Showing papers by "Stephen V. Faraone published in 1999"

Pharmacotherapy of Attention-deficit/Hyperactivity Disorder Reduces Risk for Substance Use Disorder

Abstract: Objective. To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). Methods. The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. Results. Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8–21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04–0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. Conclusions. Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging.

Abstract: Background Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. Methods Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. Results The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and fronto-orbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. Conclusion Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.

Clinical Correlates of ADHD in Females: Findings From a Large Group of Girls Ascertained From Pediatric and Psychiatric Referral Sources

Abstract: Objective The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. Method Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. Results Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. Conclusions These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females. J. Am. Acad. Child Adolesc. Psychiatry , 1999, 38(8):966–975.

Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder.

Abstract: OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat al­leles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.

Genetics of Mental Disorders: A Guide for Students, Clinicians, and Researchers

Abstract: Introduction. The Basics: Epidemiologic Foundations of Psychiatric Genetics. Variations on a Theme: Causal and Clinical Heterogeneity. Mathematical Models of Inheritance. Molecular Genetics and Mental Illness. Clinical Applications of Psychiatric Genetics. The Future of Psychiatric Genetics. Glossary. Readings in Psychiatric Genetics. Appendix: Internet Resources for Psychiatric Genetics.

Further evidence of a bidirectional overlap between juvenile mania and conduct disorder in children.

Abstract: Objective To investigate systematically the overlap between mania and conduct disorder (CD) in a sample of consecutively referred youths. It was hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the 2 disorders would have correlates of both. Method Subjects were consecutively referred children and adolescents meeting DSM-III-R diagnostic criteria on structured diagnostic interview for CD ( n = 116), mania ( n = 110), and CD+mania ( n = 76). Results Of 186 children and adolescents with mania and of 192 with CD, 76 satisfied criteria for both CD and mania, representing 40% of youths with CD and 41% of youths with mania, respectively. Examination of the clinical features, patterns of psychiatric comorbidity, and functioning in multiple domains showed that children with CD and mania had similar features of each disorder irrespective of the comorbidity with the other disorder. Conclusions The data suggest that when mania and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to mania and manic symptoms should not be viewed as secondary to CD. J. Am. Acad. Child Adolesc. Psychiatry , 1999, 38(4):468–476.

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a 4-year follow-up study.

Abstract: In a prior study of 54 relatives of patients with schizophrenia and 72 control participants, 3 neuropsychological functions met the criteria for risk indicators of the schizophrenia genotype: executive functioning, memory, and auditory attention. In an assessment of the stability of these findings, the sample was reexamined 4 years after the initial assessment. Three test scores were found to differ between groups (Immediate Verbal Memory, Delayed Verbal Memory, and Dichotic Listening Digits Detected) or to show a significant Group x Gender interaction (immediate and delayed verbal and visual memories). None of the test scores showed Group x Time interactions, suggesting that the discriminating power of the tests was stable over time. Evidence for deficits in working memory and rule learning on the object alternation test was also found. These results support the idea that neuropsychological dysfunction among relatives of patients with schizophrenia is a stable trait caused by the familial predisposition to schizophrenia.

Schizophrenia: a review of genetic studies.

Abstract: Despite the complexities of schizophrenia, notable progress has been achieved in its diagnosis and treatment over the last 25 years. In this article we review the genetic research that provides the foundation for continued advances. One of the bases of our current understanding involves the observation that schizophrenia often runs in families. The development and utilization of stringent, reliable diagnostic criteria, together with the advent of modern family, twin, and adoption paradigms, demonstrate the importance of genetic factors in understanding the familial basis of the disorder. Refinements in diagnostic criteria have also enabled advances in understanding the likely mode--or modes--of genetic transmission of both schizophrenia and related disorders. After reviewing representative studies in these areas, we examine genetic linkage studies and our progress toward identifying the genes that cause schizophrenia. Although consistent results have been difficult to obtain and much work remains to be done, evidence for areas of vulnerability has been converging at particular chromosomal sites (e.g., 6p, 8p, and 22q), allowing for cautious optimism. Finally, we discuss challenges and prospects for the new millennium, including the clinical and ethical implications of genetic investigations.

Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder.

Abstract: The objective of this study was to evaluate pharmacological approaches for attention deficit hyperactivity disorder (ADHD) in children with bioplar disorder and comorbid ADHD. The medical charts of 38 patients with diagnoses of both Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised ADHD and bipolar disorder were reviewed over multiple visits to assess improvement and prescription patterns. Logistic regression was used to model the probability of improvement at each visit, and robust standard errors were estimated in order to account for correlation among individuals using Huber's correction for clustered data. The proportion of visits at which ADHD symptoms were rated as improved following initial improvement in manic symptoms was 7.5 times greater than before initial improvement of manic symptoms. The recurrence of manic symptoms following their initial stabilization significantly inhibited ADHD response to medication. Although tricyclic antidepressants (TCAs) significantly...

Further validation of social impairment as a predictor of substance use disorders: findings from a sample of siblings of boys with and without ADHD.

Abstract: Examined predictors of substance use disorders in nonreferred siblings of boys with and without attention deficit hyperactivity disorder to further investigate whether previous findings documenting the role of social impairment in predicting substance use disorders would be replicated. Participants were comprehensively assessed at Time 1 and at 4-year follow-up. We found that social impairment was the sole significant predictor of alcohol and substance abuse and smoking after controlling for other variables previously shown to be predictors of substance use disorders. These results confirmed prior findings documenting the critical role of social impairment in predicting later substance use disorders.

Antecedents and Complications of Trauma in Boys With ADHD: Findings From a Longitudinal Study

Abstract: Objective To examine the relationship between trauma and attention-deficit hyperactivity disorder (ADHD), evaluating whether ADHD increases the risk for trauma, the risk for posttraumatic stress disorder (PTSD), or the risk for trauma-associated psychopathology. Method Data from a longitudinal sample of 260 children and adolescents with and without ADHD were examined. All were evaluated comprehensively with assessments in multiple domains of functioning including systematic assessments of trauma and PTSD. Comparisons were made between traumatized and nontraumatized youths with and without ADHD. Results No meaningful differences were detected in comparisons between ADHD and control children, either in the rate of trauma exposure or in the development of PTSD. Although trauma was associated with the development of major depression, this effect was independent of ADHD status. In contrast, bipolar disorder at baseline assessment was a significant risk factor for subsequent trauma exposure. Conclusions ADHD was not found to be a risk factor for either trauma exposure or PTSD, but childhood mania was. If confirmed, this finding stresses the potential severe clinical sequelae of childhood mania in children. J. Am. Acad. Child Adolesc. Psychiatry, 1999, 38(1):48–55.

Genetic and Environmental Influences on Transitions in Drug Use

Abstract: Genetic and environmental factors influence drug abuse, but abuse represents the culmination of a sequence of events. Different levels of use may have different determinants and these determinants may differ across drug types. Approximately 3200 male–male twin pairs from the Vietnam Era Twin Registry were interviewed by telephone. Data were obtained regarding exposure to six categories of illicit drugs, initiation of use, continuation of use, regular usage, and diagnosis of drug abuse/dependence. Genetic, common environmental, and unique environmental influences on transitions of drug involvement, defined as movement from one level of drug use to the next, were investigated. Marijuana had the highest conditional probability for the transition from exposure to use, from use to use more than five times, and from use more than five times to regular use. The rate of transition to regular use of heroin was higher than the rate for amphetamine, cocaine, sedatives, and psychedelics. Cocaine had the highest conditional probability for the transition from regular use to abuse/dependence. Significant genetic influences were observed for a number of transitions in marijuana, amphetamine, and cocaine usage.

The 4-year course of tic disorders in boys with attention-deficit/hyperactivity disorder.

Abstract: Background Despite long-standing clinical concerns, relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and tic disorders. Therefore, we examined tic disorders in an ongoing prospective follow-up study of male subjects with ADHD, a sample unselected for any comorbid disorder. Methods One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later. We characterized tic disorders along with a wide range of neuropsychiatric correlates, including other comorbid disorders and indices of psychosocial function in multiple domains (school, cognitive, social, and family). Results Compared with controls, subjects with ADHD showed more tic disorders at baseline and more new onsets were reported at follow-up. Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course: in contrast to low rates of ADHD remission, tic disorders mostly remitted. The age-adjusted rate of ADHD remission was 20% and that of tic remission, 65%. Tic disorders had little effect on the psychosocial functioning of subjects with ADHD. Conclusions These findings suggest that comorbidity with a tic disorder has a limited effect on ADHD outcome. However, because of the relatively small sample of subjects with tic disorders, our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders.

The concept of target features in schizophrenia research.

Abstract: Target features are clinical or neurobiological characteristics that are expressions of the underlying predisposition to an illness. They comprise a wide range of phenomena, from the classic signs and symptoms of psychopathology to sophisticated measures of brain structure and function. For schizophrenia, many target features have been identified. These include eye tracking dysfunction, attentional impairment, allusive thinking, neurological signs, thought disorder, characteristic auditory evoked potentials, neuropsychological impairment, structural brain abnormalities and functional brain abnormalities. In their most pathological forms, these features are present among many schizophrenic patients, yet it is their presence among their non-psychotic relatives that shows them to be target features. We discuss the theoretical background for target features, present examples and describe how the discovery of target features has implications for schizophrenia research.

Absence of Cardiovascular Adverse Effects of Sertraline in Children and Adolescents

Abstract: Objective: In a 12 week, placebo-controlled, parallel-design, multicenter study of sertraline for obsessive-compulsive disorder in 107 children and 80 adolescents, the authors prospectively assessed cardiovascular effects to doses of sertraline of Method Vital signs (blood pressure and heart rate) and electrocardiograph parameters (ECGs) were systematically evaluated at baseline and again throughout treatment. Results There were no clinically significant cardiovascular adverse events in any of the subjects enrolled in the study. Moreover, compared with baseline and placebo, sertraline treatment at an average dose of 167 mg did not result in any clinically meaningful changes in any ECG indices (PR, QRS, and QTc intervals), cardiac rhythm, blood pressure, or heart rate. Conclusions These prospectively derived results support the cardiovascular safety of sertraline at doses up to 200 mg in children and adolescents.

The genetics of schizophrenia.

Abstract: Behavioral genetic studies provide overwhelming evidence that genes contribute to schizophrenia. Recently, genetic studies have provided promising evidence that schizophrenia genes are linked to several chromosomal locations in affected family members. Despite this progress, individual genes for schizophrenia have yet to be identified. Future progress will depend, in part, on the selection of phenotypes that best reflect effects of etiologic genes. One such phenotype is schizotaxia, a clinically meaningful syndrome that reflects the genetic liability to schizophrenia in nonpsychotic individuals. The potential importance of schizotaxia, or similar concepts, for use in genetic studies, is discussed.

Sixth World Congress of Psychiatric Genetics X Chromosome Workshop.

Abstract: At the X chromosome workshop of the Sixth World Congress on Psychiatric Genetics, new data regarding psychiatric phenotypes and the X chromosome were presented. In the last year a number of groups have published linkage results for the X chromosome in schizophrenia, which provide no significant evidence for linkage. Presentations by groups from Cardiff, Oxford, State University of New York (SUNY), and Finland provide weak nonsignificant evidence for linkage of markers on the Xp11.4-p11.3, Xq21, and Xq26 with schizophrenia. However, the presence of a male-specific transmission ratio distorter (DMS1) that maps to Xp11.4-21.2 [Naumova et al., 1998: Am. J. Hum. Genet. 62:1493-1499] makes the interpretation of linkage findings in brother-brother pairs difficult in this region. Regarding bipolar affective disorder, little new data were reported, but previous reports provide evidence for linkage to Xq25-q26. Summary tables of linkage results for schizophrenia and bipolar disorder can be obtained from http://www.camh.net/ research/x-chromosome/. No linkage or transmission disequilibrium of polymorphisms of MAOA and MAOB in attention deficit hyperactivity disorder was seen. Negative results for transmission disequilibrium of polymorphisms of HTR2C and MAOA with autism were provided from German and Austrian families.

A pilot controlled family study of DSM-III-R and DSM-IV ADHD in African-American children.

Abstract: Background Very little is known about attention-deficit hyperactivity disorder (ADHD) in African-American children, and although the familial transmission of ADHD has been well established in white samples, prior work has not evaluated this feature of ADHD in African-American families. Method Subjects were 37 first-degree relatives of children with DSM-III-R -defined ADHD and 52 first-degree relatives of non-ADHD comparison children matched for ethnicity, age, and gender. DSM-III-R -based structured interviews (modified to include DSM-IV diagnoses) provided the basis for psychiatric diagnoses in relatives. Results The risks for both DSM-III-R and DSM-IV ADHD were significantly greater in first-degree relatives of ADHD probands than in relatives of controls. In addition, the relatives of ADHD probands also were at higher risk for oppositional defiant disorder, antisocial personality disorder, major depression, generalized anxiety, and substance use disorders. Conclusions These results suggest that ADHD and related disorders are familial in African-Americans. Further work is needed to confirm the familial transmission of ADHD in African-American children and to explore the role of genetics as well as environmental factors in the transmission of the disorder. J. Am. Acad. Child Adolesc. Psychiatry, 1999, 38(1):034–39.

Substance use disorders in high-risk adolescent offspring.

Abstract: Objective: To examine the risk for substance use disorders (SUD) in offspring of SUD parents who were not selected due to referral to SUD treatment centers. Method: The original sample was ascertained through two groups of index children: 140 ADHD probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. Results: We found that: 1) parental SUD was associated with SUD and all SUD subtypes in the offspring; 2) parental alcohol use disorders were associated with alcohol use disorders in the offspring as well as co-occurring alcohol and drug use disorders but not drug use disorders alone in the offspring; and 3) drug use disorders in the parents were associated with drug use disorders but not alcohol use disorders in the offspring. Conclusions: These findings suggest that alcoholism and drug abuse may breed true from parents to their offspring, but further work with larger samples is needed to confirm this idea. Our findings also sug...

Absence of Effect of Stimulants on the Pharmacokinetics of Desipramine in Children

Abstract: We conducted a retrospective chart review to examine the pharmacokinetic interaction between desipramine and the stimulants methylphenidate and dexedrine using routinely monitored desipramine serum concentrations in children receiving desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking desipramine, 29 taking desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 desipramine, 68 desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66+/-1.36 mg/kg, desipramine; 3.66+/-1.09 mg/kg, desipramine-stimulants; p=0.97), weight- and dose-normalized serum concentrations (47.26+/-39.26 [microg/L]/[mg/kg], desipramine, 39.02+/-19.92 [microg/L]/[mg/kg], desipramine-stimulants; p=0.09), and clearance (0.690+/-0.913 [L/kg]/hr, desipramine; 0.613+/-0.514 [L/kg]/hr, desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between desipramine and stimulants.

Brief Research Communication Suggestive Linkage of Chromosome 10p to Schizophrenia Is Not Due to Transmission Ratio Distortion

Abstract: Stephen V. Faraone,1,2,3,4* Joanne Meyer,5 Tara Matise,6 Dragun Svrakic,7 John Pepple,1,2 Dolores Malaspina,8 Brian Suarez,7 Carol Hampe,7 Gayan Chan,5 Avram Aelony,5 Jill Harkavy Friedman,8 Charles Kaufmann,8 C. Robert Cloninger,7 and Ming T. Tsuang1,2,3,4,9 1Harvard Medical School Department of Psychiatry at the Massachusetts Mental Health Center, Boston, Massachusetts 2Brockton/West Roxbury VA Medical Center, Brockton, Massachusetts 3Psychiatry Service, Massachusetts General Hospital, Boston, Massachusetts 4Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, Massachusetts 5Millennium Pharmaceuticals, Cambridge, Massachusetts 6Laboratory of Statistical Genetics, The Rockefeller University, New York, New York 7Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 8Department of Psychiatry, Columbia University, New York, New York 9Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion

Abstract: The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Desipramine clearance in children and adolescents: absence of effect of development and gender.

Abstract: Objective To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. Method DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). Results Mean pharmacokinetic parameters for the entire population included dose (3.78 ± 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 ± 47.39 [μg/L]/[mg/kg]), and DMI clearance (0.68 ± 1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 ± 1.40 mg/kg, 3.83 ± 1.68 mg/kg), weight-and dose-normalized serum concentrations (44.52 ± 39.6 [μg/L]/[mg/kg], 46.34 ± 34.89 [μg/L]/[mg/kg]; p = .62). and clearance (0.680 ± 0.890 [L/kg]/hr, 0.695 ± 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 ± 1.55 mg, 3.39 ± 1.84 mg), weight-and dose-normalized serum concentrations (45.15 ± 37.76 [μg/L]/[mg/kg]. 47.14 ± 34.96 [μg/L]/[mg/kg]; p = .720). and clearance (0.699 ± 0.89 [L/kg]/hr, 0.606 ± 0.535 [L/kg]/hr; p = .390). Conclusions These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population. J. Am. Acad. Child Adolesc. Psychiatry. 1999, 38(1):79–85.

Normalized Functioning in Youths With Persistent Attention‐Deficit/Hyperactivity Disorder

Abstract: Objective: The goal of this study was to examine normalization of functioning among youths with persistent attention-deficit hyperactivity/disorder (ADHD) symptoms. Research design: Subjects were 85 referred boys with persistent ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) who were followed up prospectively into mid adolescence and 68 boys without ADHD. These subjects were assessed at baseline and follow-up visits by using measures from 3 domains of functioning: school, social, and emotional. For each of these domains, we defined boys with ADHD as having normalized functioning if they attained scores above the 5th percentile of scores in the non-ADHD group. Results: Twenty percent of boys with ADHD were functioning poorly in all 3 domains, 20% were functioning well in all 3 domains, and 60% had intermediate outcomes. Increased exposure to maternal psychopathology, larger family size, DSM-III-R psychiatric comorbidity, and symptoms of impulsivity were negatively associated with normalization of functioning among children with persistent ADHD. Conclusion: Our results show that children with ADHD have a variable emotional, educational, and social adjustment despite syndromatic persistence. This suggests that normalization of functioning and syndromatic persistence of ADHD may be partially independent. (J Pediatr 1998;133:544-51)

New Approaches to the Genetics of Schizophrenia: Neuropsychological and Neuroimaging Studies of Nonpsychotic First Degree Relatives of People with Schizophrenia

Abstract: Psychiatry, with the rest of medicine, has entered the age of molecular genetics, but we are far from the stage of molecular diagnosis or treatment. Some disorders such as Alzheimer’s Disease or Huntington’s Disease are yielding relatively quickly to technological advances in molecular genetics, whereas others like schizophrenia, bipolar affective disorder, and attention-deficit hyperactivity disorder are more likely to have a complex inheritance. These latter disorders do not appear to be explained by classic Mendelian models of inheritance. An alternative is polygenic models which assume that genes found at more than one locus are responsible for the familial patterns of such disorders. In such models, genes at a range of loci may have small additive effects on the individual’s predisposition to an illness, such as schizophrenia. It is also possible that some forms of schizophrenia may result from simpler combinations of genes or even of a single gene.

Conceptualization of the liability for schizophrenia: clinical implications

Abstract: Historically, the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for schizophrenia have emphasized several features, including symptoms of psychosis, a dissociation of symptoms from their etiology, a reliance on clinical symptoms, and a categorical approach to classifying the disorder. Although these emphases are quite useful, they have limitations. We review these here, and stress the importance of incorporating recent data on the genetic /biological and neurodevelopmental origins of schizophrenia into current conceptions of the disorder. We also review "schizotaxia, " which is a concept thai embodies this point of view, occurs before the onset of psychosis, and is hypothesized to represent the liability for schizophrenia. If our hypothesis on this point is correct, the identification of schizotaxic individuals will eventually facilitate the development of prevention strategies by identifying a premorbid (but clinically significant) condition for schizophrenia. Moreover, the identification of biological or neuropsychological components of schizotaxia will provide more specific bases for developing novel treatment interventions. Our initial attempts to develop protocols for the assessment and treatment of schizotaxia are encouraging, and will be reviewed.