Bilateral Striatal Necrosis after Sydenham's Chorea in a 7-Year-Old Boy: A 2-Year Follow-Up.

Child bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous condition. An association with group A streptococcus (GAS) infection was previously reported in two cases of BSN in infancy and early childhood. We here report on a 7-year-old boy who developed chorea and dystonia 20 days after symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance imaging scans, obtained before, soon after the onset of the post-Sydenham symptoms, and 1 year later were consistent with an evolution from bilateral striatal microbleeding to necrosis, and consequently reduced basal ganglia volume and enlargement of the frontal horns. No support was found for other possible autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN. Prednisone treatment was instituted and continued for 1 year. Two years after the onset of the post-Sydenham symptoms, the child, although much improved, still has generalized dystonic-choreic movements. This case confirms and extends into school age, the link between GAS and BSN.

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.

Maternal anxiety, depression and sleep disorders before and during pregnancy, and preschool ADHD symptoms in the NINFEA birth cohort study.

AIMS.: Maternal mental disorders have been associated with the risk of attention-deficit/hyperactivity disorder (ADHD) in children. Within the context of a mother-child cohort, we examined whether maternal anxiety, depression and sleep disorders are associated with pre-school ADHD symptoms. METHODS.: The study included 3634 singletons from the Italian NINFEA (Nascita e INFanzia: gli Effetti dell'Ambiente') cohort. Maternal doctor-diagnosed anxiety, depression and sleep disorders before and during pregnancy were assessed from the questionnaires completed during pregnancy and 6 months after delivery. Mothers rated child ADHD symptoms at 4 years of age, according to the Diagnostic and Statistical Manual of Mental Disorders. Hyperactive-impulsive (ADHD-H), inattentive (ADHD-I) and total ADHD scores were analysed in the models adjusted for child's gender, first-born status, maternal age, education, alcohol consumption and smoking during pregnancy. RESULTS.: The total ADHD score at age 4 was associated with maternal lifetime anxiety (17.1% percentage difference in score compared with never; 95% CI 7.3-27.9%), sleep disorders (35.7%; 95% CI 10.7-66.5%) and depression (17.5%; 95% CI 3.2-33.8%). Similar positive associations were observed also for ADHD-H and ADHD-I traits, with slightly attenuated associations between maternal sleep disorders and child ADHD-I score, and maternal depression and both ADHD scores. All the estimates were enhanced when the disorders were active during pregnancy and attenuated for disorders active only during the pre-pregnancy period. CONCLUSIONS.: Maternal anxiety, depression and sleep disorders are associated with a relative increase in the number of ADHD-H, ADHD-I and total ADHD symptoms in preschoolers.

Medication development and testing in children and adolescents. Current problems, future directions.

Progress in pediatric psychopharmacological research has suffered notable delay, especially compared with the achievements in adult psychopharmacology. Although safety and efficacy of the use of many psychotropic agents in children remain largely unproved, their pediatric use has been increasing and their widespread off-label prescribing by practitioners has raised some important concerns. The National Institute of Mental Health, in cooperation with the Food and Drug Administration and leading researchers, has coordinated systematic efforts to identify the major obstacles to research in pediatric psychopharmacology and to propose feasible solutions. In 1995, a conference cosponsored by the national Institute of Mental Health and the Food and Drug Administration gathered more than 100 research experts, family and patient advocates, and representatives of mental health professional associations. Participants met in working groups focused on specific aspects of child research and reached consensus on various recommendations. Each of the various aspects relevant to conducting research in this area (methodological, ethical, legal, regulatory, financial, and family or community context) presents specific challenges, which are herein outlined. Recommendations for possible solutions are presented, some of which are being implemented. Because data about drug safety and efficacy in adults can rarely be extrapolated to children, there is no substitute for pediatric psychopharmacological research. Successful strategies for overcoming the many obstacles with which this research has to contend must enlist the concerted efforts of all the relevant parties (investigators, clinicians, industry, federal agencies, ethicists, families, and community representatives).

Use of mental health and substance abuse treatment services among adults with HIV in the United States.

BACKGROUND: The need for mental health and substance abuse services is great among those with human immunodeficiency virus (HIV), but little information is available on services used by this population or on individual factors associated with access to care. METHODS: Data are from the HIV Cost and Services Utilization Study, a national probability survey of 2864 HIV-infected adults receiving medical care in the United States in 1996. We estimated 6-month use of services for mental health and substance abuse problems and examined socioeconomic, HIV illness, and regional factors associated with use. RESULTS: We estimated that 61.4% of 231 400 adults under care for HIV used mental health or substance abuse services: 1.8% had hospitalizations, 3.4% received residential substance abuse treatment, 26.0% made individual mental health specialty visits, 15.2% had group mental health treatment, 40.3% discussed emotional problems with medical providers, 29.6% took psychotherapeutic medications, 5.6% received outpatient substance abuse treatment, and 12.4% participated in substance abuse self-help groups. Socioeconomic factors commonly associated with poorer access to health services predicted lower likelihood of using mental health outpatient care, but greater likelihood of receiving substance abuse treatment services. Those with less severe HIV illness were less likely to access services. Persons living in the Northeast were more likely to receive services. CONCLUSIONS: The magnitude of mental health and substance abuse care provided to those with known HIV infection is substantial, and challenges to providers should be recognized. Inequalities in access to care are evident, but differ among general medical, specialty mental health, and substance abuse treatment sectors.

Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States.

BACKGROUND: There have been no previous nationally representative estimates of the prevalence of mental disorders and drug use among adults receiving care for human immunodeficiency virus (HIV) disease in the United States. It is also not known which clinical and sociodemographic factors are associated with these disorders. SUBJECTS AND METHODS: We enrolled a nationally representative probability sample of 2864 adults receiving care for HIV in the United States in 1996. Participants were administered a brief structured psychiatric instrument that screened for psychiatric disorders (major depression, dysthymia, generalized anxiety disorders, and panic attacks) and drug use during the previous 12 months. Sociodemographic and clinical factors associated with screening positive for any psychiatric disorder and drug dependence were examined in multivariate logistic regression analyses. RESULTS: Nearly half of the sample screened positive for a psychiatric disorder, nearly 40% reported using an illicit drug other than marijuana, and more than 12% screened positive for drug dependence during the previous 12 months. Factors independently associated with screening positive for a psychiatric disorder included number of HIV-related symptoms, illicit drug use, drug dependence, heavy alcohol use, and being unemployed or disabled. Factors independently associated with screening positive for drug dependence included having many HIV-related symptoms, being younger, being heterosexual, having frequent heavy alcohol use, and screening positive for a psychiatric disorder. CONCLUSIONS: Many people infected with HIV may also have psychiatric and/or drug dependence disorders. Clinicians may need to actively identify those at risk and work with policymakers to ensure the availability of appropriate care for these treatable disorders.

Prevalence of severe ADHD: an epidemiological study in the Italian regions of Tuscany and Latium.

BACKGROUND: The rate with which attention deficit/hyperactivity disorder (ADHD) is diagnosed varies widely across countries, suggesting that cultural factors influence the clinical interpretation of child behaviour. This study estimated the point prevalence of severe ADHD among elementary and middle-school Italian children. METHOD: An epidemiological sample of 2016 children attending 2nd-8th grade in the Italian regions of Tuscany and Latium was selected based on census distribution of the school-age population. Teachers completed the Italian version of the ADHD Rating Scale for Teachers (SDAI). For children with at least six inattention symptoms and/or at least six hyperactivity/impulsivity symptoms rated 'very often' by the teachers, the parents completed the Italian ADHD Rating Scale for Parents (SDAG). Children with documented ADHD symptoms at both school and home received a complete psychiatric interview with the Kiddie Schedule for Affective Disorders and Schizophrenia-present and lifetime version (K-SADS-PL). RESULTS: Of the 1887 assessed children, 4.45% (95% CI 3.58-5.51) met the ADHD cut-off on teacher ratings, 1.43% (0.96-2.12) had ADHD symptoms endorsed by both teacher and parent, and 1.32% (0.87-1.97) were further confirmed by the psychiatric evaluation. The male:female ratio was 7:1. The inattentive type accounted for about half of the ADHD cases. CONCLUSIONS: When applying stringent criteria for both severity and pervasiveness of symptoms, it is estimated that about 1.3% of the Italian elementary and middle-school children suffer from severe ADHD.

Research on eating disorders: current status and future prospects.

This report summarizes the main themes addressed at a workshop on research on eating disorders (EDs), which was hosted by the National Institute of Mental Health in December 1998. Both basic behavioral neuroscientists and clinical investigators met in an effort to integrate areas of research and foster collaborations. Considerable advances have been made in understanding the neuroendocrinological mechanisms that regulate appetite and food intake. These achievements are in sharp contrast with the limited progress in elucidating the pathogenesis of EDs and developing effective treatment and preventive interventions. Anorexia nervosa remains a highly morbid condition with the highest mortality of any other psychiatric disorder. Besides acute refeeding techniques, no specific interventions have been proven effective in changing the long-term course of anorexia nervosa. Efficacious treatments exist for bulimia nervosa, but their underutilization calls for research on translating experimental findings into clinical practice. Closer interface between neuroscientists and clinical researchers is required for advancing our understanding of ED pathogenesis and developing effective treatments. Recent studies are suggestive of a substantial genetic contribution to EDs that deserves further investigation. Finally, there is an urgent need to examine risk and protective factors for EDs, on which safe and effective prevention can be built.

Integrating science and ethics in child and adolescent psychiatry research.

Research to elucidate the biological bases of psychopathology in children and adolescents is needed to understand pathogenesis and to develop effective and safe treatment and preventive interventions. Because of the effect of development, data collected in adults are not always applicable to youth, and direct participation of children in research is necessary. Many medications are currently used in the community to treat children and adolescents with neuropsychiatric disorders without adequate data about their safety and efficacy. Conducting research in children requires attention to specific ethical and regulatory factors. In deciding whether minors can participate in a study with potential direct benefit to the research subjects, the most important variable to consider is the balance between risks and potential benefit, in the context of the severity of the child's condition and the available alternatives. Research with no potential benefit to the participants is guided by the concepts of minimal risk (which may apply more to normal children) and minor increase over minimal risk (perhaps more relevant to children affected by psychopathology). Recently conducted studies relevant to this issue are reviewed. Of paramount importance is the ratio of risk/scientific value of the proposed experiment. In fact, no research is justifiable, no matter how low the risk may be, unless the potential yield of the study is important and may help advance our understanding of normal functioning and mental illness.

Autonomic dysfunction in patients with dementia of the Alzheimer type.

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.

Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.

Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.

Impact of psychiatric conditions on health-related quality of life in persons with HIV infection.

OBJECTIVE: Little is known about the impact of comorbid psychiatric symptoms in persons with HIV. This study estimates the burden on health-related quality of life associated with comorbid psychiatric conditions in a nationally representative sample of persons with HIV. METHOD: The authors conducted a multistage sampling of urban and rural areas to produce a national probability sample of persons with HIV receiving medical care in the contiguous United States (N=2,864). Subjects were screened for psychiatric conditions with the short form of the Composite International Diagnostic Interview. Heavy drinking was assessed on the basis of quantity and frequency of drinking. Health-related quality of life was rated with a 28-item instrument adapted from similar measures used in the Medical Outcomes Study. RESULTS: HIV subjects with a probable mood disorder diagnosis had significantly lower scores on health-related quality of life measures than did those without such symptoms. Diminished health-related quality of life was not associated with heavy drinking, and in drug users it was accounted for by presence of a comorbid mood disorder. CONCLUSIONS: Optimization of health-related quality of life is particularly important now that HIV is a chronic disease with the prospect of long-term survival. Comorbid psychiatric conditions may serve as markers for impaired functioning and well-being in persons with HIV. Inclusion of sufficient numbers of appropriately trained mental health professionals to identify and treat such conditions may reduce unnecessary utilization of other health services and improve health-related quality of life in persons with HIV infection.

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans.

The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind, randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg p.o.) +/-scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.), placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p < .01), slowed information processing (p < .01) and impaired new learning and memory (p < .01), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p < .10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade.

P.R.N. medications in child state hospital inpatients.

The authors reviewed the administration of p.r.n. medications over 12 months in 49 child psychiatry inpatients. There were 1263 p.r.n. administrations (mean +/- SD = 25.6 +/- 36.7 administrations/patient). Only 7 (14%) of the 49 patients had none; 9 (18%) had more than 50. The number of p.r.n. administrations correlated with the dose of regular neuroleptics and with the time spent in seclusion. Age, race, sex, diagnosis, neurological disorders, IQ, and self-injurious behavior were poor predictors of the number of p.r.n. administrations. Antihistaminics accounted for 54% (683) of the p.r.n. administrations, neuroleptics for 24% (303), and chloral hydrate for 17% (214). Seventy percent (891) of the p.r.n. drugs were given for disruptive behavior. Only 32% (403) of the 1263 administrations were clearly effective, 14% (170) were ineffective, and 54% (690) were dubious. A controlled trial is needed to assess the efficacy of this ubiquitous psychiatric practice.

Neuroleptic withdrawal in patients meeting criteria for supersensitivity psychosis.

In an attempt to prospectively validate the existence of supersensitivity psychosis (SSP), five schizophrenic patients meeting Chouinard's criteria for SSP and five non-SSP schizophrenic controls had neuroleptic treatment withdrawn for 2 weeks under double-blind conditions. The sudden worsening of psychotic symptoms and tardive dyskinesia postulated in the SSP group was not observed on the Brief Psychiatric Rating Scale, the Clinical Global Impressions scale, and the Abbreviated Dyskinesia Rating Scale. In conclusion, the authors' pilot data do not seem to support the existence of SSP.

P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study.

BACKGROUND: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. METHOD: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM-III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. RESULTS: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. CONCLUSION: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity.

Subtypes of aggression and their relevance to child psychiatry.

OBJECTIVE: To review the evidence for qualitatively distinct subtypes of human aggression as they relate to childhood psychopathology. METHOD: Critical review of the pertinent literature. RESULTS: In humans, as well as in animals, the term aggression encompasses a variety of behaviors that are heterogeneous for clinical phenomenology and neurobiological features. No simple extrapolation of animal subtypes to humans is possible, mainly because of the impact of complex cultural variables on behavior. On the whole, research into subtypes of human aggression has been rather limited. A significant part of it has been conducted in children. Clinical observation, experimental paradigms in the laboratory, and cluster/factor-analytic statistics have all been used in an attempt to subdivide aggression. A consistent dichotomy can be identified between an impulsive-reactive-hostile-affective subtype and a controlled-proactive-instrumental-predatory subtype. Although good internal consistency and partial descriptive validity have been shown, these constructs still need full external validation, especially regarding their predicting power of comorbidity, treatment response, and long-term prognosis. CONCLUSIONS: Our understanding and treatment of children and adolescents with aggressive behavior can benefit from research on subtypes of aggression. The differentiation between the impulsive-affective and controlled-predatory subtype as qualitatively different forms of aggressive behavior has emerged as the most promising construct. Specific therapeutic hypotheses could be tested in this context and contribute to a full validation of these concepts.