Schizophrenia (Candidate genes)

Question 1

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:-

Answer 1

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.

Question 2

COMT

Answer 2

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.

Question 3

Neuregulin

Answer 3

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.

Question 4

Dysbindin

Answer 4

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.

Question 5

Disc 1

Answer 5

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