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

Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213, USA.
Archives of General Psychiatry (Impact Factor: 14.48). 10/1998; 55(10):927-35. DOI: 10.1001/archpsyc.55.10.927
Source: PubMed

ABSTRACT Women with bulimia nervosa (BN) have disturbances of mood and behavior and alterations of monoamine activity when they are bingeing and purging. It is not known whether these alterations are secondary to pathological eating behavior or traits that could contribute to the pathogenesis of BN.
To avoid the confounding effects of pathological eating behavior, we studied 30 women after long-term recovery (>1 year with no bingeing or purging, normal weight, and regular menstrual cycles) from BN. Subjects were compared with 31 healthy volunteer women. We assessed psychiatric diagnoses and symptoms to determine whether there was any persistent disturbance of behavior after recovery. We measured cerebrospinal fluid (CSF) levels of the major metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]) as well as hormonal and behavioral response to m-chlorophenylpiperazine (m-CPP), a serotonin-specific agent.
Women who were recovered from BN had mild to moderate negative moods and obsessions with perfectionism and exactness and exaggerated core eating disorder symptoms compared with healthy volunteer women. Recovered BN women had increased levels of CSF 5-HIAA compared with control women (117 +/- 33 vs 73 +/- 15 pmol/mL; P< or =.001) but normal CSF HVA and MHPG concentrations. Recovered BN women had an anxious and disorganized behavioral response to m-CPP but a normal hormonal response.
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.

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Available from: Howard B Moss, Sep 27, 2015
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    • "Associations between serotonin genes and eating disorders, via main and G 9 E effects, align with neurobiological studies demonstrating alterations in the serotonin system in women with eating disorders . Although no longitudinal studies of serotonergic function predicting eating pathology onset exist, studies of recovered patients with AN and BN show increased cerebrospinal fluid (CSF) levels of 5-HIAA (a serotonin metabolite) compared to controls, which may reflect increased serotonin neuronal activity (Kaye, Gwirtsman, George, & Ebert, 1991; Kaye et al., 1998). Neuroimaging data also point to altered serotonin receptor activity (i.e., increased 5-HT1a and 5-HTT binding potential; reduced 5-HT2A binding potential) in several cortical and limbic regions in women recovered from AN and BN, and these serotonin receptor alterations have been associated with co-occurring features of eating disorders (i.e., increased drive for thinness and harm avoidance) (see Table 4). "
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    ABSTRACT: Eating disorders are severe psychiatric disorders with a complex etiology involving transactions among sociocultural, psychological, and biological influences. Most research and reviews, however, focus on only one level of analysis. To address this gap, we provide a qualitative review and summary using an integrative biopsychosocial approach. We selected variables for which there were available data using integrative methodologies (e.g., twin studies, gene-environment interactions) and/or data at the biological and behavioral level (e.g., neuroimaging). Factors that met these inclusion criteria were idealization of thinness, negative emotionality, perfectionism, negative urgency, inhibitory control, cognitive inflexibility, serotonin, dopamine, ovarian hormones. Literature searches were conducted using PubMed. Variables were classified as risk factors or correlates of eating disorder diagnoses and disordered eating symptoms using Kraemer et al.'s (1997) criteria. Sociocultural idealization of thinness variables (media exposure, pressures for thinness, thin-ideal internalization, thinness expectancies) and personality traits (negative emotionality, perfectionism, negative urgency) attained 'risk status' for eating disorders and/or disordered eating symptoms. Other factors were identified as correlates of eating pathology or were not classified given limited data. Effect sizes for risk factors and correlates were generally small-to-moderate in magnitude. Multiple biopsychosocial influences are implicated in eating disorders and/or disordered eating symptoms and several can now be considered established risk factors. Data suggest that psychological and environmental factors interact with and influence the expression of genetic risk to cause eating pathology. Additional studies that examine risk variables across multiple levels of analysis and that consider specific transactional processes amongst variables are needed to further elucidate the intersection of sociocultural, psychological, and biological influences on eating disorders. © 2015 Association for Child and Adolescent Mental Health.
    Journal of Child Psychology and Psychiatry 06/2015; DOI:10.1111/jcpp.12441 · 6.46 Impact Factor
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    • "Although exact cause of 5-HT dysfunction in eating disorders is unknown, but several studies presumed that alteration of 5-HT1A and 5-HT2A receptor activities, the 5-HTT (5-HT transporter), and CSF 5-HIAA levels can be involved in patients with eating disorders.15 Several studies confirmed persistence of alterations in serotonin activity,16,17 and also persistence of anxiety, perfectionism, and obsessive behavior18 after recovery from anorexia nervosa and bulimia nervosa. "
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    ABSTRACT: The development of eating disorders including anorexia nervosa, bulimia nervosa, binge eating disorder, and atypical eating disorders that affect many young women and even men in the productive period of their lives is complex and varied. While numbers of presumed risk factors contributing to the development of eating disorders are increasing, previous evidence for biological, psychological, developmental, and sociocultural effects on the development of eating disorders have not been conclusive. Despite the fact that a huge body of research has carefully examined the possible risk factors associated with the eating disorders, they have failed not only to uncover the exact etiology of eating disorders, but also to understand the interaction between different causes of eating disorders. This failure may be due complexities of eating disorders, limitations of the studies or combination of two factors. In this review, some risk factors including biological, psychological, developmental, and sociocultural are discussed.
    Annals of Neurosciences 03/2014; 20(4):157-161. DOI:10.5214/ans.0972.7531.200409
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    • "REC AN and REC BN have altered (and often different patterns of) 5-HT function (Kaye, 2008). For example, studies have shown different degrees of elevated cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (Kaye et al., 1991; Kaye et al., 1998) and altered behavioral responses to 5-HT challenges in these populations (Frank et al., 2001; Kaye et al., 2003; Smith et al., 1999; Ward et al., 1998). We have used PET and specific radioligands ([ 11 C]McN5652, [ 11 C]WAY100635 and [ 18 F]altanserin) to assess the BP of the 5-HT transporter (5-HTT) and the 5-HT 1A and 5-HT 2A receptors. "
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    ABSTRACT: RATIONALE: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. OBJECTIVE: Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. METHODS: Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding. RESULTS: There was a positive correlation between [(11)C]McN5652 binding potential (BP(non displaceable(ND))) and [(11)C]raclopride BP(ND) for the dorsal caudate (r(27)=0.62; p<0.001), antero-ventral striatum (AVS) (r(27)=0.55, p=0.003), middle caudate (r(27)=0.68; p<0.001), ventral (r(27)=0.64; p<0.001) and dorsal putamen (r(27)=0.42; p=0.03). No significant correlations were found in CW. [(11)C]raclopride BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC EDs. A linear regression analysis showed that the interaction between [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen significantly (b=140.04; t (22)=2.21; p=0.04) predicted HA. CONCLUSIONS: This is the first study using PET and the radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship between 5-HT transporter and striatal DA D2/D3 receptor binding in humans, supporting the possibility that 5-HT and DA interactions contribute to HA behaviors in EDs.
    11/2012; 211(2). DOI:10.1016/j.pscychresns.2012.06.010
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