Psychobiology Of Antisocial Behavior And Health

反社会行为与健康的心理生物学

• 批准号: 6682074
• 负责人: James Dee Higley
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6682074
• 关键词: Macaca mulatta; aggression; alcoholic beverage consumption; alcoholism /alcohol abuse; animal developmental psychology; antisocial personality; behavior test; behavioral /social science research tag; behavioral genetics; cerebrospinal fluid; circadian rhythms; ethology; gender difference; genotype; hydroxyindoleacetate; impulsive behavior; longitudinal human study; psychobiology; social behavior disorders; social dominance; socioenvironment; species difference; telemetry

I. Longitudinal Studies of Type 2 Personality In Nonhuman Primates: Follow-up of Middle-Aged Males As an investigation of Type 2 personality in nonhuman primates, beginning in 1989, we initiated a study of 104 rhesus juvenile males with varying CSF 5-HIAA concentrations. Our first samples were taken when the subjects were yearlings, still living with their mothers. The subjects have all since migrated from their natal family troop and had varied life histories. Ten years later, in the first study to longitudinally follow male rhesus from childhood through the middle-aged period of life, interesting data have emerged suggesting that the varying life history behavior patterns of individual males are consistent across time and are predicted by differences in CNS monoamine functioning early in life. 1. Continued longitudinal analyses of these males with low monoamine turnover strongly suggest that violent behavior is a life-long pattern, with both low CSF 5-HIAA concentrations, and high levels of aggression early in life predicting violent behavior in these males ten years later, as middle aged adults. 2. While our previous studies have found correlations with serotonin, for the first time our analyses show that independent of the behavior correlations with serotonin, dopamine is also correlated with the behaviors seen in these males. Both HVA and 5-HIAA were correlated with social dominance rank, with high ranking males exhibiting both low CSF HVA and 5-HIAA concentrations. 3. Males leave their natal family troop, generally sometime late in adolescence or early adulthood. When the subject population was subdivided into early migrators (during adolescence prior to maturity) and late migrators (fully mature adults), in the late migrators, there was a negative correlation between CSF HVA and age showing that males with low CSF HVA levels migrated at an earlier age than the adult males who had high CSF HVA. This was interpreted as possibly being mediated by dopamine-mediated sensation seeking, with males high in sensation seeking being more motivated to migrate during the mating season. 4. As the animals age, more have died. With an increased sample size, it remains clear that the male monkeys with low CSF 5-HIAA concentrations die at earlier ages than the monkeys with high CSF 5-HIAA concentrations. II. Studies of Females with Low CSF 5-HIAA concentrations in Feral Environments Unlike males, who live much of their lives independent of family relationships females live in closely bonded, extended families. To assess the phenotype in females, four years ago, we began to gather a sample of young female macaques with varying levels of CSF 5-HIAA. As with males, the females possessing diminished CSF 5-HIAA concentrations engaged in impulsive risk-taking as determined by an analysis of spontaneous arboreal leaping from dangerous heights. The percent of leaps that traversed long distances at dangerous heights were negatively correlated with CSF 5-HIAA. Females with low CSF 5-HIAA concentrations also engaged in high rates of aggression, however, unlike males, they did not engage in higher rates of escalated aggression, instead it was only the low level types of aggression associated with defense of status than do their high CSF 5-HIAA counterparts. CSF HVA concentrations were also found to be significantly negatively correlated with less severe types of aggression and the rate of long, dangerous leaps. CSF MHPG concentrations were associated only with the rate of leaps, and showed no significant correlation with the frequency of aggression. In addition, plasma cortisol concentrations were significantly negatively correlated with low levels of aggression. For the male population, rates of death were high and consorting and inseminating female was low in the males with low CSF 5-HIAA concentrations, which presents a paradox: if differential survival and low reproductive rates are present in males with low CSF 5-HIAA concentrations, what maintains the phenotype in the gene pool? One possibility is that the there is differential survival and reproductive rates in the females. In breeding groups within the laboratory, rates of successful pregnancies and maternal behaviors were assessed in females who were breeding for the first time. Females who failed to give birth during this first year had lower CSF 5-HIAA concentrations when compared with their counterparts who gave birth. Among those females who produced offspring, females with low CSF 5-HIAA concentrations were overly protective and restrictive with their infants. Perhaps as a result, infants born to mothers with low CSF 5-HIAA concentrations spent more time in immature clinging when compared to infants born to mothers with high CSF 5-HIAA concentrations. Independent of serotonin effects, those females with high plasma cortisol levels at the start of the study were more often targets of aggressive bouts, and infants of these females spent more time clinging to their mothers than did those of mothers with low plasma cortisol concentrations. Independent of these findings, females with low plasma cortisol concentrations exhibited high rates of aggression. In a collaboration with Drs. Suomi and DeVinney in NICHD, some of these findings were tested in an ongoing study of rhesus monkey mother-offspring pairs living in the species-normative social group maintained in the NICHD's 5-acre field enclosure in Poolesville. CSF samples were collected from mothers when their infants were 3-5 months of age and assayed for 5-HIAA and HVA (a major central dopamine metabolite); the resulting values were then compared with different aspects of maternal behavior recorded when their infants were 1-3, 4-6, and 7-9 months old, respectively. Consistent with our data from the free-ranging monkeys, measures of maternal protectiveness and infant restraint during the latter two time periods, a time when mothers are actively negotiating weaning, were negatively correlated with mothers' 5-HIAA and HVA concentrations, suggesting more difficulties in the mother-infant relationship during stressful periods, such as weaning in mothers with low CNS serotonin functioning. In contrast, measures of two forms of active infant rejection were positively correlated with concentrations of both monoamine metabolites during the latter two time periods, whereas the rate of passive rejections was not significantly related to concentrations of either metabolites during any time period. III. Impaired CNS Hemispheric Specialization A number of studies have shown that alcoholics and alcohol abusers are more likely to show abnormalities of laterality. In the rhesus there is a bias to left-handedness, with subjects showing interindividual differences in their strength of that preference. In our original study reported last year, we found that in adult subjects that live in the laboratory setting, those not showing this typical left bias were more likely as juveniles and adolescents to exhibit low CSF 5-HIAA concentrations and high cortisol, a pattern similar to that found in some human alcoholics. During the past year, these biochemical findings were replicated in our free-ranging population. In addition, males that showed the atypical bias, were more likely to be loners, spending more time alone and seldom receiving grooming from other animals. When challenged, they were more likely to exhibit submissive behavior, and to receive aggression. In what is to our knowledge the first assessment of the relationship between handedness and psychobiology in free-ranging female macaques, we found that the females who exhibit the atypical right bias were more likely to exhibit low CSF 5-HIAA and plasma cortisol concentrations. Behaviorally, they were more likely to act submissively and to receive aggression, particularly low intensity forms of aggression.

I. 非人类灵长类动物 2 型人格的纵向研究：中年男性的随访 作为对非人类灵长类动物 2 型人格的研究，我们从 1989 年开始对 104 只具有不同 CSF 5-HIAA 浓度的幼年雄性恒河猴进行了研究。我们的第一个样本是在受试者一岁的时候采集的，当时他们仍然和母亲住在一起。这些受试者都从出生家庭迁徙过来，并有着不同的生活史。十年后，在第一项纵向追踪雄性恒河猴从童年到中年的研究中，出现了有趣的数据，表明雄性恒河猴个体不同的生活史行为模式在不同时间段内是一致的，并且是通过中枢神经系统的差异来预测的。单胺在生命早期发挥作用。 1. 对这些单胺周转率低的男性的持续纵向分析强烈表明，暴力行为是一种终生模式，脑脊液 5-HIAA 浓度低，并且生命早期的攻击性高，预示着这些男性十年后的暴力行为，作为中年人。 2. 虽然我们之前的研究发现了与血清素的相关性，但我们的分析首次表明，独立于与血清素的行为相关性，多巴胺也与这些男性的行为相关。 HVA 和 5-HIAA 均与社会支配地位相关，地位较高的男性脑脊液 HVA 和 5-HIAA 浓度均较低。 3. 男性通常在青春期末或成年初期离开原生家庭。当将受试者群体细分为早期迁徙者（成熟前的青春期）和晚期迁徙者（完全成熟的成年人）时，在晚期迁徙者中，CSF HVA 与年龄之间存在负相关性，表明 CSF HVA 水平较低的男性迁徙时间为比具有高 CSF HVA 的成年男性年龄更早。这被解释为可能是由多巴胺介导的感觉寻求介导的，感觉寻求高的雄性在交配季节更有动力迁徙。 4. 随着动物年龄的增长，更多的动物死亡。随着样本量的增加，很明显，CSF 5-HIAA 浓度低的雄性猴子比 CSF 5-HIAA 浓度高的雄性猴子死亡年龄更早。 二.对野生环境中脑脊液 5-HIAA 浓度低的雌性的研究 男性大部分时间独立于家庭关系而生活，而女性则不同，女性生活在关系密切的大家庭中。为了评估雌性猕猴的表型，四年前，我们开始收集具有不同水平 CSF 5-HIAA 的年轻雌性猕猴样本。 与雄性一样，通过对从危险高度自发树上跳跃的分析确定，CSF 5-HIAA 浓度降低的雌性会进行冲动的冒险行为。在危险高度进行长距离跳跃的百分比与 CSF 5-HIAA 呈负相关。 CSF 5-HIAA 浓度低的女性也有较高的攻击性，然而，与男性不同的是，她们的攻击性并没有更高，而只是与捍卫地位相关的低水平攻击类型。高 CSF 5-HIAA 对应物。 还发现脑脊液 HVA 浓度与不太严重的攻击类型以及长而危险的跳跃率呈显着负相关。脑脊液 MHPG 浓度仅与跳跃率相关，与攻击频率没有显着相关性。此外，血浆皮质醇浓度与低水平的攻击性呈显着负相关。 对于男性群体，CSF 5-HIAA 浓度低的男性死亡率高，雌性交配和授精率低，这呈现出一个悖论：如果 CSF 5-HIAA 浓度低的男性中存在差异存活率和低繁殖率浓度，是什么维持了基因库中的表型？一种可能性是雌性的存活率和繁殖率存在差异。在实验室的繁殖组中，对首次繁殖的雌性的成功怀孕率和母性行为进行了评估。与生育过的女性相比，第一年未能生育的女性脑脊液 5-HIAA 浓度较低。在那些生育后代的雌性中，脑脊液 5-HIAA 浓度较低的雌性对其婴儿过度保护和限制。也许因此，与 CSF 5-HIAA 浓度高的母亲所生的婴儿相比，CSF 5-HIAA 浓度低的母亲所生的婴儿在不成熟依恋上花费了更多的时间。与血清素的影响无关，那些在研究开始时血浆皮质醇水平较高的女性更容易成为攻击性攻击的目标，而且这些女性的婴儿比血浆皮质醇浓度低的母亲的婴儿花费更多的时间粘在母亲身上。与这些发现无关，血浆皮质醇浓度较低的女性表现出较高的攻击性。 与博士合作。 NICHD 的 Suomi 和 DeVinney 正在对恒河猴母子进行一项研究，该研究对生活在 NICHD 位于普尔斯维尔 5 英亩场地内的物种规范社会群体中的恒河猴母子进行了测试。当婴儿 3-5 个月大时，从母亲那里采集脑脊液样本，并检测 5-HIAA 和 HVA（一种主要的中枢多巴胺代谢物）；然后将所得值分别与婴儿 1-3、4-6 和 7-9 个月大时记录的母亲行为的不同方面进行比较。与我们来自自由放养猴子的数据一致，后两个时期（母亲积极协商断奶的时期）的母亲保护性和婴儿约束措施与母亲的 5-HIAA 和 HVA 浓度呈负相关，这表明存在更多困难压力时期的母婴关系，例如中枢神经系统血清素功能低下的母亲断奶时。相比之下，两种形式的主动婴儿排斥反应的测量结果与后两个时间段内两种单胺代谢物的浓度呈正相关，而被动排斥率与任何时间段内任一代谢物的浓度均不显着相关。 三．中枢神经系统半球特化受损 许多研究表明，酗酒者和酗酒者更有可能表现出偏侧性异常。恒河猴有左撇子倾向，受试者的这种偏好强度存在个体差异。在我们去年报告的原始研究中，我们发现，在生活在实验室环境中的成年受试者中，那些没有表现出这种典型左偏的青少年更有可能表现出低 CSF 5-HIAA 浓度和高皮质醇，这种模式类似于与一些人类酗酒者身上发现的情况类似。在过去的一年里，这些生化发现在我们的自由放养种群中得到了复制。此外，表现出非典型偏见的雄性更有可能是独来独往的人，花更多的时间独处，很少接受其他动物的梳理。当受到挑战时，他们更有可能表现出顺从的行为，并受到攻击。 据我们所知，对自由放养的雌性猕猴中利手习惯和心理生物学之间关系的首次评估发现，表现出非典型右偏的雌性更有可能表现出较低的 CSF 5-HIAA 和血浆皮质醇浓度。在行为上，他们更有可能表现得顺从并受到攻击，尤其是低强度的攻击。