Abnormalities in mitochondrial structure in cells from patients with bipolar disorder.
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.
Cataldo
Anne M
AM
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
McPhie
Donna L
DL
Lange
Nicholas T
NT
Punzell
Steven
S
Elmiligy
Sarah
S
Ye
Nancy Z
NZ
Froimowitz
Michael P
MP
Hassinger
Linda C
LC
Menesale
Emily B
EB
Sargent
Laura W
LW
Logan
David J
DJ
Carpenter
Anne E
AE
Cohen
Bruce M
BM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000473:pathology*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D003599:Cytoskeleton / Q000648:ultrastructure; D004734:Energy Metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
D000928:Antidepressive Agents; D016651:Lithium Carbonate; D000255:Adenosine Triphosphate; D045304:Cytochromes c