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Differential levels of inflammatory and neuroendocrine markers in the hippocampus and anterior cingulate cortex of bipolar disorder subjects: A post-mortem study

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BRAIN BEHAVIOR AND IMMUNITY 2020年 90卷 286-293页

作者： Nascimento, Camila Nunes, Paula Villela Suemoto, Claudia Kimie Rodriguez, Roberta Diehl Paraizo Leite, Renata Elaine Grinberg, Lea Tenenholz Pasqualucci, Carlos Augusto Nitrini, Ricardo Jacob-Filho, Wilson Brentani, Helena Paula Lafer, Beny Univ Sao Paulo Dept Psychiat Med Sch Bipolar Disorder Program PROMAN Sao Paulo SP Brazil Univ Sao Paulo Biobank Aging Studies Med Sch Sao Paulo SP Brazil Univ Calif San Francisco Dept Neurol Memory & Aging Ctr San Francisco CA USA Univ Sao Paulo Dept Psychiat Med Sch Sao Paulo SP Brazil

Highlights•The brain-immune interplay in psychiatric disorders is still poorly understood. •Most neuroimmune post-mortem studies in bipolar disorder have focused on the frontal cortex. •We investigated inflammatory related-factors in hippocampus and anterior cingulate. •Hippocampus may be more susceptible to cytokine-mediated neuroinflammation. •Brain region vulnerability to inflammation may affect bipolar disorder clinical course.

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Assessing the mechanisms of brain plasticity by transcranial magnetic stimulation

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NEUROPSYCHOPHARMACOLOGY 2023年第1期48卷 191-208页

作者： Jannati, Ali Oberman, Lindsay M. Rotenberg, Alexander Pascual-Leone, Alvaro Harvard Med Sch Boston Childrens Hosp Div Epilepsy & Clin Neurophysiol Neuromodulat ProgramDept Neurol Boston MA 02115 USA Harvard Med Sch Boston Childrens Hosp FM Kirby Neurobiol Ctr Boston MA 02115 USA Harvard Med Sch Berenson Allen Ctr Noninvas Brain Stimulat Div Cognit Neurol Dept NeurolBeth Israel Deaconess Med Ctr Boston MA 02115 USA Henry M Jackson Fdn Adv Mil Med Ctr Neurosci & Regenerat Med Bethesda MD USA Harvard Med Sch Dept Neurol Boston MA 02115 USA Hebrew SeniorLife Hinda & Arthur Marcus Inst Aging Res Boston MA 02131 USA Hebrew SeniorLife Deanna & Sidney Wolk Ctr Memory Hlth Boston MA 02131 USA Inst Guttmann Guttmann Brain Hlth Inst Barcelona Spain

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in adults. In this review, we provide a brief introduction to the TMS technique with a focus on repetitive TMS (rTMS) protocols, particularly theta-burst stimulation (TBS), and relevant rTMS-derived metrics of brain plasticity. We then discuss the TMS-EEG technique, the use of neuronavigation in TMS, the neural substrate of TBS measures of plasticity, the inter- and intraindividual variability of those measures, effects of age and genetic factors on TBS aftereffects, and then summarize alterations of TMS-TBS measures of plasticity in major neurological and psychiatric disorders including autism spectrum disorder, schizophrenia, depression, traumatic brain injury, Alzheimer's disease, and diabetes. Finally, we discuss the translational studies of TMS-TBS measures of plasticity and their therapeutic implications.

关键词： Diagnostic markers Predictive markers

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Accelerating Preclinical Alzheimer's Clinical Trials through a Trial-Ready Cohort with Diverse Representation

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JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE 2020年第4期7卷 204-205页

作者： Lee, A. K. W. Correia, S. Salloway, Stephen P. Butler Hosp Memory & Aging Program Providence RI 02906 USA Brown Univ Dept Psychiat & Human Behav Warren Alpert Med Sch Providence RI 02912 USA Brown Univ Dept Neurol Warren Alpert Med Sch Providence RI 02912 USA

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Effects of chronic intranasal oxytocin on visual attention to faces vs. natural scenes in older adults

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PSYCHONEUROENDOCRINOLOGY 2024年 164卷 107018-107018页

作者： Shoenfelt, Alayna Pehlivanoglu, Didem Lin, Tian Ziaei, Maryam Feifel, David Ebner, Natalie C. Univ Florida Dept Psychol POB 112250 Gainesville FL 32611 USA Norwegian Univ Sci & Technol Kavli Inst Syst Neurosci N-7030 Trondheim Norway Norwegian Univ Sci & Technol KG Jebsen Ctr Alzheimers Dis N-7030 Trondheim Norway Univ Calif San Diego Dept Psychiat 9500 Gilman Dr La Jolla CA 92093 USA Univ Florida McKnight Brain Inst 1149 Newell Dr Gainesville FL 32610 USA Univ Florida Cognit Aging & Memory Program Clin Translat Res Program 2004 Mowry Rd Gainesville FL 32611 USA

aging is associated with changes in face processing, including desensitization to face cues like gaze direction and an attentional preference to faces with positive over negative emotional valence. A parallel line of research has shown that acute administration of oxytocin (OT) increases visual attention to social stimuli such as human faces. The current study examined effects of chronic OT administration among older adults on fixation duration to faces that varied in emotional expression, gaze direction, age, and sex. One hundred and twelve generally healthy older adults (aged 55-95 years) underwent a randomized, placebo-controlled, double-blind, between-subject clinical trial in which they self-administered either OT or placebo (P) intranasally twice a day for 4 weeks. The behavioral task involved rating the trustworthiness of faces (i.e., social stimuli) and natural scenes (i.e., nonsocial control stimuli) during eye tracking and was conducted before and after the intervention. Fixation duration to both the faces and the natural scenes declined from pre- to post-intervention, however this decline was less pronounced among older adults in the OT compared to the P group for faces but not scenes. Further, face cues (emotional expression, gaze direction, age, sex) did not moderate the treatment effect. This study provides first evidence that chronic intranasal OT maintains salience of social cues over time in older adults, perhaps buffering effects of habituation. These findings enhance understanding of OT effects on social cognition among older adults, and would benefit from follow up with a young adult comparison group to directly speak to specificity of observed effects to older adults and reflection of the aging process.

关键词： Oxytocin Chronic administration Face processing Eye tracking aging

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Right temporal degeneration and socioemotional semantics: semantic behavioural variant frontotemporal dementia

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BRAIN 2022年第11期145卷 4080-4096页

作者： Younes, Kyan Borghesani, Valentina Montembeault, Maxime Spina, Salvatore Mandelli, Maria Luisa Welch, Ariane E. Weis, Elizabeth Callahan, Patrick Elahi, Fanny M. Hua, Alice Y. Perry, David C. Karydas, Anna Geschwind, Daniel Huang, Eric Grinberg, Lea T. Kramer, Joel H. Boxer, Adam L. Rabinovici, Gil D. Rosen, Howard J. Seeley, William W. Miller, Zachary A. Miller, Bruce L. Sturm, Virginia E. Rankin, Katherine P. Gorno-Tempini, Maria Luisa Univ Calif San Francisco UCSF Weill Inst Neurosci Memory & Aging Ctr Dept Neurol San Francisco CA 94158 USA Stanford Univ Dept Neurol & Neurol Sci Stanford CA 94304 USA Univ Calif Los Angeles David Geffen Sch Med Dept Neurol Neurogenet Program Los Angeles CA 90024 USA Univ Calif Los Angeles David Geffen Sch Med Semel Inst Neurosci & Human Behav Los Angeles CA 90024 USA Univ Calif San Francisco Dept Pathol San Francisco CA 94143 USA Univ Calif San Francisco Dyslexia Ctr San Francisco CA 94158 USA

Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic and pathological profiles of these groups. In the right anterior temporal lobe-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%) and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of fam

关键词： right temporal lobe-predominant neurodegeneration loss of empathy and non-verbal semantics person-specific knowledge frontotemporal dementia FTLD-TDP type C

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Dual sensory impairment: Global prevalence, future projections, and its association with cognitive decline

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ALZHEIMERS & DEMENTIA 2025年第2期21卷 e14465页

作者： Yeo, Brian Sheng Yep Gao, Esther Yanxin Tan, Benjamin Kye Jyn Ong, Benedict Ding Chao Cho, Ryan Wei Yang Lim, Chee Yit Man, Ryan Eyn Kidd Fenwick, Eva K. Gupta, Preeti Chen, Christopher Li-Hsian Chew, Samuel Teong Huang Teo, Neville Wei Yang Toh, Song Tar Ng, Jia Hui Tan, Vanessa Yee Jueen Lamoureux, Ecosse L. Natl Univ Singapore Yong Loo Lin Sch Med Singapore Singapore Singapore Gen Hosp Dept Otorhinolaryngol Head & Neck Surg Singapore Singapore Sengkang Gen Hosp Dept Otorhinolaryngol Head & Neck Surg Singapore Singapore Duke NUS Med Sch SingHlth Duke NUS Surg Acad Clin Program Singapore Singapore Singapore Natl Eye Ctr Singapore Eye Res Inst Singapore Singapore Duke NUS Med Sch Ophthalmol & Visual Sci Acad Clin Programme Singapore Singapore Duke NUS Med Sch Hlth Serv & Syst Res Dept Singapore Singapore Natl Univ Singapore Memory Aging & Cognit Ctr Yong Loo Lin Sch Med Dept Pharmacol Singapore Singapore Natl Univ Singapore Hosp Dept Psychol Med Singapore Singapore Changi Gen Hosp Dept Geriatr Med Singapore Singapore Singhealth Duke NUS Med Acad Clin Programme Singapore Singapore Univ Melbourne Fac Med Dent & Hlth Sci Melbourne Vic Australia

There is rising public health concern surrounding dual sensory impairment (DSI), or comorbid hearing and vision impairments. Its global prevalence and the magnitude of its association with cognitive decline (CD) is unclear. Three databases were searched for epidemiological studies examining DSI prevalence or its association with CD. Independent reviewers selected studies, extracted data, and evaluated bias. Random-effects meta-analyses were performed. Projections were estimated using United Nations data. The population attributable fraction of DSI-associated CD was calculated. Among 43 studies with 5,246,796 participants, clinically assessed DSI prevalence was 5.50% (95% confidence interval [CI] = 2.88%-10.26%), with regional/ethnic/age variations. DSI prevalence is projected to increase by 27.2% from 2025 to 2050. Approximately 59.83% (95%CI = 41.03-76.12) of DSI patients had cognitive impairment. Baseline DSI was associated with incident CD (odds ratio [OR] = 1.72, 95%CI = 1.37-2.15). Globally, 3.81% (95%CI = 1.05-10.55) of incident CD may be attributed to DSI. DSI is globally prevalent, growing, and associated with CD, highlighting the need for better health policy and resource *** The global prevalence of DSI is 5.50%, with geographical, ethnical and age variations. The prevalence of DSI rises with age and is projected to increase by 27.2% by 2050. Approximately 60% of individuals with DSI may have measurable cognitive impairment. DSI was associated with a 72% greater longitudinal risk of incident CD. Globally, 3.81% of CD cases may be attributable to DSI.

关键词： cognitive decline cognitive impairment dementia dual sensory impairment hearing impairment public health vision impairment

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Factors associated with healthy aging in Latin American populations

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NATURE MEDICINE 2023年第9期29卷 2248-+页

作者： Santamaria-Garcia, Hernando Sainz-Ballesteros, Agustin Hernandez, Hernan Moguilner, Sebastian Maito, Marcelo Ochoa-Rosales, Carolina Corley, Michael Valcour, Victor Miranda, J. Jaime Lawlor, Brian Ibanez, Agustin Univ Calif San Francisco Global Brain Hlth Inst San Francisco CA 94118 USA Hosp Univ San Ignacio Bogota Ctr Memory & Cognit Intellectus San Ignacio Colombia Pontificia Univ Javeriana PhD Program Neurosci Bogota San Ignacio Colombia Univ Adolfo Ibanez Latin Amer Brain Hlth Inst Santiago Chile Univ Concepcion Fac Engn Concepcion Chile Univ San Andres Cognit Neurosci Ctr Buenos Aires Argentina Consejo Nacl Invest Cient & Tecn Buenos Aires Argentina Massachusetts Gen Hosp Dept Neurol Boston MA USA Harvard Med Sch Boston MA USA Weill Cornell Med Dept Med Div Infect Dis New York NY USA Univ Calif San Francisco Memory & Aging Ctr San Francisco CA USA Univ Peruana Cayetano Heredia Ctr Excelencia Enfermedades Cron Lima Peru Univ Peruana Cayetano Heredia Sch Med Dept Med Lima Peru London Sch Hyg & Trop Med Fac Epidemiol & Populat Hlth London England Univ New South Wales George Inst Global Hlth Sydney NSW Australia Univ Dublin Trinity Coll Dublin Dublin Ireland

Machine learning models showed that social disparities, cardiometabolic disease and mental health were the main predictors of aging in Latin American populations, with these factors being more pronounced in low- and middle-income compared to high-income Latin American countries. Latin American populations may present patterns of sociodemographic, ethnic and cultural diversity that can defy current universal models of healthy aging. The potential combination of risk factors that influence aging across populations in Latin American and Caribbean (LAC) countries is unknown. Compared to other regions where classical factors such as age and sex drive healthy aging, higher disparity-related factors and between-country variability could influence healthy aging in LAC countries. We investigated the combined impact of social determinants of health (SDH), lifestyle factors, cardiometabolic factors, mental health symptoms and demographics (age, sex) on healthy aging (cognition and functional ability) across LAC countries with different levels of socioeconomic development using cross-sectional and longitudinal machine learning models (n = 44,394 participants). Risk factors associated with social and health disparities, including SDH (& beta;> 0.3), mental health (& beta;> 0.6) and cardiometabolic risks (& beta;> 0.22), significantly influenced healthy aging more than age and sex (with null or smaller effects: & beta;< 0.2). These heterogeneous patterns were more pronounced in low-income to middle-income LAC countries compared to high-income LAC countries (cross-sectional comparisons), and in an upper-income to middle-income LAC country, Costa Rica, compared to China, a non-upper-income to middle-income LAC country (longitudinal comparisons). These inequity-associated and region-specific patterns inform national risk assessments of healthy aging in LAC countries and regionally tailored public health interventions.

关键词： Neurodegenerative diseases Psychology

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Biomarkers of endothelial dysfunction and cognition: A two-step IPD meta-analysis

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ALZHEIMERS & DEMENTIA 2024年第12期20卷 8402-8411页

作者： Beran, Magdalena Jansen, Willemijn J. Oomens, Julie E. Moonen, Justine E. F. Slagboom, P. Eline Huisman, Martijn Kok, Almar A. L. Nooyens, Astrid C. J. Verschuren, Wilhelmina Maria Monique Stehouwer, Coen D. A. Schalkwijk, Casper Koehler, Sebastian Beekman, Marian Slagboom, Pieternella Eline Wolters, Frank J. Ikram, M. Arfan Vallerga, Costanza L. van Meurs, Joyce B. J. Ghanbari, Mohsen Vonk, Jet M. J. Geerlings, Mirjam I. van Sloten, Thomas T. Schram, Miranda T. NCDC Consortium Maastricht Univ Cardiovasc Res Inst Maastricht CARIM Dept Internal Med Maastricht Netherlands Univ Med Ctr Utrecht Julius Ctr Hlth Sci & Primary Care Dept Epidemiol & Hlth Econ Utrecht Netherlands Univ Utrecht Utrecht Netherlands Maastricht Univ Dept Psychiat & Neuropsychol Maastricht Netherlands Maastricht Univ MHeNs Sch Mental Hlth & Neurosci Maastricht Netherlands Maastricht Univ Alzheimer Ctr Limburg Maastricht Netherlands Vrije Univ Amsterdam Alzheimer Ctr Amsterdam Neurol Amsterdam UMC Locat VUmc Amsterdam Netherlands Vrije Univ Amsterdam Amsterdam UMC locat Epidemiol & Data Sci Amsterdam Netherlands Vrije Univ Amsterdam Fac Social Sci Dept Sociol Amsterdam Netherlands Amsterdam Publ Hlth Ageing & Later Life Amsterdam Netherlands Natl Inst Publ Hlth & Environm Bilthoven Netherlands Leiden Univ Med Ctr Dept Biomed Data Sci Mol Epidemiol Leiden Netherlands Univ Med Ctr Erasmus MC Dept Epidemiol Rotterdam Netherlands Erasmus MC Univ Dept Radiol & Nucl Med Med Ctr Rotterdam Netherlands Erasmus MC Univ Med Ctr Dept Internal Med Rotterdam Netherlands Erasmus MC Univ Dept Orthoped & Sports Med Med Ctr Rotterdam Netherlands Univ Calif San Francisco Dept Neurol Memory & Aging Ctr San Francisco CA USA Res Inst Amsterdam Publ Hlth Res Programme Aging & Later life Amsterdam Netherlands Res Program Personalized Med Amsterdam Netherlands Res Inst Amsterdam Neurosci Res Program Neurodegenerat Res Program Mood Anxiety Psychosis Stress & Sleep Amsterdam Netherlands Locat Univ Amsterdam Dept Gen Practice Amsterdam UMC Amsterdam Netherlands Univ Med Ctr Utrecht Dept Vasc Med Utrecht Netherlands Maastricht Univ Med Ctr Heart Vasc Ctr Maastricht Netherlands

INTRODUCTIONThis study assessed the association of plasma biomarkers of endothelial dysfunction with cognitive performance and *** from 9414 individuals from eight Dutch cohorts were included (& Oslash;age-range: 57-93 years). Plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin) were combined into a standardized composite score. Cognitive outcomes included executive function, processing speed, immediate and delayed memory, attention, and language. Linear regressions and linear mixed models were run in the individual cohorts and standardized coefficients were subsequently pooled using random-effects *** higher endothelial dysfunction composite score was cross-sectionally associated with worse performance on executive function, processing speed, delayed memory, and attention, but not immediate memory or language (pooled beta-range: -0.04, -0.02). We found no association with change in cognition over *** comprehensive two-step, individual participant data (IPD) meta-analysis showed a small, consistent cross-sectional association between endothelial dysfunction and worse cognitive performance across multiple domains but no support for a longitudinal *** Prior evidence on endothelial dysfunction (ED) biomarkers and cognition is conflicting. This two-step, individual participant data (IPD) meta-analysis used data from eight Dutch cohorts. ED was consistently associated with concurrent cognition. ED was not associated with a change in cognition over time. The association of ED with current cognition may be generic.

关键词： biomarkers cognition cohort endothelial dysfunction meta-analysis

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Phase-dependent local brain states determine the impact of image-guided transcranial magnetic stimulation on motor network electroencephalographic synchronization

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JOURNAL OF PHYSIOLOGY-LONDON 2022年第6期600卷 1455-1471页

作者： Momi, Davide Ozdemir, Recep A. Tadayon, Ehsan Boucher, Pierre Di Domenico, Alberto Fasolo, Mirco Shafi, Mouhsin M. Pascual-Leone, Alvaro Santarnecchi, Emiliano Beth Israel Deaconess Med Ctr Berenson Allen Ctr Noninvas Brain Stimulat Boston MA 02215 USA Univ G dAnnunzio Dept Neurosci Imaging & Clin Sci Chieti Italy Univ G dAnnunzio Dept Psychol Sci Humanities & Terr Chieti Italy Hebrew SeniorLife Hinda & Arthur Marcus Inst Aging Res Boston MA USA Hebrew SeniorLife Deanna & Sidney Wolk Ctr Memory Hlth Boston MA USA Harvard Med Sch Dept Neurol Boston MA 02115 USA Univ Autonoma Barcelona Guttmann Brain Hlth Inst Guttmann Inst Barcelona Spain Massachusetts Gen Hosp Precis Neurosci & Neuromodulat Program Boston MA 02114 USA Harvard Med Sch Boston MA 02115 USA

Recent studies have synchronized transcranial magnetic stimulation (TMS) application with pre-defined brain oscillatory phases showing how brain response to perturbation depends on the brain state. However, none have investigated whether phase-dependent TMS can possibly modulate connectivity with homologous distant brain regions belonging to the same network. In the framework of network-targeted TMS, we investigated whether stimulation delivered at a specific phase of ongoing brain oscillations might favour stronger cortico-cortical (c-c) synchronization of distant network nodes connected to the stimulation target. Neuronavigated TMS pulses were delivered over the primary motor cortex (M1) during ongoing electroencephalography recording in 24 healthy individuals over two repeated sessions 1 month apart. Stimulation effects were analysed considering whether the TMS pulse was delivered at the time of a positive (peak) or negative (trough) phase of mu-frequency oscillation, which determines c-c synchrony within homologous areas of the sensorimotor network. Diffusion weighted imaging was used to study c-c connectivity within the sensorimotor network and identify contralateral regions connected with the stimulation spot. Depending on when during the mu-activity the TMS-pulse was applied (peak or trough), its impact on inter-hemispheric network synchrony varied significantly. Higher M1-M1 phase-lock synchronization after the TMS-pulse (0-200 ms) in the mu-frequency band was found for trough compared to peak stimulation trials in both study visits. Phase-dependent TMS delivery might be crucial not only to amplify local effects but also to increase the magnitude and reliability of the response to the external perturbation, with implications for interventions aimed at engaging more distributed functional brain networks.

关键词： brain-state dependent effect cortico-cortical connectivity mu-rhythm structural connectivity TMS-EEG

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Gene expression alterations in the postmortem hippocampus from older patients with bipolar disorder-A hypothesis generating study

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JOURNAL OF PSYCHIATRIC RESEARCH 2023年第1期164卷 329-334页

作者： Nascimento, Camila Kim, Helena Kyunghee Nunes, Paula Villela Leite, Renata Elaine Paraiso Cristina, De Oliveira Katia Barbosa, Andre Bertonha, Fernanda Bernardi Moreira-Filho, Carlos Alberto Jacob-Filho, Wilson Nitrini, Ricardo Pasqualucci, Carlos A. Grinberg, Lea Tenenholz Suemoto, Claudia Kimie Brentani, Helena Paula Lafer, Beny Univ Sao Paulo Dept Psychiat Bipolar Disorder Program Med Sch Rua Dr Ovidio Pires De Campos 785 Cerqueira Cesar BR-05403903 Sao Paulo SP Brazil Univ Sao Paulo Dept Psychiat Med Sch Sao Paulo SP Brazil Univ Toronto Dept Psychiat Toronto ON Canada Univ Sao Paulo Div Geriatr Med Sch Sao Paulo SP Brazil Fed Univ ABC Sao Bernardo Do Campo SP Brazil Univ Sao Paulo Dept Pediat Fac Med Sao Paulo SP Brazil Univ Sao Paulo Dept Neurol Med Sch Sao Paulo SP Brazil Univ Sao Paulo Dept Pathol Med Sch Sao Paulo SP Brazil Univ Calif San Francisco Memory & Aging Ctr San Francisco CA USA Univ Fed Sao Paulo Dept Byophis Sao Paulo Brazil

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old;duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.

关键词： Bipolar disorder Transcriptome Gene expression Hippocampus Postmortem brain

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