Pavol Mikolas1, Leonardo Tozzi2, Kelly Doolin3, Chloe Farrell3, Veronica O'Keane3, Thomas Frodl4. 1. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany; Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universitaet Dresden, Dresden, Germany. 2. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. 3. Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland. 4. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany; Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland. Electronic address: thomas.frodl@med.ovgu.de.
Abstract
BACKGROUND: Smaller hippocampus volume represents a consistent finding in major depression (MDD). Hippocampal neuroplasticity due to chronic stress might have differential effect on hippocampal subfields. We investigated the effects of the rs1360780 polymorphism of the hypothalamic-pituitary-axis related gene FKBP5 in combination with early life stress (ELA) on the structure of hippocampal subfields in MDD. METHODS: We assessed the hippocampal subfields volumes in 85/67 MDD/healthy controls. We investigated the effects of diagnosis, FKBP5 allelic status and their interaction as predictors of hippocampal subfield volumes as well as the effect of ELA and its interaction with FKBP5. RESULTS: MDD patients had smaller hippocampal volumes, in particular within the cornu ammonis (CA) and dentate gyrus (DG) regions. Patients exposed to ELA had larger hippocampi, in particular within the CA and DG. Among the patients exposed to ELA, the T allele carriers displayed lower volumes within the hippocampus-amygdala-transition-area (HATA) as those subjects homozygous for the C allele. LIMITATIONS: We pooled the subjects from 2 centers in order to increase the sample size. We did not include the cumulative lifetime exposure to medication. CONCLUSIONS: Hippocampal volume reductions in MDD were present particularly in the CA and DG. MDD with ELA display differential volume changes compared to MDD without ELA. The significant interaction between ELA and the rs1360780 polymorphism in HATA suggests a role of FKBP5 in the pathophysiology of structural alterations in depression.
BACKGROUND: Smaller hippocampus volume represents a consistent finding in major depression (MDD). Hippocampal neuroplasticity due to chronic stress might have differential effect on hippocampal subfields. We investigated the effects of the rs1360780 polymorphism of the hypothalamic-pituitary-axis related gene FKBP5 in combination with early life stress (ELA) on the structure of hippocampal subfields in MDD. METHODS: We assessed the hippocampal subfields volumes in 85/67 MDD/healthy controls. We investigated the effects of diagnosis, FKBP5 allelic status and their interaction as predictors of hippocampal subfield volumes as well as the effect of ELA and its interaction with FKBP5. RESULTS:MDDpatients had smaller hippocampal volumes, in particular within the cornu ammonis (CA) and dentate gyrus (DG) regions. Patients exposed to ELA had larger hippocampi, in particular within the CA and DG. Among the patients exposed to ELA, the T allele carriers displayed lower volumes within the hippocampus-amygdala-transition-area (HATA) as those subjects homozygous for the C allele. LIMITATIONS: We pooled the subjects from 2 centers in order to increase the sample size. We did not include the cumulative lifetime exposure to medication. CONCLUSIONS: Hippocampal volume reductions in MDD were present particularly in the CA and DG. MDD with ELA display differential volume changes compared to MDD without ELA. The significant interaction between ELA and the rs1360780 polymorphism in HATA suggests a role of FKBP5 in the pathophysiology of structural alterations in depression.
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