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. Author manuscript; available in PMC: 2015 Jun 1.
Published in final edited form as: Psychiatr Genet. 2014 Jun;24(3):120–121. doi: 10.1097/YPG.0000000000000026

DISC1 Loci Not Associated with Anhedonia in Individuals with Genetic Liability for Schizophrenia

Anna R Docherty 1, Scott R Sponheim 2,3, Ian R Gizer 4
PMCID: PMC4003488  NIHMSID: NIHMS561827  PMID: 24770450

Meta-analytic review has indicated that social symptoms are quite relevant to genetic liability for schizophrenia (Tarbox et al., 2011). Social anhedonia, in particular, consistently differentiates relatives of people with schizophrenia from controls, yet the biological mechanisms underlying anhedonia remain unclear. Recently, social anhedonia as a measure of psychosis-proneness has been linked to DISC1 (Disrupted-in-schizophrenia 1), and eight other genes impacting the DISC1 pathway, in a large Finnish cohort (for details of two studies, see Tomppo et al., 2009 and Tomppo et al., 2012).

The current study examined whether anhedonia is associated with DISC1 polymorphisms in a clinically-enriched sample of 346 schizophrenia probands, their first-degree relatives, and non-psychiatric controls from the Minneapolis Veterans Affairs (VA) Family Study of Schizophrenia.

Lifetime Axis I diagnoses for all participants were determined by doctoral-level psychologists through a consensus process, consistent with established guidelines, that involved review of structured diagnostic interviews, medical history, and family informant material when available. Relative and control participants were administered self-report anhedonia questionnaires identical to those used by Tomppo et al. The entire sample was additionally administered the Schizotypal Personality Questionnaire (SPQ; Raine, 1991), a measure with interpersonal and social withdrawal-related subscales. Scores across these measures were examined for association with 14 single nucleotide polymorphisms across DISC1.

SNPS included, with minor allele frequency (MAF): rs3738401 (.26); rs1954175 (.26); rs2812393 (.48); rs1322784 (.20); rs1322783 (.08); rs2255340 (.26); rs2738864 (.22); rs6675281 (.13); rs1000731 (.26); rs1000730 (.42); rs7546310 (.48); rs821597 (.37); rs821616 (.32); rs3737597 (.03). The frequencies in patients, relatives, and controls for all markers were in Hardy–Weinberg equilibrium. The QFAM-TOTAL procedure in Plink for Linux performs family-based tests of between- and within-groups association with quantitative phenotypes, while accounting for dependence between related individuals.

Consistent with previous research, groups differed across all measures (relatives and controls, Revised Social Anhedonia Scale Z(1,348) = −2.31, p <.05 and Physical Anhedonia Scale Z(1,348) = −2.12, p <.05; probands, relatives and controls, SPQ Interpersonal Factor X2(2,518) = 124.22, p <.001; SPQ No Close Friends subscale X2(2,518) = 118.92, p <.001). Probands represented the most elevated scores, followed by relatives, followed by controls. Proband and control participants differed significantly with respect to one of the DISC1 SNPs, rs1000730 (Wald = 4.382, p < .05) but this did not remain significant after correcting for multiple testing. None of the SNPs were significantly associated with any anhedonia scores after Bonferroni correction for multiple testing. Inclusion of age, sex, and ethnicity covariates did not alter results.

Anhedonia was not associated with DISC1 polymorphisms in this clinically-enriched sample, despite power being adequate to detect small-to-moderate effects (f ≥ .25 with power ≥ .80). Schizotypal anhedonia may be tied to dopaminergic innervations of prefrontal brain regions, while DISC1 may be more related to manifestations of hippocampal dependent abnormalities reflective of genetic liability for schizophrenia. Future research examining DISC1 and anhedonia would benefit from inclusion of additional DISC1 loci in biological relatives.

Acknowledgments

This research was supported by grants Merit Review grants from the Department of Veterans Affairs Clinical Science Research and Development Program (1I01CX000227), the National Institute of Mental Health (5R24MH069675) and the Minnesota Medical Foundation (SMF-2075-99) to Dr. Sponheim, and the Minneapolis VA Health Care System Mental Health Patient Service Line. Dr. Docherty was supported by a National Institute of Mental Health (NIMH; 2010-2012) Ruth Kirschstein National Research Award (NRSA)/ 1F31MH092081 and an American Psychological Foundation F.J. McGuigan Award.

References

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