The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study

Åberg, Elin; Fandiño-Losada, Andrés; Sjöholm, Louise K.; Forsell, Yvonne; Lavebratt, Catharina

doi:10.1016/j.jad.2010.08.009

Cited by 69 publications

(51 citation statements)

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“…There is some clinical evidence of increased COMT levels in depressed patients [72]. Moreover, there is evidence for genetic variations in the COMT gene that could lead to abnormal COMT function [73]. The COMT inhibitor tolcapone has been used clinically in Parkinson's patients to effectively treat their effort-related depressive symptoms [45].…”

Section: Discussionmentioning

confidence: 99%

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

et al. 2014

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Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.

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Section: Discussionmentioning

confidence: 99%

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

et al. 2014

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“…Furthermore, such individuals are at higher risk to develop mental illnesses (Hosák 2007; Kocabas et al 2010; Witte and Flöel 2012; Baumann et al 2013). Men with this Met 158 variant were found to be more at risk for depression, displayed lower motivational levels and this risk increased in combination with a problematic childhood (Åberg et al 2011). In another study the trait-anger was found to be significantly associated with both low cooperativeness and depression (Balsamo 2013).…”

Section: Discussionmentioning

confidence: 99%

The influence of COMT Val¹⁵⁸Met genotype on the character dimension cooperativeness in healthy females

2014

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ObjectivesAlthough the Val158Met catechol-O-methyltransferase (COMT) gene has been linked with the temperament dimension Novelty Seeking (NS), new insights in this polymorphism might point to a major role for character features as well. Given that individual life experiences may influence Val158 and Met158 allele carriers differently it has been suggested that the character trait cooperativeness could be implicated.Case reportA homogeneous group of eighty right-handed Caucasian healthy female university students were assessed with the TCI and genotyped for the COMT Val158Met polymorphism (rs4680). Gene determination showed that eighteen were Val158 homozygotes, forty-four Val/Met158 heterozygotes, and eighteen were Met158 homozygotes. All were within the same age range and never documented to have suffered from any neuropsychiatric illness. Bonferroni corrected non-parametric analyses showed that only for the character scale cooperativeness Val158 homozygotes displayed significant higher scores when compared to Met158 homozygotes. No significant differences on cooperativeness scores were found between Val158 and Val/Met158 carriers or between Met158 and Val/Met158 carriers. No differences were observed for the COMT Val158Met polymorphism and the other temperament and character scales.ConclusionsOur findings support the assumption that the Val158Met single nucleotide polymorphism (SNP) influences character traits and not only temperament. Our results add to the notion that Val158 homozygotes are considered to be helpful and empathic and it suggest that these cooperativeness character traits are related to the dopaminergic system.

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“…Conversely, the COMT Met allele has been associated with heightened scores of negative emotionality measured with selfreports (Lang et al 2007 ;Reuter & Hennig, 2005 ;Stein et al 2005), although inconsistent findings exist (Wray et al 2008). In addition, Met allele carriers show an increased proneness for the development of anxiety disorders (Enoch et al 2003 ;Olsson et al 2005 ;Woo et al 2004) and depression (Aberg et al 2011). Psychophysiological studies support these findings : the Met allele resulted in elevated startle responses (Armbruster et al 2011 ;Montag et al 2008) and in increased limbic and prefrontal activation in response to negative stimuli in functional magnetic resonance imaging (fMRI) studies (Drabant et al 2006 ;Rasch et al 2010 ;Smolka et al 2005 ;Williams et al 2010).…”

Section: Introductionmentioning

confidence: 91%

Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm

Armbruster¹,

Mueller

Strobel³

et al. 2011

Int. J. Neuropsychopharm.

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Dopamine and norepinephrine are key regulators of cognitive and affective processes. The enzyme catechol-O-methyltransferase (COMT) catabolizes catecholamines and the COMT Val158Met polymorphism has been linked to several neuropsychiatric variables. Additionally, stressful life events (SLEs) contribute substantially to affective processes. We used the stress-induced activation of the hypothalamic-pituitary-adrenal axis to investigate the effects of COMT and SLEs on the cortisol response in 119 healthy children (8-12 yr). Saliva cortisol was measured during and after the Trier Social Stress Test for Children. SLEs were assessed with a standardized interview with one of the children's parents. Linear regression analysis revealed a significant effect for COMT, with Met allele carriers showing a higher cortisol response (β=0.300, p=0.001). In turn, more SLEs lead to a less pronounced cortisol increase (β=-0.192, p=0.029) probably indicating increased resilience. Our results further underscore the essential and differential role of genetic variation and environmental factors on stress responsivity.

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The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study

Cited by 69 publications

References 83 publications

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

The influence of COMT Val¹⁵⁸Met genotype on the character dimension cooperativeness in healthy females

Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm

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The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study

Cited by 69 publications

References 83 publications

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

The influence of COMT Val158Met genotype on the character dimension cooperativeness in healthy females

Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm

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Product

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The influence of COMT Val¹⁵⁸Met genotype on the character dimension cooperativeness in healthy females