Impairment in Functional Capacity as an Endophenotype Candidate in Severe Mental Illness

Abstract

Impairment in everyday functioning (also referred to as "disability") is a central feature of schizophrenia (SZ) and bipolar disorder, as well as other neuropsychiatric conditions. There is a genetic contribution to both SZ and bipolar illness (BPI), and the primary putative determinant of impairments in everyday functioning across these 2 conditions, cognitive impairments, also show substantial heritability and in fact have been proposed to be endophenotypes for these disorders. In this article, we review data and make our case that impairments in functional capacity, the functional abilities that result in functional disability, may also be a heritable trait that is common across neuropsychiatric illnesses such BPI and SZ. While there has been little previous research on the heritability of these abilities, it is an area receiving substantial research attention. We consider advances in the measurement of cognitive functioning in SZ that may facilitate the discovery of genetic influences on functional capacity. Functional capacity measures are proximal to real-world impairments, measured with suitable psychometric precision to be used in heritability analyses, and appear to be minimally influenced by environmental factors that may cause disability such as environmental factors, symptoms, and disability compensation. Our conclusion is that these functional capacity measures have potential to be the target of genetic analyses and that these measures should be considered across neuropsychiatric conditions where impairments in everyday functioning are present.