Clinical implications DISC1

1 clinical implications

1.1 schizophrenia
1.2 autism , asperger’s syndrome
1.3 bipolar disorder

clinical implications

aberrations of disc1 considered generalized risk factor in major psychiatric diseases , have been implicated in memory deficits , abnormal patterns of brain activity. disc1 translocation increases risk of developing schizophrenia, bipolar disorder, or major depression 50-fold in comparison general population. efforts model disc1 disease biology in transgenic mice, drosophila, , zebrafish have provided psychiatric disease implications related disc1 mutations. however, no specific variant consistently associated development of mental disorders, indicating allelic heterogeneity in psychiatric disease. impact of variants in disc1 gene on expression , protein function not yet defined , associated variants not causative.

schizophrenia

schizophrenia affects 1% of general population , highly heritable, providing indication of genetic basis. disc1 has been associated neurological abnormalities such delusions, deficits in long term , working memory, diminution of gray matter volume in hippocampal , prefrontal regions. these abnormalities seen symptoms of schizophrenia. disc1 function involved in neurogenesis , neuroplasticity, vulnerability schizophrenia may involve dysfunction in hippocampus, brain region in adult neurogenesis occurs.

autism , asperger’s syndrome

in 2008, genetic screen of 97 finnish families affected autism , asperger’s syndrome revealed repeated dna sequences within disc1 gene in diagnosed autism. furthermore, single nucleotide change in gene found present in 83% of family members asperger’s syndrome. recent family study has reported large chromosome 1 deletion includes loss of disc1 in young boy diagnosed autism. link between disc1 duplication , autism has been suggested finding of seven-gene duplication includes disc1 carried 2 brothers autism , mild retardation. these alterations in people disorder rare, however, none found in screening of 260 belgians autism.

transgenic model organism strains generated mutated or absent disc1 suggest gene may contribute @ least autistic abnormalities. mice lowered levels of disc1 expression exhibit abnormal response electrical stimulation, decrease of dopamine synthesis, , inability filter unnecessary sensory information. studies of expression of mutant disc1 prenatally , postnatally have demonstrated varying effects, indicating possibility postnatal expression of mutant disc1 causes features of autism. many more studies necessary confirm these suggestions.

bipolar disorder

linkage studies in extended families multiply affected bipolar disorder provide evidence disc1 genetic factor in etiology of bipolar disorder. in 1998, follow-up study conducted of large scottish family in disc1 first discovered. additional family members original translocation developed major psychotic illness, including bipolar disorder, identified.