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Serotonin, suicide, and aggression: clinical studies.

Both suicidal and aggressive, impulsive behaviors have been linked to putative dysregulation in central serotonergic systems. We review data examining the role of serotonin (5-HT) in suicide from postmortem studies and clinical investigations of suicide attempters, including our own preliminary work derived from neuroendocrine challenges with the 5-HT uptake inhibitor clomipramine. Various approaches to the study of 5-HT and aggressive, impulsive behavior, including cerebrospinal fluid studies, investigations of peripheral measures of 5-HT, and neuroendocrine studies utilizing 5-HT probes, are highlighted. Several important caveats, including the challenge of quantifying "suicidality" and "aggression" in reliable and valid ways, should be considered in interpreting the results of clinical studies of 5-HT and suicide and aggression.

Adolescent↗

Gilles de la Tourette's syndrome with and without obsessive-compulsive disorder compared with obsessive-compulsive disorder without tics: which symptoms discriminate?

Stereotyped repetitive behaviors occur in Gilles de la Tourette's Syndrome (GTS) and obsessive-compulsive disorder (OCD). The present study was undertaken to compare the distribution of obsessive-compulsive and Tourette-related impulsive behaviors in GTS with (+) OCD, GTS without (-) OCD, tic-free OCD, and control subjects. Fourteen GTS + OCD, 18 GTS-OCD, 21 OCD-tic, and 29 control subjects were evaluated using a semistructured interview designed to assess GTS and OCD-related repetitive behaviors. Each reported item was evaluated on the presence of anxiety and goal-directedness. This information was subsequently used to define whether the repetitive behavior was an (anxiety-related) obsession or compulsion, or a (non-anxiety-related) OC-like behavior, impulsion. GTS + OCD subjects reported more overall Tourette-related impulsions than OCD-tic subjects, i.e., more mental play, echophenomena, and touching behaviors but similar frequencies of typical obsessive-compulsive behaviors. Further, GTS + OCD subjects exhibited more overall repetitive behaviors than GTS-OCD subjects, i.e., more Tourette-related impulsions as well as more obsessive-compulsive behaviors. The distribution of symptoms is similar in GTS with and without OCD, and differs from tic-free OCD. These differences suggest that GTS with OCD constitutes a form of GTS, not of OCD, although the possibility that GTS + OCD patients constitute a subgroup distinct from GTS and from OCD can not be excluded by this phenomenological study. Specific non-anxiety-related impulsions seem to discriminate between GTS and OCD-tic individuals. These impulsions possibly reflect differences in underlying mechanisms between GTS and OCD-tics.

Adult↗

A psychoanalytic approach to a therapeutic impasse with an impulsive adolescent: permission to speak the unspeakable.

The authors describe an impasse in the therapy of an impulsive, intermittently psychotic adolescent boy and demonstrate the usefulness of understanding the impulsive behavior according to the classical psychoanalytic definition of "acting out." Rather than being viewed as a random breaking through of impulses, this impulsive behavior can best be understood and clarified in the course of intensive psychotherapy as classical acting out under the influence of the therapy and the transference. With impulsive patients of this type they have observed a strong tendency to abandon this basic psychoanalytic formulation and the use of the verbal interventions that follow from them. Such patients often need encouragement to remember and express their painful feelings in words instead of repeating the entire emotional experience in action. The authors also describe the resistances within the treatment team that interfered with the development and utilization of this basic psychoanalytic formulation.

Acting Out↗

Effects of novelty on behavior in the adolescent and adult rat.

Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability of initiating drug use and is associated with an increased risk to develop addiction and dependency in adulthood. Human adolescents are predisposed towards an increased likelihood of risk taking behaviors (Zuckerman, 1986), including drug use or initiation. The purpose of the study was to examine differences in developmental risk taking behaviors. Adolescent and adult animals were exposed to a novel stimulus in a familiar environment to assess impulsive behaviors, novelty preference, and exploratory behaviors. Adolescent animals had greater novelty-induced locomotor activity, greater novelty preference, and showed higher approach and exploratory behaviors compared to adult animals. These data support the notion that adolescents may be predisposed toward sensation seeking and consequently, are more likely to engage in risk-taking behaviors, such as drug use initiation.

Age Factors↗

Behavioral disinhibition requires dopamine receptor activation.

RATIONALE: Behavioral disinhibition is a manifestation of impulsive behavior that is prominent in the psychopathology of various psychiatric disorders, but the underlying neural mechanisms are unclear. Behavioral disinhibition can be investigated by measuring premature responding in the 5-choice serial reaction time task (5-CSRTT) in which attentional parameters can be measured as well. OBJECTIVE: The objective of the study was to investigate the involvement of dopamine neurotransmission in behavioral disinhibition using the 5-CSRTT in rats. METHODS: The effects of amphetamine, cocaine, nicotine, the dopamine reuptake inhibitor GBR 12909, the noradrenaline reuptake inhibitor desipramine, the dopamine D1 receptor antagonist SCH 23390, and the dopamine D2 receptor antagonist eticlopride were studied in rats that were well-trained in the 5-CSRTT. Subsequently, the effects of amphetamine, cocaine, and nicotine were tested after pretreatment with SCH 23390 or eticlopride. RESULTS: What amphetamine, cocaine, and nicotine had in common is that they increased premature responding. However, these drugs had distinct effects on attentional parameters. GBR 12909 also enhanced premature responding, whereas desipramine reduced it. Eticlopride by itself had no effect on premature responding but it attenuated the increases in this parameter evoked by amphetamine, cocaine, or nicotine. SCH 23390 reduced premature responding on its own and also reduced its drug-induced enhancement. CONCLUSIONS: The present data show that behavioral disinhibition, i.e., the inability to withhold a premature response, is a common effect of drugs of abuse and that this effect is the result of enhanced dopaminergic neurotransmission. In addition, dopamine D1 and D2 receptors play important, but perhaps distinct roles, in inhibitory control of behavior.

Amphetamine↗

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors.

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.

Aggression↗

Testing an APA practice guideline: symptom-targeted medication utilization for patients with borderline personality disorder.

BACKGROUND: The goal of this study was to test whether the use of psychotropic medication treatment for borderline personality disorder (BPD) was consistent with proposals in the recently published American Psychiatric Association's Practice Guideline for the Treatment of Patients with Borderline Personality Disorder. METHOD: Medication utilization by patients with BPD was assessed prospectively over a 2-year period prior to the publication of the Guideline. Three BPD symptom clusters--cognitive-perceptual, affective dysregulation, and impulsive-behavioral dyscontrol--along with demographic and functioning variables were used to predict the use of five classes of medication. RESULTS: Symptoms of impulsive-behavioral dyscontrol significantly predicted use of both neuroleptics and anticonvulsants. Cognitive-perceptual symptoms were inversely related to anticonvulsant use. CONCLUSION: While some pre-Guideline medication practices with BPD patients were consistent with the recommended algorithms, physicians may also have been influenced by a variety of considerations, including level of functional impairment and the presence of comorbid Axis I conditions.

Adolescent↗

Beyond discounting: possible experimental models of impulse control.

Animal studies of impulsivity have typically used one of three models: a delay of reward procedure, a differential reinforcement for low rate responding (DRL) procedure, or an autoshaping procedure. In each of these paradigms, we argue, measurement of impulsivity is implicitly or explicitly equated with the effect delay has on the value of reward. The steepness by which delay diminishes value (the temporal discount function) is treated as an index of impulsivity. In order to provide a better analog of human impulsivity, this model needs to be expanded to include the converse of impulsivity - self-control. Through mechanisms such as committing to long range interests before the onset of temptation, or through bundling individual choices into classes of choices that are made at once, human decision-making can often look far less myopic than single trial experiments predict. For people, impulsive behavior may be more often the result of the breakdown of self-control mechanisms than of steep discount functions. Existing animal models of self-control are discussed, and future directions are suggested for psychopharmacological research.

Animals↗

Maternal attributions, affect, and parenting in attention deficit hyperactivity disorder and comparison families.

The goal of this study was to simultaneously examine maternal attributions, affect, and parenting in mothers of children with and without attention deficit hyperactivity disorder (ADHD) using a multimethod approach (vignettes, confederate child video clips, and video clips of mother's own child). Of the participants, 23 were 7- to 12-year-old children (19 boys, 4 girls) with ADHD and their mothers, and 29 were 7- to 12-year-old comparison children (21 boys, 8 girls) and their mothers. Results indicated that mothers of children with ADHD attributed inattentive-impulsive behavior to less controllable and intentional factors and reported more negative affect and power assertive parenting in response to it than comparison mothers. They also attributed this behavior to more internal factors than comparison mothers but only when viewing their own children and to more global/stable factors but only when viewing their own children or a confederate child. Interestingly, mothers of children with ADHD reported more positive parenting in response to prosocial behavior while attributing this behavior to less controllable and global/stable factors than comparison mothers; compliance also was seen as less controllable, global/stable, and intentional by mothers of children with ADHD.

Affect↗

Serum cholesterol, suicidal tendencies, impulsivity, aggression, and depression in adolescent psychiatric inpatients.

BACKGROUND: This study was undertaken to examine the relationship between serum cholesterol levels and suicidal behaviors in adolescent psychiatric inpatients. Any association between serum cholesterol and measures of suicidal behavior, impulsivity, aggression, anxiety, and depression was also examined. METHODS: Consecutive admissions (n = 152) to an adolescent psychiatric inpatient unit were assessed using measures of suicidal behavior, violence, impulsivity, and depression. Serum cholesterol was compared between those admitted for reasons of suicidal tendencies and those for other reasons. Correlation between serum cholesterol and measures of suicidal behavior, violence, impulsivity, and depression were examined. RESULTS: Serum cholesterol levels were significantly higher in adolescent patients who were currently suicidal than in nonsuicidal adolescents. Within the suicidal group, but not in the total inpatient group, serum cholesterol correlated negatively with the degree of suicidal behavior. No correlation between serum cholesterol levels and depression, violence, and impulsivity were detected. No significant differences were found in serum cholesterol levels between diagnoses or between suicidal and nonsuicidal patients within each diagnostic group. CONCLUSIONS: The association between cholesterol and suicidal tendencies remains complex and may depend on several variables within the population studied. Its usefulness as a biologic risk factor in clinical samples remains to be determined.

Adolescent↗

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Adolescent↗

Reduction of aggressiveness and impulsiveness during clozapine treatment in chronic neuroleptic-resistant schizophrenic patients.

Aggressive and impulsive behavior is frequently observed in schizophrenic patients. Previous studies suggest that impulsive aggression may be the most common behavioral correlate of central serotonergic system dysfunction. This study was aimed to determine if clozapine, an atypical antipsychotic agent with potent serotonergic antagonistic properties, can reduce impulsiveness and aggression in neuroleptic-resistant chronic schizophrenic patients. Fourteen neuroleptic-resistant chronic schizophrenic patients were treated with clozapine and prospectively evaluated for aggressiveness and impulsiveness for 18 weeks. Clozapine treatment induced a marked decrease in impulsiveness (32% on the Impulsivity Scale; p < 0.0001) and aggressiveness (98% on the Overt Aggression Scale; p < 0.0001). We conclude that clozapine treatment may be effective in reducing psychotic symptoms as well as in controlling aggressive and impulsive behavior in neuroleptic-resistant chronic schizophrenic patients.

Adult↗

Pathological gambling severity is associated with impulsivity in a delay discounting procedure.

Research and clinical expertise indicates that impulsivity is an underlying feature of pathological gambling. This study examined the extent to which impulsive behavior, defined by the rate of discounting delayed monetary rewards, varies with pathological gambling severity, assessed by the South Oaks Gambling Screen (SOGS). Sixty-two pathological gamblers completed a delay discounting task, the SOGS, the Eysenck impulsivity scale, the Addiction Severity Index (ASI), and questions about gambling and substance use at intake to outpatient treatment for pathological gambling. In the delay discounting task, participants chose between a large delayed reward (US $1000) and smaller more immediate rewards (US $1-$999) across a range of delays (6h to 25 years). The rate at which the delayed reward was discounted (k value) was derived for each participant and linear regression was used to identify the variables that predicted k values. Age, gender, years of education, substance abuse treatment history, and cigarette smoking history failed to significantly predict k values. Scores on the Eysenck impulsivity scale and the SOGS both accounted for a significant proportion of the variance in k values. The predictive value of the SOGS was 1.4 times that of the Eysenck scale. These results indicate that of the measures tested, gambling severity was the best single predictor of impulsive behavior in a delay discounting task in this sample of pathological gamblers.

Journal Article↗

Aggression: the testosterone-serotonin link.

The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and animals. Among other findings, there are abundant data relating low serotonergic activity--as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine--to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptor activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.

Aggression↗

Social anxiety disorder in 11-12-year-old children: The efficacy of screening and issues in parent-child agreement.

OBJECTIVE: To investigate the level of diagnostic and discriminative accuracy of The Social Anxiety Scale for Children - Revised (SASC-R) for identifying social anxiety disorder (SAD) in a community-based sample of 11-12 year-old children. Parent-child diagnostic agreement was also examined. METHOD: A questionnaire including SASC-R and items on impulsive behavior was sent to a population based sample of children, born in 1992. A total of 2568 parents returned their questionnaires (rr: 70%), and 1297 (51%) consented to further participation. An index group [50 high-scoring children on social anxiety (SA-group)] and two contrast groups [(50 high-scoring children on impulsive behavior (Imp-group) and 50 low-scoring children on SA and Imp, (Ls-group)] were selected for participation. RESULTS: SAD was assigned 35 (23%) of 150 children; 28 (80%) from the SA-group; 7 (20%) from the Imp- group and 0 from the Ls-group. The SASC-R showed relatively high discriminative accuracy for SAD, but was also influenced by other diagnoses. Mother-child agreement was fair (kappa = 0.46), and mother-only diagnoses were frequent. Both child and parent information are important when diagnosing SAD in this age group.

Child↗

Are there subgroups of bulimia nervosa based on comorbid psychiatric disorders?

OBJECTIVE: The current study sought to determine whether there are subtypes of bulimia nervosa (BN) differentiated by comorbid psychiatric disorders. METHOD: Data on comorbid psychiatric diagnoses in female relatives of probands and controls in the Collaborative Study of the Genetics of Alcoholism (COGA) who met criteria for BN (as outlined in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders) were analyzed using latent class analysis. Resulting latent classes were compared on a variety of variables related to impulsive behaviors and psychological functioning. RESULTS: The best-fitting solution, a two-class model, yielded one class (72%) characterized by substance dependence, depression, antisocial personality disorder (ASPD), and anxiety disorders, and another characterized by depression. The highly comorbid class had more suicidality, more daily smokers, sought help for emotional problems, and had lower Global Assessment of Functioning (GAF) scores compared with those in the comorbid depression only class. DISCUSSION: Latent class findings suggest the existence of two classes of BN differentiated by substance dependence, impulsive behaviors, and poorer psychological functioning.

Adult↗

Measuring impulsivity in adolescents with serious substance and conduct problems.

Adolescents with substance use and conduct disorders have high rates of aggression and attention deficit hyperactivity disorder (ADHD), all of which have been characterized in part by impulsivity. Developing measures that capture impulsivity behaviorally and correlate with self-reported impulsivity has been difficult. One promising behavioral measure, however, is a variant of the continuous performance test, the Immediate Memory Test/Delayed Memory Test (IMT/DMT). The authors showed significant group differences between adolescents in treatment for serious substance and conduct problems and community controls on impulsivity measures, both behavioral and self-report, as well as on aggression and problem behavior measures. Furthermore, the IMT/DMT correlated significantly with self-reported impulsivity. In summary, the IMT/DMT may be an effective behavioral measure of impulsivity in adolescents.

Adolescent↗