Exploring the Hypothesis of a Schizophrenia and Bipolar Disorder Continuum: Biological, Genetic and Pharmacologic Data

Abstract

: Present time nosology has its roots in Kraepelin’s demarcation of schizophrenia and bipolar disorder. However, accumulating evidence has shed light on several commonalities between the two disorders, and some authors have advocated for the consideration of a disease continuum. Here, we review previous genetic, biological and pharmacological findings that provide the basis for this conceptualization. There is a cross-disease heritability, and they share single-nucleotide polymorphisms in some common genes. EEG and imaging patterns have a number of similarities, namely reduced white matter integrity and abnormal connectivity. Dopamine, serotonin, GABA and glutamate systems have dysfunctional features, some of which are identical among the disorders. Finally, cellular calcium regulation and mitochondrial function are, also, impaired in the two.

Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models

“… 25 , 238 Finally, genes involved in neuronal cell survival, proliferation, and differentiation have also shown a link to both disorders. 109 , 239 …”

“…25,238 Finally, genes involved in neuronal cell survival, proliferation, and differentiation have also shown a link to both disorders. 109,239 Overall, strong evidence suggests common genetic factors for schizophrenia and bipolar disorder, but the genetic and phenotypic architecture of these disorders is highly complex, characterized by only a partial degree of overlap. 25 In fact, the detection of shared genetic risk factors of the 2 disorders may be influenced by the subtyping of the patients considered, with type I bipolar disorder more strongly related to schizo phrenia.…”

“…154,155 In addition, certain neuroimaging studies describe patients with bipolar disorder having functional connectivity similar to controls, while patients with schizophrenia being more similar to those with schizoaffective disorder, who might represent a phenotype intermediate between schizophrenia and bipolar disorder. 239 However, tracing links between iPSC results, which could highlight the etiopathogenesis of these disorders, and results from neuroimaging studies, which may be influenced by the impact of the illness or the use of medication, remains challenging.…”