Schizophrenia, bipolar disorder, and major depressive disorders are heritable serious mental illnesses (SMI). What does this heritability mean? What are the underlying mechanisms? Large genome-wide association studies (GWAS) have identified both shared and unique genetic risk variants for these disorders; however, causal risk variants, their molecular mechanisms, and their effects on brain circuitry are mostly unknown. Targeted, possibly individualized, therapies addressing underlying mechanisms offer the promise of improved functioning and well-being for patients. The study of the effects of the CACNA1C gene on episodic memory-associated neural circuitry by Erk et al. (
1) provides a noteworthy use of the imaging-genetics approach to aid in our understanding of biological mechanisms underlying SMI. Typically, the imaging-genetics approach refers to the use of structural or functional imaging data to evaluate genetic variation or more infrequently, the use of imaging data to discover genes related to disorders or symptoms.
- Erk S.
- Meyer-Lindenberg A.
- Schmierer P.
- Mohnke S.
- Grimm O.
- Garbusow M.
- et al.
Hippocampal and frontolimbic function as intermediate phenotype for psychosis: Evidence from healthy relatives and a common risk variant in CACNA1C.
Biol Psychiatry. 2014; 76: 466-475
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- Hippocampal and frontolimbic function as intermediate phenotype for psychosis: Evidence from healthy relatives and a common risk variant in CACNA1C.Biol Psychiatry. 2014; 76: 466-475
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Accepted: July 21, 2014
Received in revised form: July 18, 2014
Received: July 3, 2014
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Hippocampal and Frontolimbic Function as Intermediate Phenotype for Psychosis: Evidence from Healthy Relatives and a Common Risk Variant in CACNA1CBiological PsychiatryVol. 76Issue 6
- PreviewVariation in CACNA1C has consistently been associated with psychiatric disease in genome-wide association studies. We have previously shown that healthy carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate (pgACC) dysfunction during episodic memory recall. To test whether this brain systems-level abnormality is a potential intermediate phenotype for psychiatric disorder, we studied unaffected relatives of patients with bipolar disorder, major depression, and schizophrenia.