Social and environmental influences on blood serotonin concentrations in monkeys.

Dominant male adult vervet monkeys have whole-blood serotonin concentrations approximately twice those of subordinate adult males. We examined the effects of spontaneous and induced changes in social status, temporary isolation from the social group, and membership in single male groups on whole-blood serotonin concentrations. We found that in male vervet monkeys, elevated blood serotonin concentration is a state-dependent consequence of active occupation of the dominant male social position, and we believe that a reinterpretation of the significance of hyperserotonemia in humans may be warranted.

A descriptive study of individuals successful at long-term maintenance of substantial weight loss.

The National Weight Control Registry (NWCR) is, to the best of our knowledge, the largest study of individuals successful at long-term maintenance of weight loss. Despite extensive histories of overweight, the 629 women and 155 men in the registry lost an average of 30 kg and maintained a required minimum weight loss of 13.6 kg for 5 y. A little over one-half of the sample lost weight through formal programs; the remainder lost weight on their own. Both groups reported having used both diet and exercise to lose weight and nearly 77% of the sample reported that a triggering event had preceded their successful weight loss. Mean (+/-SD) current consumption reported by registry members was 5778 +/- 2200 kJ/d, with 24 +/- 9% of energy from fat, Members also appear to be highly active: they reported expending approximately 11830 kJ/wk through physical activity. Surprisingly, 42% of the sample reported that maintaining their weight loss was less difficult than losing weight. Nearly all registry members indicated that weight loss led to improvements in their level of energy, physical mobility, general mood, self-confidence, and physical health. In summary, the NWCR identified a large sample of individuals who were highly successful at maintaining weight loss. Future prospective studies will determine variables that predict continued maintenance of weight loss.

Resting energy expenditure in reduced-obese subjects in the National Weight Control Registry.

BACKGROUND: Weight loss in obese subjects is associated with a reduction in resting metabolic rate (RMR). Whether the reduction can be explained solely by a reduction in lean body mass remains controversial. OBJECTIVE: Our objective was to determine whether the reduction in RMR after weight loss was proportional to the decrease in lean mass alone or was greater than could be explained by body composition. DESIGN: We measured the RMR, fasting respiratory quotient (RQ), and body composition in 40 reduced-obese subjects [ie, 7 men and 33 women who had lost > or = 13.6 kg (30 lb) and maintained the loss for > or = 1 y] enrolled in the National Weight Control Registry and 46 weight-matched control subjects (9 men, 37 women). RESULTS: A stepwise multiple regression found lean mass, fat mass, age, and sex to be the best predictors of RMR in both groups. After adjusting RMR for these variables, we found no significant difference in RMR (5926 +/- 106 and 6015 +/- 104 kJ/d) between the 2 groups (P = 0.35). When we adjusted fasting RQ for percentage body fat and age, the reduced-obese group had a slightly higher (0.807 +/- 0.006) RQ than the control group (0.791 +/- 0.005, P = 0.05). This may have been due to the consumption of a diet lower in fat or to a reduced capacity for fat oxidation in the reduced-obese group. CONCLUSION: These results show that in at least some reduced-obese individuals there does not seem to be a permanent obligatory reduction in RMR beyond the expected reduction for a reduced lean mass.

Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences.

We examined the effects of gender, age, weight, length, body shape (ectomorphy), and matrilineal influences on cisternal cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and homovanillic acid (HVA) in 78 socially living adult and adolescent vervet monkeys. CSF 5-HIAA and the 5-HIAA:HVA ratio were higher (by 27% and 18%, respectively) in females. In both sexes, CSF 5-HIAA and the 5-HIAA:HVA ratio increased with age. Neither weight nor length were independently related to CSF 5-HIAA or HVA; however, shape correlated with CSF 5-HIAA and HVA in males (higher in thin, long subjects). Male offspring had CSF 5-HIAA concentrations and 5-HIAA:HVA ratios that were significantly closer to their mothers than did age-matched, maternally unrelated males. Repeated measures of CSF 5-HIAA and HVA in another 22 males living in unvarying settings showed that individual differences in these measures persisted over time. The data underscore the impact of gender, age, and matrilineal relationships on individual differences in CSF monoamine metabolites and highlight the importance of controlling for age and gender in neuropharmacological investigations of clinical populations.

Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys.

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 = -0.33, p <.01, n = 138). The approach, but not aggressive, component of the Impulsivity Index was the primary contributor to this relationship (partial r = -0.27, p <.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 = 6) had significantly lower Impulsivity Index scores than controls (n = 12). The results from these two investigations provide evidence for serotonergic influences on social impulsivity.

Comparison of ketamine, physical restraint, halothane and pentobarbital: lack of influence on serotonergic measures in monkeys and rats.

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys (Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.

Menstrual cycle and social behavior in vervet monkeys.

We assessed the relationship between social behavior and the menstrual cycle in 11 adult female vervet monkeys (Cercopithecus aethiops sabaeus) living in an established, stable social group. The findings indicated that fluctuations in ovarian steroids are accompanied by behavioral changes in vervet monkeys. A significant increase in aggressive action, avoidance of social overtures, and retreats from threat occurred during the late luteal phase. However, the social environment can greatly affect behavior independent of the phase of the menstrual cycle. The 10 nondominant (or subordinate) individuals not only exhibited behavioral changes across their own menstrual cycles, but also were responsive to the dominant female's cycle. During the dominant female's late luteal phase, subordinate females significantly increased aggression and decreased social activity. Some of behavioral patterns in female vervet monkeys are therefore relatively independent of direct hormonal modulation and support the contention of the dominant female as the driving force for behavioral changes related to aggression and social interaction. The differential effect of hormones and social status and other environmental factors on behavior has not been critically evaluated in human studies of the premenstrual syndrome. The present study suggests that it is important to assess which behavioral patterns in women are hormonally mediated and which are dependent on the environment.

Peripheral correlates of serotonergically-influenced behaviors in vervet monkeys (Cercopithecus aethiops sabaeus).

The associations among twelve behaviors and three potential peripheral markers of central serotonergic activity were investigated in vervet monkeys (Cercopithecus aethiops sabaeus). The behaviors monitored included approach, heterogroom, rest, eat, avoid, be solitary, be vigilant, huddle, initiate aggress, receive aggress, and engage in sexual behavior. The biochemical parameters measured were whole blood serotonin, plasma free tryptophan, and plasma total tryptophan. Throughout the study period, intraindividual variability in both the behavioral and the biochemical measures was small, although there was substantial interindividual variability in both sets of measures. Free and total tryptophan correlated positively with approach, heterogroom, and eat, and inversely with avoid and be solitary. Whole blood serotonin correlated inversely with avoid and be solitary. These data are compatible with previously reported observations on the behavioral consequences of manipulating serotonergic systems in vervet monkeys and suggest that in normal, drug naive monkeys, free and total tryptophan are better correlates of the central serotonergic activity influencing behavior than is whole blood serotonin.

Effects of chronic fenfluramine on blood serotonin, cerebrospinal fluid metabolites, and behavior in monkeys.

The effects of long term (70 days) fenfluramine treatment on selected physiological and behavioral measures were examined in four adult male vervet monkeys (Cercopithecus aethiops sabaeus). Relative to pretreatment baseline values, whole blood serotonin (WBS) and cerebrospinal fluid 5-hydroxyindole acetic acid (5-HIAA) were reduced, cerebrospinal fluid homovanillic acid (HVA) was unaltered, and aggressive and locomotor behavior were increased. Both physiological and behavioral effects were reversible: all measures returned to baseline values in the 35 day post-treatment period, with WBS resuming pretreatment values more rapidly than CSF 5-HIAA. At the relatively low doses (1-4 mg/kg/day) employed in the present study fenfluramine produced behavioral effects similar to those resulting from PCPA and opposite to those following tryptophan administration. Thus the behavioral effects of long-term fenfluramine may involve reductions in serotonergic transmission.

Whole-blood serotonin in premenstrual syndrome.

Whole-blood serotonin levels in 14 subjects with well documented premenstrual syndrome and 13 age-matched controls were compared. Serotonin levels of premenstrual syndrome subjects were significantly lower during the last ten days of the menstrual cycle. No significant differences were noted in levels of serum estradiol and progesterone. Decreased serotonin is known to be associated with depression in humans, and nonhuman primates have exhibited abnormal behavioral profiles when given serotonin antagonists. The present observation suggests that the physiologic basis of premenstrual syndrome involves an alteration in serotonin metabolism.

Dominant social status facilitates the behavioral effects of serotonergic agonists.

The effects of dominance rank on the behavioral responses to drugs that enhance central serotonergic function were examined in 45 adult male vervet monkeys living in 15 stable social groups. Each group contained 3 adult males, 3 adult females, and their immature offspring. Dominance rank was assessed by measuring success in intermale agonistic encounters. In every group one male was clearly the dominant, or alpha male, and the other two males were subordinate. Males from 5 groups received 3 doses of the serotonin reuptake inhibitor fluoxetine (0.5, 1.0 and 2.0 mg/kg/day); those from a second set of 5 groups received 3 doses of the receptor agonist quipazine (0.25, 0.50 and 1.0 mg/kg/day); those from a third set of 5 groups received the serotonin precursor tryptophan (10, 20 and 40 mg/kg/day). The 3 drug treatments produced strikingly similar behavioral effects. Each produced dose-dependent increases in approaching, grooming, resting and eating and decreases in locomoting, avoiding, being vigilant and being solitary. Dominant males were significantly more responsive behaviorally to all 3 drugs than were subordinate males: the increase or decrease in each behavioral measure was larger in dominant than in subordinate males. In combination with previous studies, these data suggest that dominant and subordinate males differ in the drug sensitivity of their serotonergic systems.

Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys.

In a counter-balanced, cross-over study, we examined the contributions of serotonergic systems to the acquisition of social dominance in adult male vervet monkeys. Subjects were members of 12 social groups, each containing 3 adult males, at least 3 adult females, and their offspring. Animals were observed in 5 intervals including a first baseline, a first experimental, a second baseline, a second experimental, and a third baseline period. At the end of the first baseline period, the dominant male was removed from each group. In each group, one of the two remaining subordinate males was selected at random for treatment and during the first experimental period, 6 of the 12 treated males received drugs that enhanced serotonergic activity (3 were given tryptophan 40 mg/kg/day and 3 fluoxetine 2 mg/kg/day). The other 6 treated males received drugs that reduced serotonergic function (3 were given fenfluramine 2 mg/kg/day and 3 cyproheptadine 60 micrograms/kg/day). At the end of the first experimental period, the original dominant male was returned to his group and the second baseline period began. In all instances, the originally dominant male regained his dominant position. The second experimental period began with the dominant male again being removed and, the 12 treated males were given the treatment they had not received in the first experimental period. At the start of the third 12-week baseline period, the original dominant male was returned to his group and resumed his dominant status. When the 12 treated subjects received tryptophan or fluoxetine, they became dominant in all instances. When they received fenfluramine or cyproheptadine, their vehicle-treated cage mates became dominant. The sequence of the behavioral changes shown by the treated males as they acquired dominance status paralleled those seen in naturalistic conditions. These observations support the distinction between dominance and aggression and strongly suggest that when hierarchical relationships are uncertain, serotonergic mechanisms may mediate the behaviors which permit a male to attain high dominance status.

Psychological symptoms in individuals successful at long-term maintenance of weight loss.

Set point theory suggests that successful maintenance of weight loss ("weight suppression") may be associated with psychological distress. This study examined the association between psychological symptoms and body weight suppression by using a registry of 629 women and 155 men who lost at least 13.6 kg (mean loss = 30 +/- 15 kg) and maintained the loss for at least 1 year (mean duration = 5.5 +/- 6.8 years). Participants completed measures of mood, distress, restraint, disinhibition, bingeing, and purging. Maintainers' levels of distress and depression were lower than those of psychiatric samples and resembled those of community-based samples. Binge-eating and purging rates were comparable to rates of community samples. Maintainers' levels of restraint and disinhibition were markedly different from those of eating-disordered samples, resembling levels found in patients recently treated for obesity. There was no evidence that long-term suppression of body weight is associated with psychological distress.

What predicts weight regain in a group of successful weight losers? .

This study identified predictors of weight gain versus continued maintenance among individuals already successful at long-term weight loss. Weight, behavior, and psychological information was collected on entry into the study and 1 year later. Thirty-five percent gained weight over the year of follow-up, and 59% maintained their weight losses. Risk factors for weight regain included more recent weight losses (less than 2 years vs. 2 years or more), larger weight losses (greater than 30% of maximum weight vs. less than 30%), and higher levels of depression, dietary disinhibition, and binge eating levels at entry into the registry. Over the year of follow-up, gainers reported greater decreases in energy expenditure and greater increases in percentage of calories from fat. Gainers also reported greater decreases in restraint and increases in hunger, dietary disinhibition, and binge eating. This study suggests that several years of successful weight maintenance increase the probability of future weight maintenance and that weight regain is due at least in part to failure to maintain behavior changes.

Interventions for weight loss and weight gain prevention among youth: current issues.

The recent increase in the prevalence of paediatric obesity is one of the most pressing public health concerns today because of the immediate and long term health consequences associated with this often intractable disease. Efforts are currently being made to reduce the prevalence of paediatric obesity. Youth weight loss studies have produced significant long term results. Most of these programmes included behaviour modification, diet and exercise. Studies have suggested that lifestyle exercise programmes may produce the best long term results. Effective components of these programmes appear to be parental involvement, reduced intake of foods having high energy density and reductions in physical inactivity. Future weight loss studies need to determine the type, intensity, and duration of exercise that will produce acceptable adherence and consequent long term weight loss, and to ascertain the reinforcing factors that determine youth behaviour choice. Weight gain prevention interventions for youth are clearly in their infancy. This review describes 3 completed and 2 ongoing weight gain prevention trials. One study showed reductions in the prevalence of obesity among junior high school girls, but not among boys. Another study among elementary school students showed significant mean decreases in body mass index in boys and girls following an intervention specifically to reduce time spent viewing television. Whether these studies altered food intake or increased physical activity remains unclear. A combination of weight loss treatment and weight gain prevention strategies employed in parallel is likely to yield the greatest benefits. Development and testing of novel intervention strategies, using innovative behavioural approaches to increase the likelihood that children will adopt healthy dietary, physical activity, and sedentary behaviour patterns, holds great promise to significantly reduce the epidemic of obesity.

Vervet monkey (Cercopithecus aethiops sabaeus) whole blood serotonin level is determined by platelet uptake sites.

Whole blood serotonin levels in adult male vervet monkeys living in social groups are sensitive to the animals' social environment. The mechanisms that translate different behavioral and environmental cues into altered whole blood serotonin levels are unknown. In this study, we have measured platelet number, size, serotonin content, and serotonin uptake, as well as the serum concentrations of tryptophan, Mg+2 and Ca+2. Results showed that whole blood serotonin levels, platelet serotonin content, and the serotonin uptake parameter Vmax were stable within animals on repeated sampling. The whole blood serotonin level was highly positively associated with platelet serotonin content, and the platelet serotonin content was highly positively associated with Vmax. These findings suggested that whole blood serotonin levels were a function of the number of platelet uptake sites.

Plasma catecholamines and social behavior in male vervet monkeys (Cercopithecus aethiops sabaeus).

Many investigations in humans indicate that epinephrine, norepinephrine and their ratio may correlate with such traits as social competence, academic achievement, and aggression. However, the socioeconomic, dietary, and environmental confounds accompanying most human studies complicate their interpretation. Social status, aggression, and other social behaviors can be reliably assessed in nonhuman primates under conditions controlling for crucial environmental factors. If interpretation of human studies is correct, dominant and subordinate male vervet monkeys should exhibit distinctive patterns of catecholamine secretion. To test this possibility, seventeen adult male monkeys living in six stable social groups were observed for 6 months. Based on their success in agonistic events, subjects were categorized as dominant or subordinate. Alpha scores were calculated from empirically derived factors to provide a noncategorical measure of dominant behavioral style. Plasma epinephrine and norepinephrine samples obtained from anesthetized subjects did not differ between dominant and subordinate males. Alpha scores, however, distinguished high from low norepinephrine/epinephrine ratio groups. These findings are consistent with studies in humans linking high epinephrine, low norepinephrine, and social competence.

Persons successful at long-term weight loss and maintenance continue to consume a low-energy, low-fat diet.

OBJECTIVES: To describe the dietary intakes of persons who successfully maintained weight loss and to determine if differences exist between those who lost weight on their own vs those who received assistance with weight loss (eg, participated in a commercial or self-help program or were seen individually by a dietitian). Intakes of selected nutrients were also compared with data from the third National Health and Nutrition Examination Survey (NHANES III) and the 1989 Recommended Dietary Allowances (RDAs). SUBJECTS: Subjects were 355 women and 83 men, aged 18 years or older, primarily white, who had maintained a weight loss of at least 13.6 kg for at least 1 year, and were the initial enrollees in the ongoing National Weight Control Registry. On average, the participants had lost 30 kg and maintained the weight loss for 5.1 years. METHODS: A cross-sectional study in which subjects in the registry completed demographic and weight history questionnaires as well as the Health Habits and History Questionnaire developed by Block et al. Subjects' dietary intake data were compared with that of similarly aged men and women in the NHANES III cohort and to the RDAs. Adequacy of the diet was assessed by comparing the intake of selected nutrients (iron; calcium; and vitamins C, A, and E) in subjects who lost weight on their own or with assistance. RESULTS: Successful maintainers of weight loss reported continued consumption of a low-energy and low-fat diet. Women in the registry reported eating an average of 1,306 kcal/day (24.3% of energy from fat); men reported consuming 1,685 kcal (23.5% of energy from fat). Subjects in the registry reported consuming less energy and a lower percentage of energy from fat than NHANES III subjects did. Subjects who lost weight on their own did not differ from those who lost weight with assistance in regards to energy intake, percent of energy from fat, or intake of selected nutrients (iron; calcium; and vitamins C, A, and E). In addition, subjects who lost weight on their own and those who lost weight with assistance met the RDAs for calcium and vitamins C, A, and E for persons aged 25 years or older. APPLICATIONS: Because continued consumption of a low-fat, low-energy diet may be necessary for long-term weight control, persons who have successfully lost weight should be encouraged to maintain such a diet.

Ethological assessment of stable and labile social behaviors during acute psychiatric disorders: clinical applications.

Results are presented which illustrate the use of naturalistic observation techniques to study ongoing patterns of postural, gestural, and spacing behaviors among psychiatric patients hospitalized for acute psychiatric disorders. Behavioral frequencies are analyzed in terms of stable and labile characteristics by week of hospitalization, clinical diagnosis, and clinical outcome. Findings are interpreted from both clinical psychiatric and ethological perspectives. The discussion emphasizes the potential value of observational data gathering techniques for disorder assessment and theory development.

Similarity of 5-HT2 receptor sites in dominant and subordinate vervet monkeys.

Pharmacological studies using serotonergic agents have revealed status-linked behavioral effects in dominant and subordinate vervet monkeys. A possible explanation for the greater drug response observed in dominant animals is that there is a CNS difference between dominant and subordinate animals. Such differences could exist at the level of serotonin receptor sites, membrane responsiveness, or interaction with other neurotransmitters. We have examined the specific 3H-ketanserin binding in various regions of vervet monkey brain to evaluate the hypothesis that dominant and subordinate vervet monkeys differ in CNS 5-HT2 receptor sites. No differences were found in the number or affinity of 3H-ketanserin binding sites between dominant and subordinate animals. Further, no differences were found in the displacement of 3H-ketanserin binding by the serotonin agonist quipazine. These results suggest the conclusion that differences at 5-HT2 binding sites do not account for status-linked differences in behavioral drug response in vervet monkeys and that other or additional mechanisms must underlie status-related drug response differences.