Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A 1H magnetic resonance spectroscopy study

Background: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. Objective: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. Methods: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. Results: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. Conclusion: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.

Automated summary

The study found that patients with bipolar disorder (BD) had higher scores on the Childhood Trauma Questionnaire (CTQ) and higher rates of severity of sexual and physical abuse compared to healthy control (HC) subjects. The severity of physical and sexual abuse was associated with changes in anterior cingulate cortex (ACC) metabolites in BD patients only, suggesting a potential link between childhood abuse and creatine metabolism in the ACC. Further research is needed to explore the mechanism underlying the association between childhood abuse and worse clinical outcomes in BD.