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Several lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naïve BD patients in a major depressive episode (n=18) and compared to 24 age-matched healthy controls. Drug-naïve BD patients did not show differences in activities of citrate synthase (p=0.79), malate dehydrogenase (p=0.17), and succinate dehydrogenase (p=0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD., (Published by Elsevier Ireland Ltd.)

Lithium, a first line treatment for bipolar disorder (BD), has been associated with significant weight gain, but the mechanisms underlying this phenomenon are still unclear. It has been suggested that changes in production/release of adipokines - molecules secreted by adipose tissue presenting anti-inflammatory (adiponectin) and pro-inflammatory (leptin, resistin) properties - might be implicated. Adiponectin, resistin and leptin were assessed in 25 acutely depressed BD individuals (88% medication-free and 68% treatment-naive) at baseline and after 6 weeks of lithium therapy, and in 23 healthy controls matched by age. The 21-item Hamilton Depression Rating Scale was used to assess depression severity. Levels of adiponectin significantly decreased after lithium monotherapy, while the levels of resistin and leptin remained stable after the follow-up period. Adipokine levels during depressive episodes in BD did not differ compared to controls. Pretreatment levels of leptin were higher in remitters and changes in resistin levels were negatively correlated to improvement of depressive symptoms with lithium. Our findings shed light in this pathophysiological process, which might be associated with metabolic syndrome, inflammation and other medical comorbidities in BD., (Published by Elsevier Ireland Ltd.)

Several studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9±127.1pg/mL) compared to pre-treatment (406.3±69.5pg/mL) (p=0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithium's direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)