Papers by Andrew Dissanayake
European Neuropsychopharmacology, Sep 30, 2023
The Canadian journal of psychiatry/Canadian journal of psychiatry, Mar 1, 2024
ABSTRACTBackgroundRacial/ethnic disparities in the prevalence of mental health diagnoses have bee... more ABSTRACTBackgroundRacial/ethnic disparities in the prevalence of mental health diagnoses have been reported but have not accounted for the prevalence of the traits that underlies these disorders. Examining rates of diagnoses in relation to traits may yield a clearer understanding of how racial/ethnic youth differ in their access to assessment and care. We sought to examine differences in self/parent-reported rates of diagnoses for obsessive-compulsive disorder (OCD), attention-deficit/ hyperactivity disorder (ADHD), and anxiety disorders after adjusting for differences in trait levels between youth from three racial/ethnic groups: White, South Asian, and East Asian.MethodsWe collected parent or self-reported ratings of OCD, ADHD and anxiety traits and diagnoses for youth (6-17 years) from a general population sample (Spit for Science). We examined racial/ethnic differences in trait levels and the odds of reporting a diagnosis using mixed-effects linear models and logistic regression...
Journal of Alzheimer's Disease
Background: Recent work suggests that APOE ɛ4/4 females with Alzheimer’s disease (AD) are more su... more Background: Recent work suggests that APOE ɛ4/4 females with Alzheimer’s disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS). Objective: To examine the interaction of sex and APOE ɛ4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n = 252) and 2) patients with probable AD (n = 7,261). Methods: Regression models examined the interactive effects of sex and APOE ɛ4 on the number of NPS experienced and NPS Severity. APOE ɛ3/4 and APOE ɛ4/4 were pooled in the at-risk cohort due to the sample size. Results: In the at-risk cohort, there was a significant sex*APOE ɛ4 interaction (p = 0.007) such that the association of APOE ɛ4 with NPS was greater in females than in males (incident rate ratio (IRR) = 2.0). APOE ɛ4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical cohort, APOE ɛ4/4 females had significa...
Journal of the American Academy of Child & Adolescent Psychiatry
Journal of the American Academy of Child & Adolescent Psychiatry
The American Journal of Geriatric Psychiatry, 2021
Introduction Apolipoprotein (APOE) e4 is one of the strongest genetic biomarkers for Alzheimer... more Introduction Apolipoprotein (APOE) e4 is one of the strongest genetic biomarkers for Alzheimer's disease (AD) however, the relationship between APOE and Neuropsychiatric Symptoms (NPS) remains unclear. Our recent analyses suggested that female sex modulated the association of APOE e4 on specific NPS domains such as psychosis 1 and nighttime behaviours 2 in an autosomal recessive manner. The goal of this new analysis was to investigate the associations between APOE and sex on overall NPS burden in a cohort of participants with a condition putting them at risk for AD: Mild cognitive impairment (MCI) and/or a history of Major Depressive Disorder (MDD). Methods Baseline Neuropsychiatric Inventory Questionnaire (NPI-Q), APOE and demographic data were obtained in 181 participants from an ongoing clinical trial, “Preventing Alzheimer's dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression (PACt-MD)”. NPS burden was measured with the NPI-Q Total score and NPI-Severity Total. One extreme outlier was omitted from analysis (>7 inter quartile ranges (IQR) from the median NPI-Severity and >2 IQR from the next nearest data point). We tested whether APOE status, sex, or an interaction of the two were associated with our two outcomes using Ordinal Least Square (OLS) regression. Subsequent models were fit adjusting for the effects of age, education and diagnosis group (i.e., MCI or MDD (with/without MCI)). APOE e3/e3, the most common isoform, was used as the baseline category in regression analysis. All findings reported are compared to this baseliine category. Results When analysing the effects of APOE and sex alone, we only found a significant inverse association between NPI-Q Total and APOE e3/e4 carriers compared to APOE e3/e3 carriers (n = 38, b = -1.04, t(170) = -2.28, p = 0.024). When analysing our interaction terms APOE e4/e4 females (n = 6) were significantly associated with higher NPI-Q total scores (b = 1.95, t(171) = 2.14, p = 0.034). We also found that APOE e2/e3 females (n = 10) were associated with higher NPI-Q total scores (b = 1.55, t(171) = 2.04, p = 0.044). Results were consistent after adjusting for covariates. Sex or APOE status alone were not associated with NPI-Q Total severity scores. When analysing the interaction terms, APOE e2/e3 females showed higher NPI-Q Total severity scores than APOE e3/e3 carriers (b = 3.57, t(171) = 2.45, p = 0.015). After adjusting for covariates, being APOE e2/e3 females (b = 3.3, t(162) = 1.49, p = 0.027) or APOE e4/e4 females (b = 3.8, t(162) = 1.78 p = 0.033) was associated with greater NPI-Severity. Conclusions In older adults at risk for progression to AD, sex may play a modulatory role in the association between APOE and NPS burden. Consistent with recent findings 1 , 2 , females who are homozygous for APOE e4 may be susceptible to the highest NPS burden. Further investigation of the interactive effects of sex and APOE e4 on NPS burden with larger samples are needed. Funding This Project has been made possible by Brain Canada through the Canada Brain Research Fund, with the financial support of Health Canada and the Chagnon Family.
Alzheimer's & Dementia, 2020
The Apolipoprotein E (APOE) ε4 allele is a well‐established genetic risk factor of Alzheimer'... more The Apolipoprotein E (APOE) ε4 allele is a well‐established genetic risk factor of Alzheimer's disease (AD). While sex may play an important modulatory role in the association between APOε4 and certain neuropsychiatric symptoms (NPS) in AD1, it is unclear whether or not this risk extends to cognitively at‐risk populations with Mild Cognitive Impairment (MCI) or a history of Major Depressive Disorder (MDD). This cross‐sectional analysis compared NPS burden between males and females in a cohort of APOε4 carriers with at‐risk cognitive conditions of AD.
Alzheimer's & Dementia, 2021
Nearly half of all Alzheimer’s Disease (AD) patients experiences psychosis at some point in their... more Nearly half of all Alzheimer’s Disease (AD) patients experiences psychosis at some point in their disease trajectory. Kim et al. (2017) found a sexual dimorphism in AD psychosis where the ε4 allele may play a larger role in influencing psychosis development in females with Lewy body (LB) pathology.
ABSTRACTObjectiveWe designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to te... more ABSTRACTObjectiveWe designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to test whether irritability consisted of several sub-dimensions that would correlate differentially with internalizing/externalizing psychopathology, age, and gender.MethodParent-report (n = 3935, mean age = 8.9) and youth self-report (n = 579, mean age = 15.1) versions of TIDES-13 were administered to a population-based sample. Exploratory and confirmatory factor analyses were conducted on separate sub-samples. We fit multivariable regression models between TIDES-13 sub-dimensions and age, gender, anxiety, depression, ODD and ADHD trait levels.ResultsA higher order model with a global irritability dimension and Proneness to Anger, Internalized Negative Emotional Reactivity, Externalized Negative Emotional Reactivity and Reactive Aggression sub-dimensions showed good to excellent fit in both parent-report and self-report. The global irritability dimension had a strong influence on all item v...
Introduction Psychosis is one of the most typical and persistent neuropsychiatric manifestations ... more Introduction Psychosis is one of the most typical and persistent neuropsychiatric manifestations of AD where nearly half of AD patients experiences psychotic symptoms such as hallucinations and/or delusions (Ropacki & Jeste., 2005). Psychotic AD patients tend to have poorer overall health (Bassiony et al., 2000) and experience greater cognitive and functional impairments (Chui et al., 1994; Fischer et al., 2012). These qualities contribute to a reduced quality of life for patients and their caregivers. Researchers from our group found that psychosis risk in neuropathologically-diagnosed AD patients is significantly higher in females who are homozygous positive for APOE e4 with the presence of Lewy body pathology (Kim et al., 2017). These results point to a sexual dimorphism in AD psychosis where the e4 allele may play a larger role in influencing psychosis development in females. We hypothesize that AD patients with this high-risk profile (female and homozygous positive for APOE e4)...
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Papers by Andrew Dissanayake