Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families

Abstract

The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.

A characteristic cerebellar biosignature for bipolar disorder, identified with fully automatic machine learning

“…The bipolar spectrum includes 7 of the 37 patients with bipolar disorder had committed suicide, a number close to known prevalence of death by suicide in BD. Suicide mainly occurs during the depressive state of the disease and – occasionally-during a manic episode and could be connected to certain patterns of gene expression [61], biomarker differences [63] and vary during an acute or prolonged depressive or manic or mixed episode) [64], including the cerebellum. Finally, the genetic characteristics of post-mortem brain tissue sampling could be divergent from the same characteristics of the living brain, in health and disease; still they remain one of the cornerstones of research on the neurobiology of the CNS and its disorders [65], [66], [67] [68].…”

Genomic and neuroimaging approaches to bipolar disorder

“… 53 Second, a comparison of bipolar disorder types 1 and 2 showed that these two groups do not have a similar profile of polygenic risk, at least regarding the risk of depression. 54 Third, bipolar disorder PRS are associated not only with other psychiatric phenotypes, but also with several clinical features and potential biomarkers in different psychiatric conditions. 55 Finally, certain clinically relevant features in bipolar disorder, such as response to lithium treatment or age at onset, are not associated with bipolar disorder PRS but are associated with other psychiatric PRS.…”

Social and environmental variables as predictors of mania: a review of longitudinal research findings

“…Many of the samples studied include individuals with a broad range of bipolar spectrum disorders, and analyses did not differentiate those with bipolar I from those with bipolar II or cyclothymic disorders. Given increasing evidence for genetic differentiation in the forms of disorder [ 81 ], examining effects within subtypes will be an important goal for future research. It is also the case that most studies were only statistically powered to examine change in the level of manic symptoms, and not the onset or recurrence of disorder.…”