Today, I review, link to, and excerpt from StatPearls‘ Bipolar Disorder, Ankit Jain; Paroma Mitra. Last Update: February 20, 2023.
All that follows is from the above resource.
Introduction
Bipolar disorder (BD) is characterized by chronically occurring episodes of mania or hypomania alternating with depression and is often misdiagnosed initially.
Bipolar and related disorders include bipolar I disorder (BD-I), bipolar II disorder (BD-II), cyclothymic disorder, other specified bipolar and related disorders, and bipolar or related disorders, unspecified. The diagnostic label of “bipolar affective disorders” in the International Classification of Diseases 10th Revision (ICD-10) was changed to “bipolar disorders” in the ICD-11. The section on bipolar disorders in the ICD-11 is labeled “bipolar and related disorders,” which is consistent with the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).[1]
A World Health Organization study showed “remarkably similar” international prevalence rates, severity, impact, and comorbidities of bipolar spectrum disorder, defined as BD-I, BD-II, and subthreshold bipolar. The aggregate lifetime prevalence of the bipolar spectrum was 2.4%.[2]
BD is often difficult to recognize because symptoms overlap with other psychiatric disorders, psychiatric and somatic comorbidity is common, and patients may lack insight into their conditions, particularly hypomania. Treatment involves pharmacotherapy and psychosocial interventions, but mood relapse and incomplete response occur, particularly with depression. Continual reevaluation and treatment modification are commonly required during the long-term care of these patients. Management of comorbid psychiatric and chronic medical conditions may also be necessary. This activity provides an overview of the etiology, classification, evaluation, and management of bipolar affective disorder.
Etiology
Currently, the etiology of BD is unknown but appears to be due to an interaction of genetic, epigenetic, neurochemical, and environmental factors. Heritability is well established.[3][4][5] Numerous genetic loci have been implicated as increasing the risk of BD; the first was noted in 1987 with “DNA markers” on the short arm of chromosome 11. Since then, an association has been made between at least 30 genes and an increased risk of the condition.[6]
Although it is difficult to establish causation between life events and the development of BD, childhood maltreatment, particularly emotional abuse or neglect, has been linked to the later development of the condition. Other stressful life events associated with developing BD include childbirth, divorce, unemployment, disability, and early parental loss.[7] In adulthood, more than 60% of patients with BD report at least one “stressful life event” before a manic or depressive episode in the preceding 6 months.[6]
The etiology of BD is thought to involve imbalances in systems associated with monoaminergic neurotransmitters, particularly dopamine and serotonin, and intracellular signaling systems that regulate mood. However, no singular dysfunction of these neurotransmitter systems has been identified.[8]
In a recent neuroimaging review article, the ENIGMA Bipolar Disorder Working Group stated, “Overall, these studies point to a diffuse pattern of brain alterations including smaller subcortical volumes, lower cortical thickness and altered white matter integrity in groups of individuals with bipolar disorder compared to healthy controls.”[9] Neuroimaging studies have also shown evidence of changes in functional connectivity.[10][11]
Epidemiology
In the World Mental Health Survey Initiative, the use of mental health services for the bipolar spectrum (BD-I, BD-II, and subthreshold BD) concluded, “Despite cross-site variation in the prevalence rates of bipolar spectrum disorder, the severity, impact, and patterns of comorbidity were remarkably similar internationally.” The aggregate lifetime prevalence of BD-I was 0.6%, BD-II 0.4%, subthreshold BD 1.4%, and bipolar spectrum 2.4%.[2]
There are two peaks in the age of onset: 15-24 years and 45-54 years, with more than 70% of individuals manifesting clinical characteristics of the condition before 25 years of age.[12][13] Bipolar disorder shows a relatively equal distribution across sex, ethnicity, and urban compared to rural areas.[7][14]
Cyclothymia is associated with a lifetime prevalence of approximately 0.4-1% and a male-to-female ratio of 1:1.[15]
Pathophysiology
As with the etiology, the pathophysiology of BD is unknown and is thought to involve interactions between multiple genetic, neurochemical, and environmental factors. A recent neurobiology review article discusses in detail the “genetic components, signaling pathways, biochemical changes, and neuroimaging findings” in BD.[10]
10. Scaini G, Valvassori SS, Diaz AP, Lima CN, Benevenuto D, Fries GR, Quevedo J. Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings. Braz J Psychiatry. 2020 Sep-Oct;42(5):536-551. [PMC free article] [PubMed] [Reference list]
Evidence supports a strong genetic component and an epigenetic contribution. Human studies have shown changes in brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in patients with BD, indicating neurotrophic signaling is a molecular mechanism associated with decreased neuroplasticity. Other proposed mechanisms include mitochondrial dysfunction, oxidative stress, immune-inflammatory imbalance, and compromised hypothalamic-pituitary-adrenal axis. Additionally, neuroimaging studies have shown “evidence of change in regional activity, functional connectivity, neuronal activity, and bioenergetics associated with BD,” and anatomic studies have revealed dendritic spine loss in the dorsolateral prefrontal cortex in the post-mortem brain tissue of patients with BD.[10][16]
16. Konopaske GT, Lange N, Coyle JT, Benes FM. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry. 2014 Dec 01;71(12):1323-31. [PMC free article] [PubMed] [Reference list]
As mentioned, imbalances in systems associated with monoaminergic neurotransmitters, particularly dopamine and serotonin, and intracellular signaling systems that regulate mood are thought to be involved. However, no singular dysfunction of these neurotransmitter systems has been identified.[8]
8. Miklowitz DJ, Johnson SL. The psychopathology and treatment of bipolar disorder. Annu Rev Clin Psychol. 2006;2:199-235. [PMC free article] [PubMed] [Reference list]
History and Physical
Because bipolar disorder is a clinical diagnosis, making the correct diagnosis requires a comprehensive clinical assessment, including the directed patient interview, preferably supplemented by interviews of their relatives and the longitudinal course of their condition. Currently, there is no biomarker or neuroimaging study to aid in making the diagnosis.
Most patients with bipolar disorder are not correctly diagnosed until approximately 6 to 10 years after first contact with a healthcare provider, despite the presence of clinical characteristics of the condition.[17] Notably, misdiagnosing BD after first contact differs from not recognizing the transition from major depressive disorder (MDD), the most common index presentation, to BD. Estimates of patients transitioning to BD within three years of an MDD diagnosis range from 20-30%; therefore, clinicians must maintain an awareness of the potential for this transition when caring for patients with MDD who initially screened negative for BD.[18] Also, subthreshold hypomanic symptoms can occur in as many as 40% of patients with MDD.[19]
Although not highly sensitive and specific, self-report screening tools for BD may aid clinicians in making an accurate diagnosis. The most studied screening tools are the Mood Disorders Questionnaire (sensitivity 80%, specificity 70%) and the Hypomania Checklist 32 (sensitivity 82%, specificity 57%).[20] Positive results should motivate the clinician to conduct a thorough clinical assessment for bipolar disorder.
