Psychiatric and Behavior Genetics
Genetics of Affective Disorders
Affective disorders are severe and common psychiatric diseases with two main clinical forms: Bipolar and Unipolar Affective Disorders (BPAD and UPAD). BPAD is characterized by major depressive episodes alternating with phases of mania (bipolar I disorder) or hypomania (bipolar II disorder). UPAD is characterized by recurrent major depressive episodes alone. Affective disorders are highly prevalent and associated with severe social disability and considerable mortality both with major economic impact.
The etiology of mood disorders is multifactorial involving genetic as well as environmental factors. Traditional methods such as family, twin and adoption studies first have provided cumulative evidence implicating genetic factors in the vulnerability for affective disorders. Using these methods however, it is difficult to delineate which genetic variables are involved as well as the exact mode of transmission of the disease.
The main focus of our research is association studies of candidate genes; linkage analysis, including genome scan and fine mapping as well as genome wide interaction and locus-heterogeneity linkage scan. The sample collection, which includes unique extended Roma families with affective disorders and epilepsy, Bulgarian trios and case-controls samples with affective disorder, is a result of systematic diagnostic work at the Psychiatry Clinic, University hospital “Aleksandrovska” and field work in the Roma community. The clinical team has invested major efforts in training for the application of standardised diagnostic instruments and neurocognitive tests in psychiatric research.
The research group has participated in many national and international research projects including contribution to the EU Consortium on Affective disorders, funded under BIOMED1 and BIOMED2 framework programs. The international collaboration of the group involves leading experts in molecular genetics (Prof. P. Propping, Institute of Human Genetics, University of Bonn and Prof. M. Noethen, Life and Brain Research Centre, Bonn, Germany; Molecular Medicine Centre and Department of Medical Genetics, Prof. D. Porteous and Dr. K. Evans,University of Edinburgh, UK).
Our research efforts over the last years aimed at fine mapping and replication study of the loci identified in the genome scan of the extended Roma Families with affective disorder and epilepsy, collection of additional extended families and trios and replication studies. In collaboration with renowned experts in epidemiology of epilepsy (Prof. J W Sander, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology); psychiatry (Prof. A. Jablensky, Centre for Clinical Research in Neuropsychiatry) and genetics of Roma population (Prof. L. Kalaydjieva, Dr. D. Angelicheva, WAIMR and UWA Centre for Medical Research, WA), the research group participates in two NHMRC funded grants on genetic and clinical investigation of bipolar disorders and epilepsy in the isolated Roma population of Bulgaria.
The current research focus is on family based association studies of candidate genes variants and neurocognitive impairments and/or personality traits in BAD patients and their first degree relatives.
Genetics of addiction
Drug addiction is a particularly disabling psychiatric disorder, characterised by severe psychological and physical dependence and withdrawal, which often prevents cessation and sustains usage. Although some individuals can stop compulsive use of tobacco, alcohol, or illegal drugs on their own, for a large number of individuals rendered vulnerable by both genetic and non-genetic factors, addiction proves to be a recalcitrant, chronic, and relapsing condition. The negative effect of this behavioural disorder on both society and economics warrants the extensive scientific research on the genetic factors associated with predisposition to drug addiction.
Addiction to heroin is of particular research interest due to its great impact on the public health. The problem is of special concern in Bulgaria, since the country is situated on the Balkan road of the heroin towards
Europe. According to the 2001 National report on the drugs situation in Bulgaria, heroin remains the main drug of regular misuse and dependence. The document refers to surveys that show an approximate number of heroin abusers in Bulgaria of about 25 000-30 000 or a little more. It is assumed that the number of people occasionally using heroin is similar. In addition, data from different assessments show an annual increase in the number of heroin overdose associated deaths as well as decrease in the median age of initiation of heroin use. Therefore, efforts to identify avenues for the prevention of heroin addiction, treatment of the abuser and prevention of relapse are sorely needed.
Evidence from several twin and adoption studies suggests that genes account for between 23 and 54% of the total liability toward heroin dependence, with the remainder of variance in liability attributable to environmental factors. In contrast to other substance use disorders, a large portion of the genetic risk for heroin dependence is conferred by genes that specifically increase risk for dependence on this substance alone, rather than by genes that predispose toward substance dependence in general. The search for genetic factor attributing to heroin dependence is therefore well warranted.
The MMC is involved in a 5 year collaborative Genetic Epidemiology of Opioid Dependence in Bulgaria study, 2006-2011, financed by National Institute on Drug Abuse (NIDA) of USA . The project consortium comprises of researchers from Washington University, St. Louise, and Medical University – Sofia. The Bulgarian team is led by Prof. I. Kremensky, MD, PhD; and includes research teams from MMC, National Genetic Laboratory and Department of Psychiatry. The participation of the heroin addicted individuals is ensured through collaboration with several non-governmental organizations e.g. Bulgarian Addictions Institute, Sofia; Initiative for Health Foundation, Sofia; local affiliations of the Red Cross and municipal centres.
Prof. Vihra Milanova, MD, PhD,
Senior Assist. Prof. Vessela Stoyanova, MD, PhD
Senior Assist. Prof. Rositza Vladimirova, MD
Spiridon Alexiev, MD
Tanya Christova, MD
Assist. Prof. Anelia Kancheva, MD, Department of Psychiatry, Medical University – Sofia.
"Association study of candidate genes for suicidal behaviour in patients with various psychiatric disorders", 2011-2012.
"Association study of candidate genes and endophenotypes in patients with Bipolar Affective disorder", 2011-2012.
“Familial associative analysis of neurocognitive disorders and DISC1 gene in bipolar affective disorder patients”, 2009-2010.
“Study of the role of polymorphic variants in metabotropic glutamate receptor 1 for predisposition to affective disorders and narcotic dependences”, 2007-2008.
“Endophenotipic characteristics of ill persons with Affective disorders”, 2007-2008.
“Genetic epidemiology of opiate dependence in Bulgaria ”, 2006-2011.
“Bipolar Affective Disorder in a Genetic Isolate”, 2005-2007.
“Fine mapping of locus 4p16 linked with bipolar affective disorder in Bulgarian families”, 2004-2005.
“Genomics of the Affective Disorders. Linkage analysis and fine mapping of families with affective disorders and epilepsy”, 2003-2007.
“Analysis for linkage of chromosome 21q22 in patients with Bipolar affective disorder from Bulgarian families”, 2001-2002.