Genetic causes of mental illness discovered

Schizophrenia and bipolar disorder are among the most common forms of mental illness in Europe. e:Med researchers from various institutions, in conjunction with international colleagues, have managed to identify new genetic areas related to these disorders. Scientists expect these results to provide starting points for the investigation of causes and the development of new therapies.

People with bipolar disorder, previously called manic-depressive disorder, suffer from episodic changes of mood and motivation, fluctuating between depressive episodes with a very gloomy mood, sometimes with suicidal thoughts, and manic phases with increased motivation and euphoric or excited mood. Schizophrenic symptoms include hallucinations, frequently associated with paranoia or the hearing of voices and disturbed thoughts. Roughly one percent of the population is affected by both disorders over their lifetime. The assumption can be made that environmental and genetic factors, and their interaction, play a role in the occurrence of diseases.
The analysis of around 2.3 million different genetic markers in a ‘genome-wide association study’ (GWAS) revealed five regions at risk related to bipolar disorder. Three of them, “ANK3”, “ODZ4” and “TRANK1” had already been described previously. The new discoveries were gene regions between “MIR2113” and “POU3F2” on chromosome six and “ADCY2” on chromosome five. The latter is code for an enzyme, which plays a key role for specific signaling pathways in the brain and thereby reveals new insights into biological mechanisms for the development of a bipolar disorder.
Genetic data for 9,747 patients with bipolar disorder was compared with data for 14,278 healthy persons in the study of an international research collaboration under the leadership of e:Med scientist Prof. Dr. Marcella Rietschel (Central Institute of Mental Health, Mannheim), Prof. Dr. Markus Nöthen (University Clinic Bonn) and Prof. Dr. Sven Cichon (University Hospital of Basel).

108 regions, which are related to schizophrenia, 83 of which had not previously been known, were discovered in an even larger GWA study by a team of 300 international authors. This study examined genetic differences between 36,989 patients suffering from schizophrenia and 113,075 control persons. All available genetic data from published and as yet unpublished studies were merged and evaluated by the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC), in which many e:Med scientists are also involved.
Existing hypotheses on the pathophysiology of schizophrenia were confirmed and new insights obtained from the analysis of identified gene regions.
For example, the results indicate that signaling pathways, which assure the transfer of information between brain cells via the glutamate and dopamine messengers, are affected in the event of schizophrenia. In addition clear evidence also exists now of the fact that the immune system, in particular the immunity acquired by mechanisms mediated via B-lymphocytes, actually plays a role in the occurrence of schizophrenia.

Both studies are the largest so far in their respective areas and were published in renowned specialist journals. The results will definitely make a large contribution to further clarifying the causes of bipolar disorder and schizophrenia in order to eventually discover or improve therapy approaches.

Publications:

(1)    Mühleisen, Leber, Schulze et al., Genome-wide association study reveals two new risk loci for bipolar disorder, Nature Communications, DOI: 10.1038/ncomms4339
(2)    Schizophrenia Working Group of the Psychiatric Genomics Consortium, Biological insights from 108 schizophrenia-associated genetic loci, Nature, DOI: 10.1038/nature13595

Contact:

Prof. Dr. Markus M. Nöthen (Publikation (1) und (2))
Institut für Humangenetik
Universitätsklinikum Bonn
phone: 0228/28751101
e-mail: markus.noethen@ukb.uni-bonn.de

Prof. Dr. Marcella Rietschel (Publikation (1) und (2))
Abteilung Genetische Epidemiologie in der Psychiatrie
Zentralinstitut für Seelische Gesundheit (ZI) Mannheim
phone: 0621 1703 6051
e-mail: marcella.rietschel@zi-mannheim.de