Bipolar Disorder - NEUR 1202 Fall 2022 PDF

Bipolar Disorder Bipolar Disorder and Related Disorders Includes Bipolar I and Bipolar II disorder, cyclothymia, and other related disorders All involve either manic or hypomanic (not full mania) episodes plus major depressive episodes Mood in a manic episode often described as euphoric,...

Bipolar Disorder Bipolar Disorder and Related Disorders Includes Bipolar I and Bipolar II disorder, cyclothymia, and other related disorders All involve either manic or hypomanic (not full mania) episodes plus major depressive episodes Mood in a manic episode often described as euphoric, excessively cheerful, high or “feeling on top of the word” – E.g., may spontaneously start extensive conversations with strangers in public Individuals often do not perceive that they are ill or in need of treatment and vehemently resist efforts to be treated May change their dress, makeup, personal appearance to a more sexually suggestive or flamboyant style May experience sharper sense of smell, hearing or vision Bipolar Disorder: Historical Background Ancient Greeks used terms “mania” and “melancholia” to describe mania and depression – Even wrote about lithium salts used in a bath to calm people 1851, French psychiatrist Jean-Pierre Falret published an article describing what he called “la folie circulaire” – translates to circular insanity – The article details people switching through severe depression and manic excitement, and is considered to be the first documented diagnosis of bipolar disorder Bipolar Disorder: Historical Background Early 1900s: Emil Kraepelin (who coined the term dementia precoce) was studying individuals who had an episodic course of periods of mania and depression: coined term “manic depressive psychosis” Included in early editions of the DSM as “Manic Depression” DSM 5: Bipolar Disorder Bipolar I: Diagnostic Features A manic episode characterized by the following: – Distinct period of abnormally elevated, expansive, or irritable mood; abnormally and persistently increased goal-directed activity or energy lasting at least 1 week and present most of the day, nearly every day – Three or more of the following Inflated self-esteem or grandiosity Decreased need for sleep More talkative Flight of ideas/racing thoughts Distractibility Increase in goal-directed activity (socially, work, school, or sexually) or psychomotor agitation (purposeless, non-goal directed activity) Excessive involvement in activities that have high potential for painful consequences (e.g., foolish business investments, buying sprees) – Causes marked impairment in social / occupational functioning A major depressive episode (see previous lecture for diagnostic criteria) Bipolar II: Diagnostic Features A hypomanic episode characterized by the following: – Distinct period of abnormally elevated, expansive, or irritable mood; abnormally and persistently increased goal-directed activity or energy lasting at least 4 consecutive days and present most of the day, nearly every day – Three or more of the same criteria as Bipolar I – Episode is associated with an unequivocal change in functioning – Disturbance in mood and change in functioning is observable by others – The episode is not severe enough to impair social/occupational functioning or result in hospitalization A major depressive episode (see lecture 13 for diagnostic criteria) [must last at least 2 weeks] Comparisons of Symptoms in Manic and Depressive Episodes Prevalence, Development and Course 12-month prevalence estimate is approximately 0.6% for bipolar I; about 0.3% for bipolar II Male:female ratio is approximately 1:1 Bipolar I: mean age of onset is 18 – More than 90% go on to have further mood episodes – Four or more mood cycles / year = rapid cycling Bipolar II: average age of onset is mid 20s – Often begins with a depressive episode; becomes more disabling over time – Can be triggered by childbirth Bipolar Disorder: Rate of Cycling Rate of cycling varies – Rapid cycling consists of four or more cycles in one year – Some individuals may cycle several times in one day – Rapid shifts in mood referred to as “lability” Genetics of Bipolar Disorder Genome-wide association (GWA) study: phenotype-first approach Individuals first classified by clinical manifestation of disease (e.g., all people with Bipolar Type I); compare with control sample Everyone gives sample of DNA – Millions of genetic variants are read using SNP arrays GWA studies for bipolar disorder reveal association of risk for BPD with SYNE1, a gene which encodes nesprin-1 – part of the complex that links the nucleoskeleton to the cytoskeleton Neurobiological Basis of Bipolar Disorder Largely unknown Any major neurobiologicial theory of Bipolar Disorder must explain the cyclical nature of the disease – Should not give antidepressants to someone with Bipolar Disorder as it may provoke a manic state – Must treat depressive and manic phases First drug to somewhat successfully treat Bipolar disorder is Lithium – Classified as a “mood stablilizer” – Exact mechanism of action is unknown – Also treated with valproic acid (valproate) Neurobiological Theories of Bipolar Disorder Dopamine theory BDNF Mitochondrial theory Dopamine Theory of BPD Based on observation that mania can be provoked in individuals who consume moderate to high doses of amphetamines (which primarily work to elevate synaptic levels of dopamine) – If hyperdopaminergia underlies the mania, might hypodopaminergia underlie depression? Traditional drugs used to treat BPD (i.e., Lithium, Valproate) do have some action on the D2/3 receptor Newer drugs (quetiapine) also has action on this receptor, among others Dopamine Theory of BPD (2) Elevated D2/3 receptor availability Increased Decreased dopamine dopamine signal signal Compensat ory increase in dopamine transporter levels A failure of dopamine receptor and transporter homoeostasis might underlie the pathophysiology of bipolar BDNF Theory of BPD Consequence of mania Evidence that brain- derived neurotrophic factor (BDNF; a measure of the plasticity of the nervous system) is decreased among patients with BPD – During manic AND depressive phases Precipitate mania – Normalized when patient is “euthymic” (experiencing ‘normal’ mood) Coincide with mania Adjusted changes in brain‐derived neurotrophic factor (BDNF) (β coefficient) of each melancholic feature measured by HAM‐D6 ordered by severity. CI, confidence interval. *Adjusted for age, sex, bipolar vs unipolar depression, and use of alcohol, tobacco, antidepressants, anti‐psychotics, and anticonvulsants de Carvalho Alves and da Rocha, 2018 Mitochondrial Theory of BPD Mitochondria are organelles responsible for multiple cellular functions (e.g., energy production); also sources for cellular growth, cell resilience and death pathways – Modulate neuronal activity, neuroplasticity – Calcium storage Mitochondrial Theory of BPD (2) Mitochondria also regulate reactive oxygen species (ROS) – Dysregulation in mitochondria can increase generation of ROS – Too much ROS = oxidative stress = cell death In BPD a wealth of evidence suggests defective mitochondrial metabolism, morphology, and function – May contribute to oxidative stress and inflammation – May also lead to cell death (apopotosis) Could explain loss of cells in bipolar patients Remember Nesprin-1!!! Lithium protective against cell death! Which Theory is Correct? Some practice questions! Revealed in class!