Can genetics inform the management of cognitive deficits in schizophrenia?
There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.
King's College London, Institute of Psychiatry, MRC SGDP Centre, London, UK. nora.vyas@nih.gov
Nora S
NS
Vyas
Syed A
SA
Shamsi
Anil K
AK
Malhotra
Katherine J
KJ
Aitchison
Veena
V
Kumari
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018377:Neurotransmitter Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000639:trends; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents