Psychosis Patients Research Articles

Psychosis in a patient with tuberous sclerosis: A rare entity

Tuberous sclerosis complex (TSC) is a rare multisystemic genetic disorder which affects 1 in 6000–10,000 people worldwide. It usually affects the central nervous system and presents with multitude of symptoms such as seizures, skin abnormalities, intellectual disability, kidney disease, and behavioral problems. Psychosis has been rarely reported in patients with TSC. The Indian data on patients with TSC are sparse. We report a patient with TSC who presented with psychotic symptoms and discussed the management. Psychosis in patients with TSC is a rare association, and therefore, it should be assessed periodically while evaluating general health issues of patients with TSC.

Association between Sociodemographic Factors and Severity of Psychiatric Symptoms with Duration of Untreated Psychosis in Patients with First Episode Psychosis: A Cross-sectional Study

Introduction: The Duration of Untreated Psychosis (DUP) is the time interval between the manifestation of the first psychotic symptom in a patient and the starting of proper treatment. Though, considered as a modifiable factor in the outcome of mental illness, many confounding variables such as sociodemographic factors and illness related factors can affect the DUP. Aim: To identify the association between sociodemographic factors and the severity of psychiatric symptoms with the DUP in patients with the first episode of psychosis. Materials and Methods: A descriptive cross-sectional study conducted in the Department of Psychiatry, Government Medical College, Kottayam, Kerala, India, from March 2018 to February 2019. The first 50 consecutive patients reporting for treatment for the first time, who were diagnosed with psychotic disorders were recruited into the study. Details of the onset of psychosis were collected from the relative based on a clear, unequivocal description of symptoms by the relative. A specially designed proforma was used to gather the sociodemographic details and Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychotic symptoms. Statistical analysis was done using independent Student’s t-test, one-way Analysis of Variance (ANOVA) and Pearson’s correlation and p-value <0.05 is considered significant. Results: The mean age of the participants was 30.46 years and males constituted 31 (62%) of the participants. A total of 32 (64%) of the participants were unmarried or married but living separately. The mean DUP was 24.3 weeks (SD=23.9 weeks) and the mean BPRS score of the participants was 57.4 (SD=10.1). Schizophrenia was the diagnosis in 28 (56%) of participants. There was a significant correlation between the DUP and BPRS with a p-value=0.021 and Pearson’s correlation coefficient of 0.326. A significant association was found between the BPRS scores and the psychiatric diagnosis, with schizophrenia having higher mean BPRS scores. Conclusion: The DUP is considered a modifiable factor in the outcome of psychotic disorders. Many factors affect the time interval between the manifestation of initial symptoms in a patient and starting of the proper treatment. A significant association was found between the DUP and the severity of psychotic symptoms as evidenced by the BPRS score.

Gene Expressions Preferentially Influence Cortical Thickness of Human Connectome Project Atlas Parcellated Regions in First-Episode Antipsychotic-Naïve Psychoses.

Altered gene expressions may mechanistically link genetic factors with brain morphometric alterations. Existing gene expression studies have examined selected morphometric features using low-resolution atlases in medicated schizophrenia. We examined the relationship of gene expression with cortical thickness (CT), surface area (SA), and gray matter volume (GMV) of first-episode antipsychotic-naïve psychosis patients (FEAP = 85) and 81 controls, hypothesizing that gene expressions often associated with psychosis will differentially associate with different morphometric features. We explored such associations among schizophrenia and non-schizophrenia subgroups within FEAP group compared to controls. We mapped 360 Human Connectome Project atlas-based parcellations on brain MRI on to the publicly available brain gene expression data from the Allen Brain Institute collection. Significantly correlated genes were investigated using ingenuity pathway analysis to elucidate molecular pathways. CT but not SA or GMV correlated with expression of 1137 out of 15 633 genes examined controlling for age, sex, and average CT. Among these ≈19%, ≈39%, and 8% of genes were unique to FEAP, schizophrenia, and non-schizophrenia, respectively. Variants of 10 among these 1137 correlated genes previously showed genome-wide-association with schizophrenia. Molecular pathways associated with CT were axonal guidance and sphingosine pathways (common to FEAP and controls), selected inflammation pathways (unique to FEAP), synaptic modulation (unique to schizophrenia), and telomere extension (common to NSZ and healthy controls). We demonstrate that different sets of genes and molecular pathways may preferentially influence CT in different diagnostic groups. Genes with altered expressions correlating with CT and associated pathways may be targets for pathophysiological investigations and novel treatment designs.

Association between Symptom Dimensions and Psychosis Risk Factors with Functioning in First Episode Psychosis: A Six Months Prospective Study.

This study aims to assess the associations of the severity of different symptom dimensions and psychosis risk factors with the overall functioning levels in first-episode psychosis (FEP) patients over a 6-month follow-up period. Psychosis symptom dimensions (positive, negative, depression, mania, attention and other cognitive), sociodemographic characteristics and environmental risk factors (alcohol-substance use, childhood traumas, current stressful life events) were prospectively assessed in 32 patients who were hospitalized for FEP during the six-month follow-up period. The associations of these variables with the longitudinal Global Assessment of Functioning (GAF) scores of these patients were analyzed using linear regression or repeated measures ANOVA. The severity of positive, negative, depression and mania dimensions reduced (p<0.001) during the follow-up period, while no significant change was found in Stroop interference effect scores (F=0.4, p=0.53). FEP patients with substance or alcohol use had significantly worse functioning during the follow-up period (F=11.2, p=0.001; F=5.3, p=0.02, respectively), and those patients' functioning improved significantly less (F=10.0, p=0.002; F=4.3; p=0.04, respectively). Stroop test performance detected at the first month of the follow-up period significantly predicted the final general functioning scores of the follow-up [Stroop test word reading time (sec): B=-0.58 (-1.13-0.03); color telling speed (sec): B=-0.35 (-0.59-0.1); interference effect: B=-0.28 (-0.57-0.01)]. The stable course and prognostic value of attention and other types of cognitive functioning in FEP patients is remarkable. Interventions for alcohol-substance use in FEP patients should be a part of routine practice.

“Well-Track”: Fitbit Based Physical Activity and Sleep Hygiene Intervention for Early Intervention in Psychosis (EIP) and At-Risk Mental State (ARMS) Service Patients

“Well-Track”: Fitbit Based Physical Activity and Sleep Hygiene Intervention for Early Intervention in Psychosis (EIP) and At-Risk Mental State (ARMS) Service Patients

Development and Validation of Unmada Symptom Checklist

ABSTRACT Background: Psychosis is explained as Unmada in Ayurveda Medical Science. Types of Unmada are based on Tridosha. General and a specific symptom of Unmada have been explained in classics exclusively. Unmada is alteration in mental functions such as behavior, emotions, intellect, memory, and character. The symptoms of Unmada are (1) Mano vibhrama - altered functions of mind, (2) Buddhi vibhrama - altered discriminative power, judgment, (3) Sanjañā jñāna vibhrama - altered consciousness, (4) Smriti vibhrama - confused memory, (5) Bhakti vibhrama - altered attachment or embellishment, (6) Śīla vibhrama - altered nature or disposition, (7) Cheshta vibhrama - altered motion or gesture, and (8) Ācāra vibhrama - altered custom or practice. Many scales such as the Brief Psychiatry Rating Scale (BPRS) and positive and negative symptom scale are available from the modern perceptive. According to the Ayurveda perceptive, Unmada-specific symptom scale to measure Tridosha in psychotic patients is available, but there is a need for a standard scale to measure general symptoms so that the treatment for behavior, emotions, intellect, and memory can be planned as per the derangement. Hence, this study has been taken. Aims and Objective: The objective of the study was to develop a simple, standardized instrument to assess symptoms of Unmada according to the Ayurveda concepts in the diagnosed patients of psychosis. Methods: This was a descriptive type of study to develop a scale. A 54-item, Unmada symptom checklist (USC) was developed based on symptoms description in Ayurvedic classics and by taking the opinions of experts (five Ayurvedic experts, five psychiatrists, and five psychologists). It was evaluated in 30 patients with the diagnosis of nonaffective psychosis to check the reliability of the instrument. Moreover, the scale was administered on 30 patients who were diagnosed with psychosis. The duration for administration was about 20–25 min. Results: The reliability of a USC was good which was supported by high internal consistency values of Cronbach’s α – 0.9144. Correlation between total scores of BPRS and US was 0.959 and P&lt;0.001, which was considered as statistically significant. Interrater reliability coefficient for each item ranged from 0.627 to 0.951. Correlation, which measures of criterion related validity, was 0.950 with BPRS, which suggested that Ayurveda concepts correlate with modern concepts. Conclusions: An USC is a simple, efficient, reliable, and valid instrument for clinicians to diagnose Unmada in patients according to the Ayurveda concept. However, further research with more number of samples, more diverse groups of psychotic disorders, and a broader range of convergent and discriminant validity are needed.

The effect of smoking on metabolite levels in the anterior cingulate cortex of first-episode psychosis patients – a case-control 1h-MRS study

The effect of smoking on metabolite levels in the anterior cingulate cortex of first-episode psychosis patients – a case-control 1h-MRS study

Identification of blood and neuronal biomarkers for disease onset and medication response in first-episode psychosis patients

Identification of blood and neuronal biomarkers for disease onset and medication response in first-episode psychosis patients

Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study.

Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

Structural connectivity alterations in first-episode of psychosis patients during intra- and inter-hemispheric communication: an fMRI driven DTI study

Structural connectivity alterations in first-episode of psychosis patients during intra- and inter-hemispheric communication: an fMRI driven DTI study

Glutamate and GABA levels in the anterior cingulate cortex in treatment resistant first episode psychosis patients

Glutamate and GABA levels in the anterior cingulate cortex in treatment resistant first episode psychosis patients

Comparing treatment delays and pathways to early intervention services for psychosis in urban settings in India and Canada.

Although extensively studied in high-income countries (HICs) and less so in low- and middle-income countries (LMICs), pathways to care and treatment delays in early psychosis have not been compared across contexts. We compared pathways to early intervention for psychosis in an HIC (Montreal, Canada) and an LMIC (Chennai, India). We hypothesised that the duration of untreated psychosis (DUP) would be longer in Chennai. The number of contacts preceding early intervention, referral sources, first contacts, and DUP and its referral and help-seeking components of first-episode psychosis patients at both sites were similarly measured and compared using chi-square analyses and t tests/one-way ANOVAs. Overall and help-seeking DUPs of Chennai (N = 168) and Montreal (N = 165) participants were not significantly different. However, Chennai patients had shorter referral DUPs [mean = 12.0 ± 34.1weeks vs. Montreal mean = 13.2 ± 28.7weeks; t(302.57) = 4.40; p < 0.001] as the early intervention service was the first contact for 44% of them (vs. 5% in Montreal). Faith healers comprised 25% of first contacts in Chennai. Those seeing faith healers had significantly shorter help-seeking but longer referral DUPs. As predicted, most (93%) Montreal referrals came from medical sources. Those seeing psychologists/counsellors/social workers as their first contact had longer DUPs. Differences in cultural views about mental illnesses and organizational structures shape pathways to care and their associations with treatment delays across contexts. Both formal and informal sources need to be targeted to reduce delays. Early intervention services being the first portal where help is sought can reduce DUP especially if accessed early on in the illness course.

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis.

In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis. Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis. FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity. Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

Evaluating construct and criterion validity of NeuroScreen in assessing neurocognition among hospitalized Ugandan first-episode psychosis patients

IntroductionNeurocognitive impairment (NCI) is commonly exhibited among patients experiencing their first episode of psychosis. However, there are few resources in many low-income countries, such as Uganda, that allow for the administration of extensive neurocognitive test batteries for the detection of NCI. NeuroScreen is a brief tablet-based neurocognitive assessment battery that can be administered by all levels of healthcare staff. We examined the validity of NeuroScreen to assess neurocognition and detect NCI in first-episode psychosis (FEP) patients in Uganda. MethodsWe enrolled 112 participants FEP patients and matched controls at Butabika Mental Referral Hospital. Each participant completed NeuroScreen and a traditionally administered neurocognitive battery: the MATRIC Consensus Cognitive Battery (MCCB). We examined correlations between participant performance on NeuroScreen and the MCCB. A ROC curve determined sensitivity and specificity of NeuroScreen to detect NCI as determined by MCCB criterion. ResultsThere was a large, statistically significant correlation between overall performance on NeuroScreen and the MCCB [r(112) = 0.64, p < .001]. Small to large correlations were found between tests in the MCCB and NeuroScreen batteries. The ROC curve of NeuroScreen performance to detect MCCB-defined NCI had an area under curve of 0.80 and optimal sensitivity and specificity of 83 % and 60 %, respectively. ConclusionThere was a moderate positive correlation between overall performance on both batteries. NeuroScreen shows promise as a valid assessment battery to assess neurocognition and detect NCI in FEP patients in Uganda. Further studies of NeuroScreen in healthy individuals and in a range of mental disorders are recommended.

A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients

ObjectiveSchizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CT&E treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients. MethodsUCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CT&E) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer. ResultsCompared to patients in the CT group, those in the CT&E group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: F(1, 35) = 4.666, P < .04). Directional tendencies were similar in the left dorsolateral prefrontal cortex (DLPFC: F(1,35) = 4.132, P < .05). ConclusionsThese findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that has emerged as a key regulator of neurotransmission in complex cognitive processes. Its expression is altered in treated schizophrenia patients, and cannabinoids modulate CDK5 levels in the brain of rodents. However, the role of this kinase, and its interaction with cannabis use in first-episode psychosis (FEP) patients is still not known. Hence, we studied the expression changes of CDK5 and its signaling partner, postsynaptic density protein 95 (PSD95) in olfactory neuroepithelial (ON) cells of FEP patients with (FEP/c) and without (FEP/nc) prior cannabis use, and in a dual-hit mouse model of psychosis. In this model, adolescent mice were exposed to the cannabinoid receptor 1 agonist (CB1R) WIN-55,212–2 (WIN: 1 mg/kg) during 21 days, and to the N-methyl-d-aspartate receptor (NMDAR) blocker phencyclidine (PCP: 10 mg/kg) during 10 days. FEP/c showed less social functioning deficits, lower CDK5 and higher PSD95 levels than FEP/nc. These changes correlated with social skills, but not cognitive deficits. Consistently, exposure of ON cells from FEP/nc patients to WIN in vitro reduced CDK5 levels. Convergent results were obtained in mice, where PCP by itself induced more sociability deficits, and PSD95/CDK5 alterations in the prefrontal cortex and hippocampus than exposure to PCP-WIN. In addition, central blockade of CDK5 activity with roscovitine in PCP-treated mice restored both sociability impairments and PSD95 levels. We provide translational evidence that increased CDK5 could be an early indicator of psychosis associated with social deficits, and that this biomarker is modulated by prior cannabis use.

The effect of early life events on glucose levels in first-episode psychosis.

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients.

Evidence of innate immune dysfunction in first-episode psychosis patients with accompanying mood disorder

BackgroundInflammation and increases in inflammatory cytokines are common findings in psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Meta-analyses of studies that measured circulating cytokines have provided evidence of innate inflammation across all three disorders, with some overlap of inflammatory cytokines such as IL-6 and TNF-α. However, differences across disorders were also identified, including increased IL-4 in BD that suggest different immune mechanisms may be involved depending on the type of disorder present.MethodsWe sought to identify if the presence or absence of an affective disorder in first-episode psychotic (FEP) patients was associated with variations in cytokine production after stimulation of peripheral blood mononuclear cells (PBMC). 98 participants were recruited and grouped into healthy controls (n = 45) and first-episode psychosis patients (n = 53). Psychosis patients were further grouped by presence (AFF; n = 22) or lack (NON; n = 31) of an affective disorder. We cultured isolated PBMC from all participants for 48 h at 37 °C under four separate conditions; (1) culture media alone for baseline, or the following three stimulatory conditions: (2) 25 ng/mL lipopolysaccharide (LPS), (3) 10 ng/mL phytohemagglutinin (PHA), and (4) 125 ng/ml α-CD3 plus 250 ng/ml α-CD28. Supernatants collected at 48 h were analyzed using multiplex Luminex assay to identify differences in cytokine and chemokine production. Results from these assays were then correlated to patient clinical assessments for positive and negative symptoms common to psychotic disorders.ResultsWe found that PBMC from affective FEP patients produced higher concentrations of cytokines associated with both innate and adaptive immunity after stimulation than non-affective FEP patients and healthy controls. More specifically, the AFF PBMC produced increased tumor necrosis fctor (TNF)-α, interleukin (IL)-1β, IL-6, and others associated with innate inflammation. PBMC from AFF also produced increased IL-4, IL-17, interferon (IFN)γ, and other cytokines associated with adaptive immune activation, depending on stimulation. Additionally, inflammatory cytokines that differed at rest and after LPS stimulation correlated with Scale for the Assessment of Negative Symptoms (SANS) scores.ConclusionsOur findings suggest that immune dysfunction in affective psychosis may differ from that of primary psychotic disorders, and inflammation may be associated with increased negative symptoms. These findings could be helpful in determining clinical diagnosis after first psychotic episode.

Effects of Masupirdine (SUVN‐502) on Agitation/Aggression and Psychosis in Patients with Probable Alzheimer’s Disease: A Post Hoc Analysis

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder in older people with manifestations of cognitive and functional decline and neuropsychiatric symptoms (NPS). Agitation/aggression and psychosis are regarded as the most distressing NPS.Serotonin‐6 receptor (5‐HT6) is a G protein‐coupled receptor and is localized almost exclusively in the central nervous system regions which are important for control of mood regulation. Masupirdine is a potent and selective 5‐HT6 receptor antagonist. Masupirdine has been evaluated for its effects on cognition in patients with probable Alzheimer’s disease.MethodMasupirdine has been evaluated in a phase‐2a proof‐of‐concept, 26‐week, randomized, double‐blind, placebo‐controlled, multicenter, parallel group clinical study in United States under active US IND. Subgroup analyses of phase‐2a study results was carried out to evaluate the beneficial effects of masupirdine on agitation/aggression, and psychosis using Neuropsychiatric Inventory (NPI‐12) scale.Masupirdine was also evaluated in animal models to assess its effect on behavior and brain neurotransmitter modulations.ResultMasupirdine showed robust efficacy in agitation/aggression scores in patients who had baseline symptoms of agitation/aggression. In patients with baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores were observed in masupirdine treatment arms. Behavioral observations from the animal models were also in accord with the post hoc observations from the masupirdine clinical trial.ConclusionObservations from the masupirdine clinical trial suggest the potential utility of masupirdine for the management of neuropsychiatric symptoms associated with agitation/aggression, and psychosis in patients with AD. Masupirdine is currently being evaluated for the management on agitation in patients with dementia of the Alzheimer’s type.

Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.