Selective Alteration of Personality and Social Behavior by Serotonergic Intervention

135

100

In monkeys increasing serotonin function enhances affiliative interactions and promotes the acquisition of dominance. To examine whether similar effects occur in humans, we treated 98 subjects for 12 days with the serotonin precursor tryptophan (1g TID) and for 12 days with placebo in a doubleThe quality and nature of social interactions are defining features of both mental health and psychiatric disorders, but the tools used to study social interaction in psychopharmacological research generally examine global functioning rather than specific aspects of social interaction. Social science research in this area has advanced greatly over the past decade, and it is possible to conceptualize major components of social interaction and how these components are interrelated. While details vary, typically interpersonal behaviors can be organized in a circle defined by two major axes (Carson 1969;Foa 1961;Kiesler 1983;Leary 1957;Wiggins 1995;Wiggins and Broughton 1985). One axis encompasses dominant and submissive behaviors. This axis has been called by various names including agency, power, and status. Dominant behaviors include setting goals for others or telling others to do something while submissive behaviors include not voicing an opinion or waiting for others to act (Moskowitz 1994). The second axis encompasses agreeable and quarrelsome behaviors. Sample agreeable behaviors include listening attentively to others and expressing reassurance while quarrelsome behaviors include showing impatience and making sarcastic comments (Moskowitz 1994). Among many labels, this axis has been referred to as communion or affiliation.The two axes of human social interaction can be studied using an event sampling method. This method assesses individuals' social behaviors and affect in individuals' natural environments rather than in the laboratory. The individual completes a brief questionnaire after each significant social interaction, throughout the 25 , NO . 2 day. Abundant evidence has accumulated demonstrating the reliability and validity of methods for sampling interpersonal behavior and affect in everyday life (Csikszentmihalyi and Larson 1987;Diener and Emmons 1984;McAdams and Constantian 1983;Moskowitz 1994). While behavior along the axes varies greatly from one social interaction to the next, aggregation of behaviors in events across several days provides measures with substantial temporal stability (Brown and Moskowitz 1998). The event-contingent recording procedure (Wheeler and Reis 1991) used in the present study has several advantages. Interpersonal situations are sampled throughout the day, providing reports of behavior and affect at home and at work. Reports of behavior and affect are recorded close in time to their occurrence, so retrospective biases are minimized. It is possible to construct behavior and affect scores for time periods of specified lengths, such as morning, afternoon, and evening, or a day, or a week. Previous research using this method has demonstrated the concurrent relation between interper...

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The Effect of Tryptophan on Social Interaction in Everyday Life A Placebo-Controlled Study

Moskowitz

Pinard

Zuroff

et al. 2001

135

100

“…These included ratings of mood, anxiety, general well being, various aspects of quality of life and personality characteristics. More subtle effects of paroxetine were observed in a subsequent study of normal volunteers (Knutson et al 1998)-a reduction in focal indices of hostility through a decrease in negative affect and an increase in a behavior index of social affiliation. These effects were already present after one week of paroxetine administration.…”

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confidence: 92%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Serotonergic receptors of the 5-HT 1A subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HTThere is considerable interest in the role of serotonergic (5-HT) receptors of the 5-HT 1A subtype in the therapeutic action of antidepressant drugs. 5-HT 1A receptors are located presynaptically on serotonergic cell bodies in the raphe nuclei where they serve as autoreceptors which inhibit cell firing and reduce 5-HT release by a negative feedback mechanism, and post-synaptically in the hippocampus, cortex and other brain areas, including the hypothalamus. Based on electrophysiological studies in rats, De Montigny and colleagues Mongeau et al. 1997) proposed that each major class of antidepressants increases 5-HT neurotransmission by a distinct mechanism involving either From the Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center (BL, YG, MEN) and the Laboratory of Applied Statistics, Hebrew University (MG), Jerusalem, Israel; the Endocrine Laboratory, Department of Medicine (BA) and Department of Psychiatry (KPL), University of Wuerzburg, Wuerzburg, Germany.Address correspondence to: Prof. Bernard Lerer, Biological Psychiatry Laboratory, Dept. of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.Received May 15, 1998; accepted August 25, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 Ipsapirone Challenge in Normal Subjects on Fluoxetine 629pre-or post-synaptic 5-HT 1A receptors. The selective serotonin re-uptake inhibitors (SSRIs), which raise 5-HT synaptic levels when given acutely, were proposed to increase 5-HT transmission on repeated administration by inducing desensitization of somatodendritic 5-HT 1A autoreceptors in the raphe nuclei and nerve terminal 5-HT 1B autoreceptors, which also mediate feedback inhibition of 5-HT release. These effects would lead to a slow increase in 5-HT levels which corresponds to the delayed clinical effect of the drugs. Evidence for subsensitivity of somatodendritic 5-HT 1A autoreceptors after chronic administration of SSRIs has been provided by microdialysis experiments in which 5-HT levels are measured in vivo in response to a challenge dose of the 5-HT 1A receptor agonist, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) (Rutter et al. 1994, Kreiss andLucki 1995;Invernizzi et al. 1994). However, other studies using SSRIs (Hjorth and Auerbach 1994; Bosker et al. 1995a,b;Invernizzi et al. 1995Invernizzi et al. , 1996 or clomipramine (Gur et al. 1999) failed to show any change in 5-HT 1A autoreceptor subsensitivity by this method. An increase in basal 5-HT levels after chronic SSRI administration, taken to be due to pre-synaptic 5-HT 1A and 5-HT 1B receptor desensitization, has been observed in cortex (Bel and Artigas 1993), hippocampus (Auerbach and Hjorth 1995) diencephalon (Rutter et al. 1994) an...

“…For example, Coccaro and Kavoussi (1997) reported that fluoxetine significantly reduced scores on the Irritability and Aggression subscales of the Overt Aggression Scale of impulsive-aggressive personalitydisordered subjects. In a study of the effects of SSRI treatment on normal volunteers, Knutson et al (1998) found that decreases in assaultiveness and irritability on the Buss-Durkee Hostility Inventory were related to plasma paroxetine levels following 4 weeks of treatment. Alcohol consumption, which has often been associated with impulsivity, has been shown to be reduced by SSRI treatment in human alcoholics (Tiihonen et al 1996) and in a rhesus monkey model of excessive alcohol consumption (Higley et al 1998).…”

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

Fairbanks

Melega

Jorgensen

et al. 2001

172

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...