Liisa A M Galea

• Ph.D.
• Professor (Full) at University of British Columbia

There are sex differences in hippocampus-dependent cognition and neurogenesis suggesting that sex hormones are involved. Estrogens modulate certain forms of spatial and contextual memory and neurogenesis in the adult female rodent, and to a lesser extent male, hippocampus. This review focuses on the effects of sex and estrogens on hippocampal learn...

The postpartum confers considerable risk for developing depression. Depressed patients have elevated cortisol concentrations and impaired hypothalamic pituitary adrenal (HPA) axis negative feedback. Chronic stress or corticosterone (CORT) induces a depressive-like phenotype in rodents, including during the postpartum. The present study examined whe...

Antidepressant drugs are too often ineffective, the exact mechanism of efficacy is still ambiguous, and there has been a paucity of novel targets for pharmacotherapy. In an attempt to understand the pathogenesis of depression and subsequently develop more efficacious antidepressant drugs, multiple theories have been proposed, including the modulati...

Adult neurogenesis in the dentate gyrus (DG) plays a crucial role for pattern separation and there are sex differences in the regulation of neurogenesis. Although sex differences, favoring males, in spatial navigation have been reported, it is not known whether there are sex differences in pattern separation. The current study was designed to deter...

Cognition and its underlying neurobiology change throughout the trajectory of aging, with prominent sex differences and influences of sex-specific factors. Research has shown that parity (pregnancy and parenthood) uniquely altered various biomarkers of brain health in middle age depending on presence of Alzheimer’s disease (AD) risk. The present st...

Menopause is a major biological transition that may influence women’s late-life brain health. Earlier estrogen depletion—via earlier menopause—has been associated with increased risk for Alzheimer’s disease (AD). Synaptic dysfunction also incites and exacerbates AD progression. We investigated whether age at menopause and synaptic health together i...

INTRODUCTION Tau pathology impacts neurodegeneration and cognitive decline in Alzheimer's disease (AD), with the dorsal raphe nucleus (DRN) being among the brain regions showing the earliest tau pathology. As a serotonergic hub, DRN activity is altered by selective serotonin reuptake inhibitors (SSRIs), which also have variable effects on cognitive...

Background Alzheimer’s disease (AD) disproportionately and uniquely affects females, and these sex differences are further exacerbated by the presence of Apolipoprotein (APOE) ε4 alleles, the top genetic risk factor for late-onset AD. To expand our understanding about how late-onset AD risk might differentially influence males and females, this stu...

Introduction Menopause and menopausal hormone therapy (MHT) can influence cognition in postmenopausal women, but previous literature remains equivocal about their effects. MHT varies based on formulation and route of administration, both of which influence dose of estradiol (E2), the estrogen with the greatest affinity to the estrogen receptor. Tra...

Considerable heterogeneity exists in the expression of complex human behaviors across the cognitive, personality and mental health domains. It is increasingly evident that individual variability in behavioral expression is substantially affected by sociodemographic factors that often interact with life experiences. Here, we formally address the urg...

Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases t...

INTRODUCTION Not all individuals who experience mild cognitive impairment (MCI) transition through progressive stages of cognitive decline at the same rate, if at all. Previous observational studies have identified the retrosplenial cortex (RSC) as an early site of hypometabolism in MCI which seems to be predictive of later transition to Alzheimer'...

Menopausal hormone therapy (MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in middle-to older aged females from the UK Biobank, assessing detailed MHT data, APOE ε4 genotype, and tissue-specific gray (GM) and white matter (WM) brain age...

Menopausal hormone therapy (MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in middle-to older aged females from the UK Biobank, assessing detailed MHT data, APOE ε4 genotype, and tissue-specific gray (GM) and white matter (WM) brain age...

Estrone and estradiol differentially modulate neuroplasticity and cognition. How they influence the maturation of new neurons in the adult hippocampus, however, is not known. The present study assessed the effects of estrone and estradiol on the maturation timeline of neurogenesis in the dentate gyrus (DG) of ovariectomized (a model of surgical men...

Purpose: We explored the funding areas of Two-Spirit, lesbian, gay, bisexual, transgender (trans), queer or questioning, and intersex individuals (2S/LGBTQI)-specific health research funded by the Canadian Institutes of Health Research (CIHR) mentioned in the grant abstracts. Methods: We analyzed the publicly available database of grant abstracts f...

Pregnancy and motherhood (parity) can have long-term effects on cognition and brain aging in both humans and rodents. Estrogens are related to cognitive function and neuroplasticity. Estrogens can improve cognition in postmenopausal women, but the evidence is mixed, in part due to differences in hormone therapy dose and composition. In addition, pa...

Background Ovarian hormones exert direct and indirect influences on the brain; however, little is known about how these hormones impact causal brain connectivity. Studying the female brain at a single time point may be confounded by distinct hormone phases. Despite this, the menstrual cycle is often overlooked. The primary objective of this pilot s...

Many physiological changes occur during pregnancy and in the postpartum, including dramatic fluctuations in circulating hormones. These changes affect the maternal brain on behavioral, molecular and cellular levels. Pregnancy in the short- and long-term influences cognition in both humans and rodents, with both improvements and declines seen in dif...

Background and Objectives Menopausal hormone therapy (MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in middle- to older aged females from the UK Biobank, assessing detailed MHT data, APOE ε4 genotype, and tissue-specific gray (GM) and...

Purpose: Gender identity and sexual orientation are essential factors that must be incorporated into health research to ensure we unearth comprehensive and inclusive insights about the healthcare needs and experiences of diverse people. Despite the calls for more focus on sex and gender in health research, scant attention has been paid to gender id...

There are prominent sex/gender differences in the prevalence, expression, and life span course of mental health and neurodiverse conditions. However, the underlying sex- and gender-related mechanisms and their interactions are still not fully understood. This lack of knowledge has harmful consequences for those with mental health problems. Therefor...

Pregnancy is marked by robust changes, including brain changes to volume, structure, connectivity and neuroplasticity. Although some brain changes are restricted to pregnancy and the postpartum, others are long-lasting. Few studies have examined possible mechanisms of these changes or the effects of multiple pregnancies. We characterized various ce...

Background The increased stress the world experienced with the coronavirus disease (COVID-19) pandemic affected mental health, disproportionately affecting females. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated. Objectives This study evaluates the effect that the first year...

Adult neurogenesis in the dentate gyrus plays an important role for pattern separation, the process of separating similar inputs and forming distinct neural representations. Estradiol modulates neurogenesis and hippocampus function, but to date no examination of estradiol's effects on pattern separation have been conducted. Here, we examined estrog...

Background Sex and gender impacts health outcomes and disease risk throughout life. The health of women and members of the Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ +) community is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations have prompted...

There are prominent sex differences in the prevalence of numerous mental health and neurodiverse conditions. Both sex and gender related factors affect the expression and diagnosis of mental health conditions. Even though, sex and gender research has been integrated in research policies, the underlying mechanisms and interactions between them are s...

Growing attention has been directed to the inclusion of females in neuroscience studies, and to the importance of studying sex as a biological variable. However, how female-specific factors such as menopause and pregnancy, affect the brain remains understudied. In this review, we use pregnancy as a case in point of a female-unique experience that c...

Pregnancy is marked by robust changes involving all organ systems, including brain changes to volume, structure, connectivity, and neuroplasticity. Although some brain changes are restricted to pregnancy and the postpartum, others are long-lasting. Few studies have examined possible mechanisms of these change or and the effects of multiple pregnanc...

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We...

Adult neurogenesis in the dentate gyrus plays an important role for pattern separation, the process of separating similar inputs and forming distinct neural representations. Estradiol modulates neurogenesis and hippocampus function, but to date no examination of the effect of estradiol on pattern separation have been conducted. Here, we examined es...

Females have a greater lifetime risk of Alzheimer’s disease (AD) compared to males, differences which are further exacerbated with possession of APOEe4 alleles, the greatest genetic risk factor for sporadic AD. Although studying sex and gender differences is important, so is studying sex‐linked factors such as parity (pregnancy and motherhood). Pre...

Background Females are more likely to present with anxiety disorders such as post-traumatic stress disorder (PTSD) compared to males, which are associated with disrupted hippocampal integrity. Sex differences in the structure and function of hippocampus exist. Here, we examined sex differences in contextual pattern separation, functional connectivi...

Sex and gender impacts health outcomes and disease risk throughout life. Women and Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, Intersex, and Asexual (2S/LGBTQIA+) health is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations has prompted funding agencies to...

The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized by distinct hormone concentration profiles. Given the difficulty of repeatedly sampling plasma steroid hormones from rodents, the primary method for classifying estrous stage is by...

Background Cognitive symptoms of major depressive disorder, such as negative cognitive bias, are more prevalent in women than in men. Cognitive bias involves pattern separation which requires hippocampal neurogenesis and is modulated by inflammation in the brain. Previously, we found sex differences in the activation of the amygdala and the hippoca...

Estrone and estradiol differentially modulate neuroplasticity and cognition but how they influence maturation pathways of new neurons is not known. The present study assessed the effects of estrone and estradiol on various aspects of neurogenesis in the dentate gyrus (DG) of ovariectomized young adult Sprague-Dawley rats using daily subcutaneous in...

The COVID-19 pandemic and public health protection measures aimed at mitigating the transmission of the virus have both resulted in tremendous physical and mental health impacts. The study at hand used a gender-based analysis and social determinants of health approach to investigate which communities had trouble coping during times of strict protec...

Background Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) a...

Objectives Gathering population-based data on prevalence of SARS-CoV-2 infection is vital to the public health response and planning. Current seroprevalence data in BC are limited with respect to considerations of how socioeconomic and demographic factors, such as age, sex, gender, income, identifying as a visibility minority and occupation, are re...

Introduction: This study assessed the relationship between intention to receive a COVID-19 vaccine and intention to receive a seasonal influenza vaccine, as well as how intention to receive a COVID-19 vaccine has changed during the pandemic. Methods: Residents of British Columbia aged 25–69 years were invited to complete an online cross-sectional s...

Purpose The increased stress the globe has experienced with the COVID-19 pandemic has affected mental health, disproportionately affecting women. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated. Methods Residents in British Columbia, Canada, were surveyed online as part of th...

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotropic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We e...

Background: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom)...

The brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data and is considered a biomarker of brain health. Understanding sex differences in brainAGE is a significant step toward precision medicine. Global and local brainAGE (G-brainAGE and L-bra...

Introduction: Rapid effects of estrogens within the hippocampus of rodents are dependent upon cell signaling cascades, and activation of these cascades by estrogens varies by sex. Whether these pathways are rapidly activated within the dentate gyrus (DG) and CA1 by estrogens across sex and the anatomical longitudinal axis has been overlooked. Meth...

COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio-demographic, vaccine hesitancy, a...

Background: Cognitive symptoms of major depressive disorder, such as negative cognitive bias, are more prevalent in women than in men. Cognitive bias involves pattern separation which requires hippocampal neurogenesis and is modulated by inflammation in the brain. Previously, we found sex differences in the activation of the amygdala and the hippoc...

The advent of greater inclusivity of minority groups in research and clinical trials is long overdue. The historical lack of representation of women and gender minorities in the medical literature has led to an over‐reliance on male physiology and experience to understand disease. It is important to recognise that to understand and respond to the k...

Objective This study sought to examine how access to contraception and cervical and breast cancer screening British Columbia, Canada, has been affected by COVID-19 pandemic. Methods From August 2020 to March 2021, 3691 female residents of British Columbia (age 25–69 y) participated in this study. We used generalized estimating equations to analyze...

Cognitive symptoms of depression, including negative cognitive bias, are more severe in women than in men. Current treatments to reduce negative cognitive bias are not effective and sex differences in the neural activity underlying cognitive bias may play a role. Here we examined sex and age differences in cognitive bias and functional connectivity...

Sex differences exist in many neurological and psychiatric diseases, but these have not always been addressed adequately in research. In order to address this, it is necessary to consider how sex is incorporated into the design (e.g. using a balanced design) and into the analyses (e.g. using sex as a covariate) in the published literature. We surve...

Sex and gender differences are seen in cognitive disturbances in a variety of neurological and psychiatry diseases. Men are more likely to have cognitive symptoms in schizophrenia whereas women are more likely to have more severe cognitive symptoms with major depressive disorder and Alzheimer’s disease. Thus, it is important to understand sex and g...

The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized by distinct hormone concentration profiles. Given the difficulty of repeatedly sampling plasma steroid hormones from rodents, the primary method for classifying estrous stage is by...

Sex differences in the structure and function of hippocampus exist. Here, we examined sex differences in contextual pattern separation, functional connectivity, and activation of new neurons during fear memory. Two-month-old male and female Sprague-Dawley rats were injected with the DNA synthesis markers, iododeoxyuridine (IdU) and chlorodeoxyuridi...

Background The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurren...

Cognitive symptoms of depression, including negative cognitive bias, are more severe in women than in men. Current treatments to reduce negative cognitive bias are not effective and sex differences in the neural activity underlying cognitive bias may play a role. Here we examined sex and age differences in cognitive bias and functional connectivity...

Background The brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data, and is considered a biomarker of brain health. Understanding sex-differences in brainAGE is a significant step toward precision medicine. Methods Global and local brainAGE...

Major life transitions often co-occur with significant fluctuations in hormones that modulate the central nervous system. These hormones enact neuroplastic mechanisms that prepare an organism to respond to novel environmental conditions and/or previously unencountered cognitive, emotional, and/or behavioral demands. In this review, we will explore...

Hippocampal neurogenesis persists across the lifespan in many species, including rodents and humans, and is associated with cognitive performance and the pathogenesis of neurodegenerative disease and psychiatric disorders. Neurogenesis is modulated by steroid hormones that change across development and differ between the sexes in rodents and humans...

Adult neurogenesis in the hippocampus is modulated by steroid hormones, including androgens, in male rodents. In this review, we summarize research showing that chronic exposure to androgens, such as testosterone and dihydrotestosterone, enhances the survival of new neurons in the dentate gyrus of male, but not female, rodents, via the androgen rec...

Objectives The SARS-CoV-2 (COVID-19) pandemic has had profound physical and mental health effects on populations around the world. Limited empirical research has used a gender-based lens to evaluate the mental health impacts of the pandemic, overlooking the impact of public health measures on marginalized groups, such as women, and the gender diver...

Sex differences are well-established in Alzheimer's disease (AD) frequency and pathogenesis, but are not mechanistically understood. Accelerated epigenetic age has been associated with both cognitive aging and AD pathophysiology, but has not been studied by sex in AD or related cognitive impairment. Using the ADNI cohort, we found that none of sex,...

Introduction: COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio-demographic, vaccin...

Introduction Rapid effects of estrogens within the hippocampus of rodents are dependent upon cell signaling cascades, and activation of these cascades by estrogens varies by sex. Whether these pathways are rapidly activated within the dentate gyrus (DG) and CA1 by estrogens and across the anatomical longitudinal axis has been overlooked. Methods G...

Sex differences exist in many neurological and psychiatric diseases. Mandates have been initiated across funding agencies for research to include males and females. What has been lacking in the literature is a detailed assessment of how sex is incorporated into the design (e.g. balanced design) and into the analyses (e.g. covariate). We surveyed pa...

The SARS-CoV-2 (COVID-19) pandemic has had profound physical and mental health effects on populations around the world. Limited empirical research has used a gender-based lens to evaluate the mental health impacts of the pandemic, overlooking the impact of public health measures on marginalized groups, such as women, and the gender diverse communit...

Untreated perinatal depression can have severe consequences for the mother and her children. However, both the efficacy to mothers and safety to exposed infants of pharmacological antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been questioned. We previously reported that maternal SSRI exposure increased hippocampal IL...

Abstract Background The success of any COVID-19 vaccine program ultimately depends on high vaccine uptake. This study determined overall intention to receive a COVID-19 vaccine and identified factors that predict intentions to be vaccinated against COVID-19 in Canada, specifically in key priority groups identified by the American Committee on Immun...

Perinatal depression (PND) affects 15% of mothers. Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line of treatment for PND but are not always efficacious. Previously, we found significant reductions in plasma tryptophan concentrations and higher hippocampal proinflammatory cytokine, IL-1b levels, due to maternal SSRI treat...

Alzheimer’s disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diag...

Perinatal depression (PND) affects 15% of mothers. Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line of treatment for PND but are not always efficacious. Previously, we found significant reductions in plasma tryptophan concentrations and higher hippocampal proinflammatory cytokine, IL-1b levels, due to maternal SSRI treat...

Objective: The success of any COVID-19 vaccine program ultimately depends on high vaccine uptake. This study determined overall intention to receive a COVID-19 vaccine and identified factors that predict intentions to be vaccinated against COVID-19 in Canada. Methods: Individuals from research cohorts from the general population of British Columbia...

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that features distinctive neuropathology and global impairments to cognition. Sex differences are seen in AD, as females with AD show increased neuropathology and steeper cognitive decline than men with AD but are often neglected in the literature. The hippocampus is one of...

Background Diagnosis rates of Alzheimer’s disease (AD) are greater in women than men, who also show greater cognitive decline and AD neuropathology. Increasing parity (pregnancy and motherhood experience) is associated with reduced grey matter volume in the brain and in the long term greater risk of dementia, earlier age of AD onset, and AD neuropa...

The efficacy of a technology-driven visual arts recreation activity, delivered virtually, was evaluated for its potential to achieve positive impacts, similar to traditional arts-interventions, on wellbeing in long-term care residents. Thirty-one residents (average age 86.8 years; SD = 9.4) engaged with the arts-intervention for 30-minutes, twice w...

Objective Older adults with amnestic mild cognitive impairment (aMCI) develop Alzheimer’s type dementia approximately 10 times faster annually than the normal population. Adrenal hormones are associated with aging and cognition. We investigated the relationship between acute stress, cortisol, and memory function in aMCI with an exploratory analysis...

Background Alzheimer’s disease (AD) disproportionately affects females with steeper cognitive decline and more neuropathology compared to males, which is exacerbated in females carrying the APOE ɛ4 allele. The risk of developing AD is also higher in female APOE ɛ4 carriers in earlier age groups (aged 65–75), and the progression from cognitively nor...

Perinatal depression (PND) can have either an antepartum or postpartum onset. Although the greatest risk factor for PND is previous depression history, de novo PND occurs with the majority of cases occurring in the postpartum. Timing of depression can impact etiology, prognosis, and response to treatment. Thus, it is crucial to study the impact of...

Decision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones a...