Epidemiologic studies link plasma cholesterol reduction to increased mortality rates as a result of suicide, violence, and accidents. Deficient central serotonergic activity is similarly associated with violence and suicidal behavior. We investigated the relationship among dietary and plasma cholesterol, social behavior, and the serotonin system as a possible explanation for these findings. Juvenile cynomolgus monkeys (eight female and nine male) were fed a diet high in fat and either high or low in cholesterol. We then evaluated their behavior over an 8-month period. Plasma lipids and cerebrospinal fluid metabolites of serotonin, norepinephrine, and dopamine were assessed on two occasions, at 4 and 5.5 months after the initiation of behavioral observations. Animals that consumed a low-cholesterol diet were more aggressive, less affiliative, and had lower cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid than did their high-cholesterol counterparts (p < .05 for each). The association among dietary cholesterol, serotonergic activity, and social behavior was consistent with data from other species and experiments and suggested that dietary lipids can influence brain neurochemistry and behavior; this phenomenon could be relevant to our understanding of the increase in suicide and violence-related death observed in cholesterol-lowering trials.
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...
BackgroundThe human apolipoprotein E (APOE) gene is polymorphic, with three primary alleles (E2, E3, E4) that differ at two key non-synonymous sites. These alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, Alzheimer’s disease risk, and longevity. The relative frequencies of these alleles vary across human populations, and the evolution and maintenance of this diversity is much debated. Previous studies comparing human and chimpanzee APOE sequences found that the chimpanzee sequence is most similar to the human E4 allele, although the resulting chimpanzee protein might function like the protein coded for by the human E3 allele. However, these studies have used sequence data from a single chimpanzee and do not consider whether chimpanzees, like humans, show intra-specific and subspecific variation at this locus.Methodology and Principal FindingsTo examine potential intraspecific variation, we sequenced the APOE gene of 32 chimpanzees. This sample included 20 captive individuals representing the western subspecies (P. troglodytes verus) and 12 wild individuals representing the eastern subspecies (P. t. schweinfurthii). Variation in our resulting sequences was limited to one non-coding, intronic SNP, which showed fixed differences between the two subspecies. We also compared APOE sequences for all available ape genera and fossil hominins. The bonobo APOE protein is identical to that of the chimpanzee, and the Denisovan APOE exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human E4 allele.ConclusionsWe found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.
Male rhesus monkeys typically disperse from their groups of birth when they are between 3 and 5 years of age. Some males, however, delay dispersal from their natal groups until after they are 5 years old. The current study evaluated central monoaminergic neurotransmitter activity as a potential correlate of such "delayed" dispersal among 54 randomly selected adolescent and adult male rhesus monkeys (Macaca mulatta) captured on Cay0 Santiago during an annual trapping season. Specifically, cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA, a serotonin metabolite), 3-methoxy-4-hydroxyphenylglycol (MHPG, a norepinephrine metabolite), and homovanillic acid (HVA, a dopamine metabolite) were compared in monkeys 60 months of age or more that had either dispersed (n = 33) or were still in their natal groups (n = 5). The monkeys still in their natal groups had higher CSF concentrations of both 5-HIAA and HVA (but not MHPG) than did the animals that had emigrated (Ps < 0.05). Subsequent analysis indicated that only 5-HIAA independently differentiated dispersing monkeys from delayed dispersers. Of monkeys less than 60 months of age (n = 161, only two had dispersed from their natal groups; in this age class, there were no significant differences between dispersing and natal individuals in any CSF monoaminergic metabolite (all Ps = NS). Finally, there was no difference in the CSF 5-HIAA concentrations of the five delayed dispersers and those of younger animals (P = NS), suggesting a failure to experience the frequently reported adolescent decline in serotonergic activity. In contrast, the CSF 5-HIAA concentrations of the dispersing animals were lower than those of the younger animals (P < 0.051, consistent with either an agerelated decline or an effect of dispersal per se. o 1995 Wiley-Liss, Inc.
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