ZNF804A gene variants have a cross-diagnostic influence on psychosis and treatment improvement in Mood Disorders
Marco Calabro 1, Laura Madelli 2, Concetta Crisafulli 1, Marco Di Nicola 3, Roberto Colombo 3, Luigi Janiri 3, Soo-Jung Lee 4, Tae-Youn Jun 4, Sheng-Min Wang 4, Prakash Masand 5, Ashwin Patkar 6, Changsu Han 7, Chi-Un Pae 4, 6, 8*, Alessandro Serretti 2
1Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy, 2Department of biomedical and neuromotor sciences, University of Bologna, Italy., 3Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy., 4Department of Psychiatry, The Catholic University, of Korea College of Medicine, Seoul, Republic of Korea, 5Global Medical Education, New York, NY, USA, 6Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA, 7Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea, 8Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Received: October 30, 2018; Accepted: November 21, 2018; Published online: November 21, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objectives: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with Major Depression and Bipolar Disorder (BPD). In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments.
Methods: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with Major Depression and 132 patients diagnosed with Bipolar Disorder and 326 healthy controls; an Italian sample composed 151 Major Depression subjects, 189 Bipolar Disorder subjects and 38 outpatients diagnosed for a primary Anxiety disorder.
Results: Our analyses reported an association of rs1344706 with psychotic phenotype in the Cross-diagnostic pooled sample (geno p=4.15x10-4, allelic p=1.06x10-4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p=0.025, allelic p=0.007).
Conclusion: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the Bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance, however further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.
Keywords: ZNF804A, depressive disorder, bipolar disorder, symptom improvement, psychosis


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