Alterations in Serotonin Activity and Psychiatric Symptoms After Recovery From Bulimia Nervosa

Kaye, Walter H.; Greeno, Catherine G.; Moss, Howard B.; Fernstrom, John D.; Fernstrom, Madelyn H.; Lilenfeld, Lisa R.; Weltzin, Theodore E.; Mann, J. John

doi:10.1001/archpsyc.55.10.927

Cited by 191 publications

(148 citation statements)

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“…32 Moreover, obesity is often comorbid with psychiatric Association between MAOA, dopamine function and BMI F Ducci et al diseases including mood and binge eating disorders, 33 and abnormal levels of CSF monoamine metabolites have been described in patients with eating disorders, and at least some of these changes appear to be trait rather than state dependent. 34 Furthermore, DA is known to modulate the rewarding properties of psychoactive drugs as well as food via the mesolimbic reward system. 35 In this regard, it has been hypothesized that a dysfunction of the DA mesolimbic reward system might underlie vulnerability to a spectrum of disorders characterized by dyscontrol and impulsive behaviors such as drug addiction and eating disorders, which probably include some forms of obesity.…”

Section: Introductionmentioning

confidence: 99%

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

Ducci¹,

Newman²,

Funt³

et al. 2006

Mol Psychiatry

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Variation in brain monoaminergic activity is heritable and modulates risk of alcoholism and other addictions, as well as food intake and energy expenditure. Monoamine oxidase A deaminates the monoamine neurotransmitters serotonin, dopamine (DA), and noradrenalin. The monoamine oxidase A (MAOA) gene (Xp11.5) contains a length polymorphism in its promoter region (MAOA-LPR) that putatively affects transcriptional efficiency. Our goals were to test (1) whether MAOA-LPR contributes to interindividual variation in monoamine activity, assessed using levels of cerebrospinal fluid (CSF) monoamine metabolites; and (2) whether MAOA-LPR genotype influences alcoholism and/or body mass index (BMI). Male, unrelated criminal alcoholics (N = 278) and controls (N = 227) were collected from a homogeneous Finnish source population. CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were available from 208 participants. Single allele, hemizygous genotypes were grouped according to inferred effect of the MAOA alleles on transcriptional activity. MAOA-LPR genotypes had a significant effect on CSF HVA concentration (P = 0.01) but explained only 3% of the total variance. There was a detectable but nonsignificant genotype effect on 5-HIAA and no effects on MHPG. Specifically, the genotype conferring high MAOA activity was associated with lower HVA levels in both alcoholics and controls, a finding that persisted after accounting for the potential confounds of alcoholism, BMI, height, and smoking. MAOA-LPR genotype predicted BMI (P < 0.005), with the high-activity genotype being associated with lower BMI. MAOA-LPR genotypes were not associated with alcoholism or related psychiatric phenotypes in this data set. Our results suggest that MAOA-LPR allelic variation modulates DA turnover in the CNS, but does so in a manner contrary to our prior expectation that alleles conferring high activity would predict higher HVA levels in CSF. Our results are consistent with an emerging literature that suggests greater complexity in how variation in MAOA expression alters monoaminergic function. Finally, our work suggests that MAOA may be involved in the regulation of BMI. Independent samples are necessary to confirm this preliminary finding.

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Section: Introductionmentioning

confidence: 99%

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

Ducci¹,

Newman²,

Funt³

et al. 2006

Mol Psychiatry

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“…Such eating behaviors occur in subjects with bulimia nervosa (BN) as well as in subjects with the binge/purge subtype of anorexia nervosa (AN-B/P). These eating disorders (EDs) are cross-transmitted in families 1 and share similar behavioral symptoms, 2 suggesting that they are related.…”

Section: Introductionmentioning

confidence: 99%

Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: A pilot study

Frank

Wagner

Achenbach

et al. 2006

Int. J. Eat. Disord.

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“…This latter conclusion is consistent with findings that elevated CSF 5-HIAA levels have been associated with overly inhibited and obsessive behavior in clinical populations. Positive correlations of CSF 5-HIAA with neuroticism and with obsessive-compulsive symptoms have been reported for patients with depression, anorexia and bulimia (Kaye et al 1991(Kaye et al , 1998Roy 1999). NEUROPSYCHOPHARMACOLOGY 2001-VOL.…”

mentioning

confidence: 98%

Social Impulsivity Inversely Associated with CSF 5-HIAA and Fluoxetine Exposure in Vervet Monkeys

Fairbanks

Melega

Jorgensen

et al. 2001

Neuropsychopharmacology

171

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Animal and human research suggests that the central serotonin system is involved in the inhibition of impulsive behavior. Two studies were designed to assess this relationship in male vervet monkeys ( Cercopithecus aethiops sabaeus ) using a standardized test of impulsivity in a social context: the Intruder Challenge. In the first study, an index of impulsivity in response to an unfamiliar adult male intruder (including latency to approach and aggressive and assertive interactions) was inversely correlated with levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (r ϭ Ϫ 0.33, p Ͻ .01, n ϭ 138). The approach, but not aggressive, component of the Impulsivity Index was the primary contributor to this relationship (partial r ϭ Ϫ 0.27, p Ͻ .01). The second experiment compared responses to the Intruder Challenge after 9 weeks of daily treatment with fluoxetine (2 mg/kg, i.m.) or vehicle. Fluoxetine-treated subjects ( n ϭ 6) had significantly lower Impulsivity Index scores than controls ( n ϭ 12Impulsivity has been proposed as the common denominator in a variety of psychological disorders and sociological conditions that have been associated with indices of low central serotonergic functioning (Linnoila et al. 1993). For example, low levels of the serotonin metabolite, 5-hydroyxindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) have been related to violent suicide attempts, impulsive fire-setting, violent and unprovoked aggression, and early onset alcoholism (Brown et al. 1982;Mann 1999;Virkkunen et al. 1994). Impulsivity and impulsive aggression have also been associated with blunted response to pharmacological challenges with serotonin agonists in personality-disordered and substance abusing men Moeller et al. 1994). Recently, Manuck et al. (1998) reported significant inverse correlations between prolactin response to fenfluramine and measures of impulsivity and aggressiveness in men from a community-based sample. This latter study suggests that psychosocial disorders involving impulsive aggression may represent the extremes of normal dimensions of personality and underlying neurochemistry. NO . 4 Social Impulsivity, 5-HIAA, and Fluoxetine 371A number of models have proposed that the monoaminergic neurotransmitters modulate the expression of basic personality dimensions (Cloninger 1987;Depue et al. 1994;Zuckerman 1996). These models generally agree that dopamine is associated with behavioral activation, and serotonin with behavioral inhibition. For example, Cloninger (1987) links the dopamine system with novelty seeking and serotonin with harm avoidance, while Zuckerman (1996) proposes that impulsive sensation seeking is a joint function of a highly reactive dopaminergic system and a weakly reactive serotonergic system. Empirical research to test the above hypotheses uses a variety of methods to measure impulsivity. Human studies typically use self-report interviews or questionnaires, but the different inventories designed to measure this construct frequ...

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Alterations in Serotonin Activity and Psychiatric Symptoms After Recovery From Bulimia Nervosa

Abstract: Persistent serotonergic and behavioral abnormalities after recovery raise the possibility that these psychobiological alterations might be trait-related and contribute to the pathogenesis of BN.

Cited by 191 publications

References 67 publications

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: A pilot study

Social Impulsivity Inversely Associated with CSF 5-HIAA and Fluoxetine Exposure in Vervet Monkeys

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