Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.

Title Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.
Authors R. Machado-Vieira; M.V. Zanetti; M.C. Otaduy; R.T. De Sousa; M.G. Soeiro-de-Souza; A.C. Costa; A.F. Carvalho; C.C. Leite; G.F. Busatto; C.A. Zarate; W.F. Gattaz
Journal J Clin Psychopharmacol
DOI 10.1097/JCP.0000000000000616
Abstract

OBJECTIVE: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy.

METHODS: Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome.

RESULTS: Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels.

CONCLUSIONS: This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.

Citation R. Machado-Vieira; M.V. Zanetti; M.C. Otaduy; R.T. De Sousa; M.G. Soeiro-de-Souza; A.C. Costa; A.F. Carvalho; C.C. Leite; G.F. Busatto; C.A. Zarate; W.F. Gattaz.Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.. J Clin Psychopharmacol. 2017;37(1):4045. doi:10.1097/JCP.0000000000000616

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Lithium

Lithium Bohr ModelSee more Lithium products. Lithium (atomic symbol: Li, atomic number: 3) is a Block S, Group 1, Period 2 element with an atomic weight of 6.94. The number of electrons in each of Lithium's shells is [2, 1] and its electron configuration is [He] 2s1. The lithium atom has a radius of 152 pm and a Van der Waals radius of 181 pm. Lithium was discovered by Johann Arvedson in 1817 and first isolated by William Thomas Brande in 1821. The origin of the name Lithium comes from the Greek wordlithose which means "stone." Lithium is a member of the alkali group of metals. It has the highest specific heat and electrochemical potential of any element on the period table and the lowest density of any elements that are solid at room temperature. Elemental LithiumCompared to other metals, it has one of the lowest boiling points. In its elemental form, lithium is soft enough to cut with a knife its silvery white appearance quickly darkens when exposed to air. Because of its high reactivity, elemental lithium does not occur in nature. Lithium is the key component of lithium-ion battery technology, which is becoming increasingly more prevalent in electronics.

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