From gene to aggressive behavior: The role of brain serotonin

This article addresses a question at the juncture of neurophysiology and neurogenetics - the role of the brain neurotransmitter serotonin in the genetic control of behavior. Published data are presented, along with results obtained from studies performed at the Behavioral Neurogenomics Laboratory. The role of protein elements of the brain serotonin system (key enzymes in serotonin metabolism and serotonin 5-HT(1A) receptors), which are subject to the direct influence of genes, in the genetic predisposition to aggressive behavior is discussed. Experimental results obtained in Norwegian rats selected over more than 50 generations for the absence of aggressivity and for high aggressivity to humans are presented, along with data from experiments on mouse lines and mice with genetic knockout of MAO A. These data provide evidence that 1) brain serotonin makes a significant contribution to the mechanisms underlying genetically determined individual differences in aggressivity, and 2) the genes encoding the main enzymes of serotonin metabolism in the brain (tryptophan hydroxylase-1 and MAO A) and the 5-HT(1A) receptor are members of a set of genes modulating aggressive behavior.     

Lateralities in normal children ages 3 to 8 and their role in cognitive performances

The presence and type of correlations between laterality and cognitive skills in normal adults or children remains controversial. This study examines relations between different lateralities, that is, handedness, footedness, eyedness, parental left-handedness, asymmetry of hand skill on a computerized version of the Peg-Moving Task (CPMT) proposed by Annett (1985), and different verbal and nonverbal skills assessed by 13 tasks in 254 normal children, aged 3 to 8 years. Results showed increasing performances with increasing dextrality on the CPMT for 2 tasks involving phonology (Phonological Fluency and Reading Nonwords), 2 tasks involving visual memory and visuospatial skills, and for finger localization. Footedness, eyedness, and parental left-handedness had no significant effect on cognitive performance. The pattern of performance according to the sinistrality-dextrality continuum was highly variable from one cognitive task to the other. The previously mentioned results suggest that relative hand skill is a better correlative of cognitive performance than the usual measures of handedness. Further study is needed to specify the pattern of associations.     

The development of naming and word fluency: evidence from Hebrew-speaking children between ages 8 and 17

Naming and word fluency tests are commonly used in neuropsychological evaluations of both children and adults. The current work examines at which age performance on these tests reaches adult level. One hundred fifty children, 30 in each of 5 age groups (8-9, 10-11, 12-13, 14-15, 16-17), and 30 adults ages 18 to 29, participated in the study. Participants completed a Hebrew naming test, a three-letter phonemic fluency task, and a three-category semantic fluency task (animals, fruits and vegetables, and vehicles). Results show that all measures increase steadily from age 8 to age 17. No difference between the 16- to 17-year-old adolescents and the adults was found on the naming test and on the phonemic fluency task, but such a difference was documented for semantic fluency. The relative contribution of the maturation of vocabulary and the development of efficient retrieval processes to performance on naming and fluency tasks is discussed.     

Menopause and sarcopenia: A potential role for sex hormones

Menopause is associated with a decline in estrogen levels, which could lead to an increase in visceral adiposity as well as a decrease in bone density, muscle mass and muscle strength. This decline in muscle mass, known as sarcopenia, is frequently observed in postmenopausal women. Potential causes of sarcopenia include age-related changes in the hormonal status, low levels of physical activity, reduced protein intake and increased oxidative stress. However, the role of sex hormones, specifically estrogens, on the onset of sarcopenia is controversial. Preventing sarcopenia and preserving muscle strength are highly relevant in order to prevent functional impairment and physical disability. To date, resistance training has been shown to be effective in attenuating age-related muscle loss and strength. However, results on the effect of hormonal supplementation to treat or prevent sarcopenia are contradictory. Further research is needed to identify other potential mechanisms of sarcopenia as well as effective interventions for the prevention and treatment of sarcopenia. Therefore, the purpose of this review will be to examine the role of sex hormonal status in the development of sarcopenia. We will also overview the physical as well as metabolic consequences of sarcopenia and the efficiency of different interventions for the prevention and treatment of sarcopenia.     

Autoimmune heart disease: role of sex hormones and autoantibodies in disease pathogenesis

Cardiovascular disease (CVD) and autoimmune diseases (ADs) are the first and third highest causes of death in the USA, respectively. Men have an increased incidence of the majority of CVDs, including atherosclerosis, myocarditis, dilated cardiomyopathy and heart failure. By contrast, nearly 80% of all ADs occur in women. However, in one category of ADs, rheumatic diseases, CVD is the main cause of death. Factors that link rheumatic ADs to CVD are inflammation and the presence of autoantibodies. In this review we will examine recent findings regarding sex differences in the immunopathogenesis of CVD and ADs, explore possible reasons for the increased occurrence of CVD within rheumatic ADs and discuss whether autoantibodies, including rheumatoid factor, could be involved in disease pathogenesis.     

Developmental trajectories of externalizing and internalizing behaviors: factors underlying resilience in physically abused children

Using a multisite community sample of 585 children, this study examined how protective and vulnerability factors alter trajectories of teacher-reported externalizing and internalizing behavior from kindergarten through Grade 8 for children who were and were not physically abused during the first 5 years of life. Early lifetime history of physical abuse (11.8% of sample) was determined through interviews with mothers during the prekindergarten period; mothers and children provided data on vulnerability and protective factors. Regardless of whether the child was abused, being African American; being male; having low early social competence, low early socioeconomic status (SES), and low adolescent SES; and experiencing adolescent harsh discipline, low monitoring, and low parental knowledge were related to higher levels of externalizing problems over time. Having low early social competence, low early SES, low adolescent SES, and low proactive parenting were related to higher levels of internalizing problems over time. Furthermore, resilience effects, defined as significant interaction effects, were found for unilateral parental decision making (lower levels are protective of externalizing outcomes for abused children), early stress (lower levels are protective of internalizing outcomes for abused children), adolescent stress (lower levels are protective of internalizing outcomes for abused children), and hostile attributions (higher levels are protective of internalizing outcomes for abused children). The findings provide a great deal of support for an additive or main effect perspective on vulnerability and protective factors and some support for an interactive perspective. It appears that some protective and vulnerability factors do not have stronger effects for physically abused children, but instead are equally beneficial or harmful to children regardless of their abuse status.     

Autoimmune heart disease: role of sex hormones and autoantibodies in disease pathogenesis

Cardiovascular disease (CVD) and autoimmune diseases (ADs) are the first and third highest causes of death in the USA, respectively. Men have an increased incidence of the majority of CVDs, including atherosclerosis, myocarditis, dilated cardiomyopathy and heart failure. By contrast, nearly 80% of all ADs occur in women. However, in one category of ADs, rheumatic diseases, CVD is the main cause of death. Factors that link rheumatic ADs to CVD are inflammation and the presence of autoantibodies. In this review we will examine recent findings regarding sex differences in the immunopathogenesis of CVD and ADs, explore possible reasons for the increased occurrence of CVD within rheumatic ADs and discuss whether autoantibodies, including rheumatoid factor, could be involved in disease pathogenesis.     

Developmental and activational effects of sex hormones on the attractiveness of dog urine

Adult male dogs were exposed to urine from five types of experimental donors: females ovariohysterectomized as adults (FOA), females treated with testosterone in utero (FTU), females treated with testosterone in early infancy (FTI), females treated with testosterone in utero and in early infancy (FTUI), males castrated as adults (MCA); and also to control urine from intact stud males (SM). Urine was collected from the five experimental groups of donors during three phases of the experiment: (a) during a period of no hormone treatment (NH); (b) following treatment with estradiol (E); and (c) following treatment with testosterone (T). Intact males were given no hormonal treatment and served as subjects and urine donors. Subjects spent about the same amounts of time investigating control SM urine in all three phases. In the NH phase, the investigation times for the five experimental samples were significantly greater than that of the SM sample. However, there were no significant differences between the investigation times of the five samples. During the E phase, in comparison with the NH phase, the investigation times were greater for all experimental samples. The increase in attractiveness was significant for FOA and FTU urine. During the T phase, compared with the NH phase, the investigation times were less for four experimental samples (FTU, FTI, FTUI and MCA urine), and FTI, FTUI and MCA urine were no longer preferred to the SM control. However, the decrease in attractiveness was significant for MCA urine only.     

The role of female sex hormones in the development and severity of allergic and non-allergic asthma

Allergic asthma is usually diagnosed by the presence of variable airway obstruction, bronchial hyperresponsiveness, and allergy. However, a significant proportion of adult asthma patients (up to 40%) are non-allergic. Patients with non-allergic asthma often have a later disease onset and greater disease severity, as reflected by more severe airway obstruction and bronchial hyperresponsiveness. Furthermore, females have a higher risk of developing non-allergic asthma. The latter suggests that hormone-related events play an important role in the development and severity of adult-onset non-allergic asthma. This paper describes the associations between asthma and hormonal changes throughout the female life-span, such as those associated with the monthly cycle of menstruation and menopausal hormonal changes.     

Maternal behavior in cyclic and androgenized female rats: role of ovarian hormones

A comparative study on the induction of maternal behavior (MB) in response to pups was carried out in cyclic and androgenized rats. Moreover, the effects of exposure to ovarian hormones on the induction of MB in response to pups were studied in cyclic and androgenized rats. A high percentage of androgenized and proestrus rats displayed MB after 48 hr of exposure to pups (87.9% and 87.5% respectively). Diestrus day-1 rats were significantly less maternal (37.5%). Ovariectomy did not impair MB in androgenized rats. High serum progesterone levels induced in androgenized rats by treatment with 10 I.U. of HCG (40 hours before pup presentation) or with progesterone silastic implants prevented the onset of MB. Ovariectomy performed 8 hours before HCG administration restored MB. When behavioral testing began 72 hours after HCG treatment, 75% of the rats were maternal 12 hr after exposure to pups. This rapid onset of MB in proestrus and androgenized rats appeared to be estrogen dependent. The presence of progesterone inhibited the maternal response of androgenized rats.     

Sex differences in open-field behavior in the rat: The inductive and activational role of gonadal hormones

Male rats are generally found to be significantly less active and to defecate more than female rats in the open-field test. In developmental studies, these differences were shown to emerge in the peripuberal period at 50–60 days of age. After gonadectomy in adult life, the sex difference in open-field activity was reduced in magnitude but did persist indicating that it was not solely dependent on the presence of gonadal secretions in either sex. In contrast, the sex difference in open-field defecation did not reach statistical significance after gonadectomy with ovariectomized females exhibiting increased defecation frequency. Estrogen-progesterone replacement stimulated activity and decreased defecation scores to pre-gonadectomy levels in females but lacked effect in males. Administration of testosterone propionate (TP) to female rats in neonatal life produced developmental changes in open-field behavior similar to those seen in the male. In addition, the response of TP treated females to gonadectomy and hormone replacement was similar to that found for the male. These results suggest that the presence of testosterone in neonatal life plays a role in the masculinisation of open-field behavior and that its effect is partly mediated by the presence of cyclic ovarian secretions in the adult female rat and their absence in the male and TP treated female.     

Developmental trajectories of cigarette smoking and their correlates from early adolescence to young adulthood

Smoking initiation typically occurs in adolescence and increases over time into emerging adulthood. Thus adolescence and emerging adulthood compose a critical time period for prevention and intervention efforts. To inform these efforts, this study used latent growth mixture modeling to identify 6 smoking trajectories from ages 13 to 23 among 5,914 individuals: nonsmokers (28%), stable highs (6%), early increasers (10%), late increasers (10%), decreasers (6%), and triers (40%). By age 23, the trajectories merged into 2 distinct groups of low- and high-frequency and their standing on age 23 outcomes reflected this grouping. Consideration of these results can help researchers identify at-risk individuals before their smoking becomes too problematic, providing an opportunity for intervention and possible prevention of nicotine dependence.     

Heart rate and skin conductance in four-year-old children with aggressive behavior

Autonomic underarousal, indicated by low heart rate (HR) and skin conductance level (SCL), is related to childhood aggression. However, results are inconsistent in preschoolers. We assessed HR, SCL, heart rate reactivity and skin conductance reactivity in four-year-old children. Comparisons were made between children with a high level and with a low level of aggressive behavior according to the Child Behavior Checklist 1½–5 as well as between children who were diagnosed with Oppositional Defiant Disorder or Conduct Disorder (ODD/CD) and children with a low level of aggression. Preschool children with a high level of aggressive behavior showed lower SCL and SCR and children with ODD/CD showed lower SCL. In contrast, we did not find lower HR and HRR in preschool children with a high level of aggressive behavior or ODD/CD. Thus, results suggest that decreased SCL, but not HR, is a characteristic of preschool children with aggressive behavior or ODD/CD.     

Developmental progression and side specialization in upper-limb movements from 4 to 8 years in children born preterm and fullterm

This study investigated developmental changes and differences in upper-limb movement organization from 4 to 8 years of age in children born preterm (PT) and fullterm (FT). Kinematic recordings of precision-demanding unimanual movements and lateral assessments were carried out in 37 children (18 PT). All children, particularly children born PT, displayed considerable gain in movement kinematics. Contrary to controls, children born PT displayed persistently less-evident side preference. Gestational age (GA) contributed significantly to kinematic differences shown, with larger upper-limb deviances in the lowest GAs, in agreement with cross-sectional findings of altered hemispheric connections and delayed side-specialization among children born very PT.     

Developmental effects of neonatal sex hormones on spatial and activity skills in the white rat.

The purpose of this experiment is to extend these experiments by using varying neonatal hormonal differentiation processes and to examine the effects of these different methods of neonatal feminization on changes in spatial and activity skills. The experiment involved three neonatally feminized groups of male rats: 'castration alone', 'estrogen alone', and 'estrogen injected castrates' together with one female sample, 'testosterone injected castrates', while treated and untreated male and female controls were also used. The data provide partial support for the major hypotheses that neonatal gonadectomy and opposite sex hormones administered to male and female castrated rats (together and independently for males) would reverse the normal sex-associated abilities of the white rate (higher male spatial learning and higher female activity). However, the feminization effect for the male 'estrogen alone' and 'castration alone' experimental groups was much greater than for the male estrogen injected castrates. The masculinized females, testosterone injected castrates, also had higher spatial learning and lower activity levels, while the feminized male's spatial and activity skills were also reversed. This confirmed in part the extent to which neonatal gonadal sex hormones are effective at critical periods of development in programming the brain in terms of sex-associated spatial and activity skills. Adult hormonal replacement therapy was also administered at 12 months and supported the hypothesis that sex hormones in adults would be mainly activational and have less marked effects than the significant directional changes obtained by these neonatal sex hormones and castration techniques.     

The impact of classroom aggression on the development of aggressive behavior problems in children

Prior research suggests that exposure to elementary classrooms characterized by high levels of student aggression may contribute to the development of child aggressive behavior problems. To explore this process in more detail, this study followed a longitudinal sample of 4,907 children and examined demographic factors associated with exposure to high-aggression classrooms, including school context factors (school size, student poverty levels, and rural vs. urban location) and child ethnicity (African American, European American). The developmental impact of different temporal patterns of exposure (e.g., primacy, recency, chronicity) to high-aggression classrooms was evaluated on child aggression. Analyses revealed that African American children attending large, urban schools that served socioeconomically disadvantaged students were more likely than other students to be exposed to high-aggressive classroom contexts. Hierarchical regressions demonstrated cumulative effects for temporal exposure, whereby children with multiple years of exposure showed higher levels of aggressive behavior after 3 years than children with primacy, less recent, and less chronic exposure, controlling for initial levels of aggression. Implications are discussed for developmental research and preventive interventions.     

Early emotion discrimination in 8- to 10-year-old children: Magnetoencephalographic correlates

Emotional cues motivate attention and modulate event-related potentials as well as magnetic fields in adults. Central components enhanced by emotional content are Early Posterior Negativity (EPN, 150–300 ms) and Late Positive Potential (LPP, >300 ms). Previous electroencephalography studies in children revealed a differentiation of the late component in response to emotional scenes, but failed to detect an EPN effect. Twenty-two children aged 8–10 years saw 200 arousing pleasant and non-arousing neutral pictures in a rapid serial visual presentation (RSVP) design, while event-related magnetic fields were recorded with whole-head magnetoencephalography (MEG). Analysis of MEG data based on individual picture ratings yielded LPP-m but also EPN-m effects with topography and latency resembling that of adults. Thus, the mechanism of motivated attention at early processing stages (>150 ms) appears mature in children of this age group.