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Biomedical subjects

A Raine

Publications and source records attributed to A Raine.

At least 19 recordsLinked to original sources

Elevated levels of cognitive-perceptual deficits in individuals with a family history of schizophrenia spectrum disorders.

This study finds that the relatives of schizophrenics have elevated scores on the cognitive-perceptual factor of the schizotypal personality questionnaire (SPQ), particularly for the 'unusual perceptual experiences' and 'ideas of reference' subscales. These results support recent findings by Kremen et al. (1998) and suggest that previous failures to demonstrate elevated scores on 'positive' symptoms of schizotypy may be a function of instrumentation.

Adult↗

Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder.

BACKGROUND: Major damage to gray and white matter in the prefrontal cortex and autonomic deficits have been found to result in pseudopsychopathic personality in patients with neurological disorders, but it is not known whether people with antisocial personality disorder (APD) in the community who do not have discernable brain trauma also have subtle prefrontal deficits. METHODS: Prefrontal gray and white matter volumes were assessed using structural magnetic resonance imaging in 21 community volunteers with APD (APD group) and in 2 control groups, comprising 34 healthy subjects (control group), 26 subjects with substance dependence (substance-dependent group), and 21 psychiatric controls. Autonomic activity (skin conductance and heart rate) was also assessed during a social stressor in which participants gave a videotaped speech on their faults. RESULTS: The APD group showed an 11.0% reduction in prefrontal gray matter volume in the absence of ostensible brain lesions and reduced autonomic activity during the stressor. These deficits predicted group membership independent of psychosocial risk factors. CONCLUSIONS: To our knowledge, these findings provide the first evidence for a structural brain deficit in APD. This prefrontal structural deficit may underlie the low arousal, poor fear conditioning, lack of conscience, and decision-making deficits that have been found to characterize antisocial, psychopathic behavior.

Adult↗

Treatment and prevention implications of antisocial personality disorder.

Recent research efforts have focused on understanding the developmental nature of antisocial personality disorder (APD) in order to better develop intervention strategies. This article reviews what is known about biologic and environmental risk factors for the development of APD as well as issues surrounding treatment. Insights into how these factors may work together, and issues involving approaches to researching them, are discussed. Given the impact of this disorder on the lives of the affected individuals as well as society, prevention of this disorder may be a more important focus than intervention.

Antisocial Personality Disorder↗

Three-factor model of schizotypal personality: invariance across culture, gender, religious affiliation, family adversity, and psychopathology.

Whilst the syndrome approach to schizotypy has recently demonstrated differential correlates of a three-factor model of schizotypal personality, variations in the nature of these factors question a basic assumption of this approach. This study tested competing models of the factor structure of schizotypal personality using the Schizotypal Personality Questionnaire (SPQ) in a sample of 1,201 Mauritians. Factor invariance across gender, ethnicity, family adversity, and religion and across a psychopathologically select group was also assessed. Results suggest that a three-factor model, Cognitive-Perceptual Deficits, Interpersonal Deficits, and Disorganization, underlies individual differences across widely varying groups. Other competing three-factor schizotypal personality models did not fit the data better. It is argued that the three-factor Disorganized model is a well-replicated model of DSM schizotypal personality in community samples but possibly not in some clinical samples.

Adult↗

Structural characterization of a mutant peptide derived from ubiquitin: implications for protein folding.

The formation of the N-terminal beta-hairpin of ubiquitin is thought to be an early event in the folding of this small protein. Previously, we have shown that a peptide corresponding to residues 1-17 of ubiquitin folds autonomously and is likely to have a native-like hairpin register. To investigate the causes of the stability of this fold, we have made mutations in the amino acids at the apex of the turn. We find that in a peptide where Thr9 is replaced by Asp, U(1-17)T9D, the native conformation is stabilized with respect to the wild-type sequence, so much so that we are able to characterize the structure of the mutant peptide fully by NMR spectroscopy. The data indicate that U(1-17)T9D peptide does indeed form a hairpin with a native-like register and a type I turn with a G1 beta-bulge, as in the full-length protein. The reason for the greater stability of the U(1-17)T9D mutant remains uncertain, but there are nuclear Overhauser effects between the side chains of Asp9 and Lys 11, which may indicate that a charge-charge interaction between these residues is responsible.

Amino Acid Sequence↗

Skin-conductance orienting deficits and increased alcoholism in schizotypal criminals.

This study tested the interaction hypothesis that a subgroup of criminals with schizotypal personality would show skin-conductance orienting deficits and increased alcoholism. In a prospective, longitudinal study of alcoholism in 134 males, schizotypy was assessed during adolescence, skin-conductance orienting was assessed at ages 18-20 years, and criminal offending and alcohol abuse were assessed at ages 30-33 years. A significant interaction between schizotypy and criminality indicated that schizotypal criminals were characterized by autonomic orienting deficits. Furthermore, the rate of alcoholism in schizotypal criminals (54.8%) was significantly higher than in criminals (23.8%), schizotypal noncriminals (13.9%), and comparisons (21.7%). It is argued that schizotypal criminals are a relatively distinct group and that prefrontal dysfunction may underlie both orienting deficits and alcoholism in this group.

Acoustic Stimulation↗

Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist.

1. We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2. One of the substances HS028 (cyclic [AcCys11, dichloro-D-phenylalanine14, Cys18, Asp-NH2(22)]-beta-MSH11-22) showed high affinity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014. 3. HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4. Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5. This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

Animals↗

Fearlessness, stimulation-seeking, and large body size at age 3 years as early predispositions to childhood aggression at age 11 years.

BACKGROUND: Previous cross-sectional research in Western societies has linked adolescent stimulation-seeking, fearlessness, and body size to antisocial behavior. However, it is unclear how early in life these factors exert their influence, and nothing is known about their specificity to aggressive behavior per se. This study tests the hypotheses that stimulation-seeking, fearlessness, and increased body size at age 3 years predict aggression at age 11 years. METHODS: Behavioral measures of stimulation-seeking and fearlessness, together with height and weight, were measured at age 3 years and related to ratings of aggression at age 11 years in 1130 male and female Indian and Creole children from the island of Mauritius. RESULTS: Aggressive children at age 11 years were characterized by increased measures of stimulation-seeking, fearlessness, height, and weight at age 3 years. Stimulation-seeking and height were independently related to aggression, whereas the fearlessness-aggression relationship was mediated by height. Large body size at age 3 years but not 11 years was related to increased aggression at age 11 years, indicating a critical period in development for the influence of body size on aggression. CONCLUSIONS: Results (1) implicate large body size, stimulation-seeking, and fearlessness in the development of childhood aggression; (2) suggest that there may be a critical period in development in which biological processes influence later aggression; and (3) highlight the importance of early processes in the etiology of aggression.

Age Factors↗

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Affect↗

Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

Adult↗

Brain abnormalities in murderers indicated by positron emission tomography.

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

Adult↗

Psychophysiology of anger and violent behavior.

Antisocial behavior is a complex phenomenon that arises out of multiple causes involving biologic, psychological, and social forces. Moreover, different forms of violent antisocial behavior may each result from different biopsychosocial pathways. The overview of human psychophysiologic findings presented in this article provides some support for this notion. In particular, the finding of psychophysiologic underarousal (e.g., reduced resting HR and SC levels, increased slow-wave EEG, poor classical conditioning) is one of the most robust and best replicated findings in antisocial populations. The majority of these studies consist of populations exhibiting nonviolent antisocial behavior or milder forms of aggression. Findings of underarousal in institutionalized criminal samples are very few in number and are not well-replicated. The relationship of psychophysiologic underarousal to antisocial behavior, therefore, may be specific to covert forms of antisocial behavior and perhaps to some less severe forms of violent behavior. On the other hand, violence associated with anger and emotional aggression (which is often more impulsive, less controlled, and reactive to some perceived provocation) may have very different psychophysiologic underpinnings. It was suggested that risk factors for emotional aggression include a predisposition to negative affect/arousal and an inability to regulate that affect/arousal. It also was suggested that this effect will be most pronounced in individuals experiencing stressors or adverse social environments, where negative affect and arousal would be increased. Laboratory studies have suggested that overarousal may facilitate aggression in situations in which someone has been provoked. Clinical studies also have indicated a relationship between increased physiologic arousal, negative emotionality, and aggression/antisocial behavior in some populations, with increases in aggression in those also exposed to adverse home environments. Thus, the relationship of increased psychophysiologic arousal to antisocial behavior may be more specific to angry or emotional violence. It is important to note that these psychophysiologic distinctions are speculative for few studies actually have differentiated type of violence in their design. Pitts did group children according to proactive or reactive aggression and found reduced HR levels in both groups, but a substantial increase in HR only in the reactive aggressive group. Lakosina and Trunova found increased SC responsivity in psychopathic individuals characterized by affective violence. These studies provide some initial support for underarousal in proactive/instrumental aggression and overarousal in emotional aggression. It is important, however, that more studies be done with subtypes of violence to test the notion of such differential psychophysiologic patterns. Lastly, some definitional and methodologic considerations need to be mentioned. First, a distinction exists between physiologic arousal and reactivity. Typically, arousal refers to psychophysiologic activity that occurs during a resting state, whereas reactivity refers to activity that occurs in response to some stimulus. Although some studies did assess measures during a resting state, the majority of findings on over-arousal in relation to emotional aggression more accurately reflect psychophysiologic and emotional reactivity to a situation or stimulus. Second, arousal or reactivity are nonspecific terms that can refer to any psychophysiologic response system (e.g., electrodermal, cardiovascular, cortical, and so on). Responses from these systems typically do not correlate in the general population. Thus, it would be worthwhile for future studies to include more than one response system (as done by Raine et al) and see if the arousal/reactivity measures converge. If the measures converge, a general model of arousal or reactivity is supported. (ABSTRACT TRUNCATED)

Affect↗

Biosocial bases of antisocial behavior: psychophysiological, neurological, and cognitive factors.

In this paper we review biosocial research and theory in the area of antisocial behavior. In particular, we focus on interactions between biological and social variables in predicting antisocial outcome. While many psychological researchers make statements concerning the potential importance of biosocial interactions, very few researchers actually test for such interactions in their data. The few studies that have reported biosocial interactions suggest that biological variables can protect against antisocial behavior in socially vulnerable individuals, and that social variables can protect against antisocial behavior in biologically vulnerable individuals. Further research is necessary to determine whether the effects of biosocial interactions on antisocial outcome are dependent upon particular biological or social factors. Preliminary evidence suggests that policy interventions that ameliorate the effects of perinatal risk factors could protect against antisocial and violent outcome.

Adolescent↗

Heart rate and skin conductance in behaviorally inhibited Mauritian children.

This study tested predictions that inhibited versus uninhibited children exhibit higher heart rate (HR) and skin conductance (SC) arousal. Mauritian children (N = 1,795) were tested at age 3 and classified as inhibited, middle, or uninhibited on the basis of social behavior. HR level and several SC measures were obtained immediately before or during a tone task. Inhibited children displayed significantly higher HR and SC levels and longer SC latency relative to uninhibited children. Results remained regardless of ethnicity, gender, height, weight, respiratory complaints, or crying behavior. Findings suggest that HR and SC levels may be early indicators of inhibited or uninhibited behavior at age 3 and support the notion of heightened sympathetic reactivity due to limbic arousal in inhibited children.

Arousal↗

Neuropsychological and psychophysiological correlates of psychosocial functioning in schizophrenia.

This study tested hypothesized relationships between neuropsychological and psychophysiological variables and concurrent levels of clinical and psychosocial functioning in schizophrenia. The sample consisted of 40 subjects diagnosed with a chronic schizophrenia spectrum disorder and living in community-based settings. The psychophysiological variables were tonic skin conductance (SC) level, SC reactivity to stressors, and SC response to orienting stimuli. The neuropsychological measures were the Stroop, the Controlled Word Association Test, and four subtests of the Wechsler Adult Intelligence Scale-Revised (block design, digit symbol, digit span, and arithmetic). The psychosocial variables were measures of symptomatology, independent living, work, and social functioning. The results suggested that higher symptoms were associated with higher resting arousal, lower stress reactivity, status as an electrodermal responder, and deficits in verbal fluency and visuo-motor functioning. The pattern for better social functioning was higher resting arousal, lower stress reactivity, and more responses to orienting stimuli. Higher levels of independent living were associated with better visuo-motor and verbal processing. Increased work functioning was associated with better complex visuo-spatial processing. These findings are discussed in terms of (1) the specificity of associations between psychosocial, psychophysiological, and neuropsychological variables and (2) a holistic perspective toward understanding these relationships and their relevance to rehabilitation in schizophrenia.

Activities of Daily Living↗

Abnormal orienting in schizotypal personality disorder.

Previous studies have found evidence for skin conductance (SC) orienting abnormalities in psychosis-prone subjects, but there have been no previous studies on subjects with a diagnosis of schizotypal personality disorder. This study assesses whether clinical schizotypal subjects show abnormal habituation to orienting stimuli. Thirteen subjects with both high scores on the Schizotypal Personality Questionnaire (SPQ) and a DSM-III-R clinical diagnosis of schizotypal personality disorder were compared to 30 controls with no such diagnosis and with low scores on the SPQ. While normals showed the expected habituation in SC orienting across trials, schizotypal subjects failed to show a decrement in responding across the first three trials. In a second study on 30 new subjects, individual differences in schizotypy correlated significantly (p = 0.47) and in the predicted direction with a dimensional measure of the orienting deficit. It is hypothesized that this retarded habituation in schizotypals reflects a deficit in preattentive template matching, which may in turn partly relate to the working memory and prefrontal deficits observed in schizotypal and schizophrenia patients.

Adolescent↗

Childhood behavior precursors of schizotypal personality disorder.

No study has yet reported specifically on the early behavior of individuals later diagnosed with schizotypal personality disorder (SPD). This study examines prospectively collected teacher reports on school behavior as a means of assessing childhood precursors of SPD. Thirty-six DSM-III-R diagnosed schizotypal subjects were compared with four other groups: 31 schizophrenia patients, 37 diagnosed as nonpsychotic mentally ill, 68 who were not mentally ill but had mothers with schizophrenia, and 60 who were not mentally ill and had normal parents. These individuals were compared on a teachers' school report questionnaire obtained when the subjects averaged 15.1 years old. Those who later developed SPD were found to be more passive and unengaged and more hypersensitive to criticisms compared with the nonschizophrenia groups. Similar results were found when males and females were examined separately, except that males who developed SPD were found to be less disruptive and hyperexcitable compared with males with schizophrenia; females with SPD did not differ from females with schizophrenia. A receiver operating characteristic analysis found these factors to predict 73.5 percent of future SPDs; the ability of these factors to predict future SPDs is comparable for males and females. These findings suggest that preschizotypal traits may be identified in late childhood or adolescence.

Adolescent↗

Low resting heart rate at age 3 years predisposes to aggression at age 11 years: evidence from the Mauritius Child Health Project.

OBJECTIVE: Previous studies indicate that low resting heart rate is probably the best-replicated biological correlate of childhood antisocial and aggressive behavior. Nevertheless, there have been few longitudinal tests of this relationship, little control over potential confounds and mediators, and no test of its cross-cultural generalizability. This study tests the hypothesis that low resting heart rate at age 3 years predicts aggression at age 11 years. METHOD: Resting heart rate at age 3 years was assessed in 1,795 male and female children from Mauritius. Aggressive and nonaggressive forms of antisocial behavior were assessed at age 11 years using the Child Behavior Checklist. RESULTS: Aggressive children had lower heart rates than nonaggressive children (p < .001). Conversely, those with low heart rates were more aggressive than those with high heart rates (p < .003). There were no interactions with gender or ethnicity. Evidence was found for specificity of low heart rate to aggressive forms of antisocial behavior. Group differences in heart rate were not attributable to 11 biological, psychological, and psychiatric mediators and confounds. CONCLUSIONS: It is concluded that low resting heart rate, a partly heritable trait reflecting fearlessness and stimulation-seeking, is an important, diagnostically specific, well-replicated, early biological marker for later aggressive behavior.

Aggression↗