Lena Palaniyappan

Lena Palaniyappan
McGill University | McGill · Douglas Mental Health University Institute

BA(Psych) MBBS MMedSci PhD FRCPC
Currently working on understanding language behaviours in psychosis. See: https://discourseinpsychosis.org/

About

341
Publications
48,129
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Introduction
I am a psychiatrist working with people experiencing first episode of mental illnesses. My interests include the phenomenology and pathophysiology of psychosis and translation of neuroscientific advances to clinical practice. More about our group can be found here - http://www.schulich.uwo.ca/neuroscience/neuroimaging_in_mental_illnesses/
Additional affiliations
January 2016 - present
Lawson Health Research Institute
Position
  • Professor (Associate)
October 2015 - present
The University of Western Ontario
Position
  • Professor (Associate)
July 2009 - February 2012
University of Nottingham
Position
  • Clinical Lecturer

Publications

Publications (341)
Article
Abstract Context: At present, no reliable predictors exist to distinguish future responders from non-responders to treatment during the first episode of psychosis (FEP). Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterise, al...
Article
For effective information processing, two large-scale distributed neural networks appear to be critical: a multimodal executive system anchored on the dorsolateral prefrontal cortex (DLPFC) and a salience system anchored on the anterior insula. Aberrant interaction among distributed networks is a feature of psychiatric disorders such as schizophren...
Article
Background: A structural neuroanatomical change indicating a reduction in brain tissue is a notable feature of schizophrenia. Several pathophysiological processes such as aberrant cortical maturation, progressive tissue loss and compensatory tissue increase could contribute to the structural changes seen in schizophrenia. Method: We studied cort...
Article
One of the few well-replicated features of schizophrenia is the demonstration of neuroanatomical abnormalities affecting cortical and subcortical grey matter (GM). Evidence to date suggests that the greatest reduction in GM occurs in the immediate post-onset phase. The predominant view to date is that the accelerated grey matter (GM) loss represent...
Article
Schizophrenia provides a quintessential disease model of how disturbances in the molecular mechanisms of neurodevelopment lead to disruptions in the emergence of cognition. The central and often persistent feature of this illness is the disorganisation and impoverishment of language and related expressive behaviours. Though clinically more prominen...
Article
Full-text available
Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word-level choices in speech are sensitive to the illness stage (i.e., acute untreated vs. stable es...
Preprint
Background Pathophysiological inquiries into schizophrenia require a consideration of one of its defining features: disorganisation and impoverishment in verbal behaviour. This feature, often captured using the term Formal Thought Disorder, still remains to be one of the most poorly understood and often understudied dimensions of schizophrenia. Aim...
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Full-text available
Introduction Symptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structu...
Preprint
Background and HypothesisActive inference has become an influential concept in psychopathology. We apply active inference to investigate language behaviour in first-episode schizophrenia. We conceptualize speech production as a decision-making process affected by the latent “conceptual organization” during the selection of words. We consider concep...
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Full-text available
Background: Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dys...
Article
Full-text available
Working memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the...
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Full-text available
In the clinical linguistics of schizophrenia, syntactic complexity has received much attention. In this study, we address whether syntactic complexity deteriorates within the six months following the first episode of psychosis in those who develop a diagnosis of schizophrenia. We collected data from a cohort of twenty-six first-episode psychosis an...
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A commentary on the idea of creating speech bank for psychiatric disorders
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Introduction A central feature of schizophrenia is the disorganization and impoverishment of language. Recently, we observed higher semantic similarity in first-episode-schizophrenia (FES) patients. In this study, we investigate if this aberrant similarity relates to the ‘causal’ connectivity between two key nodes of the word production system: inf...
Article
Full-text available
Background: Abnormalities of cortical morphology have been consistently reported in major depressive disorder (MDD), with widespread focal alterations in cortical thickness, surface area and gyrification. However, it is unclear whether these distributed focal changes disrupt the system-level architecture (topology) of brain morphology in MDD. If p...
Preprint
Background Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical changes represent a simple aggregate of...
Article
Background Cortical thinning is a well-known feature in schizophrenia. The considerable variation in the spatial distribution of thickness changes has been used to parse heterogeneity. A ‘cortical impoverishment’ subgroup with a generalized reduction in thickness has been reported. However, it is unclear if this subgroup is recoverable irrespective...
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Full-text available
Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight ¹ . Here we assemble an...
Article
Full-text available
Background and hypothesis: Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement o...
Article
Objectives Up to 70%–80% of patients with bipolar disorder are misdiagnosed as having major depressive disorder (MDD), leading to both delayed intervention and worsening disability. Differences in the cognitive neurophysiology may serve to distinguish between the depressive phase of type 1 bipolar disorder (BDD-I) from MDD, though this remains to b...
Article
Background: Cannabis use disorder among young people with a first episode of psychosis contributes to relapse, hospitalization, and impaired functioning. However, few studies have examined what young people with early-phase psychosis, particularly those from Black racialized communities, understand or appreciate about this relationship - even thou...
Preprint
BACKGROUND Cannabis use disorder among young people with a first episode of psychosis contributes to relapse, hospitalization, and impaired functioning. However, few studies have examined what young people with early-phase psychosis, particularly those from Black racialized communities, understand or appreciate about this relationship - even though...
Article
Full-text available
Background Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent the...
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Full-text available
Aberration in the asymmetric nature of the human brain is associated with several mental disorders, including attention deficit/hyperactivity disorder (ADHD). In ADHD, these aberrations are thought to reflect key hemispheric differences in the functioning of attention, although the structural and functional bases of these defects are yet to be full...
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Full-text available
Background Suicidal ideation is a common symptom of major depressive disorder (MDD) that reflects a cognitive alteration in the background of intense emotional dysregulation. Amygdala is a critical emotion processing center that facilitates moving from emotional appraisal to action. However, whether MDD patients with suicidal ideation show dysconne...
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Full-text available
Background. While grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls. The relative excess of GM may indicate putative compensatory responses though to date its r...
Preprint
Full-text available
A commentary on Kesby JP, Murray GK, Knolle F. Neural circuitry of salience and reward processing in psychosis. Biological Psychiatry Global Open Science. 2021 Dec 11. OPEN ACCESS - https://www.bpsgos.org/article/S2667-1743(22)00001-5/fulltext#relatedArticles
Article
Full-text available
Overprotection and overcontrol from parents or other family members, which are not rare in the Chinese culture, have been suggested to be traumatic experiences for some children. However, research on overprotection/overcontrol is much rarer in China compared with other childhood trauma subtypes. One of the possible reasons for this is the lack of e...
Article
Common and distinct neural bases of Schizophrenia (SZ) and bipolar disorder (BP) have been explored using resting-state fMRI (rs-fMRI) functional connectivity (FC). However, fMRI is an indirect measure of neural activity, which is a convolution of the hemodynamic response function (HRF) and latent neural activity. The HRF, which models neurovascula...
Article
This patient’s case raises several important issues regarding the treatment of psychosis in women. While the patient’s sex frequently influences diagnostic decisions, choice of medications and dose-related decisions are not always tailored to women. Most guidelines on antipsychotic use are not sex-specific, but a large body of evidence now suggests...
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Full-text available
Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have inv...
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Full-text available
Reliable mapping of system-level individual differences is a critical first step towards precision medicine for complex disorders such as schizophrenia. Disrupted structural covariance indicates a system-level brain maturational disruption in schizophrenia. However, most studies examine structural covariance at the group-level. This prevents subjec...
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Full-text available
Automated extraction of quantitative linguistic features has the potential to predict objectively the onset and progression of psychosis. These linguistic variables are often considered to be biomarkers, with a large emphasis placed on the pathological aberrations in the biological processes that underwrite the faculty of language in psychosis. Thi...
Article
The importance of advancing anti-racism within research has gained recent attention. Academic medical organizations have attempted to increase diversity while seeking structural reforms to advance equity. However, efforts remain constrained while persons from racialized groups continue to experience discrimination. Mental health research is not imm...
Preprint
Full-text available
Overprotection and overcontrol from parents or other family members, which are not rare in the Chinese culture, have been suggested to be traumatic experiences for some children. However, research on overprotection/overcontrol is much rarer in China compared with other childhood trauma subtypes. One of the possible reasons for this is the lack of e...
Article
Full-text available
Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic reso...
Article
Full-text available
Ketamine is a dissociative anesthetic drug, which has more recently emerged as a rapid-acting antidepressant. When acutely administered at subanesthetic doses, ketamine causes cognitive deficits like those observed in patients with schizophrenia, including impaired working memory. Although these effects have been linked to ketamine’s action as an N...
Article
Full-text available
Patients with schizophrenia diverge in their clinical trajectories. Such diverge outcomes may result from the resilience provided by antioxidant response system centered on glutathione (GSH). Proton Magnetic Resonance Spectroscopy (1H-MRS) has enabled the precise in vivo measurement of intracortical GSH; but individual studies report highly variabl...
Preprint
Patients with schizophrenia diverge in their clinical trajectories. Such diverge outcomes may result from the resilience provided by antioxidant response system centered on glutathione (GSH). Proton Magnetic Resonance Spectroscopy (1H-MRS) has enabled the precise in vivo measurement of intracortical GSH; but individual studies report highly variabl...
Article
Full-text available
Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has sugge...
Preprint
Full-text available
The multilayer dynamic network model has been proposed as an effective method to understand how the brain functions dynamically. Specially, derived from the definition of clustering coefficient in static networks, the temporal clustering coefficient provides a direct measure of topological stability of dynamic brain networks and shows potential in...
Preprint
Full-text available
Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word level choices in speech are sensitive to illness stage (i.e. acute untreated vs. stable establi...
Article
Aberrations in intracortical myelination are increasingly being considered as a cardinal feature in the pathophysiology of schizophrenia. We investigated the network-level distribution of intracortical myelination across various cortex depths. We enrolled 126 healthy subjects and 106 first-episode drug-naïve schizophrenia patients. We used T1w/T2w...
Preprint
Full-text available
Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Several lines of evidence from preclinical, genetic and biochemical studies suggest a role for high oxidative stress in poor functional outcomes. The measurement of intracortical glutathione...
Preprint
Full-text available
Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has sugge...
Preprint
Full-text available
Cholinergic dysfunction has been implicated in the pathophysiology of psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here...
Preprint
Objective: Overlap of brain changes across mental disorders has reinforced transdiagnostic models. However, the developmental basis for this overlap is unclear as are neural differences among internalizing, externalizing and thought disorders. These issues are critical to inform the theoretical framework for hierarchical transdiagnostic psychiatric...
Article
Full-text available
Background: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown pe...
Article
Background Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitiv...
Article
Full-text available
Although approximately 1/3 of individuals with schizophrenia are Treatment Resistant (TR), identifying these subjects prospectively remains challenging. The Treatment Response and Resistance in Psychosis working group defines <20% improvement as an indicator of TR, though its utility in First Episode Schizophrenia (FES) remains unknown. In a prospe...
Article
Full-text available
A substantial number of individuals with clinical high-risk (CHR) mental state do not transition to psychosis. However, regardless of future diagnostic trajectories, many of these individuals develop poor social and occupational functional outcomes. The levels of glutathione, a crucial cortical antioxidant, may track variations in functional outcom...
Article
Full-text available
Background Frontal variant frontotemporal dementia is a common cause of presenile dementia. A hexanucleotide expansion on chromosome 9 has recently been recognized as the most common genetic mutation cause of this illness. This sub-type tends to present psychiatrically with psychosis being a common presenting symptom before the onset of cognitive c...
Article
Full-text available
Background: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cogniti...
Article
Full-text available
Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the...
Preprint
Schizophrenia provides a quintessential disease model of how disturbances in the molecular mechanisms of neurodevelopment lead to disruptions in the emergence of cognition. The central and often persistent feature of this illness is the disorganisation and impoverishment of language and related expressive behaviours. Though clinically more prominen...
Preprint
Full-text available
Over the past 25 years, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, there are no reference standards against which to anchor measures of individual differences in brain morphology, in contrast to growth charts for traits such as height and weight. Here, we built an interactive online...
Article
Full-text available
Aims To identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness. The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded wi...