Perhaps the finding by these researchers may help explain the significant clinical improvement in OCD signs with the use of N-acetylcysteine recently reported by the Lafleur group . I refer to the study by Aoyama et al. in which they find that the neuronal glutathione deficiency with consequent oxidative stress and neurodegeneration in EAAC1-deficient mice is restored with the use of N-acetylcysteine. This benefit might indicate that these SNPs associated with OCD result in reduced EAAC1 activity. Another interesting study by Gu and colleagues finds that β amyloid inhibits Na(+)/K(+)-ATPase and EAAC1. Maybe you could kill two birds with one stone here, as Studer et al. find that N-acetylcysteine downregulates APP gene transcription in neuroblastoma cells. Perhaps a study reporting APP gene transcription in those with Down syndrome treated with N-acetylcysteine would be very beneficial.
1. Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, Swanson RA. Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse.
Nat Neurosci. 2006 Jan;9(1):119-26. Epub 2005 Nov 27.
2. Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, Sanacora G, Krystal JH, Coric V. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder.
Psychopharmacology (Berl). 2006 Jan;184(2):254-6. Epub 2005 Dec 22.
3. Gu QB, Zhao JX, Fei J, Schwarz W. Modulation of Na(+),K(+) pumping and neurotransmitter uptake by beta-amyloid.
4. Studer R, Baysang G, Brack C. N-Acetyl-L-Cystein downregulates beta-amyloid precursor protein gene transcription in human neuroblastoma cells.
View all comments by Mary Reid
Another intriguing link with schizophrenia is the relatively frequent occurrence of obsessional symptoms when schizophrenia patients are started on the newer antipsychotics clozapine or olanzapine (see, e.g., Ongur and Goff, 2005).View all comments by James L. Kennedy
Perhaps the study by Fournier and Robinson (2006), reporting that "SNAP-23 that lacks a domain required for SNARE complex assembly decreased the fraction of EAAC1 found on the cell surface and decreased total EAAC1 expression" may also have us suspect a role for SNAP-23(15q21-22)in OCD. Interesting that 15q21 is also a dyslexia locus.View all comments by Mary Reid