Evidence of a role for the 5-HTTLPR genotype in the modulation of motor response to antidepressant treatment

Putzhammer, Albert; Schoeler, A.; Rohrmeier, Thomas; Sand, Philipp; Hajak, Goeran; Eichhammer, Peter

doi:10.1007/s00213-004-1995-3

Cited by 27 publications

(23 citation statements)

References 29 publications

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“…Smaller motor cortex activation in carriers of the 5-HTT short allele is consistent with the modulatory role of serotonin in motor processes (36). To the extent that the short allele is associated with depression (37), and depression with psychomotor retardation (38), our data are also consistent with a recent report (39) that depressed patients who carry the 5-HTT short allele show less nocturnal motor behavior than non-carriers.…”

Section: Discussionsupporting

confidence: 90%

Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task

Canli

Omura

Haas

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

333

278

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Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes.amygdala ͉ polymorphism ͉ 5-HTT

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Section: Discussionsupporting

confidence: 90%

Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task

Canli

Omura

Haas

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

333

278

View full text Add to dashboard Cite

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“…In animal models, sleep deprivation can entrain the circadian clock and alter gene expression within the SCN , affect the genetic transcriptional-translational feedback loop of the clock by increasing the expression of per1 and per2 mRNA (Wisor et al, 2002), and causes phase-advance of the circadian activityrest rhythm of about 2 h because in the SCN, it markedly enhances the release of 5-HT (Grossman et al, 2000), which mediates the non-photic entrainment of the clock (Glass et al, 2003). These 5-HT enhancing effects of TSD and LT could also explain the sleep reduction in responders, a phenomenon observed in the present study, because pharmacogenetic studies have showed that human homozygotes for the long variants of the serotonin promoter gene polymorphism, which respond better to both antidepressant TSD and serotonergic drugs (Benedetti et al, 1999), also reduce their sleep and increase their nighttime locomotor activity when treated with SSRIs (Putzhammer et al, 2005). Moreover, the DA-enhancing effects of TSD could contribute to the observed effects, because DA can entrain the activity-rest rhythm (Fertl et al, 1993;Honma & Honma, 1995), regulate the generation of sleep-wake states (Dzirasa et al, 2007), and exert complex effects on the physiological functions of sleep and dream mentation (Dahan et al, 2006).…”

Section: Discussionsupporting

confidence: 62%

Phase Advance Is an Actimetric Correlate of Antidepressant Response to Sleep Deprivation and Light Therapy in Bipolar Depression

Benedetti

Dallaspezia

Fulgosi

et al. 2007

Chronobiology International

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The combination of total sleep deprivation (TSD) and light therapy (LT) in bipolar depression causes rapid antidepressant effects, and its mechanism of action has been hypothesized to involve the enhancement of all of the monoaminergic systems targeted by antidepressant drugs (serotonin, dopamine, norepinephrine). It is still unknown if the clinical effects are paralleled by changes in biological rhythms. In a before/after design of a study of biological correlates of response, 39 inpatients affected by Type I Bipolar Disorder whose current depressive episode was without psychotic features were treated for one week with repeated TSD combined with morning LT. Wrist actigraphy was recorded throughout the study. Two-thirds of the patients responded to treatment (50% reduction in Hamilton Depression score). Responders showed an increase in daytime activity, phase-advance of the activity-rest rhythm of 57 min compared to the pre-treatment baseline, and reduced nighttime sleep. Non-responders did not show significant changes in the parameters of their activity-rest rhythm. Phase advance of the activity-rest rhythm is an actimetric correlate of the antidepressant response to TSD and LT in bipolar depression. Results are consistent with the known effects of sleep-wake manipulations and neurotransmitter function on the suprachiasmatic nucleus.

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“…This distinction has not been reported before and is not simple to explain, particularly in our study, which lacked detailed information about medication use in these women. Interpretations are further complicated by evidence suggesting that medication efficacy can vary by genotype (Arias et al 2003; Lee et al 2004; Putzhammer et al 2005;Smits et al 2004) and by the possibility that treatment seeking and referral patterns may be related to life stressors.…”

Section: Discussionmentioning

confidence: 99%

Depressive symptoms in mid‐pregnancy, lifetime stressors and the 5‐HTTLPR genotype

Scheid

Holzman

Jones

et al. 2006

Genes Brain and Behavior

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Few studies of gene-environment interactions for the serotonin transporter promoter polymorphism (5-HTTLPR), life stressors and depression have considered women separately or examined specific types of stressful life events. None have looked at depression during pregnancy. In the Pregnancy Outcomes and Community Health (POUCH) Study, women were queried about history of stressful life events and depressive symptoms at the time of enrollment (15-27 weeks gestation). Stressful life events were grouped a priori into ''subconstructs'' (e.g. economic, legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and total stressful life event score. The effect of genotype on the association between stressful life events and elevated depressive symptoms was assessed in 568 white non-Hispanic participants. The relationship between exposure to abuse and elevated depressive symptoms was more pronounced in the s/s group (OR 5 24.5) than in the s/ l group (OR 5 3.0) and the l/l group (OR 5 7.7), but this significant interaction was detected only after excluding 73 (13%) women with recent use of psychotropic medications. There was no evidence of gene-environment interaction in analytic models with other stressful life events subconstructs, total subconstruct score or total stressful life events score. These data offer modest support to other reports of gene-environment interaction and highlight the importance of considering specific stressful life events.

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Evidence of a role for the 5-HTTLPR genotype in the modulation of motor response to antidepressant treatment

Abstract: Homozygosity for the long variant of the 5-HTTLPR may cause a predisposition to increased night-time motor activity in conjunction with SSRI treatment.

Cited by 27 publications

References 29 publications

Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task

Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task

Phase Advance Is an Actimetric Correlate of Antidepressant Response to Sleep Deprivation and Light Therapy in Bipolar Depression

Depressive symptoms in mid‐pregnancy, lifetime stressors and the 5‐HTTLPR genotype

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