Genetic explanation for psychotic persecutory delusions.
> 11/12/2005 4:18:53 PM

The mapping of the Human Genome is beginning to define the origins of genetic abnormalities that cause mental illness. A recent article in the American Journal of Psychiatry  by Marcella Rietschel, M.D. etal highlights the importance of these efforts and their potential toalleviate human suffering. This study analyses the previouslydiscovered gene that has been linked to both Schizophrenia and BipolarDisorder. the authors hypothesize "Giventhe presumed role of DAOA/G30 in the neurochemistry of psychosis andits localization in a schizophrenia and bipolar affective disorderlinkage region (13q34), it was hypothesized that the bipolar affectivedisorder finding would be mainly due to an association with psychoticfeatures."


They conclude after an analysis of the patients with this genetic variant the following "Formalgenetic analyses have suggested that psychotic symptoms are aninherited predisposition common to both schizophrenia and bipolaraffective disorder. The observation in our study that therisk-conferring DAOA/G30 haplotype is the same in both bipolaraffective disorder and schizophrenia indicates that not only the samegene but the same (hitherto undetected) variant contributes to bothdisorders. The reported genotype-phenotype correlation furtherpinpoints the nature of the DAOA/G30-mediated genetic overlap betweenschizophrenia and bipolar affective disorder. While our findingssupport the idea of a genetic overlap between schizophrenia and bipolaraffective disorder, the question remains whether the symptom"persecutory delusion" per se is important or rather some other traitthat correlates with it. What could that be? A patientís idea of futureharm triggering anxiety-associated processes has been suggested as akey feature of persecutory delusions. One could speculate that adelusional patient with a genetic proneness to anxiety may be morelikely to have delusions of a persecutory nature than a patient withoutthis predisposition. Put another way, delusions of reference orinfluence that are accompanied by fear are more likely to be labeled aspersecutory delusions. Clinical experience has long taught us about aconnection between anxiety and persecutory delusions in the context oftoxic psychoses such as PCP and amphetamine intoxication, where extremeanxiety, panic, and persecutory delusions usually occur together With this in mind, it is intriguing that we recently identifiedthe same DAOA/G30 markers and haplotypes as potential risk factors forpanic disorder."

Insimpler terms there appears to be a common underlying geneticabnormality that accounts for the expression  of persecutorydelusions  in both Bipolar Disorder and  Schizophrenia. Thissame genetic abnormality may also predispose individuals to suffer fromPanic Disorder. These are amazing findings.

Thesediscoveries call into question the entire categorization of patients bydiagnostic criteria and should encourage us to see patients on a muchless formal basis. We need to believe in their symptoms as expressionsof underlying genetic abnormalities that are dynamic expressions ofthese genetic variants that can wax and wane based on better control ofstress and negative social circumstances or usage of psychotropicmedications. Patients with these symptoms can feel better knowing theysuffer from an underlying genetic variant rather than feelingstigmatized by the harsh diagnostic criteria of being labeledSchizophrenic or Bipolar. 

These are evolving findings worth following closely!


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