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Decoding the Risk Gene for Bipolar Disorder
Context:
Researchers from the Max Planck Institute of Psychiatry have decoded a risk gene associated with bipolar disorder, providing new insights into the genetic underpinnings of this complex psychiatric condition.
- Recent genome-wide association studies (GWAS) have repeatedly identified the gene adenylyl cyclase 2 (ADCY2) as a risk factor for the disorder.
Bipolar disorder
- It is a mental illness characterised by extreme mood swings, including manic episodes of high energy and elation and depressive episodes of sadness and hopelessness.
- There are three main types:
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- Bipolar I involves severe manic episodes lasting at least 7 days and often includes depressive episodes.
- Bipolar II is marked by less severe hypomanic episodes and depressive episodes.
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- Cyclothymic disorder, featuring milder, shorter mood swings that don’t meet the full criteria for mania or depression.
- The disorder often starts in late adolescence or early adulthood and requires lifelong treatment to manage symptoms and improve quality of life.
Key Highlights:
- Researchers focused on ADCY2, which is involved in producing the signalling molecule cyclic AMP (cAMP). This molecule is crucial for transmitting information within cells and influencing various cellular processes.
- Scientists used cell cultures and mouse models, discovering that the risk variant of ADCY2 reduced cAMP production. They then introduced this genetic mutation into mice.
- Mice with the mutated gene displayed mania-like behaviours, such as increased activity and exploration, resembling manic symptoms in bipolar disorder.
- They also showed cognitive impairments similar to those seen in humans with the disorder.
- Lithium, a well-known treatment for bipolar disorder, effectively reduced mania-like symptoms in these mice, demonstrating its therapeutic potential in this model.
Dopamine and Stress Responses
- Mice with the ADCY2 mutation had heightened responses to amphetamine, which boosts dopamine release—a neurotransmitter associated with mania.
- This increased dopamine release and strengthened neuronal networks in the mice’s brains resembling patterns seen in bipolar disorder.
- Additionally, the study found that these mice transitioned more quickly from manic to depressive states under stress, highlighting how genetic risk factors interact with environmental triggers.
Implications:
- The findings suggest that cAMP, the second messenger affected by the ADCY2 mutation, could be a promising target for new therapeutic strategies.
- This is due to its central role in various signalling pathways and its direct involvement in the protein activity altered by the mutation.