Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder

Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.

Automated summary

This study found that patients with adult ADHD had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1), sphinganine-1-phosphate (S1P d18:0), anandamide (AEA), and arachidonoylglycerol, while patients with affective disorders had increased long chain ceramides, particularly Cer22:0, but lower levels of endocannabinoids. Patients with comorbid ADHD and affective disorders displayed intermediate levels of sphingolipids compared to non-comorbid patients. The ratio of S1P d18:1 to Cer22:0 may be a potential diagnostic or prognostic tool.