Vinod Srihari

• Yale University

In February 2024, the Program for Specialized Treatment Early in Psychosis (STEP) in Connecticut launched the STEP Learning Collaborative (STEP-LC), a statewide learning health system. As part of this initiative, STEP-LC introduced a free consultation service to support clinicians, administrators, and healthcare leaders in the continuing care of yo...

Background Early intervention can improve outcomes for individuals with first-episode psychosis (FEP). We hypothesized that an early detection campaign (ED) targeting the Duration of Untreated Psychosis (DUP) can significantly improve functional outcomes in Coordinated Specialty Care (CSC) patients. Design Functional outcomes were compared for FEP...

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: This study explored how baseline insight predicts psychiatric hospitalization risk among 186 individuals with first-episode psychosis (FEP) in Coordinated Specialty Care (CSC). We hypothesized that insight, a potentially modifiable factor, moderates the relationship between CSC enrollment and outcomes, with a high baseline and stable hi...

Introduction Insight in psychosis, defined as a patient’s awareness and judgment of their mental illness, is a complex and evolving concept. Historically, the absence of insight was considered a defining characteristic of psychosis, but recent decades have seen the development of structured tools for its assessment. This systematic review aims to c...

Understanding the relationship between insight, depression, and suicidality in first-episode psychosis (FEP) is crucial for improving clinical outcomes and preventing suicide during early treatment stages. This longitudinal cohort study examined 264 participants enrolled in coordinated specialty care (CSC) services for FEP to inves- tigate how insi...

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...

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...

Introduction: Insight in psychosis, defined as a patient's awareness and judgment of their mental illness, is a complex and evolving concept. Historically, the absence of insight was considered a defining characteristic of psychosis, but recent decades have seen the development of structured tools for its assessment. This systematic review aims to...

Aims: The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. Methods: The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high r...

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: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome - a constellation of symptoms which may occur before the onset of psychosis - has been increasingly recognized as having utility. However, it is unclear what proportion of patients exper...

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015-2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual de...

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...

Highlights 2  Higher Personal income (PI) was associated with a small reduction in DUP to community based first-episode psychosis services.  An effective early detection campaign amplified this disparity by causing a marginally greater reduction in DUP for higher vs lower PI patients.  These disparities based on personal income were reassuringly...

Objective: Prolonged duration of untreated psychosis (DUP) is predictive of poor outcome in first-episode psychosis and is often linked to low socioeconomic status (SES). We aimed to determine a) if personal income (PI), used as a proxy for SES, predicts DUP and b) whether PI impacted the effect of an early detection (ED) campaign, Mindmap, on DUP...

We investigated the impact of COVID-19 restrictions on the duration of untreated psychosis (DUP). Participants (n = 101) with first-episode psychosis were recruited to the STEP clinic in Connecticut during pre-pandemic and pandemic times. DUP decreased significantly (p = .0015) in the pandemic, with the median reducing from 208 to 56 days. Subseque...

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015-2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual de...

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore association...

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in...

Mismatch negativity (MMN) reductions are among the most reliable biomarkers for schizophrenia and have been associated with increased risk for conversion to psychosis in individuals at clinical high risk for psychosis (CHR-P). Here, we adopt a computational approach to develop a mechanistic model of MMN reductions in CHR-P individuals and patients...

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015-2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual de...

Over the past two decades, research and clinical resources on clinical high risk (CHR) for psychosis have both expanded, with goals to better understanding risk and protective factors on the course of illness and inform early intervention efforts. However, some studies have highlighted potential sampling bias among CHR research studies, raising que...

Background Mismatch negativity (MMN) reductions are among the most reliable biomarkers for schizophrenia and have been associated with increased risk for conversion to psychosis in individuals at clinical high risk for psychosis (CHR-P). Here, we adopt a computational approach to develop a mechanistic model of MMN reductions in CHR-P individuals an...

Objective An extensive international literature demonstrates that understanding pathways to care (PTC) is essential for efforts to reduce community Duration of Untreated Psychosis (DUP). However, knowledge from these studies is difficult to translate to new settings. We present a novel approach to characterize and analyze PTC and demonstrate its va...

Recent COVID-19-related federal legislation has resulted in time-limited increases in Mental Health Block Grant (MHBG) set-aside dollars for coordinated specialty care (CSC) throughout the United States. The state of Ohio has opted to apply these funds to establish a learning health network of Ohio CSC teams, promote efforts to expand access to CSC...

Structural alterations or quantitative abnormalities of some mitochondrial ion channels and exchangers are associated with altered neuronal functions and increased susceptibility to mental illness. Here we have assessed levels of functionally prominent mitochondrial calcium ion channel proteins in plasma neuron‐derived extracellular vesicles (NDEVs...

Duration of untreated psychosis (DUP), the period between psychosis onset and entry into care, is a time of great vulnerability. Longer DUP predicts poorer outcomes, and delayed treatment access can limit the effectiveness of coordinated specialty care (CSC) services. This column details one component of a broader early detection campaign, a qualit...

This invited commentary provides a conceptual history of modern early intervention services, briefly reviews the accomplishments of an international clinical and research community, and offers proposals for how such services might participate in the next generation of progress. In keeping with the theme of this column, we make the argument that suc...

Cannabis has been implicated as both a potential cause and adverse prognostic factor in psychotic disorders. Investigating the contributory role of cannabis toward the overall burden of psychotic illnesses may represent an important step toward psychosis prevention and treatment. The current study samples consecutive admissions (N = 246) to two com...

Objective Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign (‘Mindmap’) can reduce DUP in a US community setting. Methods In this non-randomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Great...

To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pre...

Purpose Delay in receiving effective treatment for psychosis adversely impacts outcomes. We investigated the timing of the first help-seeking attempt in individuals with recent onset non-affective psychosis by comparing those who sought help during the prodrome to those who sought help after psychosis onset across sociodemographic and clinical char...

Aims First‐episode services (FES) improve outcomes in recent onset psychosis, but there is growing concern about how patients fare after discharge from these time‐limited services. Methods A quality improvement approach (QI) was used to improve patient engagement in the discharge planning process (disposition), and successful engagement in care 3...

Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural‐derived exosomes from ten first‐episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte‐derived extracellular vesicles (ADEVs) and neuron‐derived extracellular vesicles (NDEVs) were immunoabsorbed sepa...

Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron tra...

Aim: This study describes antipsychotic prescription patterns for drug-naïve inpatients diagnosed with first-episode schizophrenia-spectrum (FES) disorders and factors associated with practices deviating from China's current guidelines. Methods: All inpatients aged 7 to 45 years experiencing a first episode of schizophrenia-spectrum disorder wit...

Background The Specialized Treatment Early in Psychosis (STEP) program has delivered a specialty-team based first-episode service (FES) since 2006 in New Haven. In 2015, STEP launched a 4-year early detection (ED) campaign (Mindmap), adapted from the Scandinavian TIPS approach, to shorten Duration of Untreated Psychosis (DUP) in a 10-town catchment...

Background In the U.S., individuals affected by a first episode psychosis endure 74 mean weeks of delay in receiving effective treatment. Facilitating their access to care has become a public health priority. This delay has proven to have adverse consequences both in short and long-term outcomes. Moreover, aversive pathways to care can imperil subs...

Background Antipsychotics represent the core of treatment for first-episode schizophrenia (FES). The choice of the first antipsychotic in drug-naïve FES patients is delicate, as it could influence both adherence to medications and the course of the illness. In China, mental health care for schizophrenia is mainly provided by psychiatric hospitals,...

Experts discuss the potential of early intervention to transform outcomes for people with mental disorders. Mental illness represents one of the largest disease burdens worldwide, yet treatments have been largely ineffective in improving the quality of life for millions of affected individuals—in part because approaches taken have focused on late-s...

Background Although the clinical high risk (CHR) for psychosis paradigm has become well-established over the past two decades, one key component has received surprisingly little direct investigative attention: the validity of the conversion to psychosis or transition criteria. This lack of evidence is surprising because many CHR treatment and predi...

Aim To report on the development of an early intervention service in Modena, Italy, with information relevant to the first 4 years of implementation. Methods The 2‐year service was offered to people aged 18‐35 with psychotic manifestations, within 2 years from psychosis onset/or naïve to antipsychotics, by teams placed within community mental heal...

Identification of neurophysiological abnormalities associated with schizophrenia that predate and predict psychosis onset may improve clinical prediction in the psychosis risk syndrome (PRS) and help elucidate the pathogenesis of schizophrenia. Amplitude reduction of the P300 event-related potential component reflects attention-mediated processing...

Mounting evidence has indicated that early intervention leads to improved clinical and functional outcomes for young persons experiencing recent onset psychosis. As part of a large early detection campaign, the present study aimed to investigate subjective experiences during the duration of untreated psychosis (DUP), or time between psychosis onset...

Aim To apply spatial analytics to an underway first episode psychosis program to identify areas of significant variation in the geographical distribution of program enrollees from an underlying at‐risk population. Methods Adaptive bandwidth kernel smoothing was used to estimate spatial density functions from program enrollee home addresses and a c...

Background Early interventions services (EIS) for psychosis are not uniformly available in the Italian public mental health care system. In 2012, Region Emilia Romagna funded the implementation of a comprehensive population based program to deliver EIS. These services provide a package of care including psychiatric consultation, family psychoeducat...

Background Prolonged duration of untreated psychosis (DUP) is associated with poor outcome. The Scandinavian TIPS study deployed an early detection (ED) campaign to halve DUP. However, while reducing DUP will improve outcomes for most patients, there are some for whom prolonged DUP is a byproduct of an insidiously illness rather than a modifiable p...

In first-episode psychosis there is a heightened risk of aggression and subsequent criminal justice involvement. This column reviews the evidence pointing to these heightened risks and highlights opportunities, using a sequential intercept model, for collaboration between mental health services and existing diversionary programs, particularly for p...

Background: Reducing excessive delays in care, as measured by Duration of Untreated Psychosis (DUP), can improve outcomes for schizophrenia spectrum disorders. The program for Specialized Treatment Early in Psychosis (STEP) has delivered a best practice approach to coordinated care for early psychosis since 2006 in greater New Haven, and in 2014 be...

Background: Treatment guidelines for the clinical high risk (CHR) syndrome for psychosis currently recommend psychotherapies such as cognitive behavior therapy and focused family therapy as first line treatment. Antipsychotic medications are generally discouraged for routine use, partly because of concern for adverse effects and partly due to a pau...

The first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP. A comprehensive literatu...

Schizophrenia and other psychotic disorders are a source of significant morbidity, both for patients and caregivers. The first 2-5 years after the onset of psychosis are a critical period wherein treatment might effect disproportionate improvements in long-term outcomes. Specialized services have been developed with the goal of providing early and...

Objective: This study sought to determine the effectiveness of a comprehensive first-episode service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual treatment. Methods: This pragmatic randomized controlled trial enrolled 120 patients with first-episode ps...

Neurophysiological abnormalities in auditory deviance processing, as reflected by the mismatch negativity (MMN), have been observed across the course of schizophrenia. Studies in early schizophrenia patients have typically shown varying degrees of MMN amplitude reduction for different deviant types, suggesting that different auditory deviants are u...

Background: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter catego...

Background: Insomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-bli...

Objective Patients with schizophrenia have high rates of obesity and cardiovascular morbidity, which are strongly associated with Obstructive Sleep Apnea (OSA). The prevalence and risk factors for OSA are not well studied in patients with Schizophrenia. The purpose of this study was to evaluate the frequency of OSA symptoms in a sample of outpatien...

Background: Gamma-band oscillations and their synchronization have been implicated in the coordination of activity between distributed neuronal assemblies in the service of sensory registration of stimuli and perceptual binding of their features. Prior electroencephalographic (EEG) studies of chronic schizophrenia patients have documented deficits...

Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with nonclini...

Background: The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) p...

Background: Obesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substanti...

There is growing recognition that motivation among individuals with psychosis may influence both participation in and response to psychosocial interventions. Consequently, there is an increasing call for organizing treatment settings in ways that increase motivation among individuals with psychosis. However, empirical evidence suggests that whether...

Objective: Better understanding of the temporal development of cardiovascular risk will permit more targeted prevention of premature cardiovascular mortality in schizophrenia. Methods: The sample for this analysis was drawn from referrals (between 2006 and '11) to an early psychosis clinic based in a U.S. urban community mental health center. 76...

Services that provide comprehensive, early intervention (EI) have shown promise in improving long-term outcomes in schizophrenia. This article reviews the rationale and salient concepts relevant to understanding the growing EI literature. A selective review of studies evaluating the effectiveness of integrated EI is followed by a discussion of feas...

Background: Individuals with schizophrenia have a life expectancy that is 20 years less than the general population, along with high rates of obesity and cardiovascular disease (CVD) mortality. Objective: This study assessed the 10-year general CVD risk and vascular ages of 106 obese schizophrenia spectrum patients and 197 demographically matche...

Self-determination theory (SDT) postulates that satisfaction of three basic psychological needs (i.e., autonomy, competence, and well-being) promotes motivation, well-being, and growth across domains of functioning. Thus, per SDT, we examined satisfaction of basic psychological needs among individuals with first-episode psychosis. First, we quantif...

Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word m...

Sleep difficulties are common in schizophrenia, however these complaints are often overshadowed by more prominent clinical concerns. The point prevalence of insomnia in this population is not well documented. Poor sleep is associated with lower quality of life, impaired cognition, and weight gain. The objectives of this study are to evaluate the pr...

Discontinuities in health insurance coverage may make it difficult for individuals early in psychosis to receive the services that are critical in determining long-term outcome. This study reports on the rates and continuity of insurance coverage among a cohort of early-psychosis patients enrolled in Specialized Treatment Early in Psychosis (STEP)...

Neurodegenerative disorders can include diverse neuropsychiatric symptoms. Here we present a case referred to a "first-episode" psychosis clinic with socio-occupational decline, auditory hallucinations and paranoid ideation who subsequently exhibited a rapid, severe cognitive and behavioral decline. The brain magnetic resonance imaging findings of...

Studies in first episode psychosis samples about status of cardiovascular risk factors have shown discordant results. We aimed to determine the 10-year risk of developing coronary heart disease in a sample of first episode psychosis patients referred to an early intervention clinic and compared the same with age, gender, and race matched controls f...

The goal of this paper is to provide clarification with regard to the nature of mediator and moderator variables and the statistical methods used to test for the existence of these variables. Particular attention will be devoted to discussing the ways in which the identification of mediator and moderator variables may help to advance the field of e...

Given the growing interest in the study of first-episode psychosis, clinical and research programmes would benefit from a conceptual clarification of how to operationalize 'first-episode psychosis'. We review the variety of definitions in use and discuss their relative merits with respect to both clinical (e.g. early treatment) and research (e.g. o...

Early intervention may improve long-term outcomes for psychotic illnesses. Early-intervention services in other countries have focused on reducing the duration of untreated illness and adapting interventions for younger patients. This column describes the process of building such a service, called specialized treatment early in psychosis (STEP), at...

Family psychoeducation is considered part of optimal treatment for first-episode psychosis, but concerns about the cost of this intervention have limited its availability. Although evidence suggests that family psychoeducation is cost-effective, many cost-effectiveness analyses have suffered from limitations that reduce their utility in guiding dec...

Several recent studies of individually administered cognitive behavior therapy (CBT) for early psychosis have reported only modest treatment benefits. The purpose of the current study was to review the literature to determine how outcomes of group CBT differ from outcomes of individually administered CBT among early cases. Our findings suggest that...

Background: Many people (up to 50%) with schizophrenia also have co-morbid depression. It has been suggested that new atypical antipsychotic drugs are beneficial for people with the two diagnoses. Objectives: To assess the effects of atypical antipsychotic drugs on people who have a diagnosis of both schizophrenia and depression. Search strategy We...

Evidence-based medicine has an important place in the teaching and practice of psychiatry. Attempts to teach evidence-based medicine skills can be weakened by conceptual confusions feeding a false polarization between traditional clinical skills and evidence-based medicine. The author develops a broader conception of clinical expertise consisting o...

A 45 year old man with schizophrenia began experiencing auditory hallucinations at the age of 25. These were well controlled for several years by a monthly intramuscular injection of haloperidol decanoate. One year after he switched to oral haloperidol, the intensity of the hallucinations increased and included a voice commanding him to end his lif...

Background: Many people (up to 50%) with schizophrenia also have co-morbid depression. It has been suggested that new atypical antipsychotic drugs are beneficial for people with the two diagnoses. Objectives: To assess the effects of atypical antipsychotic drugs on people who have a diagnosis of both schizophrenia and depression. Search strateg...