Evolutionary genetics of affective disorders

Abstract

I review evolutionary-genetic models for the generation, maintenance and loss of allelic variation underlying polygenic disease, in the context of affective disorders and related conditions. Genetically-based liability to these disorders appears to be due to some combination of mutation-selection balance involving common, small-effect variants and rare, large-effect variants, and natural selection involving antagonistic pleiotropy and balancing selection. At present, the primary usefulness of evolutionary genetics in the study of affective disorders is that it provides important insights into choices of genes, alleles, and haplotypes for analysis via genome-scan and association studies, and motivates a focus on the potential for pleiotropic, beneficial effects of alleles and genotypes that also influence disease risk.

Molecular Signatures of Natural Selection for Polymorphic Genes of the Human Dopaminergic and Serotonergic Systems: A Review

“…Similarly, tradeoffs may exist for alleles that lead to susceptibility for psychiatric disorders. For example, alleles associated with schizophrenia in some individuals may in other individuals be associated with creativity, problem-solving, or other cognitive functions ( Nettle, 2006 ; Crespi et al, 2007 ; Crespi, 2009 ).…”

Genomic imprinting in the development and evolution of psychotic spectrum conditions

“…Like the autistic spectrum, conditions on the psychotic spectrum exhibit strong genetic components to their expression, but with many genes involved and different combinations of these genes capable of contributing to the phenotypes (Rapoport et al , 2005; Tamminga & Holcomb, 2005). Autism, schizophrenia, schizotypy, bipolar disorder, and major depression usually exhibit a polygenic and idiopathic (cause unknown) basis (Crespi 2009), but they may also be associated with specific syndromes involving losses or gains of genes or chromosomal regions, or alterations to imprinting (Table 1). ‘Autistic’ behaviour has been described for Klinefelter syndrome, velocardiofacial syndrome and Prader‐Willi syndrome, but these psychiatric phenotypes apparently reflect personality premorbid for schizophrenia or aspects of negative schizotypy and they are not underlain by autistic‐spectrum neurological or physiological traits (Eliez 2007; Feinstein and Singh 2007; Crespi & Badcock 2008).…”

“…‘Autistic’ behaviour has been described for Klinefelter syndrome, velocardiofacial syndrome and Prader‐Willi syndrome, but these psychiatric phenotypes apparently reflect personality premorbid for schizophrenia or aspects of negative schizotypy and they are not underlain by autistic‐spectrum neurological or physiological traits (Eliez 2007; Feinstein and Singh 2007; Crespi & Badcock 2008). As for autism, the psychotic spectrum can be considered as a highly convergent set of conditions, with strong genetic, epigenetic and environmental heterogeneity yielding a relatively limited range of phenotypes (Keverne, 1999; Seeman et al , 2005; Badcock & Crespi, 2006; Crespi, 2009). By the hypothesis discussed here, one underlying cause of these convergent phenotypes is dysregulation of imprinted genes that influence cognition and behaviour.…”