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Neanderthal‐derived genetic variation in living humans relates to schizophrenia diagnosis, to psychotic symptom severity, and to dopamine synthesis
Author(s) -
Gregory Michael D.,
Eisenberg Daniel P.,
Hamborg Madeline,
Kippenhan J. Shane,
Kohn Philip,
Kolachana Bhaskar,
Dickinson Dwight,
Berman Karen F.
Publication year - 2021
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32872
Subject(s) - neanderthal , schizophrenia (object oriented programming) , psychosis , dopamine , disease , psychology , ancient dna , evolutionary biology , neuroscience , psychiatry , genetics , biology , medicine , pathology , population , history , archaeology , environmental health
Abstract Schizophrenia has been hypothesized to be a human‐specific condition, but experimental approaches to testing this idea have been limited. Because Neanderthals, our closest evolutionary relatives, interbred with modern humans prior to their disappearance from the fossil record, leaving a residual echo that survives in our DNA today, we leveraged new discoveries about ancient hominid DNA to explore this hypothesis in living people in three converging ways. First, in four independent case–control datasets totaling 9,362 individuals, individuals with schizophrenia had less Neanderthal‐derived genetic variation than controls ( p = .044). Second, in 49 unmedicated inpatients with schizophrenia, having more Neanderthal admixture predicted less severe positive symptoms ( p = .046). Finally, using 18 F‐fluorodopa PET scanning in 172 healthy individuals, having greater Neanderthal introgression was significantly associated with lower dopamine synthesis capacity in the striatum and pons ( p 's < 2 × 10 −5 ), which is fundamentally important in the pathophysiology and treatment of psychosis. These results may help to elucidate the evolutionary history of a devastating neuropsychiatric disease by supporting the notion of schizophrenia as a human‐specific condition. Additionally, the relationship between Neanderthal admixture and dopamine function suggests a potential mechanism whereby Neanderthal admixture may have affected our gene pool to alter schizophrenia risk and/or course.