Abnormalities in Mitochondrial Structure in Cells from Patients with Bipolar Disorder

Abstract

Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial morphology is often linked to altered energy metabolism, we investigated whether changes in mitochondrial structure were present in brain and peripheral cells of patients with BD. Mitochondria from patients with BD exhibited size and distributional abnormalities compared with psychiatrically-healthy age-matched controls. Specifically, in brain, individual mitochondria profiles had significantly smaller areas, on average, in BD samples (P = 0.03). In peripheral cells, mitochondria in BD samples were concentrated proportionately more within the perinuclear region than in distal processes (P = 0.0008). These mitochondrial changes did not appear to be correlated with exposure to lithium. Also, these abnormalities in brain and peripheral cells were independent of substantial changes in the actin or tubulin cytoskeleton with which mitochondria interact. The observed changes in mitochondrial size and distribution may be linked to energy deficits and, therefore, may have consequences for cell plasticity, resilience, and survival in patients with BD, especially in brain, which has a high-energy requirement. The findings may have implications for diagnosis, if they are specific to BD, and for treatment, if they provide clues as to the underlying pathophysiology of BD.

Inositol-Related Gene Knockouts Mimic Lithium’s Effect on Mitochondrial Function

“…Unexpectedly, only mitochondrial function was shown by all three bioinformatics approaches to be enriched among these genes. This finding corroborates previous reports of downregulation of mitochondriarelated genes (Konradi et al, 2004;Sun et al, 2006), mitochondrial dysfunction (Stork and Renshaw 2005), and mitochondrial structural abnormalities (Cataldo et al, 2010) in bipolar patients. The results are also consistent with studies showing beneficial effects of mood stabilizers on mitochondrial function (Maurer et al, 2009;Valvassori et al, 2010) and oxidative stress (Lai et al, 2006).…”

508. Perturbations in the Apoptotic Pathway and Mitochondrial Network Dynamics in Peripheral Blood Mononuclear Cells from Bipolar Disorder Patients

“…Moreover, decreased Mfn2 protein levels were correlated with the activity of citrate synthase and mtDNA, suggesting that Mfn2 is essential for the regulation of mitochondrial morphology by tipping the balance towards mitochondrial fragmentation. Our results are supported by a study published by Cataldo et al 53 demonstrating that prefrontal cortex neurons of postmortem brain from patients with BD and peripheral cells from BD patients display morphological abnormalities (more mitochondria of smaller size) and an abnormal pattern of clumping and marginalization in the intracellular distribution of mitochondria. Taken together, these results suggest that these mitochondrial structural abnormalities may represent an attempt to overcome a reduced mitochondrial network connectivity, as determined by the balance between fusion and fission processes.…”

N-acetyl Cysteine Treatment Rescues Cognitive Deficits Induced by Mitochondrial Dysfunction in G72/G30 Transgenic Mice

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