Bioenergetic measurements in children with bipolar disorder: a pilot 31P magnetic resonance spectroscopy study
Elif M Sikoglu1, J Eric Jensen, Gordana Vitaliano
1Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Insights
This study found lower global inorganic phosphate (Pi) and higher phosphocreatine-to-Pi ratios in adolescents with Bipolar Disorder (BD), suggesting altered mitochondrial phosphorylation. Further research is needed to understand these differences in pediatric BD.
Area of Science:
- Neuroscience
- Biochemistry
- Pediatric Psychiatry
Background:
- Limited research exists on mitochondrial dysfunction in pediatric Bipolar Disorder (BD).
- Previous studies indicated abnormal cerebral pH and mitochondrial activity in adults with BD.
- No studies have investigated these markers in children diagnosed with BD.
Purpose of the Study:
- To investigate mitochondrial function in adolescents with BD using Phosphorus Magnetic Resonance Spectroscopy ((31)P MRS).
- To compare cerebral pH, phosphocreatine (PCr), and inorganic phosphate (Pi) levels between pediatric BD patients and healthy controls.
- To explore potential links between these metabolic markers and BD phenotypes in youth.
Main Methods:
- (31)P MRS was employed to measure pH, PCr, and Pi levels.
- The study included 8 subjects with BD and 8 healthy comparison subjects (HCS), aged 11-20.
- Cerebral metabolites were analyzed in relation to age and clinical severity (YMRS).
Main Results:
- No significant difference in overall pH was observed between BD patients and HCS.
- Frontal lobe pH increased with age in BD patients, unlike in HCS.
- Global Pi was significantly lower, and the PCr/Pi ratio was significantly higher in subjects with BD compared to HCS.
Conclusions:
- Altered Pi levels and unchanged PCr in pediatric BD suggest impaired mitochondrial phosphorylation.
- Findings indicate potential differences in mitochondrial dysfunction manifestation between pediatric and adult BD.
- Further investigation with larger cohorts is recommended to confirm these metabolic alterations in pediatric BD.
Background:
Research exploring Bipolar Disorder (BD) phenotypes and mitochondrial dysfunction, particularly in younger subjects, has been insufficient to date. Previous studies have found abnormal cerebral pH levels in adults with BD, which may be directly linked to abnormal mitochondrial activity. To date no such studies have been reported in children with BD.
Methods:
Phosphorus Magnetic Resonance Spectroscopy ((31)P MRS) was used to determine pH, phopshocreatine (PCr) and inorganic phosphate (Pi) levels in 8 subjects with BD and 8 healthy comparison subjects (HCS) ages 11 to 20 years old.
Results:
There was no significant difference in pH between the patients and HCS. However, frontal pH values for patients with BD increased with age, contrary to studies of HCS and the pH values in the frontal lobe correlated negatively with the YMRS values. Global Pi was significantly lower in subjects with BD compared with HCS. There were no significant differences in PCr between the groups. Global PCr-to-Pi ratio (PCr/Pi) was significantly higher in subjects with BD compared with HCS.
Conclusions:
The change in Pi levels for the patients with BD coupled with the no difference in PCr levels, suggest an altered mitochondrial phosphorylation. However, our findings require further investigation of the underlying mechanisms with the notion that a mitochondrial dysfunction may manifest itself differently in children than that in adults.
Limitations:
Further investigations with larger patient populations are necessary to draw further conclusions.
