Mania gene responsible for bipolar disorder

Gene identified as the cause of mania

03/09/2012

So-called bipolar disorders, also referred to as mania, are significantly conditioned by a particular gene. Researchers at the University of Bonn and the Central Institute for Mental Health in Mannheim came to this conclusion in a joint study published in the journal "The American Journal of Psychiatry".

Manic Depression: "Heaven-high or deathly sad"
Heavenly exulting or distressed to death. According to the scientists of the University of Bonn and the Central Institute of Mental Health, the mania gene "NCAN" is responsible for the euphoric phases of patients with bipolar disorder on a molecular level. Scientists have succeeded in deciphering how the gene NCAN leads to manic symptoms in bipolar disorder.

As the researchers report, people with bipolar disorder go through a constant roller coaster of emotions. "In depressive phases, they suffer from very depressed mood, reduced drive and often also with suicidal thoughts", while in the "manic episodes restlessness, euphoria and megalomania" are typical features, according to the announcement of the University of Bonn. Professor Andreas Zimmer, Director of the Institute of Molecular Psychiatry, and Professor Markus M. Nöthen, Director of the Institute of Human Genetics, had in the current press release the successful cooperation with the experts around Prof. Dr. med. Marcella Rietschel from the Central Institute for Mental Health in Mannheim stressed. Together, the researchers were able to demonstrate in their comprehensive study, "how the NCAN gene in the development of mania is involved." Although it was previously known, according to Prof. Nöthen that "the NCAN gene has a significant impact on the development of a bipolar Disturbance ", but the functional relationship has remained unclear.

Mechanism of the mania gene is decrypted
To decipher the mechanism of action of the mania gene, the scientists evaluated the genetic data and associated symptom descriptions of 1,218 patients with bipolar disorder. Based on the data obtained, the researchers were able to examine which symptoms of bipolar disorder are particularly closely related to the NCAN gene. It has been shown "that the NCAN gene is very closely and specifically correlated with the manic symptoms," explained Prof. Rietschel. The expert from the Central Institute of Mental Health concludes that the gene is responsible only for the manic episodes of the disease - but not for the depressive ones. The findings gained from the patient data were examined by Prof. Zimmer and colleagues in experiments with so-called knockout mice, in which the NCAN gene was switched off. Here, too, "it turned out that these animals do not show depressive behavior, but manic symptoms," explained Prof. Zimmer.

For example, according to the expert, the knockout mice were significantly more active than the control group and showed greater willingness to take risks. In addition, they often showed excessive indulgence in the sugar solution offered to them by the researchers, suggesting an excessive or misguided reward behavior. Comparable behavior is also "known by people who often overconsumption and often consume drugs in manic phases," according to the Bonn University Communication.

In the further course of the experiment, the scientists administered the manic knockout mice lithium, which is used in humans as a standard therapy for the treatment of bipolar disorders. "The lithium dose completely suppressed the hyperactivity of the animals," explained Prof. Zimmer. The experiments have shown that in lithium, too, the reactions of humans and mice are virtually identical regarding the NCAN gene, so the scientists concluded. "We were surprised how strong the findings in the mice and the patients agree," said Prof. Nöthen. This is rarely the case in this clarity. The scientists are now hoping for new approaches to therapy.

It had already been known from previous studies that a developmental disorder in the brain occurs when the NCAN gene is switched off, thereby preventing the formation of the protein "Neurocan". Now it is becoming increasingly clear that "as a consequence of this molecular disorder, the manic symptoms manifest themselves later on," said Prof. Zimmer. The discovery of the molecular mechanism of action could possibly help in the development of new drugs. In addition, hereditary components and psychosocial factors of the environment play an important role in the development of the disease, which should also be taken into consideration in the context of therapy. (Fp)

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