Article

Review of the Literature on Major Mental Disorders in Adult Patients With Mitochondrial Diseases

The Cleveland Clinic Foundation, OH, USA.
Psychosomatics (Impact Factor: 1.86). 02/2006; 47(1):1-7. DOI: 10.1176/appi.psy.47.1.1
Source: PubMed

ABSTRACT

Mitochondria are intracellular organelles crucial to the production cellular energy. Mitochondrial disease results from a malfunction in this biochemical cascade. These disorders can affect any organ system, producing diverse signs and symptoms, including psychiatric ones. Several authors argue that mitochondrial dysfunction is related to the pathophysiology of bipolar disorder and schizophrenia. Also, the authors retrieved 19 case reports that describe patients with mitochondrial diseases and psychiatric disorders. Most of these patients have psychiatric presentations that preceded the diagnosis of mitochondrial disease. The most common physical findings are fatigue, muscle weakness with or without atrophy, and hearing loss.

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    • "Neurons require large amounts of energy, mainly produced by the mitochondrial respiratory system, to maintain the ion gradient between the extracellular and intracellular membranes. Several studies have shown that genetic and structural abnormalities of mitochondria are associated with various psychiatric diseases (Cataldo et al., 2010; Fattal et al., 2006). Mitochondrial metabolism is also important for ROS production. "
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    ABSTRACT: Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation,which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus–pituitary–adrenal (HPA) axis have close interactionswith pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.
    Full-text · Dataset · Jan 2016
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    • "As such, the brain is the most susceptible organ to damage from mitochondrial dysfunction. In patients with mitochondrial diseases, depressive episodes are often seen with comorbidity (Fattal et al., 2006). Major depressive disorder (MDD) is a severe neuropsychiatric disease, characterized by pervasive and persistent sad moods, which are accompanied by physiological and psychological characteristics, such as lack of energy, fatigue or difficulties with concentration. "
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    ABSTRACT: Background: There is ample evidence supporting the idea that mitochondrial dysfunction and altered expression of complex I subunits play important roles in the pathophysiology of mental disorders. Early literature reports have implicated NDUFV2, a nuclear-encoded mitochondrial complex I subunit gene, in bipolar disorder and schizophrenia. There has been no genetic study to investigate whether there is an association between NDUFV2 and major depressive disorder (MDD). Methods: This study recruited 744 patients with MDD and 767 well-matched healthy controls in a Chinese Han population, and genotyped 9 SNPs within NDUFV2. Results: Initial analysis showed statistically significant differences for 2 SNPs (rs4798765 and rs12964485) in the genotypic distribution and for 1 SNP (rs4797356) in the allelic distribution between the case and control groups. Nevertheless, no significance was demonstrated following multiple testing corrections. Haplotype analysis showed that the T-C haplotype, consisting of rs12457810 and rs12964485, was significantly associated with MDD (P=0.005, corrected P=0.04 after a 10,000 permutation test). We performed an eQTL analysis and found that rs12964485 was significantly associated with NDUFV2 expression in the occipital cortex (P=0.036), albeit this significance did not survive after Bonferroni correction. Limitation: This is a preliminary investigation with a relatively modest sample size. Conclusion: Our findings provided preliminary evidence that a haplotype T-C consisting of rs12457810 and rs12964485 in the 5'-upstream region of NDUFV2 may be a protective factor for the development of MDD in Han Chinese.
    Full-text · Article · Oct 2015 · Journal of Affective Disorders
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    • "Neurons require large amounts of energy, mainly produced by the mitochondrial respiratory system, to maintain the ion gradient between the extracellular and intracellular membranes. Several studies have shown that genetic and structural abnormalities of mitochondria are associated with various psychiatric diseases (Cataldo et al., 2010; Fattal et al., 2006). Mitochondrial metabolism is also important for ROS production. "

    Full-text · Dataset · Sep 2015
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