Antidepressant effects of light therapy combined with sleep deprivation are influenced by a functional polymorphism within the promoter of the serotonin transporter gene (original) (raw)
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American Journal of Psychiatry
Objective: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTTlinked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. Method: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. Results: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. Conclusions: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.
Journal of Affective Disorders, 2010
Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. It is a current area of debate whether rs4680 can influence antidepressant response in major depressive disorder, and whether this influence extends to bipolar depression. Chronotherapeutic interventions, such as sleep deprivation and light therapy, are multi-target in nature and are effective in bipolar depression. Here we studied the effect of rs4680 on response to sleep deprivation combined with light therapy (36 h awake followed by a night of undisturbed sleep, with 10,000 lx light administered for 30 min during the night awake and upon awakening) in 87 bipolar depressed inpatients. Patients who were homozygotic for the Val/Val variant showed a significantly less efficient antidepressant effect after the night awake than those who were heterozygotic and homozygotic for the Met variant. This effect of rs4680 is similar to its observed influence on response to serotonergic and noradrenergic drug treatments in major depressive disorder. This is the first study reporting an influence of rs4680 on antidepressant response in bipolar depression. This finding supports the hypothesis of a major role for catecholamines in the mechanism of action of chronotherapeutics, and for rs4680 in modulating this effect.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2008
Keywords: 5-HT 2A receptor Bipolar disorder Major depression Serotonin Sleep deprivation 5-HT 2A receptor density in prefrontal cortex was associated with depression and suicide.5-HT 2A receptor gene polymorphism rs6313 was associated with 5-HT 2A receptor binding potential, with the ability of individuals to use environmental support in order to prevent depression, and with sleep improvement after antidepressant treatment with mirtazapine. Studies on response to antidepressant drugs gave inconsistent results.
Antidepressant Response and the Serotonin Transporter Gene-Linked Polymorphic Region
Biological Psychiatry, 2010
Background-The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44bp long region gives rise to short 'S' and long 'L' forms of the promoter region, the 'S' form being associated with reduced serotonin transporter expression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2005
The definition of a genetic liability profile for specific antidepressant treatment will soon be available offering considerable help in early detection of effective therapy in affective disorders. The search for genetic factors predisposing to drug response or side-effects in affective disorders started only in the last few years. The efficacy of antidepressant action was associated with several polymorphisms, located on coding genes of proteins thought to be involved in the different mechanisms of action of antidepressant treatments. Among these, gene variants in sequences of serotonin pathway proteins were candidate, both for the well known evidence of its involvement in the development of depressive symptomathology and for the wide-world use of selective serotonin reuptake inhibitors as first choice treatment of depression. A polymorphism in the promoter region of the serotonin transporter (SERTPR) was independently associated with efficacy for a range of treatments, other polymorphism located on the tryptophan hydroxylase gene, 5-HT2a receptor and G-protein beta 3 showed some association, while other candidate genes were not associated with treatment efficacy. Possible liability genes controlling at least to some extent both acute and long-term treatment were identified, and the further objective is to identify other candidate genes in order to define individualized treatments according to genetic profile in a future. The present paper reviews the pharmacogenetic studies published to date, focusing the attention on the serotonergic pathway. D
In vivo (Athens, Greece)
A functional polymorphism in the promoter region of the 5-hidroxytryptamine transporter gene (5-HTTLPR), alters its transcription. Short allele (SS) variation decreases the transcriptional efficacy of serotonin, causing psychiatric disorders, major depressive disorder (MDD) and major depression in response to stressful life events. The aim of this study was to determine the current understanding of the role of 5-HTTLPR polymorphism in the development of depressive episodes and its response to treatment. Twenty-five articles were identified from PubMed, utilizing the following keyword, 5-HTT transporter gene, polymorphism, depression, stressful condition, psychiatric disorder. All articles were read and notes were made regarding study participant, measures, data analysis and results, and were used to write this review. The distribution of the SS allele in patients is associated with an increased risk of MDD following exposure to stressful events of life. Additionally, this genetic va...
Molecular Psychiatry, 2002
The serotonin transporter (5-HTT) is the site of primary action for the selective serotonin reuptake inhibitors (SSRIs). Previous Western reports have demonstrated that the l allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with better SSRI antidepressive effects than the s allele, however, another study of a Korean population has produced a contrasting finding. The present study tested the hypothesis that the 5-HTTLPR genetic polymorphism is associated with SSRI antidepressant response by evaluating total and cluster depressive symptoms for 121 Chinese patients diagnosed with major depression. Analysis of the results reveals that patients with the l/l genotype had a significantly better response to SSRI (fluoxetine) when compared with s allele carriers, as evaluated on the basis of total (P = 0.013), core (P = 0.011), and psychic-anxiety (P = 0.005) and somaticanxiety (P = 0.002) Hamilton Depression Rating Scale-score percentage change. Our findings confirm reports that the l allele is associated with better SSRI response.
Effects of Serotonin Transporter Promoter Polymorphisms on Serotonin Function
Neuropsychopharmacology, 2004
The serotonin transporter promoter polymorphism (5-HTTLPR) has been associated with vulnerability to stress-induced depressive symptoms and with the speed and rate of response to antidepressant treatment. The goal of the present study was to evaluate the association between the 5-HTTLPR and the functional response of the serotonin system as measured by the neuroendocrine and cerebral metabolic response to intravenous administration of the selective serotonin reuptake inhibitor citalopram in normal control subjects. Genotyping was performed for 5-HTTLPR insertion/deletion polymorphism long (l) and short (s) variant alleles. The ll genotype was compared with the combined sl รพ ss and with the ss genotype alone. Citalopram plasma concentrations did not differ significantly between groups. The s allele was associated with a less of an increase in prolactin and cortisol than the ll genotype. The s allele was associated with greater decreases in left frontal, precentral and middle temporal gyri compared to the ll genotype. The ll genotype was associated with greater decreases in right frontal, insula and superior temporal gyrus compared to the ss genotype. These findings suggest that 5-HTTLPR is associated with an altered functional response of the serotonin system, which may represent a neurobiologic substrate for the differential response to antidepressant treatment in late life and the emergence of neuropsychiatric symptoms in neurodegenerative disorders.