Child Biomarkers Linked to BD Parents

Biomarkers have been identified in children of patients with bipolar disorder that suggest that at the molecular level the disorder is linked to the process of apoptosis and related disturbance of mitochondrial function.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Since the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, investigators at the University of Texas Health Science Center at Houston measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls.

To carry out this study, the investigators analyzed peripheral blood mononuclear cells from 18 children and adolescents in three matched groups: bipolar patients, unaffected offspring of bipolar parents, and children of parents with no history of psychiatric disorders. The investigators determined levels of several pro-apoptotic and anti-apoptotic protein factors, as well as the expression of mitochondrial fission/fusion proteins in peripheral blood mononuclear cells (PBMCs).

The results revealed that levels of the anti-apoptotic proteins Bcl-xL, survivin, and Bcl-xL/Bak dimer were significantly decreased, while active caspase-3 protein levels were significantly increased in PBMCs from BD patients. The mitochondrial fusion-related proteins Mfn2 (mitofusin-2) and Opa1 (mitochondrial dynamin like GTPase) were downregulated, while the fission protein Fis1 (mitochondrial fission 1 protein) in PBMCs from BD patients was upregulated in terms of gene expression and protein levels. A significant decrease in citrate synthase activity was also found. Finally, the investigators reported a positive correlation between Mfn2 and Opa1 with mitochondrial content markers, as well as a negative correlation between mitochondrial fission/fusion proteins and apoptotic markers.

"We have known that children of patients with bipolar disorder have a higher risk of developing the illness but the biological mechanisms are largely unknown," said contributing author Dr. Gabriel R. Fries, a post-doctoral research fellow in the psychiatry and behavioral sciences at the University of Texas Health Science Center at Houston. "By analyzing the blood of children of controls and comparing it to children of bipolar patients, we identified several genes or markers that can explain the increased risk. All combine to modulate the response to stress in these children. We know from clinical studies of behavior and the environment that when children are chronically exposed to stressors, they are at a higher risk of developing bipolar disorder. Bipolar parents may struggle because of their disease, leading to higher environmental stress. Their children, because of the genetic markers they have, could be more vulnerable to stress."

The study was published in the May 2, 2017, online edition of the journal Translational Psychiatry.