Maternal inheritance in recurrent early-onset depression

Abstract

Major depressive disorder (MDD) is believed to have a genetic factor in its pathogenesis. On the basis of studies in MDD showing brain energy depletion and maternal inheritance in some families, we hypothesize that some of the genetic factor is likely maternally inherited on the mitochondrial DNA (mtDNA). Six hundred and seventy-two pedigrees from the Genetics of Recurrent Early-Onset Depression project were analyzed for matrilineal/nonmatrilineal pairs. Pairs were constructed to control for sex, age and autosomal gene contribution (e.g. maternal vs. paternal aunts). Individuals with and without any mood disorder were tallied and compared across five different pairs. Matrilineal relatives (with the same mtDNA sequence as the proband) were significantly more likely to suffer from a mood disorder than were nonmatrilineal relatives (with another mtDNA sequence; odds ratio 2.0, 95% confidence interval: 1.5-2.6, P = 3 x 10(-6)). Our data show a modest maternal bias in the susceptibility towards the development of depression, suggesting that predisposing genetic factors likely reside on the mtDNA. Thus, our data strengthen the hypothesis that energy metabolism may be involved in the pathogenesis of depression.

Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: A 31-phosphorus magnetic resonance spectroscopy study

“…The Genetics of Recurrent Early-Onset Depression (GenRED) project found that matrilineal relatives, i.e. those with the same mitochondrial genome as the proband, were more likely to suffer from a mood disorder than non-matrilineal relatives (Bergemann and Boles, 2010). …”

Sex differences in anxiety and emotional behavior

“…Since the Y chromosome contains a very limited number of genes and the Barr body (second X chromosome in females) remains largely inactive in healthy cells of the female body [73, 74], the impact of chromosomal differences in the classic sense [19, 299] on anxiety-related behavior is probably small in comparison to developmental or adult neuroendocrine sex differences, but not negligible [35, 89, 241]. The role of the maternally inherited mitochondrial genome and its effects on energy balance should also not be ignored because a higher predisposition for anxiety and depressive disorders is detected in mothers and matrilineal relatives of children with maternally inherited mitochondrial diseases [48], and clinical in vitro fertilization studies among offspring of genetically related or unrelated mothers suggest that, in many cases, affective and anxiety-linked genetic traits may be inherited from the mother [38, 307, 308]. It also to be expected that anxiety-relevant biological sex differences exist with regard to stress vulnerability, meaning how the female brain perceives and processes stressful events, and that some of these differences should be detectable on a molecular level.…”

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

“…There is abundant evidence of mitochondrial abnormalities in these patients. For example, one study demonstrated that individuals with early onset MDD are significantly more likely to have a mother with MDD than a father with the disorder, thus supporting the possibility of maternal mitochondrial inheritance in MDD via mutations in mtDNA [207]. However, evidence of variations in mtDNA in clinical populations with MDD is limited.…”