CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season

Mehlman, Patrick T.; Higley, J. Dee; Fernald, Beth J; Sallee, Floyd R.; Suomi, Stephen J.; Linnoila, Markku

doi:10.1016/s0165-1781(97)00084-x

Cited by 77 publications

(68 citation statements)

References 33 publications

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“…In this long-term study trait-like variation in CSF 5-HIAA is correlated with an array of deleterious behavioral patterns which include severe aggression and wounding (inverse), risky, impulsive leaping (inverse), sociality (positive), early death (inverse), and sexual interactions with insemination (positive) (Higley et al 1996b;Higley et al 1992a;Higley et al 1996a;Higley et al 1996c;Joseph and Kennett 1980;Mehlman et al 1995;Mehlman et al 1994;Mehlman et al 1997). The present study adds to the growing profile of behaviors associated with natural variation in CSF 5-HIAA concentrations by showing an inverse correlation between central serotonin turnover rate and total nighttime activity.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 89%

“…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%

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

Mehlman

2000

Neuropsychopharmacology

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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...

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Section: Discussionmentioning

confidence: 99%

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confidence: 89%

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

Mehlman

2000

Neuropsychopharmacology

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“…In previous studies among free-ranging male rhesus macaques, low CSF 5-HIAA has been associated with infrequent consort relationships, low copulation rates, and infrequent observable sperm plugs (Mehlman et al, 1997). Within our laboratory, males with relatively low CSF 5-HIAA concentrations are less like to produce offspring, irrespective of age (Gerald et al, 2002).…”

Section: Discussionmentioning

confidence: 46%

Physiological Predictors of Reproductive Outcome and Mother–Infant Behaviors in Captive Rhesus Macaque Females (Macaca mulatta)

Cleveland¹,

Westergaard²,

Trenkle³

et al. 2003

Neuropsychopharmacol

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Abuse and Alcoholism, USAPrevious research has shown that offspring of females with low cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations are less likely to survive the first year of life than are offspring of females with high CSF 5-HIAA concentrations. In addition, studies of free-ranging rhesus macaque males have suggested that individuals with low CSF 5-HIAA concentrations suffer reduced reproductive success relative to their high serotonin counterparts. We examined CSF concentrations of the monoamine metabolites 5-HIAA and homovanillic acid (HVA), and plasma cortisol concentrations as predictors of first-time adult reproductive potential, maternal behavior, and overall social interactions in two groups of captive female rhesus macaques and their first offspring. Repeated CSF and blood samples were obtained from adult females in two social groups, and focal observations were performed for both new mothers and infants during the first month following parturition. We found that the reproductively aged nulliparous females who failed to give birth to their first offspring showed significantly lower CSF 5-HIAA concentrations than those females who gave birth. Among those females that gave birth to offspring, females with low CSF 5-HIAA concentrations and females with high plasma cortisol concentrations were overly protective and restrictive with their infants. CSF HVA concentration was not associated with reproductive output, social behavior, aggression, or mother-infant interactions in this sample of rhesus macaque females. We conclude that low CNS serotonin activity and high stress, measured by high plasma cortisol, are correlated with reduced reproductive success and patterns of high maternal restrictiveness in young adult female rhesus macaques.

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“…Levels of HVA have been related to aggressive behavior, wounding, sexual behavior, and social dominance in vervets and macaques (12,(20)(21)(22)(23). Numerous studies suggest associations between CSF MA metabolite concentrations and various human behavioral disorders (15,24,25), but other than relationships of CSF 5-HIAA to suicidal and aggressive behaviors (26), these associations remain mostly equivocal and nonreplicated, in part because of the difficulty in obtaining CSF from sufficient human subjects.…”

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confidence: 99%

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

Freimer

Ophoff²,

Jasinska³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (<10 Mb). The SNP discovery exploited conserved segments between human and rhesus macaque reference genome sequences. Our findings demonstrate the potential of using existing primate reference genome sequences for designing high-resolution genetic analyses applicable across a wide range of NHP species, including the many for which full genome sequences are not yet available. Leveraging genomic information from sequenced to nonsequenced species should enable the utilization of the full range of NHP diversity in behavior and disease susceptibility to determine the genetic basis of specific biological and behavioral traits.comparative genomics ͉ genetic mapping ͉ homovanillic acid ͉ vervet T he genetic investigation of non-human primates (NHPs) has the potential to generate enormous insights into the development, degeneration, and structure of the human brain and the biological basis of human behavior. Like humans, NHPs experience a prolonged period of postnatal development, together with strong family ties and complex social relationships. Furthermore, most features of human behavior have recognizable counterparts in NHPs, enabling the examination of traits such as anxiety and impulsivity, which are central components of human behavioral disorders. The pronounced interindividual variability observed in such traits within pedigreed primate colonies has stimulated interest in identifying genetic variants associated with these variable traits.There are several advantages in genetically investigating behavior-related traits in NHPs compared with humans. It is feasible to assess systematically a given trait in all members of large multigenerational NHP pedigrees, providing power to detect genetic variants of relatively small effect. It is also possible to obtain measures related to brain structure and function in

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CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season

Cited by 77 publications

References 33 publications

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

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

Physiological Predictors of Reproductive Outcome and Mother–Infant Behaviors in Captive Rhesus Macaque Females (Macaca mulatta)

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

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