Recent-onset Psychosis Patients Research Articles

Alterations of Functional Connectivity Dynamics in Affective and Psychotic Disorders

BackgroundPatients with psychosis and patients with depression exhibit widespread neurobiological abnormalities. The analysis of dynamic functional connectivity (dFC) allows for the detection of changes in complex brain activity patterns, providing insights into common and unique processes underlying these disorders. MethodsWe report the analysis of dFC in a large sample including 127 patients at clinical high risk for psychosis, 142 patients with recent-onset psychosis, 134 patients with recent-onset depression, and 256 healthy control participants. A sliding window–based technique was used to calculate the time-dependent FC in resting-state magnetic resonance imaging data, followed by clustering to reveal recurrent FC states in each diagnostic group. ResultsWe identified 5 unique FC states, which could be identified in all groups with high consistency (mean r = 0.889 [SD = 0.116]). Analysis of dynamic parameters of these states showed a characteristic increase in the lifetime and frequency of a weakly connected FC state in patients with recent-onset depression (p < .0005) compared with the other groups and a common increase in the lifetime of an FC state characterized by high sensorimotor and cingulo-opercular connectivities in all patient groups compared with the healthy control group (p < .0002). Canonical correlation analysis revealed a mode that exhibited significant correlations between dFC parameters and clinical variables (r = 0.617, p < .0029), which was associated with positive psychosis symptom severity and several dFC parameters. ConclusionsOur findings indicate diagnosis-specific alterations of dFC and underline the potential of dynamic analysis to characterize disorders such as depression and psychosis and clinical risk states.

Brain texture as a marker of transdiagnostic clinical profiles in patients with recent-onset psychosis and depression

The inter-relationships of voxels can be captured by the radiomics texture features across multiple spatial scales. Prediction models of brain texture changes captured by the contrast texture feature in recent-onset psychosis (ROP) and recent-onset depression (ROD) have recently been proposed, although the validation of these models transdiagnostically at the individual level and the investigation of the variability in clinical profiles are lacking. Established prevention and treatment approaches focus on specific diagnoses and do not address the heterogeneity and manifold potential outcomes of patients. Here we aimed to investigate the cross-sectional utility of brain texture changes for (1) identification of the psychopathological state (ROP and ROD) and (2) the association of individualized brain texture maps with clinical symptom severity and outcome profiles. We developed transdiagnostic models based on structural magnetic resonance imaging data for 116 patients with ROD, 122 patients with ROP and 197 healthy control participants from the PRONIA (Personalized pROgNostic tools for early psychosIs mAnagement) study by applying a set of tools and frameworks to explain the classification decisions of the deep-learning algorithm (named explainable artificial intelligence) and clustering analysis. We investigated the contrast texture feature as the key feature for the identification of a general psychopathological state. The discrimination power of the trained prediction model was >72% and was validated in a second independent age- and sex-matched sample of 137 ROP, 94 ROD and 159 healthy control participants. Clustering analysis was implemented to map the changes in texture brain produced from an explainable artificial intelligence algorithm, in a group fashion. The explained individualized brain contrast map grouped into eight homogeneous clusters. In the clinical group, we investigated the association between the explained brain contrast texture map and clinical symptom severity as well as outcome profiles. Different patterns in the explained brain contrast texture map showed unique associations of brain alterations with clinical symptom severity and clinical outcomes, that is, age, positive, negative and depressive symptoms, and functionality. In some clusters, the mean explained brain contrast texture map values and/or brain contrast texture voxels that contributed significantly to the classification decision predicted accurately the PANSS (positive and negative symptom scale) scores, functionality and change in functionality over time. In conclusion, we created homogeneous clusters which predict the clinical severity and outcome profile in ROP and ROD patients.

A multivariate cognitive approach to predict social functioning in recent onset psychosis in response to computerized cognitive training

Clinical and neuroimaging data has been increasingly used in recent years to disentangle heterogeneity of treatment response to cognitive training (CT) and predict which individuals may achieve the highest benefits. CT has small to medium effects on improving cognitive and social functioning in recent onset psychosis (ROP) patients, who show the most profound cognitive and social functioning deficits among psychiatric patients. We employed multivariate pattern analysis (MVPA) to investigate the potential of cognitive data to predict social functioning improvement in response to 10 h of CT in patients with ROP. A support vector machine (SVM) classifier was trained on the naturalistic data of the Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study sample to predict functioning in an independent sample of 70 ROP patients using baseline cognitive data. PRONIA is a part of a FP7 EU grant program that involved 7 sites across 5 European countries, designed and conducted with the main aim of identifying (bio)markers associated with an enhanced risk of developing psychosis in order to improve early detection and prognosis. Social functioning was predicted with a balanced accuracy (BAC) of 66.4% (Sensitivity 78.8%; Specificity 54.1%; PPV 60.5%; NPV 74.1%; AUC 0.64; P = 0.01). The most frequently selected cognitive features (mean feature weights > ± 0.2) included the (1) correct number of symbol matchings within the Digit Symbol Substitution Test, (2) the number of distracting stimuli leading to an error within 300 and 200 trials in the Continuous Performance Test and (3) the dynamics of verbal fluency between 15 and 30 s within the Verbal Fluency Test, phonetic part. Next, the SVM classifier generated on the PRONIA sample was applied to the intervention sample, that obtained 54 ROP patients who were randomly assigned to a social cognitive training (SCT) or treatment as usual (TAU) group and dichotomized into good (GF-S ≥ 7) and poor (GF-S < 7) functioning patients based on their level of Global Functioning-Social (GF-S) score at follow-up (FU). By applying the initial PRONIA classifier, using out-of-sample cross-validation (OOCV) to the sample of ROP patients who have undergone the CT intervention, a BAC of 59.3% (Sensitivity 70.4%; Specificity 48.1%; PPV 57.6%; NPV 61.9%; AUC 0.63) was achieved at T0 and a BAC of 64.8% (Sensitivity 66.7%; Specificity 63.0%; PPV 64.3%; NPV 65.4%; AUC 0.66) at FU. After SCT intervention, a significant improvement in predicted social functioning values was observed in the SCT compared to TAU group (P ≤0.05; ES[Cohens' d] = 0.18). Due to a small sample size and modest variance of social functioning of the intervention sample it was not feasible to predict individual response to SCT in the current study. Our findings suggest that the use of baseline cognitive data could provide a robust individual estimate of future social functioning, while prediction of individual response to SCT using cognitive data that can be generated in the routine patient care remains to be addressed in large-scale cognitive training trials.

The impact of cannabidiol treatment on resting state functional connectivity, prefrontal metabolite levels and reward processing in recent-onset patients with a psychotic disorder

The first clinical trials with cannabidiol (CBD) as treatment for psychotic disorders have shown its potential as an effective and well-tolerated antipsychotic agent. However, the neurobiological mechanisms underlying the antipsychotic profile of CBD are currently unclear. Here we investigated the impact of 28-day adjunctive CBD or placebo treatment (600 mg daily) on brain function and metabolism in 31 stable recent-onset psychosis patients (<5 years after diagnosis). Before and after treatment, patients underwent a Magnetic Resonance Imaging (MRI) session including resting state functional MRI, proton Magnetic Resonance Spectroscopy (1H-MRS) and functional MRI during reward processing. Symptomatology and cognitive functioning were also assessed. CBD treatment significantly changed functional connectivity in the default mode network (DMN; time × treatment interaction p = 0.037), with increased connectivity in the CBD (from 0.59 ± 0.39 to 0.80 ± 0.32) and reduced connectivity in the placebo group (from 0.77 ± 0.37 to 0.62 ± 0.33). Although there were no significant treatment effects on prefrontal metabolite concentrations, we showed that decreased positive symptom severity over time was associated with both diminishing glutamate (p = 0.029) and N-acetyl-aspartate (NAA; neuronal integrity marker) levels (p = 0.019) in the CBD, but not the placebo group. CBD treatment did not have an impact on brain activity patterns during reward anticipation and receipt or functional connectivity in executive and salience networks. Our results show that adjunctive CBD treatment of recent-onset psychosis patients induced changes in DMN functional connectivity, but not prefrontal metabolite concentrations or brain activity during reward processing. These findings suggest that DMN connectivity alteration may be involved in the therapeutic effects of CBD.

Personality traits and coping strategies in recent-onset psychosis: Associations with symptom severity and psychosocial functioning

BackgroundPersonality and coping may be related to symptom severity and psychosocial functioning in patients with recent-onset psychosis. This study aimed to investigate associations of personality traits and coping strategies with concurrent and follow-up symptom severity and functioning in those patients, and identify whether coping mediates relations between personality and symptoms or functioning. MethodsAt baseline, 527 recent-onset psychosis patients (73 % male, mean age = 28 years) received assessments on personality (Neuroticism-Extraversion-Openness – Five-Factor Inventory), coping (Utrecht Coping List), symptom severity (Positive And Negative Syndrome Scale) and psychosocial functioning (Global Assessment of Functioning Scale). Of those, 149 also received symptom and functioning assessments at follow-up. Multivariable linear regression analyses were performed to assess cross-sectional associations of personality and coping with symptoms and functioning at baseline. Longitudinal associations of baseline personality and coping with follow-up symptomatic remission and functioning were analyzed with multivariable linear and binary logistic regression analyses, respectively. Lastly, it was investigated whether coping mediated associations between personality and symptoms or functioning. ResultsHigher baseline Agreeableness (B = -0.019, [95%CI: −0.031; −0.007]) and Neuroticism (B = -0.017, [95%CI: −0.028; −0.006]) were associated with lower concurrent symptom severity. Reassuring Thoughts were associated with better functioning at baseline (B = 0.833, [95%CI: 0.272; 1.393]). Neither personality nor coping were associated with follow-up symptomatic remission or functioning. Coping did not mediate associations between personality and symptoms or functioning. ConclusionOnly the coping strategy Reassuring Thoughts is associated with better baseline functioning in patients with recent-onset psychosis. Personality traits seem to have limited clinically relevant relations with symptom severity or functioning.

A randomized controlled trial of a peer-facilitated self-management program for people with recent-onset psychosis

Early patient-centered interventions can improve mental health and prevent psychotic relapse in people with recent-onset psychosis (ROP). However, limited effective peer-facilitated early interventions are found worldwide. We aimed to test the effects of a four-month peer-facilitated self-management intervention (PFSMI) for Chinese patients with ROP compared with a psychoeducation group (PEG) and treatment-as-usual (TAU) group. A randomized controlled trial was conducted at six Integrated Community Centers for Mental Wellness in Hong Kong. The primary outcome was level of recovery. Secondary outcomes were improvement of problem-solving ability, insight into illness/treatment, and functioning, and reducing psychotic symptoms and re-hospitalization rates. Overall, 180 ROP patients were randomly selected, and after collecting baseline data, randomly assigned to the PFSMI, PEG or TAU (60 per group). Their outcomes were measured at 1-week and 6-month post-intervention. One hundred and sixty-one patients (89.4 %) completed their interventions, with an overall attrition rate of 7.8 % (n = 14). Based on intention-to-treat principle, results of generalized estimating equation test indicated that the PFSMI group reported significantly greater improvements in levels of recovery, functioning and insight into illness/treatment and reductions in psychotic symptoms and duration of re-hospitalizations (p = 0.0007–0.02, with moderate to large effect sizes) than the TAU group at 1-week post-intervention, and both the TAU and PEG at 6-month post-intervention. Significantly fewer PFSMI participants were hospitalized than the TAU and PEG over 6-month follow-up (p = 0.003). The findings support that PFSMI can produce medium-term positive effects on the mental health and functioning of patients with ROP.

Risk factors for metabolic syndrome in individuals with recent-onset psychosis at disease onset and after 1-year follow-up

Metabolic syndrome (MetS) is a cluster of parameters encompassing the most dangerous heart attack risk factors, associated with increased morbidity and mortality. It is highly prevalent in recent-onset psychosis (ROP) patients. In this pilot study, we evaluated MetS parameters (fasting glucose, high-density lipoprotein (HDL) cholesterol (HDL-c), fasting triglycerides, waist circumference, and systolic and diastolic blood pressure), clinical symptoms, pharmacological treatment, lifestyle, and inflammatory markers in 69 patients with ROP and 61 healthy controls (HCs). At baseline, waist circumference (p = 0.005) and fasting triglycerides (p = 0.007) were higher in patients with ROP than in HCs. At the 1-year follow-up, patients showed clinical improvement, with a reduction in the positive and negative syndrome scale (PANSS) score (p < 0.001), dietary intake (p = 0.001), and antipsychotic medication dose (p < 0.001); however, fasting glucose (p = 0.011), HDL-c (p = 0.013) and waist circumference worsened (p < 0.001). We identified sex, age, BMI, dietary intake, physical activity, daily tobacco use, daily cannabis use, and antipsychotic doses as risk factors contributing to baseline MetS parameters. After 1-year follow-up, those factors plus the PANSS and Calgary Depression Scale for Schizophrenia (CDSS) scores were associated with MetS parameters. Further studies are needed to understand the contributions of the studied risk factors in patients with ROP at onset and during disease progression.

Symptom dimensions stability over time in recent onset psychosis: A prospective study

BackgroundThe factorial structure of schizophrenia symptoms has been much debated but little is known on its degree of unicity, specificity as well as its dynamic over time. Symptom differentiation is a phenomenon according to which patients' symptoms could differentiate from one another during illness to form more independent, distinct dimensions. On the contrary, symptom dedifferentiation is an increase in the correlations between those symptoms over time. The goal of this study was to investigate symptom differentiation or dedifferentiation over time in recent onset psychosis using the Positive and Negative Syndrome Scale. MethodsA confirmatory factor analysis model based on the consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia was estimated on seven different time points over a three-year period. A general factor capturing common variance between every symptom was also included. Explained common variance was computed for the general factor and each specific factor. ResultsThree hundred and sixty-two recent onset psychosis patients were assessed. Results showed no evidence for either symptom differentiation or dedifferentiation over time. Specific symptoms accounted for >70 % of the variance suggesting a high degree of specificity of the symptomatology. ConclusionsOverall, this study adds support for a highly multidimensional approach to clinical symptom assessment with an explicit focus on depression. The premise behind the staging approach being inherently one-dimensional, implications for further research is discussed.

Immune regulatory gene polymorphisms, frequent cannabis use, and psychosis: implications to Treg hypofunction

IntroductionWe have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.ObjectivesTo explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.MethodsWe genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).ResultsWe found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).ConclusionsVariation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).DisclosureNo significant relationships.

The factor structure and clinical utility of clinician-rated dimensions of psychosis symptom severity in patients with recent-onset psychosis: Results of a 1-year longitudinal follow-up prospective cohort study

The classic subtype classification of schizophrenia has been removed, and DSM-5 now includes the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). In the present study, a factor analysis of the CRDPSS was performed, and we assessed whether patient classification using the derived factor structure helps predict the clinical course. The participants were 390 patients with recent-onset psychosis enrolled in the Korean Early Psychosis Cohort Study (KEPS). Two factors were identified: psychotic (including delusions, hallucinations, disorganization, and abnormal psychomotor behavior) and negative-cognitive (including negative symptoms and impaired cognition). Patients were grouped based on the factor structure and changes in clinical course were monitored over 1 year. The negative-cognitive group demonstrated longer duration of untreated psychosis, earlier onset, and a higher rate of psychiatric comorbidities. Baseline Positive and Negative Syndrome Scale (PANSS) total and Clinical Global Impression-Severity (CGI-S) scores were higher in psychotic group, but group differences were not observed after 2 months. Conversely, the PANSS negative scale score was significantly higher in negative-cognitive group throughout follow-up, and CGI-S score was reversed at 12 months. The findings indicate that the factor structure derived herein for the CRDPSS could be helpful for predicting the clinical course of recent-onset psychosis patients.

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Heterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach.

Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ2 = 14.874; P < .001; GMV model: χ2 = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ2 = 1.956; P = 0.162; GMV model: χ2 = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.

Longitudinal investigation of the relationship between omega-3 polyunsaturated fatty acids and neuropsychological functioning in recent-onset psychosis: A randomized clinical trial

Alterations in polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, have been implicated in the pathophysiology of psychotic disorders, but little is known about their associations with neuropsychological functioning. The present study includes 46 recent-onset psychosis patients who participated in a larger (n = 50) double blind, placebo-controlled randomized clinical trial comparing 16 weeks of treatment with either risperidone + fish oil (FO) (EPA 740 mg and DHA 400 mg daily) or risperidone + placebo and completed neuropsychological assessments at the baseline timepoint. We investigated the relationship between baseline omega-3 (i.e., eicosapentaenoic acid, EPA; docosapentaenoic acid, DPA and docosahexaenoic acid, DHA) and omega-6 (i.e., arachidonic acid, AA) PUFA with baseline MATRICS Consensus Cognitive Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS) scores. Twenty-five patients had neuropsychological data available at 16 weeks following participation in the clinical trial, which included 12 patients assigned to risperidone + FO and 13 patients assigned to risperidone + placebo. At baseline both higher DHA and EPA correlated significantly with better social cognition after controlling for functioning on other neuropsychological domains, total BPRS score, AA level and substance use. Also, at baseline higher AA correlated significantly with hostility/uncooperativeness after controlling for DHA + EPA + DPA, overall neuropsychological functioning and substance use. Patients treated with risperidone + FO demonstrated a significant longitudinal increase in social cognition that was significantly higher at 16 weeks compared to patients treated with risperidone + placebo. DHA also correlated significantly with social cognition at the 16-week timepoint. This study provides novel evidence for a differential role of omega-3 vs. omega-6 PUFA in neuropsychological deficits and symptoms in recent-onset psychosis and its treatment.

Modeling Social Sensory Processing During Social Computerized Cognitive Training for Psychosis Spectrum: The Resting-State Approach.

Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. Here, we investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are (1) related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and (2) associated with unique resting-state functional connectivity (rsFC).Methods: Twenty-six ROP patients completed 10 h of CCT over the period of 4–6 weeks. Subject-specific improvement in one CCT exercise targeting early sensory processing—a speeded facial Emotion Matching Task (EMT)—was studied as potential proxy for target engagement. Based on the median split of SPC from the EMT, two patient groups were created. Resting-state activity was collected at baseline, and bold time series were extracted from two major default mode network (DMN) hubs: left medial prefrontal cortex (mPFC) and left posterior cingulate cortex (PCC). Seed rsFC analysis was performed using standardized Pearson correlation matrices, generated between the average time course for each seed and each voxel in the brain.Results: Based on SPC, we distinguished improvers—i.e., participants who showed impaired performance at baseline and reached the EMT psychophysical threshold during CCT—from maintainers—i.e., those who showed intact EMT performance at baseline and sustained the EMT psychophysical threshold throughout CCT. Compared to maintainers, improvers showed an increase of rsFC at rest between PCC and left superior and medial frontal regions and the cerebellum. Compared to improvers, maintainers showed increased rsFC at baseline between PCC and superior temporal and insular regions bilaterally.Conclusions: In ROP patients with an increase of connectivity at rest in the default mode network, social CCT is still able to induce sensory processing changes that however do not translate into social cognitive gains. Future studies should investigate if impairments in short-term synaptic plasticity are responsible for this lack of response and can be remediated by pharmacological augmentation during CCT.

A 16-week randomized placebo-controlled trial investigating the effects of omega-3 polyunsaturated fatty acid treatment on white matter microstructure in recent-onset psychosis patients concurrently treated with risperidone

We examined the impact of treatment with fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids (n-3 PUFA), on white matter in 37 recent-onset psychosis patients receiving risperidone in a double-blind placebo-controlled randomized clinical trial. Patients were scanned at baseline and randomly assigned to receive 16-weeks of treatment with risperidone + FO or risperidone + placebo. Eighteen patients received follow-up MRIs (FO, n = 10/Placebo, n = 8). Erythrocyte levels of n-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) were obtained at both time points. We employed Free Water Imaging metrics representing the extracellular free water fraction (FW) and fractional anisotropy of the tissue (FA-t). Analyses were conducted using Tract-Based-Spatial-Statistics and nonparametric permutation-based tests with family-wise error correction. There were significant positive correlations of FA-t with DHA and DPA among all patients at baseline. Patients treated with risperidone + placebo demonstrated reductions in FA-t and increases in FW, whereas patients treated with risperidone + FO exhibited no significant changes in FW and FA-t reductions were largely attenuated. The correlations of DPA and DHA with baseline FA-t support the hypothesis that n-3 PUFA intake or biosynthesis are associated with white matter abnormalities in psychosis. Adjuvant FO treatment may partially mitigate against white matter alterations observed in recent-onset psychosis patients following risperidone treatment.

A multivariate neuromonitoring approach to neuroplasticity-based computerized cognitive training in recent onset psychosis

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.

Glycated Haemoglobin Is Associated With Poorer Cognitive Performance in Patients With Recent-Onset Psychosis.

BackgroundGlucose abnormalities and cognitive alterations are present before the onset of schizophrenia. We aimed to study whether glucose metabolism parameters are associated with cognitive functioning in recent-onset psychosis (ROP) patients while adjusting for hypothalamic-pituitary adrenal (HPA) axis measures.MethodsSixty ROP outpatients and 50 healthy subjects (HS) were studied. Cognitive function was assessed with the MATRICS Consensus Cognitive Battery. Glycated haemoglobin (HbA1c), glucose, insulin, and C-peptide levels were determined in plasma. The HOMA-insulin resistance index was calculated. Salivary samples were obtained at home on another day to assess the cortisol awakening response and cortisol levels during the day. Univariate analyses were conducted to explore the association between glucose metabolism parameters and cognitive tasks. For those parameters that were more clearly associated with the cognitive outcome, multiple linear regression analyses were conducted to adjust for covariates. Each cognitive task was considered the dependent variable. Covariates were age, sex, education level, diagnosis, antipsychotic and benzodiazepine treatment, body mass index (BMI), smoking, and HPA axis measures. Potential interactions between diagnosis and glucose parameters were tested.ResultsThere were no significant differences in HPA axis measures or glucose parameters, with the exception of C-peptide (that was higher in ROP patients), between groups. ROP patients had a lower performance than HS in all cognitive tasks (p < 0.01 for all tasks). Of all glucose metabolism parameters, HbA1c levels were more clearly associated with cognitive impairment in cognitive tasks dealing with executive functions and visual memory in both ROP patients and HS. Multivariate analyses found a significant negative association between HbA1c and cognitive functioning in five cognitive tasks dealing with executive functions, visual memory and attention/vigilance (a ROP diagnosis by HbA1c negative interaction was found in this latter cognitive domain, suggesting that HBA1c levels are associated with impaired attention only in ROP patients).ConclusionsOur study found that HbA1c was negatively associated with cognitive functioning in both ROP patients and HS in tasks dealing with executive functions and visual memory. In ROP patients, HbA1c was also associated with impaired attention. These results were independent of BMI and measures of HPA axis activity.

S44. NEUROBIOLOGICAL FINGERPRINTS OF COGNITIVE SUBTYPES IN RECENT ONSET PSYCHOSIS PATIENTS

BackgroundNeurocognitive impairment plays a central role in pathogenesis and course of psychotic disorders. Patients suffering from psychosis or psychosis-related diseases show general and specific neurocognitive impairments that often precede the onset of manifest symptoms. Neurocognitive impairments are frequently associated with reduced psychosocial functioning along with altered brain morphology and function. Quantifying neurocognitive heterogeneity in impairment in schizophrenia patients, cluster analytic approaches differentiated several cognitive subtypes, including a generally impaired and generally spared subgroup. An independent set of findings provided evidence that neurocognitive subgroups of cognitively spared and impaired SZ patients can also be differentiated based on their brain morphology. The current study aims to (1) subtype a first episode psychosis sample based on neurocognitive performance using cluster analysis and (2) investigate grey matter (GM) differences between the obtained cognitive subtypes and healthy volunteers.Methods121 recent onset-psychosis (ROP) patients and 201 healthy controls (HC) were recruited within the framework of the Personalized Prognostic Tool for Early Psychosis Management (PRONIA) project. Patients fulfilled DSM-IV-TR criteria of a first affective or non-affective psychotic episode in the last 3 month with onset in the last 24 months. Cognitive subtypes of the ROP patients were derived from 83 variables of 10 neurocognitive tasks using a kmeans clustering algorithm. A resampling approach implemented in R was used to assess the statistical stability of the results. Neuropsychological and clinical cluster characteristics were assessed using t tests. GM volume of the obtained patient clusters was compared by means of intracranial volume corrected t tests with age, sex and site matched HCs using SPM.ResultsThe analysis reveals a stable two-cluster solution: A higher cognitive performance cluster (HCP; N=71) and a lower cognitive performance cluster (LCP; N=39). Patients assigned to HCP performed significantly (p < 0.01) worse in 4 out of 10 neuropsychological tasks. Patients assigned to LCP performed significantly (p < 0.01) worse in 9 out of 10 neuropsychological tasks. LCP patients show significantly lower premorbid IQ (p < 0.001) and General Assessment of Functioning score (GAF; p < 0.01), lower occupational functioning (p < 0.01) and higher values on the negative component of the Positive and Negative Syndrom Scale (PANSS; p < 0.05). They show no demographical differences regarding age, sex, education years and study site. LCP patients reveal widespread GM reductions in bilateral temporal, parietal and frontal brain regions as compared to healthy controls. GM reductions of the HCP cluster are more restricted and evident in temporal, occipital regions and in the anterior cingulum.DiscussionTwo homogeneous, neurocognitive subgroups of patients suffering from a recent psychotic episode were identified and show distinctive psychopathological and neuroanatomical patterns. The obtained GM reductions in LCP go in line with the neuro-developmental origin of the disease affecting premorbid cognitive and occupational functioning as well as the STG which was reported to be decreased in the early course of the disease. Finding subgroups within early stage psychotic patients with minimal intake of antipsychotic medication, suggests different underlying patho(-physio)logical mechanisms predating manifest illness expression. This evidence offers the opportunity for personalizing interventions like neurocognitive trainings to enhance patients’ odds for recovery after psychosis.

M59. THE ASSOCIATIONS BETWEEN THEORY OF MIND AND NEUROCOGNITION IN RECENT ONSET PSYCHOSIS

BackgroundDeficits in theory of mind (ToM), the ability to infer the mental states of others, are common in psychotic disorders and are associated with functioning difficulties. While ToM is a social cognitive process, several neurocognitive processes are involved when inferring the mental states of others. A better understanding of the associations between ToM and neurocognitive domains could help better target treatment for ToM in schizophrenia. A recent meta-analysis has revealed that all neurocognitive domains are moderately associated with ToM in schizophrenia, but very few studies have looked at these associations in recent onset psychosis. These studies showed associations between ToM and speed of processing, episodic memory and executive functions although few neurocognitive domains have been assessed in each study. The aim of this study was to determine the associations between ToM and the key neurocognitive domains in recent onset psychosis.MethodsThese results are part of a larger study that aimed to determine the cognitive predictors of return to work or school in recent onset psychosis. Twenty-seven recent onset psychosis patients were recruited for this study, with a mean age of 24.9 years. The clinical assessment included the Combined Stories Test for ToM and the Matrics Consensus Cognitive Battery (MCCB) for neurocognition. The MCCB assesses the key cognitive domains relevant for schizophrenia, including attention/vigilance, speed of processing, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. Pearson correlations were conducted between the ToM scores of the Combined Stories Test and each neurocognitive domain of the MCCB.ResultsCorrelations revealed a moderate to strong association between ToM and working memory (r = 0.443, p = 0.021), visual learning (r = 0.493, p = 0.009) and verbal learning (r = 0.443, p = 0.021). The correlations between ToM and attention/vigilance, speed of processing and reasoning/problem solving were not significant (p > 0.05).DiscussionThis is the first study that has assessed the associations between ToM and the neurocognitive domains of the MCCB in recent onset psychosis. This study did not show association between ToM and speed of processing nor executive functions, but rather with working memory and learning. These contradictory results could be explained by the large heterogeneity of tasks used across studies, particularly ToM tasks that often present with psychometric limitations such as ceiling effect. Learning processes highlighted here should be considered in the understanding of the therapeutic response following a cognitive remediation therapy for ToM in recent onset psychosis.

Cognitive correlates of abnormal myelination in psychosis

Psychotic illness has consistently been associated with deficits in cognitive function and reduced white matter integrity in the brain. However, the link between white matter disruptions and deficits in cognitive domains remains poorly understood. We assessed cognitive performance and white matter myelin water fraction (MWF) using multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) in recent-onset psychosis patients and age-matched healthy controls (HC). Psychosis patients showed deficits in working memory, phonological and semantic fluency, general intelligence quotient and reduced MWF in the left temporal white matter compared to HC. MWF in the left inferior fronto-occipital fasciculus and inferior longitudinal fasciculus was positively associated with intelligence quotient and verbal fluency in patients, and fully mediated group differences in performance in both phonological and semantic verbal fluency. There was no association between working memory and MWF in the left temporal white matter. Negative symptoms demonstrated a negative association with MWF within the left inferior and superior longitudinal fasciculi. These findings indicate that psychosis-related deficits in distinct cognitive domains, such as verbal fluency and working memory, are not underpinned by a single common dysfunction in white matter connectivity.