Serum phosphatidylinositol as a biomarker for bipolar disorder liability

Abstract

Objectives Individuals with bipolar disorder (BPD) exhibit alterations in their phospholipid levels. It is unclear whether these alterations are a secondary consequence of illness state, or if phospholipids and illness risk overlap genetically. If the latter were true, then phospholipids might provide key insights into the pathophysiology of the illness. Therefore, we rank-ordered phospholipid classes by their genetic overlap with BPD risk in order to establish which class might be most informative in terms of increasing our understanding of illness pathophysiology. Methods Analyses were conducted in a sample of 558 individuals, unselected for BPD, from 38 extended pedigrees (average family size=14.79, range=2–82). We calculated a coefficient of relatedness for all family members of nine individuals with BPD in the sample (N=185); this coefficient was set to be zero in unrelated individuals (N=373). Then, under an endophenotype ranking value (ERV) approach, this scalar index was tested against 13 serum-based phospholipid concentrations in order to rank-order lipid classes by their respective overlap with BPD risk. Results The phosphatidylinositol class was significantly heritable (h2=0.26, P=6.71 × 10−05). It was the top-ranked class, and was significantly associated with BPD risk after correction for multiple testing (β=−1.18, P=2.10 × 10−03, ERV=0.49). Conclusions We identified a peripheral biomarker, serum-based phosphatidylinositol, which exhibits a significant association with BPD risk. Therefore, given that phosphatidylinositol and BPD risk share partially common etiology, it seems that this lipid class warrants further investigation, not only in terms of treatment, but also as a promising diagnostic and risk marker.

Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

“…They found that inhibition of Vps34, a kinase phosphorylating phosphatidylinositol (PI) to PI(3)P, causes endolysosomal dysfunction with secretion of exosomes containing APP C-terminal fragments. Knowles et al (2017) recently reported that serum levels of PI, the precursor of phosphoinositides like PI(3)P and PI(3,5)P 2 , is negatively associated with a proxy of genetic susceptibility to BIP.…”

Metabolic Profiling in Bipolar Disorder Patients During Depressive Episodes

“…Previous studies identified a panel of metabolic biomarkers that could discriminate patients with BD from healthy controls (13)(14)(15)(16)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Lan et al (14) found several differential metabolites in post-mortem brain tissue, indicating that the balance of excitatory/inhibitory neurotransmission is the core of BD.…”

“…The results indicated that isocitric acid played a key role in the onset of BD. Other studies has also identified some potential biomarkers for BD diagnosis both in blood and urine (15,16,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). However, the patients included in these studies were in different episodes.…”

Urinary metabolite signature in bipolar disorder patients during depressive episode

“…Lan et al found several significantly altered metabolites in the brain tissue of BD patients [7]. Another study found that the serum phosphatidylinositol might be a potential biomarker for BD liability [8]. Our previous studies have also identified some potential biomarkers for BD diagnosis [9, 10].…”