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PubMed2004

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

Animals↗
PubMed1999

Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1.

Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p.

Abnormalities, Multiple↗
PubMed2000

Behavioral methods used in the study of long-chain polyunsaturated fatty acid nutrition in primate infants.

Domains of behavior may be broadly categorized as sensory, motor, motivational and arousal, cognitive, and social. Differences in these domains occur because of changes in brain structure and function. Docosahexaenoic acid (DHA; 22:6-23) and arachidonic acid (AA; 20:4-26) are major structural components of the brain that decrease when diets deficient in the essential fatty acids (EFA) alpha-linolenic acid and linoleic acid are consumed. Early electrophysiologic and behavioral studies in EFA-deficient rodents showed behavioral effects attributable to lower-than-normal accumulation of DHA and AA in the brain. More recently, electrophysiologic and behavioral studies in EFA-deficient primate infants and analogous studies in human infants have been conducted. The human infants were fed formulas that could result in lower-than-optimal accumulation of long-chain polyunsaturated fatty acids (LCPUFAs) in the brain during critical periods of development. This article describes the behavioral methods that have been used to study primate infants. These methods may be unfamiliar to many physicians and nutritionists who wish to read and interpret the human studies. The behavioral outcomes that have been evaluated in LCPUFA studies represent only a fraction of those available in the behavioral sciences. Specific developmental domains have been studied less often than global development, even though studies of nonhuman primates deficient in EFAs suggest that the former provide more information that could help target the underlying mechanisms of action of LCPUFAs in the brain.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Patterns and correlates of supervision in child pedestrian injury. The Kids 'N' Cars Research Team.

Described supervision in 142 child pedestrian injuries (PI), based on presence and proximity of supervisors and/or peers. Children (5-12 years), families, sites, and PI events were described via record reviews, interviews, questionnaires, and site investigation. Supervision of PI victims varied with family size and cohesion, and with children's age, self-help skills, nearness to home, and activity (playing or journey). Peer presence was associated with more impulsive behavior among supervised (but not among unsupervised) PI victims. Definitions of supervision parameters offered here can aid research on the complex relationship between supervision and PI risk.

Accidents, Traffic↗
PubMed1992

Clomipramine in autism: preliminary evidence of efficacy.

This report provides preliminary evidence for the efficacy of clomipramine in the treatment of young adults with autistic disorder. Four of five outpatients with autistic disorder showed significant improvement in social relatedness, obsessive compulsive symptoms, and aggressive and impulsive behavior with clomipramine treatment. These findings are consistent with previous evidence, suggesting that serotonin neurotransmission may be relevant to the treatment, and possibly the pathophysiology, of some symptoms of autistic disorder.

Adolescent↗
PubMed1996

Bupropion hydrochloride in attention deficit disorder with hyperactivity.

OBJECTIVE: This is a multisite, double-blind, placebo-controlled trial to determine the safety and efficacy of bupropion in the treatment of children with attention deficit disorder with hyperactivity (ADDH). METHOD: In a four-center, double-blind comparison of bupropion (n = 72) and placebo (n = 37), children aged 6 to 12 years meeting DSM-III criteria for ADDH were randomized to receive bupropion 3 to 6 mg/kg per day or placebo, administered twice daily, at 7 A.M. and 7 P.M. Measures of efficacy included the Conners Parent and Teacher Questionnaires (93-item, 39-item, and 10 item), Clinical Global Impressions Scales of Severity and Improvement, the Sternberg Short-Term Memory Task, and the Continuous Performance Test. Screen and posttreatment physical examinations, electrocardiograms, electroencephalograms, and clinical laboratory evaluations were performed. Height, weight, and vital signs were measured and adverse experiences were assessed weekly. RESULTS: A significant treatment effect, apparent as early as day 3, was present for both conduct problems and hyperactivity on the Conners 10-item and 39-item teacher's checklist, and at day 28 for conduct problems and restless-impulsive behavior on the 93-item parent questionnaire. Findings were of smaller magnitude for parent ratings than teacher ratings. Significant treatment effects were present on both the Continuous Performance Test and memory retrieval test. Effect sizes of bupropion/placebo differences for teacher and parent ratings in this study were somewhat smaller than for standard stimulant drugs used to treat ADDH. Bupropion appeared to be well tolerated in most children. Dermatological reactions were twice as frequent in the drug group as the placebo group, with four reactions involving rash and urticaria that were serious enough to require discontinuation of medication. CONCLUSIONS: Bupropion may be a useful addition to available treatments for ADDH. Comparative trials with such standard drugs as methylphenidate are warranted to determine the relative clinical merits of bupropion.

Antidepressive Agents, Second-Generation↗
PubMed2002

Preschool attention deficit hyperactivity disorder: a review of prevalence, diagnosis, neurobiology, and stimulant treatment.

The clinical use of stimulant medications for 3- to 6-year-old preschool children who meet diagnostic criteria for attention deficit hyperactivity disorder (ADHD) is becoming more common. A systematic computerized literature search extending back to 1970 identified nine controlled studies of stimulant treatment and two controlled trials of stimulant side effects in preschool ADHD children. Treatment benefits are reported for eight of nine (89%) controlled stimulant trials involving a total of 206 preschool subjects. In comparison with school-aged ADHD youth, there may be a greater variability of stimulant response in ADHD preschoolers. Domains assessing cognition, interpersonal interactions, and hyperactive-impulsive behavior are noted to improve on drugs relative to placebos. Side effects in this age range are generally reported as mild. ADHD preschool children may experience slightly more and different types of stimulant-induced side effects compared with older children. High rates of behavior reported as stimulant side effects are found for children receiving a placebo, necessitating a baseline evaluation for medication side effects before stimulants are initiated. Despite the lack of research assessing stimulant effects on the very young and developing brain and the need for more controlled medication trials in this age range, this review of the extant literature finds stimulants to meet evidence based criteria as beneficial and safe for carefully diagnosed ADHD preschool children aged 3 years and older.

Attention Deficit Disorder with Hyperactivity↗
PubMed1989

Amitriptyline versus haloperidol in borderlines: final outcomes and predictors of response.

The authors report the final results of a 4-year study of amitriptyline and haloperidol in 90 symptomatic borderline inpatients. Medication trials were double-blind and placebo controlled and lasted 5 weeks. Haloperidol (4-16 mg/day) produced significant improvement over placebo in global functioning, depression, hostility, schizotypal symptoms, and impulsive behavior. Significant effects of amitriptyline (100-175 mg/day) were generally limited to measures of depression. Factor analysis identified three symptom change patterns: a global depression, hostile depression, and schizotypal symptom pattern. Medication effects favoring haloperidol were most prominent for hostile depression. Variables predicting favorable response to haloperidol included severity of schizotypal symptoms, hostility, and suspiciousness. Schizotypal symptoms and paranoia predicted poor outcome on both depression patterns with amitriptyline. Placebo effects were most prominent on acute state symptoms, with severe character traits predicting poor response.

Amitriptyline↗
PubMed2001

Attention deficit/hyperactivity disorder and substance abuse. Diagnostic and therapeutic considerations.

Patterns of association between attention deficit hyperactivity disorder (ADHD) and substance-use disorders are considered. Recent investigations have found that up to 50% of individuals with continuing ADHD symptoms have a substance-use disorder. ADHD appears to represent an independent risk factor for substance abuse. We review clinical challenges posed by the diagnosis of ADHD in substance-abusing populations. Nicotine dependence is also substantially more common among adults with ADHD (40%) than in the general population (26%). While several classes of substances of abuse may ameliorate various symptoms of ADHD, individuals with ADHD may also be vulnerable to substance use because of poor judgment or impulsive behavior in social settings. Evidence is reviewed from genetic studies examining the role of the dopamine D2 (DRD2) gene in the etiology of ADHD. The presence of ADHD may affect the course of adolescent substance abuse in several ways: predicting earlier age of onset, longer duration of substance-use disorder, and progression of alcohol abuse to another drug-use disorder. Individuals with ADHD have been noted to have a shorter interval between the onsets of drug abuse and drug dependence. Such individuals are also at greater risk for treatment failure, as their disruptive behaviors interfere with treatment access and response. Lastly, we review advances in pharmacotherapeutic agents used for treating ADHD and consider the impact of these interventions on comorbid substance-use disorders. We suggest promising areas of focus for clinical research trials targeting the subpopulation of substance abusers with concurrent ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Event-related potentials to emotional and neutral stimuli in alcoholism.

Several studies have demonstrated that the emotional value of stimuli affects P300 amplitude. In the present study, the influence of alcohol-related stimuli in alcoholic patients was investigated. Subjects were 10 alcoholic inpatients (3 female) and 10 age- and sex-matched controls. Eight alcohol-related and 8 neutral words served as stimuli in a visual oddball paradigm. Acohol-related words were targets (48 stimuli, 33%) and neutral words were standard stimuli (96 stimuli, 66%). Results showed that P300 amplitude for targets did not differ significantly between the two groups. However, P300 latency for targets as well as reaction time were significantly shorter in male alcoholic patients. In contrast, P300 latency was increased in female alcoholic patients but reaction time did not differ. These results suggest that male alcoholics process information linked to alcohol cues more rapidly than neutral cues, probably because a specific semantic network is activated in these patients. The decreased reaction time confirms the impulsive behavior frequently found in male alcoholism, as it has been described in type II alcoholism. Besides, the results imply that information processing was delayed in female alcoholic patients. Therefore this study demonstrates a gender-dependent impact of alcohol-related stimuli on information processing.

Adult↗
PubMed1975

Elements of resistance to a combined medical and psychotherapeutic program in anorexia nervosa. An overview.

According to several follow-up studies in the literature, anorexia nervosa has to be considered as an affection with a grave prognosis. We have studied the outcome in a group of 32 female patients who could be considered as homogeneous in a number of aspects. The following five criteria, on which the delineation of the syndrome is based, were realized in all the patients: considerable weight loss; limited food intake; amenorrhea; juvenile age of onset; absence of primary organic or specific psychotic disorder. All of them presented a serious symptomatology and had undergone some previous treatment under the form of ambulatory psychotherapy and/or forced feeding. They all received, during their admission in the same hospital, the same form of combined intensive medical and psychotherapeutic treatment. All of them maintained regular psychotherapeutic contacts with the same psychiatrist. According to the outcome, the patients could be categorized into three groups: the cured, the improved, the unimproved. In order to circumscribe some prognostic elements, we have compared a number of clinical, family and personality variables in these groups. As favorable clinical factors can be mentioned: younger age at admission and shorter duration of the illness. Manifestations of impulsive behavior (automutilation, kleptomania, fugues, etc. ...) and sucide attempts are unfavorable. No definite family factors can be defined, although the absence of psychological interaction with the father seems to be unfavorable. A better prognostic outcome is offered by the following personality characteristics, determined by psychological testing: lower neuroticism and higher self-defensiveness on the ABV; a lower general profile and especially a lower score on the schizophrenia scale of the MMPI; less pronounced tendencies to infantile regression, passivity and sexual repression as these are expressed in the TAT.

Adolescent↗
PubMed1987

Cognitive style of patients with bulimic and diet-restricting anorexia nervosa.

Recent studies have reported that subjects with bulimic anorexia nervosa are more behaviorally impulsive than those with diet-restricting anorexia nervosa. This study found that bulimic anorexic patients made significantly more errors on the Matching Familiar Figures Test than restricting anorexic and comparison groups. This preliminary finding leads to the speculation that bulimic patients are more cognitively impulsive than restricting anorexic patients.

Adult↗
PubMed2003

Personality traits and striatal dopamine synthesis capacity in healthy subjects.

OBJECTIVE: Neuroimaging and genetic studies suggest that individual differences in the brain dopaminergic system contribute to the normal variability of human personality (e.g., social detachment and novelty seeking). The authors studied whether presynaptic dopamine function is also associated with personality traits. METHOD: Presynaptic dopamine synthesis capacity in the brain was measured with positron emission tomography and [(18)F]fluorodopa in 33 healthy adults, and personality traits were assessed with the Karolinska Scales of Personality. Associations were studied by using a linear regression model controlling for the effects of age and gender on both variables. RESULTS: High scores on two of the anxiety-related personality scales, somatic anxiety and muscular tension, and on one aggressivity-related scale, irritability, were significantly associated with low [(18)F]fluorodopa uptake in the caudate. No statistically significant associations were observed between [(18)F]fluorodopa uptake and the detachment scale or scales related to novelty-seeking behavior (impulsiveness and monotony avoidance). CONCLUSIONS: The results suggest a role for the dopaminergic system in the regulation of anxiety in healthy subjects. Together with previous studies, they also indicate differential involvement of various components of the dopaminergic system in normal and pathological personality traits.

Adult↗
PubMed1997

Need and responsiveness in the treatment of a severely traumatized patient: a relational perspective.

Severely traumatized patients may exhibit poor functioning and a great deal of dependence upon the therapist. The question is raised as to what such patients truly need from a therapist, and the concept of optimal responsiveness is described. These patients may display complex blends of deficits, resulting from inadequate structuralization, together with pathological internal representations. Their expressed needs in therapy may be true requirements and/or expressions of wishes to be compensated for past suffering and refusal to assume adult functioning. Discerning what might constitute optimal responsiveness to true needs may be further complicated by the propensity some of these patients have for dysfunctional and impulsive behavior. A case is presented that illustrates some of the difficulties in determining how to respond to intense expressions of need, including needs for constant availability of the therapist and for physical contact. It is concluded that although this patient did not need everything from the therapist that she initially thought that she did, her needs were so great that an outpatient treatment situation often seemed insufficient. Despite an overall positive outcome for the patient, the treatment experience was very difficult for the therapist.

Adult↗
PubMedDate not supplied

Comorbidity of reading disability and attention-deficit/hyperactivity disorder: differences by gender and subtype.

This study used a community sample of 494 twins with a reading disability (223 girls, 271 boys) and 373 twins without a reading disability (189 girls, 184 boys) to assess the relation between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). Symptoms of DSM-III and DSM-IV ADHD were classified into symptoms of inattention and symptoms of hyperactivity-impulsivity (H/I). Results indicated that individuals with RD were more likely than individuals without RD to meet criteria for ADHD and that the association between RD and ADHD was stronger for symptoms of inattention than for symptoms of H/I. Parents and teachers reported similar rates of ADHD, suggesting that ADHD symptoms were pervasive across settings and were not solely attributable to academic frustration. Analyses of possible gender differences revealed that RD was significantly associated with inattention in both girls and boys but associated with H/I only in boys. This difference may provide a partial explanation for the discrepancy between the gender ratio obtained in referred (approximately 4 boys to 1 girl) and nonreferred (1.2 to 1.5 boys to 1 girl) samples of individuals with RD. Specifically, the hyperactive and impulsive behaviors exhibited by boys with RD may be more disruptive than the inattentive behaviors exhibited by girls and may therefore precipitate more frequent referrals for clinical attention.

Adolescent↗
PubMed2005

Validation of three dimensions of childhood psychopathology in young clinic-referred boys.

Short measures of child inattention-overactivity (IO), aggression-defiance (AG), and anxiety-depression or emotionality (EM) derived through a double validation procedure are administered to mothers of 243 clinic-referred suburban New York boys between 6 and 10 years of age. Mother-rated IO is uniquely related to poor performance on cognitive and achievement tests; observed inattentive, hyperactive, and impulsive behaviors in a restricted academic setting; less father education and lower family income; and most mother-reported impairments and treatment use. Mothers of high-IO boys describe themselves and their sons as having similar childhood symptoms. AG is uniquely related to child-reported disruptive behavior and sensation seeking, many measures of family conflict and negative parenting styles, and mother-reported symptom pervasiveness and number of treatments. EM is uniquely related only to poorer cognitive and achievement test performance, living with one parent, parents who considered themselves too busy, and fewer friends. Each dimension also is associated with parallel teacher-rated factors.

Achievement↗