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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences The Neurobiology of Violence and Aggression Allan F. Mirsky and Allan Siegel Over the past four decades, there has been an increasing body of data in the human literature on neuropsychiatric disorders that raises the question about a possible relationship between the abnormal function of specific regions of the brain and the occurrence of violent and aggressive behavior. The view that violence and aggression are human behaviors symptomatic of an underlying brain disorder, rather than simply acts to be punished under law, is relatively new. It is true that the distinction "between the harmful act that was traceable to fault and that which occurred without fault" extends back to ancient Hebrew law (American Bar Association, 1983:7–271). However, the scientific facts that have been offered as the basis for what Monroe has referred to as "the episodic dyscontrol syndrome" (Monroe, 1970) or other involuntary acts, are of relatively recent origin. The region of the brain most often linked with this form of behavioral dysfunction is referred to as the ''limbic system." Research on the limbic system (Figure 1) identified an apparently unitary cerebral region or limbic lobe (Broca, 1878) at the juncture of the forebrain and brain stem, which Papez (1937) and MacLean (1952) later identified as Allan F. Mirsky is at the Laboratory of Psychology and Psychopathology, National Institutes of Health; and Allan Siegel is at the Department of Neurosciences, New Jersey Medical School.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences FIGURE 1 Diagrammatic representation of the principal subcortical connections of the limbic system viewed from the mesial surface of one hemisphere. Important connections to the brain stem reticular formation have been omitted, and others are only approximately represented. Some abbreviations: A, anterior nucleus of thalamus; Ant., anterior; AMYG, amydala; Int., intermediate; CM, center median; Sens., sensory; Occip., occipital; G., gyrus; Stria Ter., stria terminalis; St. Med., stria medullaris; MD, medial dorsal nucleus of thalamus; O.B., olfactory bulb; Ling., lingual; Temp., temporal; Hypoth., hypothalamus; MM, mammillary bodies; Parolf., parolfactory; H., habenular nucleus. SOURCE: Penfield and Jasper (1954). the cerebral substrate of emotional behavior. The work of Klüver and Bucy (1939) and of Rosvold et al. (1954) is also relevant here. These researchers demonstrated that monkeys surgically deprived of portions of their limbic system had major changes in their social and affective behavior. These studies had a significant impact on the thinking about the relation between cerebral structures and/or systems and abnormal behavior, including a number of neuropsychiatric disorders. In terms of its overall organization, the limbic system includes the hippocampal formation, amygdala, septal area, cingulate gyrus, and prefrontal cortex (according to some authors). Several other brain structures have been considered
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences part of this system because of their neural associations with limbic structures. These include the hypothalamus and midbrain periaqueductal gray matter (PAG). Collectively, these regions comprise a functional unit that is sometimes referred to as the "limbic-hypothalamic-midbrain axis." The importance of this research was that there was a brain system that could be implicated in neuropsychiatric disorders, including those in which violence or aggressiveness was a major symptom. This system could be a focus of research, both clinical and laboratory based, and could provide the target or basis for new treatment possibilities. Some of this research is reviewed in the section of this paper on human studies of aggression and violence. In 1974, one of the authors reviewed the literature on the relationship between aggressive behavior and brain disease, and concluded that the available evidence did not support the view that aggressive behavior in humans could be attributed to brain disease (Mirsky and Harman, 1974). The question arises as to whether, in the ensuing 16 years since that paper was written, sufficient additional data have been gathered to alter that conclusion. Recent studies related to that question are also reviewed below. In view of the putative relationship between brain dysfunction and aggressive behavior, it is the purpose of this paper to summarize briefly the neural mechanisms of aggressive behavior as discovered from animal models, and to review human studies on the relationships among brain dysfunction, neuropsychiatric disorders (including abnormal development), cognitive processes, and the symptoms of violence and aggression. The section that deals with animal models focuses on two behaviors that can be readily elicited in the cat: quiet biting "predatory" attack and affective defense. It is our belief that the neural substrates and mechanisms underlying these distinctive forms of aggressive behavior in the cat may also regulate aggressive reactions at the human level or, possibly, provide a framework for understanding human violence and aggression. In the thesis advocated here, an analogy can be made between the relationship of the limbic system to the hypothalamus and midbrain PAG and that of the motor cortex and reticulospinal fibers to the spinal cord concerning the modulation of "emotional" and "motor" systems, respectively. With respect to motor systems, the final common output pathways for the expression of motor responses such as fine movements of the extremities or walking movements are governed by the activity of cells located
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences in the gray matter of the ventral horn of the spinal cord. In contrast, descending neurons from the reticular formation and motor systems of the cerebral cortex that synapse upon the neurons of the ventral horn serve to modulate their activity and program the sequence of their neuronal discharge patterns, respectively. In a similar manner, the hypothalamus and midbrain PAG constitute the integrating mechanisms whose outputs serve as the "final common pathway" for the expression of aggressive forms of behavior. We propose that the limbic system thus serves the critically important function of modulating the activity of neurons in the hypothalamus and PAG and of programming the sequence of neuronal discharge patterns within these structures. We illustrate this in the examples of research cited below. ANIMAL MODELS OF AGGRESSION FELINE MODELS OF AGGRESSIVE BEHAVIOR ELICITED BY BRAIN STIMULATION Our focus is on two models of aggression that can be elicited by electrical or chemical stimulation of the hypothalamus and midbrain periaqueductal gray matter in the cat—quiet biting "predatory" attack behavior and effective defense behavior. Affective defense behavior may be classified as having aversive properties (such as those associated with fear), whereas predatory attack is associated with more positively reinforcing objectives such as the acquisition of food. The study of these two forms of aggression in the cat may thus provide a more complete picture of the neural substrates of aggression than either model studied alone; moreover, research in the cat has been very systematic and has certain elegant qualities. Quiet biting attack is predatory in nature and is characterized by stalking of the prey object (usually an anesthetized rat), which is then followed by biting of the back of its neck. The cat may also strike the rat with its forepaw (Flynn et al., 1970; Wasman and Flynn, 1962). This behavior occurs under natural conditions, and includes capturing and killing of a rat or a mouse in the open field (Leyhausen, 1979). In the laboratory, predatory attack behavior can be elicited by electrical stimulation along a region beginning from the rostrolateral and perifornical hypothalamus (Wasman and Flynn, 1962; Siegel and Pott, 1988) and extending caudally through the ventral aspect of the midbrain (Bandler and Flynn, 1972) and ventral aspect of the midbrain PAG (Bandler,
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences 1984; Siegel and Pott, 1988) to the lateral tegmental fields of the pons (Berntson, 1973). Affective defense behavior was originally described by Hess and Brugger (1943). This form of attack behavior, in contract with predatory attack, is associated with noticeable affective signs such as piloerection, retraction of the ears, arching of the back, marked pupillary dilatation, vocalization, and unsheathing of the claws. This response can also be evoked under natural environmental conditions. Examples include the affective defense reactions that occur when a cat's territory is invaded by another animal, when a threatening stimulus is introduced into the cat's environment, or when a female cat perceives that its kittens are threatened by another animal. Furthermore, electrical or chemical stimulation applied at the appropriate forebrain or brain stem sites in a cat will elicit affective defense responses with its forepaw that are directed at a moving object such as an awake rat, cat, or experimenter. Although predatory attack requires the presence of a prey object for an attack response to occur, affective defense can be elicited in an impoverished environment. It should be noted that affective defense behavior is explosive in nature, oftentimes directed at conspecifics; produces a powerful sympathoadrenal response; and thus may share common features with violent "episodic dyscontrol" behavior in the human. Affective defense reactions are generally elicited from sites located throughout the rostrocaudal extent of the medial preoptico-hypothalamus and dorsal aspect of the PAG (Wasman and Flynn, 1962; Fuchs et al., 1985a,b; Shaikh et al., 1987; Siegel and Pott, 1988). ORGANIZATION AND CONTROL OF AGGRESSIVE BEHAVIOR IN THE CAT A number of basic research problems have been considered over the past several decades with respect to affective defense behavior and predatory attack in the cat. Due mainly to the pioneering efforts of John Flynn, a number of the basic properties associated with predatory attack have been clearly delineated. For example, one class of studies has provided an analysis of how selective components of the central nervous system linked to the expression of quiet biting attack interact with sensory stimuli to facilitate the occurrence of this response (MacDonnell and Flynn, 1966a,b; Bandler and Flynn, 1972). Another set of studies was directed at identifying the mechanisms that regulate motor control of the attack response. Such studies helped to produce a
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences better understanding of how the motor cortex and trigeminal system regulate such responses as paw striking and jaw closure (Edwards and Flynn, 1972; MacDonnell and Fessock, 1972). In this paper, we have chosen to summarize or provide references to information that we believe is critical to understanding the neural bases of aggressive behavior as studied in the cat. This includes (1) the anatomic substrates and pathways that underlie the expression and control of each of these forms of attack behavior; (2) the regions along the limbic-midbrain axis that serve to enhance or diminish the likelihood of these responses; this encompasses, as well, the effects of temporal lobe seizures on attack behavior; and (3) the role of the opioid peptide system in the regulation of affective defense behavior. It should be noted that the structures of the limbic-hypothalamic-PAG axis would appear to constitute the neural substrates for the motivational properties of the response mechanism. In contrast, the outputs of the hypothalamus and PAG to lower brain stem neurons appear to constitute the initial neurons in a system of pathways that descend to the spinal cord or that make synapse with lower motor neurons of the brain stem. This system of fibers, therefore, may comprise part of the motor components of the behavioral response. A second level of motor function may arise from the cerebral cortex. In this context, Flynn et al. (1970) postulated a "patterning mechanism" in which it was hypothesized that sensory and motor regions of the cerebral cortex receive inputs from hypothalamic cell groups linked to the attack response. In turn, the pattern of neuronal responses evoked in the cerebral cortex thus results in a set of output signals to motor and autonomic regions of the lower brain stem and spinal cord that constitute a coordinated attack response. THE ANATOMY OF AGGRESSIVE BEHAVIOR PREDATORY ATTACK Afferent Connections Predatory attack can be elicited from a variety of regions throughout the forebrain and brain stem, an area that extends from the anterior hypothalamus through the midbrain PAG to the level of the pontine tegmentum (see Figures 2A and 2B). Concerning the hypothalamic sites from which predatory attack can be elicited, Smith and Flynn (1980a) identified cells in a
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences FIGURE 2A Distribution of regional sites within the preoptico-hypothalamus from which affective defense (stippled area), quiet biting attack (striped area), and flight behavior (dark area) can be elicited most frequently by electrical stimulation. Data for this figure and for Figure 2B are based on experiments conducted in the laboratory of Allan Siegel. Number in upper left-hand corner of figure indicates the frontal plane of the section. Abbreviations: AH, anterior hypothalamus; F, fornix; IC, internal capsule; LH, lateral hypothalamus; MB, mammillary bodies; OC, optic chaism; OT, optic tract; RE, nucleus reuniens; VM, ventromedial nucleus. number of regions that are known or believed to modulate this response. Several of these key structures include the midbrain PAG, locus coeruleus, substantia innominata, bed nucleus of the stria terminalis (BNST), and central nucleus of the amygdala. Other afferent sources of the lateral hypothalamus include the lateral septal nucleus, diagonal band of Broca (Brutus et al., 1984; Krayniak et al., 1980), and midline thalamus (Siegel et al., 1973). A more detailed discussion of the anatomic pathways from limbic nuclei that modulate the attack response is presented below in the section "Limbic-Midbrain Modulation of Aggressive Behavior in the Cat." The other major sites from which predatory attack can be elicited include the following brain stem regions: the midbrain PAG, ventral tegmental area, and pontine tegmentum. A major
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences FIGURE 2B Distribution of regional sites within the midbrain periaqueductal gray matter from which affective defense (stippled area), quiet biting attack (striped area), and light (dark area) can be elicited most frequently by electrical stimulation. Number on the left side of each figure indicates the frontal plane of the section. Note that flight and affective defense sites are generally situated dorsal to those sites from which quiet biting attack is elicited. A recent study by Bandler (1984), however, has suggested that affective defense reactions characterized by howling and growling can also be elicited from ventral portions of the periaqueductal gray, especially when stimulation is applied at caudal aspects of this structure. SOURCE: Siegel and Pott (1988).
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences input to the PAG arises from predatory attack sites in the perifornical lateral hypothalamus (Chi and Flynn, 1971; Fuchs et al., 1981). With respect to the ventral tegmental area, the major projections to this structure arise from the gyrus proreus (prefrontal cortex) and perifornical hypothalamus. The key role of the ventral tegmental area in predatory attack is supported by the studies of Bandler and Flynn (1972), Proshansky et al. (1974), and Goldstein and Siegel (1980). The precise sites at which attack was obtained included mainly the parabrachial region of the tegmentum. Structures that may influence pontine control of predatory attack include the perifornical lateral hypothalamus, PAG, BNST, and central and lateral nuclei of the amygdala (Smith and Flynn, 1979). Efferent Connections In an early study, Chi and Flynn (1971) placed lesions at sites in the lateral hypothalamus from which predatory attack was elicited. The procedures enabled these investigators to trace the course of the degenerating axons from the lesion site. The results demonstrated both ascending and descending projections from lateral hypothalamic attack sites. Ascending projections were noted to pass through the preoptic zone into the diagonal band of Broca and septal area, regions known to modulate the attack response. Descending projections could be followed through the hypothalamus into the midbrain ventral tegmental area and PAG. More recently, Fuchs et al. (1981) examined the projection system from lateral hypothalamic attack sites. The anteriorly directed projections from the attack sites were similar to those described by Chi and Flynn (1971). Fibers were traced through the anterior hypothalamus to the preoptic region, diagonal band of Broca, and lateral septal area. The significance of these projections remains unknown, but these fibers may constitute part of a "feedback" pathway that serves to regulate how these limbic forebrain structures, in turn, control the attack mechanism at the levels of the hypothalamus and brain stem. With regard to the descending projections, fibers were followed caudally through the medial forebrain bundle into the ventral tegmental area and PAG. Of particular interest is the fact that fibers traced from attack sites in the perifornical region were also observed to terminate in the locus coeruleus and motor nucleus of the trigeminal complex as well as the tegmental fields of the pons (Figure 3). The significance of the latter (trigeminal) projection is that it
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences FIGURE 3 Diagram indicating the principal ascending and descending projections of the perifornical lateral hypothalamus associated with quiet biting attack behavior. Of particular interest and presumed importance are the connections from the perifornical region to the periaqueductal gray, tegmental fields, locus coeruleus, and the motor nucleus of the fifth nerve. SOURCE: Siegel and Pott (1988).
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences establishes the anatomic substrate by which jaw opening and jaw closing are controlled by the perifornical hypothalamus for the biting component of the attack response. Furthermore, the projection to the locus coeruleus provides the possible substrate by which noradrenergic pools from this nucleus can be activated to generate the arousal component of the attack response. Other research (Shaikh et al., 1987) suggests that the predatory attack system at the level of the PAG (see Figure 4) is organized along several possible plans: (1) that the PAG serves as a feedback system to the perifornical hypothalamus from which the primary integrated output to the lower brain stem is organized; and/or (2) that the PAG serves as a feed-forward relay of the perifornical hypothalamus, but does so through the use of short axons passing to the tegmental fields. The precise function of such fibers remains unknown, but they might comprise part of a multisynaptic pathway (presumably via reticulospinal fibers) for the regulation of autonomic and somatic motor components of the predatory attack response. The projection to the raphe nucleus, however, is more likely to be associated with the modulation of the attack response. This judgment is based on the fact that stimulation of the raphe nucleus has been shown to suppress predatory attack (Shaikh et al., 1984) and that administration of para-chlorophenylalanine (a monamine suppressor) can facilitate the occurrence of this response (MacDonnell et al., 1971). In this discussion, the likely anatomic substrates are described over which the autonomic and several of the somatic motor components of the predatory attack response are expressed. However, little has been said of the anatomic substrates governing how the hypothalamus might regulate visual processes central to the organization of the attack response. Research by Pott and MacDonnell (1986) and by Ogren and Hendrickson (1976) provides suggestions as to how this may be accomplished. The projection from the posterior lateral hypothalamus to the pulvinar represents the initial limb in a disynaptic pathway from the hypothalamus to the visual cortex that may be essential for the integration of visual information as well as for controlling visual pursuit movements during the attack sequence. AFFECTIVE DEFENSE BEHAVIOR Afferent Connections As noted earlier in this chapter, the sites in the brain at which affective defense reactions can be elicited have been identified
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Author(s) Title/Date Population Studied Procedure Results/Conclusions Needleman, H. L., Schell, A., Bellinger, D., Leviton, A. and Allred, E. Long Term Effects of Childhood Exposure to Lead at Low Dose; An Eleven-Year Follow-Up Report 1989 132, of an original 270 children tested in 1979, 18 to 19 year olds. Dentine levels measured in 1976–1977 for each subject were used to for computing mean concentrations. Venous blood lead levels were obtained in the present study as well. After the first 48 subjects, in which lead levels exceeding 7 µg/dl did not exist, venous blood withdrawal was discontinued. One examiner, blind to lead status, rated subjects on behavior. Subjects were administered the CPT, Symbol digit substitution, hand-eye coordination, simple visual reaction time, finger tapping, pattern memory, pattern comparison, serial digit learning, vocabulary, switching attention, mood scales, California Verbal Learning Test, Boston Naming Test, Rey-Osterreith Complex Figures Test, Word Identification Test, Self Report of Drug Use, Self Report of Delinquency, and review of school records was carried out. The present study showed that the effects of lead on academic progress and cognitive function found in earlier studies continue to be apparent in this population as young adults. A seven-fold increase in failure to graduate from high school was found along with lower class standing, greater absenteeism, impaired reading skills (scores 2 grades below expected - which qualify as reading disability), deficits in vocabulary, fine motor skills, reaction time and hand-eye coordination. All of these indicate "a serious impairment in life success." The estimates of cognitive and academic difficulties made on the basis of these 132 subjects taken from the original sample are probably conservative. Those not tested in the present study tended to have more lead, lower IQ scores, lower teachers' ratings and were generally of lower socioeconomic status than those tested. "The association between lead and outcome reported here meet six observational criteria that support the validity of causal inference: proper temporal sequence, strength of association, presence of a biological gradient, non spuriousness, consistency and biological plausibility."
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Thomson, G. O. B., Raab, G. M., Hepburn, W. S., Hunter, R., Fulton, M., and Laxen, D. P. H. Blood-Lead Levels and Children's Behaviour--Results from the Ed Edinburgh Lead Study 1989 501 boys and girls ages 6–9 years in ta defined central Edinburgh area. 43% of the families of these children were in social class I or II and 85% owned their own homes. These 501 children were tested in school by a trained psychologist. The British Ability Scales and tests of mental speed were administered. The children's teachers completed the Rutter behavior questionnaire. The family of each child was interviewed and one parent (usually the mother) received an ability test. Shed deciduous teeth were collected and the child's exposure to environmental lead was assessed. Results showed a significant relationship between blood-lead and measures of deviant behavior taking into account any confounding variables. The 501 children tested had a mean blood-lead level value of 10.4 µg/dl. The measures of deviant behavior were shown to be influenced by sex, mother's performance on a matrices test, history of family disruption and total number of cigarettes smoked in the household. There was a stronger effect for boys than for girls in a lead by sex interaction, but evidence for such an interaction is limited. Data from the Edinburgh study suggest that a small tendency exists for an association between blood-lead and deviant behavior even after controlling for confounders. "This relationship may reflect a causal association whereby low level lead exposure acts to influence deviant anti-social and hyperactive behaviour in pupils." Lead and behavior could possibly be associated by reverse causality which means the way children behave may lead to variations in body lead burden. "The hyperactive, acting out aggressive child may well behave in ways which increase his/her lead levels. Despite this caveat the results reported here add to the growing evidence that lead at low levels of exposure probably has a small but harmful effect on children's behavior."
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Table 16 Alcohol Ingestion in Pregnancy--Cognitive Effects Author(s) Title/Date Population Studied Procedure Results/Conclusions Streissguth, A. P., Martin, D. C., Barr, H. M., and MacGregor Sandman, B. Kirchner, G. L., Darby, B. L. Intrauterine Alcohol and Nicotine Exposure: Attention and Reaction Time in 4-Year-Old Children. 1984 452 singleton-born children - a 4-year-old follow-up cohort. The present study is part of a longitudinal prospective study which started when the mothers were pregnant. Those included in the longitudinal study were children of heavier drinkers, more moderate drinkers, infrequent and nondrinkers. For the present evaluation, subjects were 4 years and 3 months of age. The mothers were predominantly white (87%); married (86%); and middle-class (80%). For the 4-year olds in the present study, follow-up rate was 86% from those seen at 8 months. Independent variables measured were maternal alcohol use, maternal nicotine use, maternal caffeine, maternal drug use, and maternal diet. A psychometrist, blind to the drinking history of the children's mothers and prior assessments of development, administered a vigilance task at the end of a 1.5 hr test battery. The child was required to press a button each time a kitten appeared on the window of a Victorian house. The psychometrist recorded the total amount of time (in the 13 minute task) that the child was nonoriented to the stimulus board and whether the child was oriented to the apparatus at each stimulus presentation. Both alcohol and nicotine were related significantly to errors of omission and commission, and to the ratio of correct responses to total responses. "These findings held up even when the test for alcohol was adjusted for nicotine, when the test for nicotine was adjusted for alcohol, and when both were also adjusted for maternal caffeine use, nutrition and education and child's birth order." Alcohol effects were still present upon removal of the children of the smoking mothers from the analysis leaving 248 subjects. Upon deletion of the heavier drinkers from the analysis, leaving 285 subjects who were children of lighter drinkers, a significant nicotine main effect remained. That increased attentional errors and longer reaction time occurs in 4-year-old children exposed to heavier doses of alcohol in utero is a new finding. These children pressed to significantly fewer of the target stimuli and made significantly more extraneous button presses. They did not differ significantly in their orientation to the target stimuli. Speed of responding, in these children, became significantly slower as the session went on. On the contrary, nicotine exposed children showed significantly less frequent orientation to the target stimuli. Their errors of omission could be explained by this. Alterations in reaction time were no associated with nicotine exposure. Decreased orientation and attention in children exposed to nicotine is consistent with studies carried out by Denson et al. (1975) and Nichols and Chen (1981) that showed a relationship between hyperkinesis in young children and maternal smoking during pregnancy. "Attentional errors assessed from a vigilance paradigm such as the one used in the present study have been previously associated with poor academic achievement (Kirchner and Knopf, 1974) and hyperactivity (e.g., Porrino et al., 1983) in school-age children." These attentional errors are considered to be the basis of learning disabilities found in school-age children (Doyle, 1976).
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Streissguth, A. P., Barr, H. M., Sampson, P. D., Parrish-Johnson, J. C., Kirchner, G. L., and Martin, D. C. Attention, Distraction and Reaction Time at Age 7 Years and Prenatal Alcohol Exposure. 1986 486 subjects of the original 500 that began the longitudinal study (Streissguth, 1981) were brought in for the 7.5 year examination. Of these, 475 had a least partial valid data for this study. This sample included 255 boys and 220 girls. Age range was from 6.5 to 8.5 yrs. Again the independent variables were maternal alcohol use, maternal smoking, maternal caffeine use, maternal drug use and maternal diet. The subjects were administered the CPT vigilance task. They participated in both the X and the AX tasks. Subjects were examined, after a 2.5 hour psychological battery by one of eight examiners blind to prior developmental assessments and mother's scores on independent variables. Following statistical adjustment for a variety of variables that may be potentially confounding, results showed that prenatal alcohol exposure was significantly related to attentional deficiencies and reaction time. The results remained "essentially unchanged" even in the presence of various potential confounders. Levels of alcohol exposure where effects on attention can be observed appear to depend on the task and the type of alcohol score used. "Among the tasks derived from this CPT paradigm, MRT and EC-AX (EC = errors of commission), by virtue of their highly significant partial correlations with terms linear in alcohol exposure, were the most sensitive attentional outcomes for assessing the long term effects of prenatal alcohol exposure." It seemed for these two measures that the magnitude of the effect increased with increased exposure or increased number of drinks per occasion. The authors suggest that strong conclusion can only be drawn from these two measures and the vigilance summary score. The fact that EC-AX seemed to be a more sensitive result than EC-X may be due to the subjects' inability to withhold a response (i.e. responding to A in anticipation of X). This would be consistent with the clinical observation (made by the authors) that children suffering from FAS are frequently uninhibited and impulsive (1985). An alternative explanation may be that EC-AX was the last task in the battery and attention was probably waning. Observations made by examiners on distractibility also showed that the most highly exposed children were most easily distracted. The authors state that an important consideration in choosing outcome variables for such studies is that they are suitable for all subjects in the population. In the present study, one child out of 475 was not able to take the CPT task and only 3% showed some resistance to it. They conclude that the CPT is a "suitable endpoint" for attentional studies in these children.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Author(s) Title/Date Population Studied Procedure Results/Conclusions Streissguth, A. P., Sampson, P. D., and Barr, H. M. Neurobehavioral Dose-Response Effects of Prenatal Alcohol Exposure in Humans from Infancy to Adulthood. 1989 Study 1 included 92 subjects with FAS or FAE (Fetal Alcohol Effects) who were 12 yrs. of age or older. Age range was 12 – 42 with a mean of 18.4 years. 58 were diagnosed as having FAS and 34 as having FAE. 61% were male, 55% were reservation Indians, 22% nonreservation Indians, and 23% non-Indians. Study 2 included a cohort of about 500 children whose mothers were interviewed in the fifth month of pregnancy Of the 1,500 women interviewed all heavier drinkers and a proportion of moderate, light, and infrequent drinkers and nondrinkers were included. The women in this sample were predominantly white (87%) married (86%), middle class (80%), and well educated (58% - some college) Study 1. Each subject was administered the following tests (standardized conditions were maintained): an IQ test appropriate for the age of the subject; WISC-R or WAIS-R; an auditory receptive ability test; the PPVT; an adaptive and maladaptive behavior test; the VABS; and the Symptom Checklist (SC) developed for this study. Data are not available for all subjects on all tests. Study 2. To measure maternal alcohol, a quantity-frequency-variability interview was conducted and scored according to 25 alcohol scores. Alcohol scores were taken twice, once "during pregnancy" and "prior to pregnancy" (a month or two prior). Both were self reports. The use of cigarettes, caffeine, and other drugs was also taken into consideration. Information on other variables such as major life changes mother-child interaction, age of siblings, injuries and illnesses, etc. were obtained to assess influence on development. A full list of the 150 covariates examined here can be gotten from Streissguth et al. (1986). Dependent variables were assessed on the first and second day, at 8 and 18 months, and at 4 and 7 years. "Prenatal alcohol exposure produces a wide variety of effects of offspring including intellectual decrements, learning problems, attentional and memory problems, fine and gross motor problems, and difficulty with organization and problem solving. In patients with FAS/FAE, psychosocial problems are observable in adolescence and adulthood that may have their roots in early cognitive deficits. Psychosocial problems associated with moderate exposure levels have not yet been evaluated." In general, prenatal alcohol exposure effects on neurobehavioral variables show a dose response relationship where ''high levels of exposure are associated with large magnitude effects, while moderate levels of exposure are associated with more subtle effects." Self-reported binge drinking (5 drinks or more at a given time) and self-reported drinking in the period prior to pregnancy recognition are two of the strongest predictors of later neurobehavioral deficits. No evidence was found that these effects are due to confounding with other drugs or can be accounted for by a small group of outliers. "The comparable findings from the clinical study, the epidemiologic study and the animal literature present convincing evidence of the neuroteratogenicity of alcohol and the long-lasting effects on prenatally-exposed offspring."
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Table 17 Cocaine, Opiates, and Tobacco: Effects on Cognitive Development Author(s) Title/Date Population Studied Procedure Results/Conclusions Chasnoff, I. J., and Griffith, D. R. Cocaine: Clinical Studies of Pregnancy and the Newborn. 1989 Two groups of cocaine using women. Group 1 comprised 23 women who reached abstinence by the end of the first trimester and did not use cocaine for the remainder of the pregnancy. Group 2 comprised 52 women who used cocaine throughout the pregnancy. The neonates were all examined at birth by a physician who did not know of the prenatal history. Weight, crown to heel length, and fronto-occipital head circumference were measured. When the infants reached 12 to 72 hours of age the Neonatal Behavioral Assessment Scale was administered. Performances on the NBAS showed that the children of both groups of women demonstrated impairment in motor ability, orientation, state regulation, and number of abnormal reflexes. Group 1 showed significantly poorer performance on motor cluster than Group 2. 7 of 16 in Group 1 and 8 of 36 in Group 2 could not reach alert states at all during testing and thus were unable to engage in any orientation. Those infants in Group 1 were significantly more fragile and "less robust" in capability to complete the testing. This study did show that reaching abstinence from cocaine use at the first trimester increased the number of pregnancies carried to term and improved obstetric outcome. Results of this study support findings that "exposure to cocaine during the prenatal period leads to significant impairment in neonatal neurobehavioral capabilities." The greater impairment in Group 1 infants is difficult to explain. The authors suggest replicating the study with larger samples.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Chasnoff, I. J., Burns, W. J., Schnoll, S. H., and Burns, K. A. Cocaine Use in Pregnancy. 1985 23 infants born to cocaine-using women. The women were divided into groups according to use or nonuse of narcotics along with the cocaine. These groups were compared to two control groups. Group 1 was made up of 12 women who had conceived while using cocaine, had not history of opiate use, 4 used alcohol at least twice monthly, 6 used marijuana at least 3 times monthly in the first two trimesters of pregnancy. 7 smoked cigarettes throughout pregnancy. Group 2 comprised 11 women who had conceived while using both cocaine and heroin. 2 used alcohol at least twice monthly, 5 used marijuana at least 3 times monthly through the first two trimesters, and 8 smoked cigarettes throughout pregnancy. Group 3 comprised 15 women who conceived while using heroin. 3 used alcohol at least twice monthly, 7 used marijuana at least three times monthly in the first two trimesters, and 11 smoked throughout pregnancy. Group 4 comprised 15 women who did not abuse drugs. However, 3 used alcohol at least twice monthly, 7 used marijuana at least three times monthly in the first two trimesters, and 10 smoked cigarettes throughout pregnancy. Group 2 and Group 3 women were started on methadone treatment upon admission to the Perinatal Addiction Project. About 60% of the women in Groups 1 and 2 used cocaine throughout pregnancy. All women except those in Group 4 were enrolled in the Perinatal Addiction Project. Experimenters reviewed the reproductive history of all of the women in the study. Groups 1 and 2 had used cocaine in all prior pregnancies, and Group 3 women had used opiates. At birth all neonates were weighed, measured from crown-to-heel, and fronto-occipital head circumference was recorded. At three days of age, the infants were administered the Brazelton Neonatal Behavioral Assessment Scale by examiners blind to the child's prenatal history. Results showed that infants exposed to cocaine in utero showed and increase in depressed interactive abilities and significant impairment in organizational abilities as compared with infants whose mothers used methadone and control infants. "Cocaine exposure in utero interferes with an infant's ability to maintain adequate state control in the neonatal period. This puts the infant at high risk. Group 2 infants displayed weaker reflexes and decreased state control than did control infants (Group 4), but they showed no significant deficits in orientation, neither auditory nor visual. The authors feel that this may be the result of a Type II error. The interaction of cocaine and methadone in these infants may have been antagonistic since one is a CNS depressant and one a CNS stimulant. Alcohol, marijuana, and nicotine use in all four groups was similar and thus could not account for discrepancies in the findings.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Author(s) Title/Date Population Studied Procedure Results/Conclusions Olofsson, M., Buckley, W., Andersen, G. E., and Friis-Hansen, B. Investigation of 89 Children Born by Drug-Dependent Mothers. 1983 A reinvestigation of 72 of 89 previously examined children 11 months to 10 years of age (mean = 3.5 yrs.). 62 mothers (10 of which had 2 children among the 89). None of the mothers had been drug-free for 5 years or more. 19% had been drug-free for 14 days to 5 years. 45% were taking mainly i.v. opiates, 26% were taking methadone, and 10% were using minor tranquilizers. 66% had no job, 16% were working, 18% were in prison on sick leave or participating in an educational program. Psychomotor development of the children was determined by the Denver Development Screening Test (DDST). Data on physical, social and behavioral history were obtained from interviews with guardians and/or mothers, and other professionals involved in the child's life (i.e. private practitioners visiting health nurses, social welfare authorities and school- and day-care personnel. Fifteen children (21%) showed an impaired psycho-motor-development. Two of the fifteen retarded children showed major organic abnormality and in another four minor brain damage was suspected. 56% were considered behaviorally abnormal. Lack of concentration, hyperactivity, aggressiveness and lack of social inhibition were the predominant signs.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Rush, D. and Callahan, K. R. Exposure to Passive Cigarette Smoking in Child Development. 1989 Extensive Literature Review. The authors looked at the designs of and highlight strengths and weaknesses of all of the studies on maternal smoking and fetal development known to them. They then summarized relationships with somatic, cognitive and behavioral development across all studies. Detailed results are provided in tables within the text. There is a consistent pattern of depressed cognitive development and tests of school achievement associated with maternal smoking during pregnancy. It still remains beyond current knowledge that these are causally related though a trend is apparent. A consistent pattern of behavioral abnormalities are also reported. Several studies are cited. Again, a causal relationship was not supported based on the available data. A strong and highly significant relationship between amount of cigarette smoking prior to pregnancy and the psychomotor developmental index was observed.
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Author(s) Title/Date Population Studied Procedure Results/Conclusions Wilson, G. S., McCreary, R., Kean, J. and Baxter, J. C. The Development of Preschool Children of Heroin-Addicted Mothers: A Controlled Study. 1979 77 children, 40 boys and 37 girls, 3 years 1 month to 6 years 4 months of age (mean = 4 years 7 months). 30 had Latin American surnames, 30 were black, 17 were Anglo-American Three groups were compared with the heroin exposed group. Heroin exposed group: 22 children of mothers who used heroin (as the predominant drug) continuously throughout pregnancy. In one case use of all drugs was terminated at one month of gestation, in another methadone was substituted at six months, and another two substituted other drugs in the last trimester. 7 abused other along with the heroin. Drug environment group: 20 children of mothers who did not use heroin during pregnancy but were involved in the "drug culture". The high-risk comparison group: 15 children labelled as such because of medical factors such Hospital records were examined for maternal drug use, obstetric complications, amount of prenatal care, complications of labor or delivery, one-minute Apgar score, gestational age, birth weight, type and severity of nursery morbidity, and duration of hospitalization. They received a general physical exam and a neurological evaluation. A structured social service interview was carried out at each child's home. A 19-item scale (Kasmar and Altman) was used by a social worker to rate physical environment of each home. Parental Attitude Research Inventory was given. Standardized tests used: Illinois Test of Psycholinguistic Abilities, the Columbia Mental Maturity Scale, the McCarthy Scales of Children's Abilities, and the Minnesota Child Development Inventory. A perceptual battery designed by Deutsch and Schumer was modified and administered. Parents completed the three subtest of Child Behavior Rating Scales. Pediatricians rated the subjects on alertness, cooperation, attention, activity level, and intensity. During a 5-minute free-play period children were videotaped and rated on attention, activity level, cooperation, independence and confidence by a psychologist. Speech was assessed by a speech pathologist during the No significant difference was found in the educational attainment, occupational level, and Hollingshead index of social position of the families. Heroin exposed children lived with a substitute mother more commonly than children in any of the three comparison groups. No group differences were found in physical environment. IQ did not differ between groups. Heroin-exposed children showed poorer performance than comparison groups on the General Cognitive Index, on three out of five subtests of the McCarthy Scales of Children's Abilities (perceptual performance, quantitative and memory), on measures of visual, tactile, and auditory perception. The McCarthy tests of skills are "considered organizational processes in the ITPA categorization. They require attention, concentration, short-term memory and the internal manipulation of symbols. Groups did not differ significantly on verbal and motor scales. They were rated as more active, and by parents as having increased difficulty in self-adjustment, social-adjustment and physical-adjustment areas. Group differences could not be based on age, sex, ethnic group, socioeconomic status, or participation in school readiness programs. These were controlled for initially. "Behaviorally, the problems of the heroin-exposed group were related to impulsiveness, aggressiveness, and peer relations. These behavior problems may also be manifestations of impaired attention and organizational abilities."
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Understanding and Preventing Violence: Volume 2, Biobehavioral Influences Wilson, G. S., McCreary, R., Kean, J. and Baxter, J. C. The Development of Preschool Children of Heroin-Addicted Mothers: A Controlled Study. as dysmaturity, intra-uterine growth retardation, fetal distress, and disturbed transition. Mothers claim to have abstained from psychotropic drug use at any time. Finally, the socioeconomic comparison group: 20 children who were born without complications. There were no significant group differences in age, sex or socioeconomic status. same doll play task.
Representative terms from entire chapter: