Biomedical subjects

S J Suomi

Publications and source records attributed to S J Suomi.

At least 19 recordsLinked to original sources

PubMed2006

Structural variation of the monoamine oxidase A gene promoter repeat polymorphism in nonhuman primates.

By conferring allele-specific transcriptional activity on the monoamine oxidase A (MAOA) gene in humans, length variation of a repetitive sequence [(variable number of tandem repeat (VNTR)] in the MAOA promoter influences a constellation of personality traits related to aggressive and antisocial behavior and increases the risk of neurodevelopmental and psychiatric disorders. Here, we have analyzed the presence and variability of this MAOA promoter repeat in several species of nonhuman primates. Sequence analysis of MAOA's transcriptional control region revealed the presence of the VNTR in chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), rhesus macaque (Macaca mulatta) and Gelada baboon (Theropithecus gelada). The majority of P. troglodytes and P. paniscus showed a single repeat with a sequence identical to the VNTR sequence in humans. In contrast, analyses of the remaining species revealed shorter sequences similar to the first 18 bp of human VNTR. Compared with other nonhuman primates, the VNTR sequence of M. mulatta showed the highest length variability with allele frequencies of 35, 25 and 40% for the five, six and seven repeat variants, respectively. The extent of variability of the MAOA promoter repeat in both rhesus monkeys and humans supports the notion that there may be a relationship between functional MAOA expression and aggression-related traits in humans and rhesus macaque populations.

Animals↗

PubMed2004

Biobehavioural correlates of hand preference in free-ranging female primates.

In this research we examined biological and behavioural correlates of handedness in a subject cohort of 41 free-ranging young female rhesus macaques (Macaca mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), prolactin, and multiple indices of social behaviour, including proximity to other animals, grooming, submission, and aggression. Handedness was determined through systematic observation of animals reaching for food in their unrestricted home environment. We found a population-level bias for left-hand use in this cohort of young females. The frequency of right versus left hand use was positively correlated with CSF 5-HIAA, plasma cortisol concentrations, the frequency of submissive behaviour, and with the frequency of bouts in which animals received low-level aggression. The positive correlation between right versus left hand use, submissive behaviour, and received aggression found here in females contrasts with the negative correlation among these same variables that we have previously reported in rhesus males. We conclude that these results may be explicable in terms of sex-based differences in rhesus life-history patterns, and that the influence of the serotonergic system on patterns of male aggression, social behaviour, and handedness, and the associations between handedness and social behaviour found previously among males may not be generalised to female rhesus macaques.

Adrenocorticotropic Hormone↗

PubMed2004

Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

BACKGROUND: Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. METHODS: Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. RESULTS: Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. CONCLUSIONS: These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

Animals↗

PubMed2003

Serotonin transporter availability correlates with alcohol intake in non-human primates.

A low level of alcohol intoxication upon initial exposure and impulsive aggressiveness predispose humans to alcoholism. In non-human primates, central serotonin transporter availability and turnover rate were associated with aggressive behavior and a low response to initial alcohol exposure. We assessed the respective effects of these factors on alcohol intake in a free choice paradigm. Serotonin transporter availability in the raphe area, the origin of central serotonergic projections, was measured with single-photon emission computed tomography and the radioligand [(123)I]beta-CIT in 11 rhesus monkeys with low and high central serotonin turnover. The amount of alcohol intake in the 3-month observation period was positively correlated with serotonin transporter availability (R=0.76, P=0.006), but not with aggressiveness (R=0.19, P=0.6) or alcohol response upon first exposure (R=-0.48, P=0.2). In a linear multiple regression analysis with serotonin transporter availability, alcohol response, and aggressiveness as independent variables, 82% of the variance of alcohol intake was explained and serotonin transporter availability emerged as the only statistically significant factor (beta=7.81, P=0.006). These observations indicate that there may be a direct relationship between serotonin transporter availability and alcohol intake after controlling for aggression and alcohol response on first exposure.

Aggression↗

PubMed2003

The utility of the non-human primate; model for studying gene by environment interactions in behavioral research.

Variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been associated with anxiety and harm avoidance and is weakly associated with a number of neuropsychiatric disorders, including Type II alcoholism, which has a high rate of comorbidity with antisocial personality disorder. Studies have also demonstrated interactions between 5-HTLPR variation and environmental stress on the incidence of depression. As in humans, there is a serotonin transporter gene promoter length polymorphism in rhesus macaques that produces similar decreases in transcriptional efficiency. Macaques with histories of early-life stress have been shown to exhibit impulsive aggression, incompetent social behavior and increased behavioral and endocrine responsivity to stress. In this paper, we review studies performed previously in our lab and present preliminary data examining interactions between early rearing and serotonin transporter gene promoter variation on the incidences of play behavior and aggression in infant rhesus macaques. The data presented here highlight the importance of considering gene-environment interactions when studying childhood risk factors for aggression, anxiety and related neuropsychiatric disorders and support the use of the nonhuman primate for studing gene by environment interactions in behavioral research.

Animals↗

PubMed2003

Left-handedness is correlated with CSF monoamine metabolite and plasma cortisol concentrations, and with impaired sociality, in free-ranging adult male rhesus macaques (Macaca mulatta).

In this research we examined biological and behavioural correlates of handedness in free-ranging adult male rhesus macaques (Macaca mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), and multiple indices of social behaviour, including occurrences of proximity to other animals, grooming, submission, and aggression. We determined handedness through systematic observation of animals reaching for food in their unrestricted home environment. The frequency of right- versus left-hand use was significantly positively correlated with CSF 5-HIAA, CSF MHPG, and plasma cortisol concentrations, and with social proximity and the frequency and duration of bouts in which animals received grooming. The frequency of right- versus left-hand use was significantly negatively correlated with the frequency of submissive behaviour, and with the frequency and intensity of bouts in which animals received aggression. We conclude that handedness is associated with an array of biological and behavioural processes in free-ranging adult male rhesus macaques and that left-handedness may be used to identify individuals at increased risk for impaired functioning of the serotonin, norepinephrine, and hypothalamic-pituitary-adrenal systems, and for social isolation and susceptibility to violent attack.

Journal Article↗

PubMed2002

Early experience and serotonin transporter gene variation interact to influence primate CNS function.

Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

Alleles↗

PubMed2002

Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates.

A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association study was conducted on 115 rhesus macaque infants either homozygous for the long 5HTTLPR variant (l/l) or heterozygous for the short and long form (l/s). To assess contributions of genotype and early rearing environment, 36 mother-reared monkeys (l/l = 26, l/s = 10) and 79 nursery-reared monkeys (l/l = 54, l/s = 25) were assessed on days 7, 14, 21, and 30 of life on a standardized primate neurobehavioral test designed to measure orienting, motor maturity, reflex functioning, and temperament. Both mother-reared and nursery-reared heterozygote animals demonstrated increased affective responding relative to l/l homozygotes. Nursery-reared, but not mother-reared, l/s infants exhibited lower orientation scores than their l/l counterparts. These results demonstrate the contributions of rearing environment and genetic background, and their interaction, in a nonhuman primate model of behavioral development.

Aging↗

PubMed2002

Handedness is associated with immune functioning and behavioural reactivity in rhesus macaques.

In the present study we examined the relationship among handedness, immune functioning, and behavioural reactivity in rhesus macaques. We used the absolute number of CD4+ (T-helper) and CD8+ (T-suppressor) cells as dependent measures of immune functioning. We derived reactivity profiles from behavioural responses to a threat, and hand preference profiles from a quadrupedal food-reaching test. The results indicate positive correlations between the frequency of right versus left hand reaches and the absolute number of CD4+ cells, and between the frequency of right versus left hand reaches and the degree of human-directed aggression in response to an invasive threat. Immune measures were not associated with the strength of hand preference. These results are consistent with and extend previous findings obtained with rodents to nonhuman primates and provide further support for the view that behavioural lateralisation is associated with immune functioning and behavioural reactivity.

Journal Article↗

PubMed2001

Initial ethanol exposure results in decreased heart rate variability in ethanol-naive rhesus monkeys.

Ethanol's effects on heart rate variability may contribute to the increased cardiac disease and mortality observed in alcoholics. We assessed cardiac response to ethanol in seven previously ethanol-naive monkeys given a standard dose of ethanol, or saline. Ethanol exposure reduced cardiac signal complexity [mean+/-S.D. (ethanol: Hurst parameter=0.39+/-0.02; saline: Hurst parameter=0.32+/-0.06)] and increased the spectral exponent (ethanol: beta=1.36+/-0.35; saline: beta=1.12+/-0.35) when compared to saline, while heart rate itself was unaffected (saline: interbeat interval=303.57+/-24.57; ethanol: interbeat interval=308.14+/-20.45). Taken together with data that show autonomic disregulation in alcoholics, these findings provide further evidence of deleterious ethanol effects on cardiac signal dynamics.

Animals↗

PubMed2001

Stress correlates of hand preference in rhesus macaques.

In this research we examined stress-related correlates of hand preference in monkeys. Specifically, we tested the hypothesis that stress reactivity and plasma levels of the stress hormone cortisol are developmentally related to handedness in rhesus macaques (Macaca mulatta). We found a significant positive correlation between cortisol levels sampled in juveniles and the frequency of right- versus left-hand use sampled in these same animals during adulthood. Right-hand preference was negatively correlated with stress reactivity. These data are consistent with the view that stress functioning and reactivity are associated with the development of hemispheric specialization in primates.

Animals↗

PubMed2001

Plasma cortisol is associated with handedness in infant rhesus monkeys.

In this research we examined the relationship between plasma cortisol and handedness in infant rhesus macaques (Macaca mulatta). Specifically, we tested the hypothesis that stress functioning is related to hemispheric specialization and manifested in a positive correlation between cortisol levels and the frequency of right- versus left- hand use. We found a significant positive relationship between cortisol levels sampled at ages 1 and 3 months and lateral bias toward greater use of the right hand versus left hand sampled between ages 4 and 11 months. Further, we found a significant negative relationship between cortisol sampled at age 5 months and strength of lateral bias (independent of direction). These data suggest an early developmental influence of stress functioning on hemispheric specialization for manual control in infant monkeys.

Age Factors↗

PubMed2000

Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.

We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose-response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity.

Administration, Oral↗

PubMed2000

Ondansetron modulates pharmacodynamic effects of ketamine on electrocardiographic signals in rhesus monkeys.

Electrocardiographic signal dynamics were examined in rhesus monkeys (Macaca mulatta) before and after treatment with ketamine and/or ondansetron. Ketamine exerts differential pharmacodynamic effects on behavior in animals stratified according to a measure of central serotonergic turnover. We hypothesized that measures of serotonergic turnover might explain some of the variance in the electrocardiographic (ECG) response to ketamine. Electrocardiographic recordings of animals were obtained at baseline, after administration of either saline or ondansetron (0.125 mg/kg), and after administration of ketamine (15 mg/kg). Electrocardiographic signal dynamics were measured using an algorithm that extracts the Hurst parameter (H) of the interbeat interval (IBI) time-series. H decreased after ketamine administration, (mean+/-S.E.M.), 0.33+/-0.04 vs. 0.12+/-0.02, P</=0. 001, n=10. Cerebrospinal fluid 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations, a measure of serotonergic turnover, predicted the monkeys' response to ketamine, H=0.001 (5-HIAA, pmol/ml)-0.130, R=0.66, P</=0.003, n=18. Ondansetron attenuated the response to ketamine, 0.14+/-0.02 vs. 0.08+/-0.02, P</=0.05, n=8, ondansetron vs. saline. These data provide evidence that naturally occurring differences in serotonin function alter the ECG response of the animals to ketamine and that activation of the serotonin type-3 receptor by ketamine is involved.

Animals↗

PubMed2000

Handedness and cortisol in tufted capuchin monkey infants.

In this research, we examined the relationship between handedness and levels of plasma cortisol in infant monkeys (Cebus apella). Specifically, we sought to test the hypothesis that stress functioning is related to hemispheric specialization and is manifested in a positive correlation between cortisol levels and the frequency of right- versus left-hand use. We found a significant relationship between stress cortisol at age 6 months and lateral bias towards greater use of the right versus left hand at ages 6 and 12 months. These data suggest an early developmental influence of stress reactivity on the emergence of hemispheric specialization for manual control in infant monkeys through the 1st year of postnatal life.

Age Factors↗

PubMed2000

A comparative study of aimed throwing by monkeys and humans.

This research examined hand preference and postural characteristics of aimed throwing in capuchin monkeys and humans. We sought to directly compare the throwing performances of these primates, particularly the extent to which target distance influences hand preference, throwing posture, and throwing accuracy. For both species we found positive correlations between target distances for throwing accuracy, direction and strength of hand preference, percentage of bipedal vs tripedal throws, and percentage of overarm vs underarm throws. Throwing accuracy did not vary as a function of right vs left hand use although for monkeys throwing accuracy was positively associated with hand preference strength. We noted a sex difference among humans as males threw more accurately than did females. Between-species analysis indicated that humans exhibited greater right- vs left-hand use, greater hand preference strength, a greater relative percentage of bipedal vs tripedal throws, and a lower relative percentage of overarm vs underarm throws than did monkeys. We believe that the capuchin monkey is an informative nonhuman primate model of aimed throwing in humans and that research examining the throwing behavior of capuchins provides insight into the neurological and behavioral characteristics that underlie coordinated multi-joint movements across the primate order.

Adult↗

PubMed2000

Hormonal correlates of hand preference in free-ranging primates.

In this research we examined hormonal correlates of hand preference in free-ranging primates. Specifically, we tested the hypothesis that levels of the stress hormone cortisol and the male sex hormone testosterone are correlated with handedness in male rhesus macaques (Macaca mulatta). We found significant positive relationships between cortisol and testosterone levels sampled during adolescence and the frequency of right- versus left-hand use sampled during adulthood. These data indicate that adolescent measures of cortisol and testosterone are correlated with hemispheric specialization in adult free-ranging primates.

Adrenocorticotropic Hormone↗

PubMed2000

Seasonal variation in CSF 5-HIAA concentrations in male rhesus macaques.

Seasonal changes in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations were assessed on multiple occasions in 103 free-ranging male rhesus macaques (Macaca mulatta). At the time of sampling subjects ranged between the ages of 2 and 6 years. CSF samples were collected between the hours of 0900 and 1600 throughout the Fall, Winter, and Spring from 1990 through 1994. Data were analyzed in a general linear mixed model with random intercepts. Results indicated that CSF 5-HIAA concentrations decreased with age. CSF 5-HIAA concentrations were significantly increased in the Fall (October and November), which is the height of the breeding season, with no evidence of differences between Winter and Spring. There was also some evidence that the seasonal variation in CSF 5-HIAA concentrations was blunted in younger, more immature subjects.

Aging↗