Matcheri Keshavan

• MD
• Professor at Harvard Medical School

Fostering a diverse, equitable, and inclusive academic environment to drive scientific innovation is paramount. However, historically underrepresented individuals continue to encounter significant barriers to advancing careers in neuroscience. We define diversity here as the wide range of human differences, that include among others: Race, ethnicit...

Aim This study aimed to evaluate associations in bipolar disorder (BD) across multimodal measures of white matter microstructure (using diffusion tensor imaging; DTI), cognitive, behavioral, and brain electrophysiological measures (using electroencephalography; EEG). Methods Subjects were recruited through the Psychosis and Affective Research Doma...

Purpose of review The debate over renaming schizophrenia has gained international momentum, driven by concerns about stigma and scientific accuracy. This review examines the arguments for and against renaming schizophrenia, highlighting research data from the US and international efforts. Recent findings Proponents argue that the current term perp...

Background/objectives: Most individuals who have a familial or clinical risk to develop psychosis remain free from psychopathology. Identifying neural markers of resilience in these at-risk individuals may help clarify underlying mechanisms and yield novel targets for (early) intervention. However, in contrast to studies on risk biomarkers, studies...

Objective The visual system is a significant site of pathology in psychosis spectrum disorders. However, there is limited research investigating human visual cortex (VC) subregions in this population. Using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes Consortium (BSNIP-1, BSNIP-2, PARDIP), this study examined structural me...

Background This study examined the relationship between the Duration of Untreated Psychosis (DUP) and functional outcomes at baseline, 6 months, and 12 months after admission to Coordinated Specialty Care (CSC). Methods A total of 246 participants from two U.S. public-sector CSC programs were categorized into Low and High DUP groups using two crit...

Background We previously reported that machine learning could be used to predict conversion to psychosis in individuals at clinical high risk (CHR) for psychosis with up to 90% accuracy using the North American Prodrome Longitudinal Study-3 (NAPLS-3) dataset. A definitive test of our predictive model that was trained on the NAPLS-3 data, however, r...

Background Investigations of causal pathways for psychosis can be guided by the identification of environmental risk factors. A recently developed composite risk tool, the exposome score for schizophrenia (ES-SCZ), which controls for intercorrelations between risk factors, has shown fair to good performance. We tested the transdiagnostic psychosis...

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Po...

Background Individuals with psychosis symptoms are at high risk for suicidal ideation and attempts. The prevalence and correlates of suicidal ideation and attempts in clinical high risk for psychosis (CHR‐P) have yet to be clarified. This study reports on the prevalence and clinical correlates of suicidal ideation and attempts in a clinical CHR‐P s...

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Pol...

Background: Given that protein expression mediates genetic vulnerability, proteomics—the comprehensive study of proteins—is regaining prominence in neuropsychiatric research. This resurgence is driven by novel technical advancements that enable the simultaneous examination of multiple proteins. Numerous studies have demonstrated the potential of pr...

We investigated the impact of COVID-19 restrictions on the duration of untreated psychosis (DUP). First-episode psychosis admissions ( n = 101) to the STEP Clinic in Connecticut showed DUP reduction ( P = 0.0015) during the pandemic, with the median reducing from 208 days pre-pandemic to 56 days in the early pandemic period, and subsequently increa...

Objective The B-SNIP consortium validated neurobiologically defined psychosis Biotypes (BT1, BT2, BT3) using cognitive and psychophysiological measures. B-SNIP’s biomarker panel is not practical for most settings. Previously, B-SNIP developed an efficient classifier of Biotypes using only clinical assessments (called ADEPT-CLIN) with acceptable acc...

Background Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical,...

Background and Hypothesis Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator. St...

The Clinical High Risk (CHR) stage of psychosis is characterized by subthreshold symptoms of schizophrenia including negative symptoms, dysphoric mood, and functional deterioration. Hyperconnectivity of the default-mode network (DMN) has been observed in early schizophrenia, but the extent to which hyperconnectivity is present in CHR, and the exten...

Background: Early intervention in first-episode psychosis (FEP) is critical for improving patient outcomes. While Coordinated Specialty Care (CSC) is effective, the additional impact of reducing the Duration of Untreated Psychosis (DUP) within CSC programs is less understood. This study investigates the effect of an early detection campaign on func...

Schizophrenia is a complex, heritable brain disorder characterized by psychotic, negative, cognitive, mood, and motor symptoms. This pictorial review explores the multifaceted nature of schizophrenia, from its etiology to prevention strategies. We discuss the interplay of genetic and environmental risk factors, neurobiological underpinnings, and st...

The tripartite classification of mental faculties into cognition, affect, and conation (motivation and action) continues to be the edifice on which the mind and the methods to address mental afflictions are studied. Eastern spiritual traditions offer insights into mental health as it pertains to each of these domains. Following up on our previous p...

Introduction Schizophrenia is a mental health condition that severely impacts well-being. Cognitive impairment is among its core features, often presenting well before the onset of psychosis, underscoring a critical need to study it in the psychosis proneness stage, to maximize the benefits of interventions and to improve clinical outcomes. However...

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectu...

Background Neurocognitive deficits have been widely reported in clinical high-risk for psychosis (CHR) populations. Additionally, rates of cannabis use are high among CHR youth and are associated with greater symptom severity. Cannabis use has been sometimes shown to be associated with better neurocognition in more progressed psychosis cohorts, the...

Background The time following a recent onset of psychosis is a critical period during which intervention may be maximally effective. Studying individuals in this period also offers an opportunity to investigate putative brain biomarkers of illness prior to the long-term effects of chronicity and medication. The Human Connectome Project for Early Ps...

Traditional cognitive assessments in schizophrenia are time-consuming and necessitate specialized training, making routine evaluation challenging. To overcome these limitations, this study investigates the feasibility and advantages of utilizing smartphone-based assessments to capture both cognitive functioning and digital phenotyping data and comp...

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Her...

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined catego...

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulat...

Background and Hypothesis The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric str...

We investigated the impact of COVID-19 restrictions on the duration of untreated psychosis (DUP). First-episode psychosis admissions (n=101) to STEP Clinic in Connecticut showed DUP reduction (p=.0015) in the pandemic, with the median reducing from 208 days during the pre-pandemic to 56 days in the early pandemic period and subsequently increasing...

Background and Hypothesis Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the...

Aims For over 30 years, combined research and treatment settings in the US have been critical to conceptualizing care for first‐episode psychosis (FEP). Here we describe an early example of such a context, the Services for the Treatment of Early Psychosis (STEP) clinic, which is affiliated with the University of Pittsburgh. Methods We describe STE...

Background: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) have subthreshold psychosis symptoms without known genetic risk factors. Whether common neural substrates underlie these distinct high-risk populations...

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC ab...

The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium’s transdiagnostic dimensional model of psychopathology has considerable support; however, this model has been underresearched in individuals at clinical high risk for psychosis (CHR-P), a population that may advance the model. CHR-P individuals not only have attenuated psychotic sympto...

Aim Early interventions are well understood to improve psychosis outcomes, but their successful implementation remains limited. This article introduces a three‐step roadmap for advancing the implementation of evidence‐based practices to operate as a learning health system, which can be applied to early interventions for psychosis and is intended fo...

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of...

Background Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. Methods The study included 751 participants (174 with schiz...

Background Past research has found that family involvement in psychosis treatment leads to better patient outcomes. Thus, caregiver communication skills training can be a viable approach to reducing caregiver stress and increasing self‐efficacy and communication. Aim The purpose of this qualitative study was to describe family caregivers' percepti...

Transcranial electric stimulation (tES) may improve cognition in psychosis spectrum disorders. However, few studies have used novel tES approaches, such as high definition tES (HD-tES) to target specific brain circuits. Recently, the extrastriate visual cortex (V5/MT) has been causally linked to visual hallucinations through lesion network mapping...

Humans have asked themselves the question “who am I” from ancient times. Vedic, upanishadic and buddhist philosophers have pointed out over millennia the illusive nature of the individual self, and posit either a no-self, or a universal Self. Vedantic scholars also posit the illusory nature of the universe (Maya) and suggest that the only reality i...

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) has categorized psychosis disorders (Schizophrenia, Schizoaffective Disorder and Bipolar Disorder) into three distinct Biotypes, based on neurobiological measurements in a multi-ancestry sample. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores...

Apart from the characteristic body exercises performed in yoga (that places greater emphasis on static strength, maintenance of the posture and flexibility) which is in contrast to slow and stable body movements performed in other mind-body therapies such as Tai chi and Baduanjing, and Yijingjin, the effects of yoga may also be contributed by the f...

Background: This study examined the relationship between the Duration of Untreated Psychosis (DUP) and functional outcomes at baseline, 6 months, and 12 months after admission to Coordinated Specialty Care (CSC). Methods: A total of 246 participants from two U.S. public-sector CSC programs were categorized into Low and High DUP groups using two cri...

The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 th...

Abstract Background The proposed research aims to test the effects and mechanisms of a six-month yoga-based intervention as an add-on to standard treatment in opioid use disorder (OUD) by conducting a randomized controlled study with the following primary outcome variables: 1) clinical: abstinence (opioid negative urine test), and reductions in pai...

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