CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors

Men with low CNS serotonin turnover, as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid : Sleep, serotonin, impulsivity, primate, aggression Psychiatric research suggests that a reduced turnover rate of serotonin in the central nervous system (CNS), as measured by cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA), is a risk factor for impaired impulse control, violent behavior, and premature mortality from suicide and violence (Faustman et al. 1990;Kruesi et al. 1990;Lidberg et al. 1985;Linnoila et al. Received February 12, 1999; revised June 16, 1999; accepted August 20, 1999. Dr. P.T. Mehlman and Dr. G.C. Westergaard are to be considered as co-first authors whose names are interchangeable. Dr. Mehlman was the Principal Investigator when the study was designed, the data were collected and analyzed, and was the first author when this manuscript was originally submitted. Dr. Westergaard was the Principal Investigator when the manuscript was revised and resubmitted for publication in this journal. Virkkunen et al. 1994). Research using nonhuman primates has replicated and extended many of these findings (Higley et al. 1996a;Higley et al. 1992a;Higley et al. 1996b;Kaplan et al. 1994;Mehlman et al. 1995;Mehlman et al. 1994;Mehlman et al. 1997;Raleigh 1987;Raleigh et al. 1983a;Raleigh et al. 1983b;Raleigh et al. 1980;Raleigh and McGuire 1994). Further, this research has demonstrated that inter-individual differences in CSF 5-HIAA concentrations are stable across time and experimental settings and can be attributed to genetic and early environmental influences that produce lasting modifications in the CNS serotonin response (Higley et al. 1996b;Higley et al. 1994;Higley et al. 1996a).Serotonin-mediated behavioral deficits are thought to result in part from an inability to maintain a homeostatic response in a number of physiological systems (Virkkunen et al. 1989a;Virkkunen and Narvanen 1987;Virkkunen et al. 1994). Various lines of evidence indicate that central serotonin neurotransmission contributes to regulation of sleep-wake cycles and circadian activity patterns. For example, several decades of research has shown that the sleep-wake cycle is partially modulated by serotonin release from projections of the ralphe nuclei (Jacobs 1991;Jouvet 1974;Jouvet 1967;Koella 1985;Koella and Czicman 1966;Maeda et al. 1989;Puizillout et al. 1981). Further, administration of p-chlorophenylalanine (PCPA), which inhibits the synthesis of serotonin, causes a reduction in total sleep in the cat (Jouvet 1974), rat (Torda 1967), and monkey (Weitzman et al. 1968). Finally, experimentally induced lesions of the ralphe system lead to nerve terminal decreases in 5-HT and 5-HIAA which are directly proportional to the degree of insomnia produced by the lesions (Jouvet 1974). These findings support the view that increases in CNS serotonin turnover rate promote sleep, in particular NREM sleep, and that deficits in serotonergic transmission are associated with insomnia, high levels of nighttime activity and/or...

Section: Discussionmentioning

confidence: 99%

“…Preliminary assessments of CSF 5-HIAA concentrations showed that these subjects were representative of the overall population sample. More details on the study population can be found in previous publications (Higley et al 1992a,b;Higley et al 1996b;Higley et al 1996c;Mehlman et al 1995;Mehlman et al 1994;Mehlman et al 1997;Taub and Mehlman 1989). …”

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confidence: 99%

CSF 5-HIAA and Nighttime Activity in Free-Ranging Primates

Mehlman

2000

“…Work by numerous investigators suggests that, in monkeys, monoamine metabolite concentrations in CSF are stable over time and across environments; furthermore, CSF concentrations observed in young animals are often predictive of those observed in the same individuals later in life. (Lewis et al 1990;Higley et al 1991Higley et al , 1996bRaleigh et al 1992). In the current study, animals were housed in unisexual groups of five or six animals (five groups of males, four groups of females) that were initially composed of social strangers, but which had been allowed to stabilize for at least one year prior to CSF collection.…”

Section: Social Dominance Is a Fundamental Component Of Both Human Anmentioning

confidence: 99%

“…Additionally, this concept is often extended, in people, to include dimensional variation in personality traits such as extraversion or social potency (Wiggins and Pincus 1992;Wiggins and Trapnell 1996). Recent studies also suggest that differences in dominance status in monkeys and dominance-related personality traits in humans partially reflect variation in aspects of central nervous system monoaminergic activity (Raleigh et al 1983(Raleigh et al , 1991Depue et al 1994;Higley et al 1996aHigley et al , 1996bShively 1998).…”

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confidence: 99%

Central Nervous System Monoamine Correlates of Social Dominance in Cynomolgus Monkeys (Macaca fascicularis)

Kaplan

Manuck

Fontenot³

et al. 2002

100

Social dominance is a fundamental component of both human and nonhuman primate sociality. However, its neurobiological correlates remain incompletely understood. We evaluated the association between dominance status and monoamine metabolite concentrations in cisternal cerebrospinal fluid (CSF) in adult male (n ϭ 25) and female (n ϭ 21) cynomolgus macaques ( Macaca fascicularis ) housed in unisexual social groups. Concentrations of the metabolites of dopamine (homovanillic acid [HVA]), norepinephrine ) and serotonin Social dominance reflects an asymmetry of relationship among individuals, as defined by the outcomes of dyadic encounters of a competitive or agonistic nature, and has long been thought to represent a fundamental component of sociality in nonhuman primates (Bernstein 1981;Silk 1987;Walters and Seyfarth 1987). Dominance-related behaviors may also comprise a primary axis of interpersonal behavior in the structure of human social relationships (Wiggins and Trapnell 1996). Additionally, this concept is often extended, in people, to include dimensional variation in personality traits such as extraversion or social potency (Wiggins and Pincus 1992;Wiggins and Trapnell 1996). Recent studies also suggest that differences in dominance status in monkeys and dominance-related personality traits in humans partially reflect variation in aspects of central nervous system monoaminergic activity (Raleigh et al. 1983(Raleigh et al. , 1991Depue et al. 1994;Higley et al. 1996aHigley et al. , 1996bShively 1998).In monkeys, serotonin has figured prominently in behavioral research relating to social dominance. For example, male vervet monkeys ( Cercopithecus aethiops ) become dominant in their social groups following treat- Corresponding Author: Jay R. Kaplan, Ph.D., Professor of Pathology (Comparative Medicine), Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, Tel.: (336) 716-1522, Fax: (336) 716-1515, E-mail: jkaplan@ wfubmc.edu Received February 12, 2000 revised July 5, 2001; accepted July 25, 2001.Online publication: 7/27/01 at www.acnp.org/citations/Npp 072701155. 432 J.R. Kaplan et al. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 26 , NO . 4 ment with either the serotonin precursor tryptophan or the serotonin reuptake inhibitor fluoxetine, and take a subordinate position when treated chronically with the serotonin releasing/depleting agent fenfluramine (chronic administration depletes serotonin) (Raleigh et al. 1991). Naturally-occurring differences in cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) also covary positively with dominance rank in female rhesus monkeys ( Macaca mulatta ), although a similar relationship has not been clearly described for adult male rhesus monkeys (Higley et al. 1996a). In contrast, dominant female cynomolgus monkeys ( M. fascicularis ) exhibit lower central serotonergic activity (as indexed by a low prolactin response to the serotonin agonist fenfluramine) than subordinates (Shi...

“…Clinical studies have also suggested that serotonin-mediated impulse control deficits might underlie alcohol abuse and associated behavioral problems (Linnoila et al 1993;Stein et al 1993). Studies of rhesus macaques with low CSF 5-HIAA concentrations show that when they are compared with control subjects, subjects with low CSF 5-HIAA concentrations exhibit impaired impulse control, entering traps more often, engaging more often in physically dangerous behaviors (Mehlman et al 1994;Higley et al 1996c), and consuming more alcohol when provided free access (Higley et al 1996e). In the current study, when mean home cage, nonstress alcohol consumption was correlated with mean CSF 5-HIAA concentrations collected at the same time, there was a negative correlation that approached statistical significance (r ϭ Ϫ0.66, p Ͻ .08).…”

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confidence: 99%

The Serotonin Reuptake Inhibitor Sertraline Reduces Excessive Alcohol Consumption in Nonhuman Primates: Effect of Stress

Higley

Hasert²,

Suomi³

et al. 1998

Many monkeys that are reared without adult influence, with only peers, voluntarily consume alcohol in amounts producing intoxication on a relatively regular basis. Using a cross-over design, eight adolescent, peer-reared rhesus monkeys were allowed unfettered access to an 8.4% ethanol solution and treated with 20 mg/kgA large number of preclinical studies have reported high rates of alcohol consumption among animals with reduced central nervous system (CNS) serotonin functioning (for reviews, see Sellers et al. 1992;LeMarquand et al. 1994b). Among humans, clinical studies show evidence of reduced CNS serotonin functioning in subjects at risk for or who exhibit early onset alcohol abuse and alcoholism (for recent reviews see LeMarquand et al. 1994a;Litten et al. 1996;Pettinati 1996). Some recent studies show that selective serotonin reuptake inhibitors (SSRIs) are promising as adjunctive pharmacological treatment for maintenance of abstinence (see LeMarquand et al. 1994b). Preclinical studies with rodents show that the SSRIs reduce alcohol consumption (LeMarquand et al. 1994b). Similarly, in a number of small scale studies, SSRIs have shown promise as an adjunct treatment for alcohol abuse and alcoholism (LeMarquand et al. 1994a;Pettinati 1996). The controlled studies conducted by Gorelick (1989) and Kranzler et al. (1995) showed, however, that fluoxetine was ineffective in promoting maintenance of abstinence among treatment-seeking alcoholics. More recently, researchers used a controlled study to demonstrate that citalopram was efficacious in promoting maintenance 18 , NO . 6 of abstinence among early-onset, violent male alcoholics thought to have reduced central serotonin functioning (Tiihonen et al. 1996). Because of the conflicting reports on the efficacy of the SSRIs in the maintenance of abstinence, we decided to investigate sertraline as a potential treatment for excessive alcohol intake, using a nonhuman primate model with monkeys known to have reduced central serotonin functioning (Higley et al. 1996d,e). Furthermore, we designed the study specifically to examine the role that stress plays in excessive alcohol consumption among nonhuman primates and to test the efficacy of sertraline in mitigating the effects of stress on alcohol consumption.Until recently, it was widely believed that nonhuman primates would not voluntarily consume alcohol in appreciable quantities (e.g., Mello and Mendelson 1971;Meisch et al. 1975;Crowley et al. 1983); consequently, they were not typically used in research on alcohol abuse. More recent studies have shown, however, that for many species of primates, many (but not all) subjects will freely consume alcohol in quantities that produce pharmacological effects when an alcohol solution is palatable (Higley et al. 1991;Higley 1996;Higley and Linnoila 1997). Within some species, such as rhesus macaques and other Old World primate species, some individual subjects will routinely consume sufficient quantities of alcohol to produce blood levels exceeding the limits of legal in...