Dysfunction of the Purinergic System in Bipolar Disorder.

OBJECTIVE: To verify the purinergic hypothesis of bipolar disorder (BD), we assessed the concentration of various components of the purinergic system in manic and depressed bipolar patients. METHODS: Sixty-two patients (19 male and 43 female), aged 22-69 (49 ± 14) years, with BD were studied. Twenty-three patients (9 male and 14 female) were assessed during a manic episode and subsequent remission, and 39 patients (10 male and 29 female) were investigated in a depressive episode and the following remission. Twenty-two healthy subjects (8 male and 14 female), aged 19-70 (41 ± 14) years, served as the control group (CG). The severity of symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The concentrations of uric acid (UA) were estimated by the uricase-based method, whereas xanthine dehydrogenase (XDH), adenosine (Ado), and adenosine deaminase (ADA) by ELISA. RESULTS: The mean score in the acute episode was 32 ± 8 points in the YMRS for mania and 31 ± 8 in the HDRS for depression. UA levels were significantly higher in female bipolar patients compared to the females in the CG. The concentrations of XDH, Ado, and ADA were significantly lower in bipolar patients both during an acute episode and remission compared to CG. CONCLUSIONS: A significant dysfunction of the purinergic system in patients with BD was observed. In most instances, the disturbances were not different in the acute episode than in remission what qualifies them as trait dependent. The results may confirm the role of the purinergic system in the pathogenesis of BD.

International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic).

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.