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PubMed1994

Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism.

BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Adult↗
PubMed2004

Nicotine craving and cue exposure therapy by using virtual environments.

Smokers who are exposed to cues associated with smoking show cardiovascular reactivity and an increase in smoking urges as compared to when they are presented with neutral cues. Cue exposure therapy (CET), which refers to the repeated exposure to drug-related cues in order to extinguish this learned association, has increasingly been proposed as a potential treatment of addictive behaviors, including tobacco smoking. The result of our pilot study suggests that a cue elicited using a virtual environment (VE) is more effective than other cue exposure devices. The VE was composed of craving environments (virtual bar) and objects (an alcoholic drink, a packet of cigarettes, a lighter, an ashtray, a glass of beer, and advertising posters) that are likely to trigger craving, a smoking avatar, and an audio environment that included the noisy sound and music of a restaurant. Sixteen late-adolescent males who smoked at least 10 cigarettes a day were recruited to participate in the VE-CET study. The CET virtual bar program consisted of six sessions, and the participants were exposed repeatedly to each session using different questions and procedures. Although the effects of CET did not yield significant reductions in all of the dependent variables, the craving for cigarettes was gradually decreased during the course of the sessions. This tendency was closely related to the reduction in the smoking count between the morning before the experiment and the start of the experiment. Based on these preliminary results, it appears that VE-CET maybe a useful tool to use in treatment programs to help reduce craving in those who are nicotine dependent.

Adolescent↗
PubMed1997

Behavioral self-regulation: correlates and 2 year follow-ups for boys at risk for substance abuse.

This investigation demonstrated the heuristic construct of behavioral self-regulation (BSR) as a salient component of the liability to substance abuse. Three dimensions of childhood behaviour were employed to create a dimensional model of BSR: inattention, impulsivity/hyperactivity and aggressivity. Multiple measures and multiple informants were employed to develop indices of the three traits in a sample of 10-12 year old sons of substance abusing fathers (high risk (HR); n = 180) and normal controls (low average risk (LAR); n = 200). Informants included mothers, boys and their teachers. The results confirmed the presence of a first-order latent trait of BSR. HR boys had significantly higher scores on BSR than LAR boys. Concurrent validity of the BSR trait scores was supported by significant associations with measures of family dysfunction, deviant peer affiliations and poor school performance. These latter problems are commonly prodromal to substance abuse. Predictive validity of the BSR trait baseline scores (age 10-12 years) was supported at 2 year follow-up by significant associations of BSR scores with magnitude of deviant peer affiliations; trends toward significance were found for family dysfunction and poor school performance. Taken together, these results confirm and extend previous findings which indicate that poor BSR is prodromal to substance abuse.

Aggression↗
PubMedDate not supplied

Bone lead levels in adjudicated delinquents. A case control study.

BACKGROUND: Lead exposure shares many risk factors with delinquent behavior, and bone lead levels are related to self-reports of delinquent acts. No data exist as to whether lead exposure is higher in arrested delinquents. The goal of this study is to evaluate the association between lead exposure, as reflected in bone lead levels, and adjudicated delinquency. METHODS: This is a case-control study of 194 youths aged 12-18, arrested and adjudicated as delinquent by the Juvenile Court of Allegheny County, PA and 146 nondelinquent controls from high schools in the city of Pittsburgh. Bone lead was measured by K-line X-ray fluorescence (XRF) spectroscopy of tibia. Logistic regression was used to model the association between delinquent status and bone lead concentration. Covariates entered into the model were race, parent education and occupation, presence of two parental figures in the home, number of children in the home and neighborhood crime rate. Separate regression analyses were also conducted after stratification on race. RESULTS: Cases had significantly higher mean concentrations of lead in their bones than controls (11.0+/-32.7 vs. 1.5+/-32.1 ppm). This was true for both Whites and African Americans. The unadjusted odds ratio for a lead level > or =25 vs. <25 ppm was 1.9 (95% CL: 1.1-3.2). After adjustment for covariates and interactions and removal of noninfluential covariates, adjudicated delinquents were four times more likely to have bone lead concentrations >25 ppm than controls (OR=4.0, 95% CL: 1.4-11.1). CONCLUSION: Elevated body lead burdens, measured by bone lead concentrations, are associated with elevated risk for adjudicated delinquency.

Adolescent↗
PubMed2000

Evaluation of the supervisory system in elderly subjects with and without disinhibition.

UNLABELLED: Disinhibition and irritability, defined as loss of behavioral and emotional control, are frequent in the elderly. The working hypothesis for this study was that these disorders are associated with a cognitive alteration of control processes that manifests as non-routine behavior because of the dysfunction of a general executive component known as the supervisory attentional system (SAS). METHODS: A total of 28 elderly subjects with mild cognitive impairment were recruited and divided into two groups using the Neuropsychiatric Inventory. Fourteen subjects were allocated to the disinhibited group and 14 subjects matched for age, sex and educational level formed a disinhibition-free control group. The neuropsychological battery included the following tests: Mini Mental Score Evaluation, Boston Naming test, Token test, Trail Making and Verbal Fluency. Two tasks were specifically designed to stress the SAS: 1) A specific verbal sentence arrangement task in which subjects had to use sequential reasoning with verbal material. Each test sequence consisted of a series of words shown in jumbled order. The construction of some sequences had to be done by using familiar routine associations (valid conditions). In contrast, other sequences required the overriding selection of familiar routine associations, which were inappropriate within the general context of the task (invalid conditions). 2) Using the Continuous Performance Test, four aspects were evaluated: sustained, selective, preparation and suppressive attention. RESULTS: The only group differences in neuropsychological test results were the following: 1) the sentence arrangement task. In comparison with the control group, the disinhibited group was impaired in invalid conditions and the calculated difference between the number of correct responses in invalid conditions minus that in valid conditions was significantly higher; and 2) the CPT. Disinhibited subjects had a significantly lower number of hits, exclusively in the 'suppressive attention' paradigm. These results suggest that subjects with disinhibition have impaired supervisory system function.

Aged↗
PubMed2006

Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone.

CONTEXT AND OBJECTIVE: In Sweden, from 1985 through 1995, 40 fetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) to prevent virilization of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment. DESIGN AND PATIENTS: Prenatally treated children, 7 to 17 yr old, were assessed with standardized neuropsychological tests (A Developmental Neuropsychological Assessment and Wechsler Intelligence Scales for Children) and child-completed questionnaires measuring self-perceived scholastic competence (Self-Perception Profile for Children). A parent-completed questionnaire (Child Behavior Checklist/4-18 School Scale) was used to evaluate whether the treatment had any impact on the children's school performance. In addition, a child-completed questionnaire measuring social anxiety (The Social Anxiety Scale for Children-Revised) was completed by the prenatally treated children aged 8 to 17 yr (n = 21) and age- and sex-matched controls (n = 26). RESULTS: Of 40 DEX-treated children, 26 (median age, 11 yr) participated in the study. Thirty-five sex- and age-matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory. Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). This group also showed increased self-rated social anxiety assessed by The Social Anxiety Scale for Children-Revised (P = 0.026). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child's full-scale IQ. CONCLUSIONS: This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and on certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.

Adolescent↗
PubMed1994

Splitting as a consequence of severe abuse in childhood.

Clinical data suggest that Kernberg's description of splitting as a defense mechanism is useful in conceptualizing the psychological consequences of abuse in childhood in certain patients. The splitting in these patients is similar to his description of splitting in borderline patients in that it compartmentalizes and sequesters certain overwhelming and painful ego states accompanying negative introjects of the betraying primary object and the betrayed self. These sequestered introjects, furthermore, act as automatons, generating behaviors that arbitrarily re-enact their content even though the patient remains consciously unaware of their historical meaning. Another consequence of the sequestration of these traumatic introjects is that their affects retain their initial power and primitive quality, unmodulated by the usual homogenizing process that is a part of the synthesis of part-object introjects into whole-object introjects; the sequestration, therefore, often painful in itself, must nevertheless be rigidly maintained lest traumatic anxiety in the face of overwhelming affects be re-experienced. Shengold calls the sequence of events that results in this brittle but stubborn painful constriction of the personality "soul murder." He borrowed the phrase from Freud who used it to refer to what Schreber had suffered at the hands of his sadistic father. That phrase--"soul murder"--may sound melodramatic, but it powerfully conveys what these patients communicate of their experience of themselves. As with Kernberg's patients, the defensive splitting serves to protect the positive introjects. These patients fear their negative introjects, even more than they feel uncomfortable about the split. They fear their desperate rage will destroy their love objects, and leave them feeling abandoned and hating themselves. As one of my patients put it: "I fear that my destructive anger will leave me all alone in a sea of rubble of my own making." In the transference, he feared destroying me and our positive bond. In these cases it would seem that the turning to splitting occurred at a later age than it does with Kernberg's borderline patients. His proposition is that the developmentally normal "splitting," related to the undifferentiation of the infantile ego, persists as a defensive splitting, perhaps as a consequence of a consistently derailed mother-child dialogue; whereas in my patients it would seem that the normal developmental splitting had waned as ego differentiation proceeded, but that in the face of overwhelming traumata at perhaps 3 or 4 years of age, the primitive defense was invoked regressively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1977

Differentiation of alcoholics. Childhood history of minimal brain dysfunction, family history, and drinking pattern.

Alcoholics were differentiated into two subgroups on the basis of drinking patterns and subjective response to alcohol. Severe drinkers (primary alcoholics) retrospectively reported more symptoms of childhood minimal brain dysfunction than less severe drinkers (secondary alcoholics), psychiatric patients, and normals. The alcoholics as a group reported a greater incidence of familial alcohol abuse than the psychiatric subjects, but a difference on this factor was not observed between the primary and secondary subgroups. In terms of clinical status, the primary alcoholics presented Minnesota Multiphasic Personality Inventory profile more indicative of normality than the other groups, but scored significantly higher on the MacAndrew Alcoholism Scale. These findings are discussed in light of further delineating a specific subtype of alcoholism that may have a genetic-constitutional relationship with other pathological disorders.

Achievement↗
PubMed1998

A functional magnetic resonance imaging study of tic suppression in Tourette syndrome.

BACKGROUND: The inability to inhibit unwanted behaviors and impulses produces functional debility in a broad range of neuropsychiatric disorders. A potentially important model of impulse control is volitional tic suppression in Tourette syndrome. METHODS: Tic suppression was studied in 22 adult subjects with Tourette syndrome by using functional magnetic resonance imaging. Images acquired during periods of voluntary tic suppression were compared with images acquired when subjects allowed the spontaneous expression of their tics. The magnitudes of signal change in the images were then correlated with measures of the severity of tic symptoms. CONCLUSIONS: Significant changes in signal intensity were seen in the basal ganglia and thalamus and in anatomically connected cortical regions believed to subserve attention-demanding tasks. The magnitudes of regional signal change in the basal ganglia and thalamus correlated inversely with the severity of tic symptoms. These findings suggest that the pathogenesis of tics involves an impaired modulation of neuronal activity in subcortical neural circuits.

Adolescent↗
PubMed2002

Blunted prefrontal cortical 18fluorodeoxyglucose positron emission tomography response to meta-chlorophenylpiperazine in impulsive aggression.

BACKGROUND: Impulsive aggression is a prevalent problem and yet little is known about its neurobiology. Preclinical and human studies suggest that the orbital frontal cortex and anterior cingulate cortex play an inhibitory role in the regulation of aggression. METHODS: Using positron emission tomography, regional metabolic activity in response to a serotonergic stimulus, meta-chlorophenylpiperazine (m-CPP), was examined in 13 subjects with impulsive aggression and 13 normal controls. The anterior cingulate and medial orbitofrontal regions were hypothesized to respond differentially to m-CPP in patients and controls. In the frontal cortex, regional metabolic glucose response to m-CPP was entered into a group (impulsive aggressive, control) x slice (dorsal, middle, orbital) x position (medial, lateral) x location (anterior, posterior) x hemisphere (right, left) mixed-factorial analysis of variance design. A separate group (impulsive aggressive, controls) x anteroposterior location (Brodmann areas 25, 24, 31, 29) x hemisphere (right, left) analysis of variance was used to examine regional glucose metabolism in the cingulate gyrus. RESULTS: Unlike normal subjects, patients with impulsive aggression did not show activation specifically in the left anteromedial orbital cortex in response to m-CPP. The anterior cingulate, normally activated by m-CPP, was deactivated in patients; in contrast, the posterior cingulate gyrus was activated in patients and deactivated in controls. CONCLUSIONS: The decreased activation of inhibitory regions in patients with impulsive aggression in response to a serotonergic stimulus may contribute to their difficulty in modulating aggressive impulses.

Aggression↗
PubMed2003

Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression.

BACKGROUND: Lower serotonergic activity correlates with high-lethality suicide attempts in major depression. Postmortem studies of serotonin receptors in suicides localize changes to the ventral prefrontal cortex (PFC). We studied serotonergic response in ventral PFC in depressed patients surviving a high-lethality suicide attempt. METHODS: Depressed patients with a history of a high-lethality suicide attempt (n = 16) were compared with those with low-lethality attempts (n = 9) for level of depression, suicidal intent and ideation, impulsivity, aggression, and neuropsychological test performance. Subjects were scanned while medication free after a single-blind placebo and after fenfluramine hydrochloride administration on a second day. Brain responses were measured by positron emission tomography imaging of fludeoxyglucose F 18 and serial prolactin levels. Scans were compared by means of statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical and neuropsychological measures were assessed. RESULTS: Depressed high-lethality suicide attempters had lower rCMRglu in ventral, medial, and lateral PFC compared with low-lethality attempters. This difference was more pronounced after fenfluramine administration. Lower ventromedial PFC activity was associated with lower lifetime impulsivity, higher suicidal intent (planning), and higher-lethality suicide attempts. Higher verbal fluency was positively correlated with rCMRglu in the same regions. CONCLUSIONS: Prefrontal localized hypofunction and impaired serotonergic responsivity are proportional to the lethality of the suicide attempt and may mediate the effects of suicide intent and impulsivity on lethality. Positron emission tomographic neuroreceptor studies are needed to determine whether postmortem serotonin receptor findings are also present in vivo and contribute to the abnormal rCMRglu responses.

Adult↗
PubMed2006

Criminality among individuals testing positive for the presence of anabolic androgenic steroids.

CONTEXT: Observations suggest that the use of anabolic androgenic steroids (AAS) may trigger uncontrolled, violent rage. Other observations indicate that certain groups of criminals may use AAS with the intention of being capable of committing crime more efficiently. OBJECTIVE: To examine the proposed association between the use of AAS and criminality. DESIGN: A controlled retrospective cohort study of registered criminal activity among individuals tested for AAS use during the period of January 1, 1995, to December 31, 2001. SETTING: All individuals in Sweden who were tested for AAS use during this period. These individuals were referred for testing from both inpatient and outpatient clinics as well as from centers for treatment of substance abuse. PARTICIPANTS: Individuals testing positive for AAS (n=241), with those testing negative for AAS during the same period (n=1199) serving as the control group. MAIN OUTCOME MEASURES: The ratios (expressed as relative risk [RR]) of the incidences of several categories of crime in the 2 study groups. RESULTS: The risk of having been convicted for a weapons offense or fraud was higher among individuals testing positive for AAS than among those testing negative (RR, 2.090 and 1.511, respectively; 95% confidence interval [CI], 1.589-2.749 and 1.208-1.891, respectively) whereas there were no significant differences with respect to violent crimes (RR, 1.116; 95% CI, 0.981-1.269) or crimes against property (RR, 0.942; 95% CI, 0.850-1.044). When patients referred from substance abuse centers were excluded, a lower risk for crimes against property was observed for the individuals who tested positive for AAS (RR, 0.761; 95% CI, 0.649-0.893) and the risk for fraud in the 2 groups was equalized (RR, 1.117; 95% CI, 0.764-1.635). The increased risk for a weapons offense among the individuals testing positive for AAS remained virtually unchanged. CONCLUSIONS: In addition to the impulsive violent behavior previously shown to be related to AAS use, such use might also be associated with an antisocial lifestyle involving various types of criminality. However, the existence and nature of this possible association remain unclear and call for further investigation.

Adult↗