Completed Mental Health Brain & Nervous System

DISC1 complex: Neurosignalling and genetics

In plain English

AI plain-English summary

A single gene called DISC1 acts as a master organiser for proteins that build memories and shape brain development, and when it goes wrong, it may trigger schizophrenia, bipolar disorder, or depression. This matters because severe mental illnesses affect up to one in fifty people at some point in their lives, yet their biological roots remain poorly understood. The researchers have already identified DISC1 and a second risk gene, PDE4B, which regulates a molecule called cAMP that is critical for memory formation. They now need to understand how DISC1 coordinates PDE4B and other proteins during brain development and sensory processing, and what breaks down in that system in people with mental illness. This is fundamental science. It has no immediate treatment or diagnostic application. The long-term hope is that a detailed understanding of these molecular processes will point toward better therapies. In the past, similar work on basic brain signalling mechanisms has led to drugs for depression and anxiety. A fuller picture of how DISC1 organises neural development could also reveal how the healthy brain builds its circuits and processes information—knowledge that may eventually inform entirely new approaches to psychiatric treatment.

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Bipolar affective disorder and schizophrenia are severe and debilitating forms of mental illness that together affect up to one in fifty persons at some point in their life. These illnesses tend to cluster in families. This and other evidence points to genetic (inherited) factors being important. Recently, we identified one such factor, called Disrupted in Schizophrenia 1, or DISC1 for short. There is now a lot of support from many studies for this being an important risk factor not just in schizophrenia, but also bipolar disorder and depression. Recently, we identified another risk factor gene called PDE4B. PDE4B was already thought to be important in building memories in the brain. It does so by regulating the amount of a molecule called cAMP, the level of which is key to many brain processes. It turns out that DISC1 acts as a kind of master organiser not just of PDE4 but also other proteins that are believed to be important for how the brain develops, and processes sensory information. Our research is aimed at understanding these complex processes in more detail, to understand what makes them go wrong in persons with mental illness, with the long term hope that this knowledge and understanding may bring us closer to better treatments for these devastating illnesses. In the process, we also expect to reach a fuller understanding of how the brain normally develops, and of how the mind works.

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Researchers

David Porteous (Co-Investigator)David Wyllie (Co-Investigator)Joanne Millar (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Neurobiology of the DISC1 pathway
The role of DISC1 in synaptic function and circuit formation during critical periods of cortical development
Genetic susceptibility to a deficit in context processing across the schizophrenia / bipolar disorder diagnostic divide.
Integrating psychological models with biological pathways in psychosis
What Lies Behind Susceptibility to Schizophrenia? Investigation of the Correlation Between Endophenotypes of Working Memory and Expression Levels of DISC1 Pathway Genes

Original classification

Research Grant

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