Lactate in bipolar disorder: A systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 29726068 · doi:10.1111/pcn.12671
What was done
A systematic review and random-effects meta-analysis evaluated 12 studies comparing lactate levels (a marker of mitochondrial dysfunction) between patients with bipolar disorder and healthy controls. Measurement modalities included proton magnetic resonance spectroscopy (MRS) or echo-planar spectroscopy for brain lactate (6 studies), cerebrospinal fluid (CSF) analysis (2 studies), and peripheral blood analysis (2 studies). Five brain spectroscopy studies were pooled using standardized mean differences in a random-effects model.
What was found
Five of 6 brain spectroscopy studies and both CSF studies reported significantly higher lactate concentrations in individuals with bipolar disorder compared to controls. Two peripheral lactate studies found no significant differences. The pooled meta-analysis of 5 brain lactate studies showed a borderline significant elevation in bipolar disorder (Z = 1.97, P = 0.05), accompanied by substantial heterogeneity (I² = 86%) and suspected publication bias.
Why it matters
Elevated central lactate levels provide preliminary biological support for mitochondrial and bioenergetic dysfunction in the pathophysiology of bipolar disorder. However, inconsistencies across tissue compartments and high study heterogeneity indicate lactate is not yet established as a viable clinical biomarker.
Limits
The meta-analysis included only 5 studies with severe statistical heterogeneity (I² = 86%) and potential publication bias. Peripheral measurements failed to mirror central findings, total participant count was not reported in the abstract, and several included studies excluded female participants or lacked standardized spectroscopy methodologies.
Cited by
- supports Lactate and GDF15 levels tend to be elevated in individuals with mental illness.