Schizophrenia (Candidate genes)
Schizophrenia is linked to a number of 'candidate genes'. No single gene is thought to be responsible and it appears to be a case of the more genes, the greater the risk.
Important Candidate genes for schizophrenia include:-
Neuregulin, dysbindin, and DISC1 are the most replicated and plausible genes. Also make a specific effort to remember COMT.
COMT
COMT (Catechol-O-Methytransferase) has been extensively investigated due to it's role in dopamine metabolism (especially in the prefrontal cortex). It plays a major role in the degradation of catecholamines including the neurotransmitters dopamine, epinephrine, and norepinephrin. Clearing dopamine from synapses is a major effect of COMT. Low activity of the COMT gene is associated with obsessive-compulsive disorder, as well as schizophrenia. COMT is the strongest schizophrenia candidate among approximately 27 genes in a 1.5-3 million nucleotide region of chromosome 22 that is deleted in Velocardiofacial disorder. About 20% of Velocardiofacial disorder patients have schizophrenia or psychosis.
Neuregulin
NRG1 was found in an Icelandic sample in 2002 and replicated in a Scottish sample. It has subsequently been implicated in other studies. Neuregulin 1 (NRG1) is a growth factor that stimulates neuron development and differentiation. Increased neuregulin signaling in schizophrenia may suppress the NMDA receptor, leading to lowered glutamate levels.
Dysbindin
DTNBP1 has been reported in Irish families. Not all studies have replicated the association. Dystrobrevin-binding Protein 1 (DTNBP1, dysbindin) is widely distributed in muscle and brain tissue, and is involved in the biogenesis of lysosome-related organelles. Dysbandin expression is decreased in schizophrenia, and RNAi knockdown of DTNBP1 reduces glutamate levels in cultured cells.
DISC1
DISC1 is disrupted in Schizophrenia. It is located at the breakpoint of a balanced translocation identified in a large Scottish family with schizophrenia, schizoaffective disorder, and other major mental illnesses. The locus has been linked to schizophrenia in other populations as well. DISC1 encodes a multifunctional protein that influences neuronal development and adult brain function, including neurite architecture, neuronal migration, intracellular transport and synaptic transmission
Important Candidate genes for schizophrenia include:-
- DTNBP1 (dysbindin) - chromosome 6 (6p 22.3)
- COMT - chromosome 22
- NRG1(neuregulin 1) - chromosome 8 (8p 21-22)
- G72 - chromosome 13
- RGS4 - chromosome 1
- DAOA - chromosome 13
- DISC1 - chromosome 1
- DRD2 - chromosome 11
Neuregulin, dysbindin, and DISC1 are the most replicated and plausible genes. Also make a specific effort to remember COMT.
COMT
COMT (Catechol-O-Methytransferase) has been extensively investigated due to it's role in dopamine metabolism (especially in the prefrontal cortex). It plays a major role in the degradation of catecholamines including the neurotransmitters dopamine, epinephrine, and norepinephrin. Clearing dopamine from synapses is a major effect of COMT. Low activity of the COMT gene is associated with obsessive-compulsive disorder, as well as schizophrenia. COMT is the strongest schizophrenia candidate among approximately 27 genes in a 1.5-3 million nucleotide region of chromosome 22 that is deleted in Velocardiofacial disorder. About 20% of Velocardiofacial disorder patients have schizophrenia or psychosis.
Neuregulin
NRG1 was found in an Icelandic sample in 2002 and replicated in a Scottish sample. It has subsequently been implicated in other studies. Neuregulin 1 (NRG1) is a growth factor that stimulates neuron development and differentiation. Increased neuregulin signaling in schizophrenia may suppress the NMDA receptor, leading to lowered glutamate levels.
Dysbindin
DTNBP1 has been reported in Irish families. Not all studies have replicated the association. Dystrobrevin-binding Protein 1 (DTNBP1, dysbindin) is widely distributed in muscle and brain tissue, and is involved in the biogenesis of lysosome-related organelles. Dysbandin expression is decreased in schizophrenia, and RNAi knockdown of DTNBP1 reduces glutamate levels in cultured cells.
DISC1
DISC1 is disrupted in Schizophrenia. It is located at the breakpoint of a balanced translocation identified in a large Scottish family with schizophrenia, schizoaffective disorder, and other major mental illnesses. The locus has been linked to schizophrenia in other populations as well. DISC1 encodes a multifunctional protein that influences neuronal development and adult brain function, including neurite architecture, neuronal migration, intracellular transport and synaptic transmission
