are related to social functioning in individuals with psychotic disorders (PD). The present study used a network approach to (1) evaluate the interactions between autistic symptoms, psychotic symptoms, and social functioning, and (2) investigate whether relations are similar in individuals with and without PD. We estimated an undirected network model in a sample of 504 PD, 572 familial risk for psychosis (FR), and 337 typical comparisons (TC), with a mean age of 34.9 years. Symptoms were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (SFS; 7 nodes). We identified statistically significant differences between the FR and PD samples in global strength (P < .001) and network structure (P < .001). Our results show autistic symptoms (social interaction nodes) are negatively and more closely related to social functioning (withdrawal, interpersonal behavior) than psychotic symptoms. More and stronger connections between nodes were observed for the PD network than for FR and TC networks, while the latter 2 were similar in density (P = .11) and network structure (P = .19). The most central items in strength for PD were bizarre experiences, social skills, and paranoia. In conclusion, specific autistic symptoms are negatively associated with social functioning across the psychosis spectrum, but in the PD network symptoms may reinforce each other more easily. These findings emphasize the need for increased clinical awareness of comorbid autistic symptoms in psychotic individuals.

Imbalance Model of Heart Rate Variability and Pulse Wave Velocity in Psychotic and Nonpsychotic Disorders.

OBJECTIVES: Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. METHODS: In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). RESULTS: All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. CONCLUSIONS: HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia.

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.

Prediction of Early Symptom Remission in Two Independent Samples of First-Episode Psychosis Patients Using Machine Learning.

BACKGROUND: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4-6-week remission following a first episode of psychosis. METHOD: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts. RESULTS: Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naïve. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P < .0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P < .0001), demonstrating reliability. CONCLUSIONS: Using items from common and validated clinical scales, our model significantly predicted early remission in patients with first-episode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians' assessment should be undertaken to evaluate the possible utility as a routine clinical tool.

Sleep Disturbance in Individuals at Clinical High Risk for Psychosis.

INTRODUCTION: Disturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time. METHODS: Data were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations. RESULTS: Disturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar. DISCUSSION: The critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.

Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study.

BACKGROUND: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ). METHODS: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ. RESULTS: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR-total scores were negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ. CONCLUSIONS: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically.