Posted by zeugma on April 20, 2006, at 19:27:58
In reply to Re: Drugs versus Psychotherapy - Backlash? » zeugma, posted by linkadge on April 20, 2006, at 18:52:48
> I mean, if you said that SS varient represented only a minority of depressed persons, then the theory would still look good on paper. But if the majority of depressed people actually posess the SS varient then it would be an arguement against the purported mechanism.
>
> Its great to say that SSRI's work well for people with the L/S or L/L varients, but if they only represent the minority of depressed persons, then it might not look so good.
>
> Linkadge
This is actually quite fascinating. The link you posted connected the s/s serotonin transporter with stress/anxiety and reactive depression. In generalized anxiety disorder it seems that it breaks down this way:Psychopharmacology (Berl). 2006 Mar 9; [Epub ahead of print]
Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder.Stein MB, Seedat S, Gelernter J.
Departments of Psychiatry and Family & Preventive Medicine, University of California, 9500 Gilman Drive (0985), La Jolla, San Diego, CA, 92093-0985, USA, mstein@ucsd.edu.
OBJECTIVES: To determine whether variation in the serotonin transporter gene promoter (5HTTLPR) influences the efficacy of selective serotonin reuptake inhibitors (SSRIs) in generalized social anxiety disorder (GSAD). METHODS: Consecutive series of N=32 patients with DSM-IV GSAD for whom DNA and standardized outcome data from a 12-week SSRI trial were available. After ensuring that neither clinical response [clinical global impression of change scale (CGI-C)] nor 5HTTLPR genotype was confounded by ethnicity or sex, we determined whether the number of copies (0, 1, or 2) of hi-risk alleles using either the diallelic L-S system or the triallelic La-Lg-S system, predicted response and change in Liebowitz social anxiety scale (LSAS) and brief social phobia scale (BSPS) scores during SSRI treatment. RESULTS: Twenty-one patients (66%) were responders to SSRI (i.e., CGI-C much or very much improved). A trend was seen for a linear association between 5HTTLPR genotype and likelihood of response to SSRI: diallelic classification L/L 7/8 (88%), L/S 12/18 (67%), S/S 2/6 (33%), p=0.051; triallelic classification L'/L' 4/5 (80%), L'/S' 14/19 (74%), S'/S' 3/8 (38%), p=0.093. Reduction in LSAS (and BSPS) scores during SSRI treatment was significantly (p<0.02) associated with 5HTTLPR genotype using either the diallelic or triallelic classification. CONCLUSIONS: Variation in a functional polymorphism known to influence serotonin reuptake is associated with SSRI response in patients with GSAD. Independent replication in larger samples is required before the predictive utility of this information can be confirmed and generalized to clinical settings.
This is exactly what I would have thought from reading your link. But consider this:
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar 30; [Epub ahead of print]
Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.Ng CH, Easteal S, Tan S, Schweitzer I, Ho BK, Aziz S.
Professorial Unit, The Melbourne Clinic, University of Melbourne, Australia.
The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.
Who knows? I'm inclined to say that the s/s genotype is more prone to anxiety, and that the serotonin transporter polymorphisms might have a closer bearing on anxiety states than depression. But it is obviously complex and also there are so many other variables (MAO, COMT, etc.). But I am pretty sure that the s/s polymorphism really is associated with a a poorer response to conventional antidepressants, despite the study above. It's also worth noting that the l/l and l/s genotypes were more common in the Causcasian patients in that study.
-z
poster:zeugma
thread:629584
URL: http://www.dr-bob.org/babble/20060417/msgs/635373.html