Biomarker discovery using machine learning in the psychosis spectrum.

The past decade witnessed substantial discoveries related to the psychosis spectrum. Many of these discoveries resulted from pursuits of objective and quantifiable biomarkers in tandem with the application of analytical tools such as machine learning. These approaches provided exciting new insights that significantly helped improve precision in diagnosis, prognosis, and treatment.

Uncovering key predictive channels and clinical variables in the gamma band auditory steady-state response in early-stage psychosis: a longitudinal study.

Objective: Psychotic disorders are characterised by abnormalities in the synchronisation of neuronal responses. A 40 Hz gamma band deficit during auditory steady-state response (ASSR) measured by electroencephalogram (EEG) is a robust observation in psychosis and is associated with symptoms and functional deficits. However, the majority of ASSR studies focus on specific electrode sites, while whole scalp analysis using all channels, and the association with clinical symptoms, are rare.

Identify Potential Causal Relationships Between Cortical Thickness, Mismatch Negativity, Neurocognition, and Psychosocial Functioning in Drug-Naïve First-Episode Psychosis Patients.

Background: Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP.

A spectrum of altered non-rapid eye movement sleep in schizophrenia.

Background: Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et.

Is auditory processing measured by the N100 an endophenotype for psychosis? A family study and a meta-analysis.

Background: The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients.

Methods: We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls.

Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis.

Background: Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables.

Exploring the influence of functional architecture on cortical thickness networks in early psychosis - A longitudinal study.

Cortical thickness reductions differ between individuals with psychotic disorders and comparison subjects even in early stages of illness. Whether these reductions covary as expected by functional network membership or simply by spatial proximity has not been fully elucidated. Through orthonormal projective non-negative matrix factorization, cortical thickness measurements in functionally-annotated regions from MRI scans of early-stage psychosis and matched healthy controls were reduced in dimensionality into features capturing positive covariance.

Annotation of Trauma-related Linguistic Features in Psychiatric Electronic Health Records for Machine Learning Applications.

Psychiatric electronic health records (EHRs) present a distinctive challenge in the domain of ML owing to their unstructured nature, with a high degree of complexity and variability. This study aimed to identify a cohort of patients with diagnoses of a psychotic disorder and posttraumatic stress disorder (PTSD), develop clinically-informed guidelines for annotating these health records for instances of traumatic events to create a gold standard publicly available dataset, and demonstrate that the data gathered using this annotation scheme is suitable for training a machine learning (ML) model to identify these indicators of trauma in unseen health records. We created a representative corpus of 101 EHRs (222,033 tokens) from a centralized database and a detailed annotation scheme for annotating information relevant to traumatic events in the clinical narratives.

Subfield-specific longitudinal changes of hippocampal volumes in patients with early-stage bipolar disorder.

Background: The hippocampus is a heterogeneous structure composed of biologically and functionally distinct subfields. Hippocampal aberrations are proposed to play a fundamental role in the etiology of psychotic symptoms. Bipolar disorder (BPD) has substantial overlap in symptomatology and genetic liability with schizophrenia (SZ), and reduced hippocampal volumes, particularly at the chronic illness stages, are documented in both disorders.

Test-retest reliability of the Childhood Trauma Questionnaire in psychotic disorders.

Background: Childhood trauma is common and associated with worse psychiatric outcomes. Yet, clinicians may not inquire about childhood trauma due to a misconception that patients cannot provide reliable reports. The goal of this study was to examine the reliability of self-reports of childhood trauma in psychotic disorders.

Impact of Substance Use Disorder on Between-Network Brain Connectivity in Early Psychosis.

The Triple Network Model of psychopathology identifies the salience network (SN), central executive network (CEN), and default mode network (DMN) as key networks underlying the pathophysiology of psychiatric disorders. In particular, abnormal SN-initiated network switching impacts the engagement and disengagement of the CEN and DMN, and is proposed to lead to the generation of psychosis symptoms. Between-network connectivity has been shown to be abnormal in both substance use disorders (SUD) and psychosis.

Smoking as a Common Modulator of Sensory Gating and Reward Learning in Individuals with Psychotic Disorders.

Motivational and perceptual disturbances co-occur in psychosis and have been linked to aberrations in reward learning and sensory gating, respectively. Although traditionally studied independently, when viewed through a predictive coding framework, these processes can both be linked to dysfunction in striatal dopaminergic prediction error signaling. This study examined whether reward learning and sensory gating are correlated in individuals with psychotic disorders, and whether nicotine-a psychostimulant that amplifies phasic striatal dopamine firing-is a common modulator of these two processes.

Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis.

The early stage of psychosis (ESP) is a critical period where effective intervention has the most favorable impact on outcomes. Thalamic connectivity abnormalities have been consistently found in psychosis, and are associated with clinical symptoms and cognitive deficits. However, most studies consider ESP patients as a homogeneous population and fail to take the duration of illness into account.

Auditory event-related potentials, neurocognition, and global functioning in drug naïve first-episode schizophrenia and bipolar disorder.

Background: Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.

Transcriptome-wide association study reveals two genes that influence mismatch negativity.

Mismatch negativity (MMN) is a differential electrophysiological response measuring cortical adaptability to unpredictable stimuli. MMN is consistently attenuated in patients with psychosis. However, the genetics of MMN are uncharted, limiting the validation of MMN as a psychosis endophenotype.

Longitudinal relationships between mismatch negativity, cognitive performance, and real-world functioning in early psychosis.

Background: Reduced mismatch negativity (MMN) is observed in early psychosis (EP) and correlated with cognition and functioning, but few studies have examined their longitudinal relationships and diagnostic specificity. We examined MMN, neuro- and social-cognition, and functional measures in EP patients with schizophrenia-spectrum (SZ) or bipolar disorder (BD) over a 1-year follow-up.

Methods: 54 EP patients (SZ: n = 24; BD: n = 30) and 42 healthy controls completed baseline measures: MMN, neuro- and social-cognition, and functional assessments.

Incorporating Risk Factor Embeddings in Pre-trained Transformers Improves Sentiment Prediction in Psychiatric Discharge Summaries.

Reducing rates of early hospital readmission has been recognized and identified as a key to improve quality of care and reduce costs. There are a number of risk factors that have been hypothesized to be important for understanding re-admission risk, including such factors as problems with substance abuse, ability to maintain work, relations with family. In this work, we develop RoBERTa-based models to predict the sentiment of sentences describing readmission risk factors in discharge summaries of patients with psychosis.

Identifying Clinically and Functionally Distinct Groups Among Healthy Controls and First Episode Psychosis Patients by Clustering on EEG Patterns.

Objective: The mismatch negativity (MMN) is considered as a promising biomarker that can inform future therapeutic studies. However, there is a large variability among patients with first episode psychosis (FEP). Also, most studies report a single electrode site and on comparing case-control group differences.

Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study.

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN).