Pooling pharmacogenetic studies on the serotonin transporter: a mega-analysis.

Pharmacogenetic studies on antidepressants have reported an association between the promoter of the serotonin transporter gene (SERTPR) and response to antidepressant treatment. In the present study, individual subject data from three pharmacogenetic studies on SERTPR were pooled ('mega-analysis') to investigate the role of this gene in the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs). A group of 548 patients who were treated with different SSRIs in a double blind design were included; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression.

Temperature regulation in depression: functional 5HT1A receptor adaptation differentiates antidepressant response.

Observations in humans and animals have indicated that chronic, but not acute, antidepressant treatment (ADT) can desensitize 5-HT1A receptor-mediated responses, such as hypothermia. We hypothesized that 5-HT1A desensitization would be necessary for an antidepressant response (ADR) to occur. To test this hypothesis, we examined 5HT1A-agonist ipsapirone (IPS)-induced hypothermia in 28 depressed patients being treated with fixed doses of nortriptyline (75 mg) at 3-day and 3-week treatment points.

Open-label risperidone for Asperger's disorder: negative symptom spectrum response.

Objective: Asperger's disorder consists of negative symptoms similar to those seen in schizophrenia, autism, schizoid personality disorder, and schizotypal personality disorder. We investigated whether risperidone, which is effective in treating the negative symptoms of schizophrenia, would improve such symptoms observed in Asperger's disorder in a prospective, open-label trial.

Method: Thirteen male patients aged 6 to 18 years who were diagnosed with Asperger's disorder by DSM-IV criteria were enrolled in a 12-week, prospective, open-label pilot study from March 13, 2002 to August 11, 2003.

Initial conditions of psychotropic drug response: studies of serotonin transporter long promoter region (5-HTTLPR), serotonin transporter efficiency, cytokine and kinase gene expression relevant to depression and antidepressant outcome.

The Hypothesis of Initial Conditions posits that differences in psychotropic drug response result from individual differences in receptor site kinetics, and differences in the sensitivity of downstream receptor-linked responses. This work examines data consistent with the hypothesis, specific to genetic and kinetic differences of the serotonin (5-HT) transporter (SERT), as they may be linked to divergent antidepressant response (ADR). The mechanisms for divergent ADR in association with different initial SERT function are considered within the context of SERT trafficking as sensitive to various different kinase and cytokine signals, some of which are dependent on the 5-HTTLPR polymorphism of the SERT gene.

Serotonin transport kinetics correlated between human platelets and brain synaptosomes.

Rationale: Blood platelets have been used extensively as a model system for investigating the role of the serotonin transporter (SERT) in various psychiatric disorders, especially depression. However, to date, it is not known whether platelet serotonin (5-HT) transport would be related to that in brain.

Objectives: We examined 5-HT transport kinetics simultaneously in human blood platelets and human cortical brain synaptosomes to determine whether they were correlated.

Improved potency of escitalopram on the human serotonin transporter: demonstration of an ex vivo assay technique.

The potency of escitalopram ("Lexapro," s-citalopram, LU-26-054) was compared with that of racemic citalopram ("Celexa") using plasma samples from drug-treated normal controls applied to an assay of human serotonin [5-hydroxytryptamine (5-HT)] transport inhibition in blood platelets. Samples were available for both 4-hour and 24-day drug administration. The data indicated that 5-HT transport inhibition was fully manifest for each drug within 4 hours of administration, without significant increase in platelet transport inhibition by 24-day treatment.

Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome.

According to the hypothesis of initial conditions, drug response may be determined by different initial states of neurotransmitter protein recognition systems. Platelet serotonin (5-HT) transport kinetics were studied as initial-conditions predictors of antidepressant response in 24 depressed patients before and after 3 weeks of treatment with nortriptyline (75 mg). The initial affinity of the 5-HT transporter (5-HTT) correctly predicted 71% of the outcome.

Historical studies of premenstrual tension up to 30 years ago: implications for future research.

The biology and treatment of premenstrual tension syndrome has advanced significantly in the past 30 years. Newer research expands on earlier literature that has been accumulated before 1972. This review selectively considers this earlier literature, because it defines the nature and impact of what was then considered to be premenstrual tension syndrome.

Initial conditions of serotonin transporter kinetics and genotype: influence on SSRI treatment trial outcome.

Background: Fifty-one patients with major depression were classified for 5-HTT promoter region polymorphism and platelet 5-HTT kinetics before treatment with fluoxetine, and then examined for treatment outcome.

Methods: Dose was stratified from 1.25 mg to 40 mg per day to allow for the possibility that one genotype could express a lower-dose fluoxetine response.

An hypothesis of initial conditions: receptor-effector systems as determinants of psychopharmacologic drug response.

A variety of biological factors have been sought to explain why psychopharmacologic drug response varies between patients. In addition to variables such as age, race, gender, age of onset, severity, number of previous episodes, prior drug treatment, comorbidity and hormonal state, there have been investigations also into a variety of pharmacokinetic and pharmacodynamic variables such as dose, absorption, metabolism, distribution, globulin/protein binding, excretion and rate of titration, all potentially considered to explain differences in drug response. However, it is clear that, in many cases, such variables do not fully account for differences in drug response.