Martin Lepage

• Ph.D
• James McGill Professor at McGill University

Background From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to...

Objective: Hospitalization in psychiatry is a challenging experience associated with increased levels of distress, anxiety, and loneliness. Novel technologies are being developed to help alleviate these symptoms and support the treatment and rehabilitation of these individuals. This study aims to explore the perspectives of individuals with lived e...

Objectives Patients with schizophrenia spectrum disorders (SSD) present with cognitive, behavioral, and emotional difficulties. Affected individuals often exhibit poor insight into aspects of their illness, such as awareness of the illness itself or the need for treatment, which can hinder treatment adherence and complicate clinical outcomes. This...

Virtual reality (VR) programs can support multiple aspects of well-being and have been developed by marginalized groups for these purposes, but there is still a systemic power imbalance. Marginalized groups have a place in digital well-being and can lead efforts directed towards resources that they desire. To better support these efforts and mobili...

Partial least squares (PLS) is actively leveraged in neuroimaging work, typically to map latent variables (LVs) representing brain–behaviour associations. LVs are considered statistically significant if they tend to capture more covariance than LVs derived from permuted data, with a Procrustes rotation applied to map each set of permuted LVs to the...

Cognitive impairments are a core feature of psychotic disorders, but their long-term trajectory remains contentious. Previous meta-analyses were focused on the first 5 years following psychosis onset. Here, we evaluated the change in cognitive impairments in psychotic disorders through a meta-analysis of studies with follow-ups of 5+ years. Followi...

Psychotic disorders are a class of heterogeneous disorders for which there is evidence of numerous structural and functional brain abnormalities. One proposed neural marker for psychosis is a disruption in white matter, the structural architecture for connectivity throughout the brain. The role of white matter integrity, often measured via Fraction...

Individuals living with severe mental illness experience persistent symptoms impacting their level of functioning, including vocational trajectories. Maintaining employment represents a challenge for most and improvements to existing supported employment programs could be made to specifically address this issue. The objective of the present study w...

Social anxiety disorder (SAD) is a frequent comorbidity in first-episode psychosis (FEP) and may increase cognitive impairments. Cognitive remediation (CR) is an effective treatment for cognition, particularly in a group format. This study aims to assess the efficacy, acceptability and engagement of group CR on cognitive outcomes in FEP+SAD compare...

Background Schizophrenia spectrum and other psychotic disorders (SSPD) are among the most debilitating of all mental disorders. While the evidence for psychosocial interventions such as cognitive behavioral therapy and peer support has significantly improved, access to these services remains limited. This paper describes a protocol for a pragmatic...

Negative symptoms and social cognition (SC) are intertwined in schizophrenia spectrum disorders (SSD) but the structure of this interaction is not yet fully understood. We employed cluster analyses to advance our understanding of the relationship between negative symptom severity and SC. We sought to identify discrete groups of patients as a functi...

Clinical course after first episode psychosis (FEP) is heterogeneous. Subgrouping longitudinal symptom trajectories after FEP would be useful for developing personalized treatment approaches, and being able to predict these trajectories at baseline would facilitate individual-level treatment planning. We utilized k-means clustering to identify dist...

Background and Hypothesis. Cognitive impairment is a core feature of schizophrenia spectrum disorders (SSD). While the relationship between cognition and symptoms in SSD has been extensively studied, there is a lack of research focusing on individual item-level analysis rather than relying on summary score methodology. Our previous study on a firs...

Schizophrenia and related psychoses are characterized by significant reductions in hippocampal volume and morphometric hippocampal-cortical connectivity. No study to date has addressed the temporal relationship between deviations in volume and connectivity across the heterogeneous spectrum of psychosis. To explore this relationship, we sampled cros...

Background. We previously proposed a neurocognitive model of psychosis in which reduced morphometric hippocampal-cortical connectivity precedes impaired episodic memory, social cognition, negative symptoms, and functional outcome. We provided support for this model in a patient subtype, and aimed to extend these findings in the modality of resting-...

Purpose High rates of Not in Education, Employment or Training (NEET) are seen in people with first episode of psychosis (FEP). Sociodemographic and clinical factors were reported to be associated with NEET status in FEP patients. This study follows Intersectionality to examine the independent and additive effects, and most importantly the intersec...

Importance Despite growing interest in the phenomenology of delusions in psychosis, at present little is known about their content and evolution over time, including whether delusion themes are consistent across episodes. Objective To examine the course of delusions and thematic delusion content across relapse episodes in patients presenting to an...

Partial least squares (PLS) is actively leveraged in neuroimaging work, typically to map latent variables (LVs) representing brain-behaviour associations. Canonically, LVs are considered statistically significant if they tend to capture more covariance than LVs derived from permuted data, with a Procrustes rotation applied to map each set of permut...

Background Schizophrenia spectrum disorders (SSDs) are a group of psychiatric disorders characterized by positive and negative symptoms as well as cognitive impairment that can significantly affect daily functioning. Method We reviewed evidence-based strategies for improving cognitive function in patients with SSDs, focusing on the Canadian landsc...

Background: From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early interventions servives (EIS), this study aimed...

Background: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be s...

Background Cognitive impairments are a key aspect of schizophrenia spectrum disorders (SSDs), significantly affecting clinical and functional outcomes. The COVID-19 pandemic has heightened concerns about mental health services and cognitive stimulation opportunities. Despite evidence-based interventions like action-based cognitive remediation (ABCR...

Aim To evaluate whether internalized stigma predicts social anxiety, functioning, and subjective recovery in first episode psychosis differently between group cognitive-behavioral therapy that addressed internalized stigma and cognitive remediation. Methods Data was derived from a randomized controlled trial comparing group cognitive-behavioral the...

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which le...

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard cl...

Purpose: High rates of Not in Education, Employment or Training (NEET) are seen in people with first episode of psychosis (FEP). Sociodemographic and clinical factors were reported to be associated with NEET status in FEP patients. This study follows Intersectionality to examine the independent and additive effects, and most importantly the interse...

BACKGROUND Social cognitive impairments are prevalent in schizophrenia spectrum disorder (SSD) and have detrimental effects on functioning. Cognitive remediation (CR) has shown its efficacy to improve social cognitive impairments, though the transfer of these skills to daily life and the personalization of these interventions remain challenging. RC...

Background Social cognitive impairments are prevalent in schizophrenia spectrum disorder (SSD) and have detrimental effects on functioning. Cognitive remediation (CR) has shown its efficacy in improving social cognitive impairments, although the transfer of these skills to daily life and the personalization of these interventions remain challenging...

Background and hypothesis: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our und...

Background and Hypothesis Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to...

Background Individuals with schizophrenia spectrum and related psychotic disorders (SSD) experience significant impairments in social cognition that impede functioning. Social cognition is a multidimensional construct consisting of four domains: 1. theory of mind, 2. emotion processing, 3. attributional style and 4. social perception. Metacognitive...

Social cognitive deficits are key predictors of negative symptoms and poor functional outcome in schizophrenia. We propose a neurocognitive disease progression model of social cognitive deficits in psychosis, developing from hippocampal volume deterioration to impairments in verbal memory, emotion recognition and theory of mind. We characterized th...

Polypharmacy is relatively common in early psychosis, but little attention has been paid to the anticholinergic burden of medication use (cumulative effect of medications that block the cholinergic system). Evidence suggests that anticholinergic burden is associated with cognitive deficits and that hippocampal dysfunction may be involved in those i...

There is robust evidence for sex differences in domain-specific cognition, where females typically show an advantage for verbal memory, whereas males tend to perform better in spatial memory. Sex differences in brain connectivity are well documented and may provide insight into these differences. In this study, we examined sex differences in cognit...

Background and Hypothesis. Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs is widely researched. The most well-replicated finding is an association between episodic memory and negative symptoms; however, the aspects of negative symptoms that underpin...

Background Identifying risk factors for suicidal ideation and attempt among first-episode psychosis patients is essential to prevent suicide in this high-risk population. We investigated risk factors at admission for suicidal ideation and attempt during a 2-year early intervention program. Methods Our sample included patients aged 18–35 years who...

Background: Negative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations betw...

Background and HypothesisSuicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to...

Psychosis represents a heterogeneous collection of biological and behavioural alterations that evolve over time. We propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impaired episodic memory and social cognition, worsening negative symptoms and lowering functional outcome. In two cro...

Psychiatric disorders are characterized by cognitive deficits, which have been proposed as a transdiagnostic feature of psychopathology (“C” factor). Similarly, cognitive biases (e.g., in attention, memory, and interpretation) represent common tendencies in information processing that are often associated with psychiatric symptoms. However, the que...

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate...

Objectives: Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory,...

Open science provides a compelling framework for accelerating global collaborations and enabling discoveries to understand and treat mental health disorders. Herein, we discuss the advantages and obstacles to adopting open science in mental health research, considering the particularities of sensitive and diverse data types, the potential of co-des...

Unlabelled: Horyzons is a digital health intervention designed to support recovery in young people receiving specialized early intervention services for first-episode psychosis (FEP). Horyzons was developed in Australia and adapted for implementation in Canada based on input from clinicians and patients (Horyzons-Canada Phase 1) and subsequently p...

Digital health innovations may help to improve access to psychosocial therapy and peer support; however, the existence of evidence-based digital health interventions for individuals recovering from a first-episode psychosis (FEP) remains limited. This study aims to investigate the feasibility, acceptability, safety, and pre-post outcomes of Horyzon...

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophre...

Introduction Schizophrenia-spectrum disorders (SSD) represent one of the leading causes of disability worldwide and are usually underpinned by neurodevelopmental brain abnormalities observed on a structural and functional level. Nuclear medicine imaging studies of cerebral blood flow (CBF) have already provided insights into the pathophysiology of...

Across subthreshold psychotic and nonpsychotic syndromes, symptoms experienced before the onset of a first episode of psychosis (FEP) may index distinct illness trajectories. We aimed to examine the associations between three types of pre-onset symptoms (self-harm, suicide attempts, and subthreshold psychotic) and outcome trajectories during FEP. P...

Aim: Dropping out of psychological interventions is estimated to occur in up to a third of individuals with psychosis. Given the high degree of attrition in this population, identifying predictors of attrition is important to develop strategies to retain individuals in treatment. We observed a particularly high degree of attrition (48%) in a recen...

Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, i.e., a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core featu...

Cognitive biases are systematic tendencies in the processing, selection and remembering of information. They are prevalent in schizophrenia-spectrum disorders (SSD) and are particularly associated with positive symptoms. The bias against disconfirmatory evidence (BADE) refers to a reluctance to integrate information that contradicts one’s beliefs a...

Background: Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected...

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences i...

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate...

Introduction: The Transverse Patterning (TP) task has been used to measure episodic relational memory (RM) deficits in clinical populations. Individuals with schizophrenia often fail to learn TP with standard, and sometimes extensive training. Identifying the differences between TP learners and non-learners can improve our understanding of success...

Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a sc...

In 2021, UNESCO issued official recommendations on Open Science. For the field of mental health research, Open Science provides a compelling framework for accelerating global collaborations to understand and treat mental health disorders. Herein we first discuss the advantages and obstacles to Open Science adoption in mental health research, consid...

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard cl...

Objective: Despite increasing recognition of the difficulties faced by persons with psychosis with respect to intimacy and sexuality, there is a lack of valid and reliable instruments to measure these areas of functioning in this population. This study aimed to evaluate the psychometric properties (i.e., construct and convergent validity, internal...

There is robust evidence for sex differences in domain-specific cognitive performance in the general population, where females typically show an advantage for verbal memory (VM), while males tend to perform better on tasks of spatial memory (SM). Sex differences in brain structure and connectivity are also well-documented and may provide insight in...

Background and hypothesis: Previous studies have suggested links between clinical symptoms and theory of mind (ToM) impairments in schizophrenia spectrum disorders (SSD), but it remains unclear whether some symptoms are more strongly linked to ToM than others. Study design: A meta-analysis (Prospero; CRD42021259723) was conducted to quantify and...

Background: Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk of experiencing self-stigma, and some cultures are more stigmatizing towards SSD than others. The first purpose of this review is to provide an estimate of the relationship between self-stigma and clinical and psychosocial outcomes. The second purpose is to e...

Persistent negative symptoms (PNS) are linked to poor functional outcomes and may be primary or caused by secondary factors. Although several studies have examined PNS in first-episode psychosis (FEP), a comparison with a data-driven approach is lacking. Here, we compared clinically defined PNS subgroups with class trajectories identified through l...

Purpose While the prevalence of delusional themes appears to be consistent across geographic contexts, little is known about the relative prevalence of such themes within a given setting over periods of time. We therefore investigated delusional themes across 12 years of presentation to a catchment-based early intervention service for first episode...

Episodic memory research in schizophrenia has a long history already which has clearly established significant impairments and strong associations with brain measures and functional outcome. The purpose of this chapter is not to make an exhaustive review of the recent literature but to highlight some relatively recent developments in the cognitive...

Verbal memory (VM) dysfunction is prevalent in first-episode psychosis (FEP) and has major impacts on long-term functional and clinical outcomes. Nevertheless, a substantial proportion of FEP patients have VM performance in the norm, called normal-range (NR) VM, and only a few studies have explored its relation to outcomes. Moreover, probable decre...

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences i...

Aim: Childhood trauma increases social functioning deficits in first-episode psychosis (FEP) and is negatively associated with higher-order social cognitive processes such as emotion recognition (ER). We investigated the relationship between childhood trauma severity and ER capacity, and explored sex as a potential factor given sex differences in...

Importance: A substantial increase in the number of trials examining metacognitive training (MCT) for psychosis necessitates an updated examination of the outcomes associated with MCT. Objectives: To review the immediate and sustained associations of MCT with proximal (directly targeted) and distal (indirectly influenced) outcomes and assess tre...

Background Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected b...

Objective: Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods to characterize the patterns of symptom clustering and how clusters relate to one another.Methods: We analyzed publicly-available data from 153 particip...

Objective Using concurrent transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG), this study aims to compare the effect of three intermittent theta-burst stimulation (iTBS) doses on cortical activity in the left dorsolateral prefrontal (DLPFC) cortex. Methods Fourteen neurotypical participants took part in the following thre...

Background Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the...

Background Psychotic disorders are among the most disabling of all mental disorders. The first-episode psychosis (FEP) often occurs during adolescence or young adulthood. Young people experiencing FEP often face multiple barriers in accessing a comprehensive range of psychosocial services, which have predominantly been delivered in person. New mode...

Severe cognitive impairments and cognitive distortions are core to schizophrenia-spectrum disorders (SSDs) and are associated with deteriorated social functioning. Despite well-established efficacy of group psychosocial therapies targeting cognitive health in SSDs, dissemination of these programs remains limited. Remote delivery offers a promising...

Schizophrenia is characterized by cognitive impairments and widespread structural brain abnormalities. Brain structure-cognition associations have been extensively studied in schizophrenia, typically involving individual cognitive domains or brain regions of interest. Findings in overlapping and diffuse brain regions may point to structural alterat...

Introduction: Relational memory (RM) is severely impaired in schizophrenia. Unitisation can circumvent RM impairments in clinical populations as measured by the transverse-patterning (TP) task, a well-established measure of RM capacity. We compared memory performance on a new ecological RM measure, the Relational Trip Task (RTT), to that of TP at...