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Danute Balkeliene d,e Algirdas Utkus d,e and Edgaras Dlugauskas a,e Background The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype. MethodsWe assessed the CYP2C19 genotypepredicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the selfrated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results. ResultsSeventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; η p 2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; η p 2 = 0.131 and P = 0.030; η p 2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.Conclusions Intermediate CYP2C19 polymorphismpredicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.

Background: In Huntington’s disease psychiatric symptoms may manifest prior to motor dysfunction. Such symptoms negatively impact people’s quality of life and can worsen the course of the primary disease. The aim of the present study was to assess and compare depression, anxiety and hopelessness rates in individuals with and without an abnormal expansion of CAG repeats in the huntingtin (HTT) gene and healthy controls.Materials and methods: Study involved 31 individuals referred for genetic testing for Huntington’s disease and a control group of 41. Depressive and anxiety symptoms were assessed using Beck Hopelessness Scale (BHS) and Hospital Anxiety and Depression Scale (HADS). Results between groups were compared using the Mann–Whitney U test. Two-sided Bonferroni corrected p-value was set at ≤0.017.Results: Individuals with HTT gene mutation (“gene mutation positive”, GMP) (N=20) scored higher on the HADS depression subscale (5.90 ± 4.52 vs 1.36 ± 1.91; p ≤ 0.017) than those without HTT gene mutation (“gene mutation negative”, GMN) (N=11). GMP and control groups scored higher than the GMN group on the BHS (5.65 ± 3.91 vs 2.09 ± 1.64 and 5.27 ± 4.11 vs 2.09 ± 1.64, respectively; p ≤ 0.017). No differences in anxiety levels were found.Conclusions: Depressive symptoms and hopelessness were more prevalent in individuals with HTT gene mutation than in individuals who were tested but had no said mutation. Such results emphasise the importance of timely diagnosis and treatment of psychiatric comorbidities in individuals affected by Huntington’s disease.