Paul J. Ambrosini

Historical development and present status of the schedule for affective disorders and schizophrenia for school-age children (K-SADS).

OBJECTIVES To review the historical development, reliability, validity, administrative characteristics, and uses of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). METHOD The various past and current K-SADS editions were reviewed as was the literature describing their uses. RESULTS Three DSM-IV-compatible versions of the K-SADS are in general use, 1 present state (K-SADS-P IVR) and 2 epidemiological editions (K-SADS-E and K-SADS-P/L). All 3 interviews provide a current diagnostic assessment. The K-SADS-P IVR also evaluates the worst past episode during the preceding year, while the K-SADS-E and -P/L provide a lifetime diagnosis. The K-SADS-E and -P/L are primarily categorical diagnostic interviews while the K-SADS-P IVR, which also measures symptom severity, can be used to monitor treatment response. All editions have good rater reliability. However, the quality of the validating data set for the K-SADS is limiting. CONCLUSIONS The K-SADS is a viable interview schedule to assess current, past, and lifetime diagnostic status in children and adolescents. It is has the potential to further aide in the validation of psychiatric disorders. The substantial rater training required for reliable administration and the need for more validation work remain its drawbacks.

Concurrent Validity and Psychometric Properties of the Beck Depression Inventory in Outpatient Adolescents

The concurrent validity of the Beck Depression Inventory (BDI) was evaluated in 122 outpatient adolescents referred to a clinic for depression. Criterion validators were Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS) generated diagnoses and a 17-item clinician-rated depression scale extracted from the K-SADS. Initial BDI scores of greater than 13 yielded sensitivity, specificity, and positive predictive powers of 86%, 82%, and 83%, respectively, in differentiating syndromal major depressive disorder (MDD) from nonaffective disordered patients. In repeated interviews in 2 weeks with a BDI score of greater than 13, these parameters were 89%, 88%, and 93%, respectively, in those meeting MDD criteria. The BDI correlated significantly with the 17-item depression score in depressed females but not depressed males because BDI scores were more than 30% higher in females. BDI internal consistency among all cases was 0.91 and was higher in depressed than nondepressed patients.

Videotape Reliability of the Third Revised Edition of the K-SADS

Videotaped interrater reliability was assessed with the K-SADS-III-R on 25 children with a mean age of 10:9. Kappa statistics were computed in syndromes with a frequency rate of at least 20%. The following mean kappas were obtained: major depression = 0.83; overanxious disorder = 0.85; separation anxiety = 0.85; simple phobic disorder = 0.64; oppositional disorder = 0.89; attention deficit disorder = 0.88. The mean kappa for mother derived diagnoses was 0.86; for child derived diagnoses 0.79; and, for all diagnoses combined 0.84. These reliability findings are comparable to reports with similar methodology in the child literature. The improved kappas for the anxiety disorders achieved a primary goal for this revision of the K-SADS. This study has shown that the K-SADS-III-R has sufficient reliability for research purposes.

ADHD characteristics: I. Concurrent co-morbidity patterns in children & adolescents

Objective342 Caucasian subjects with attention deficit/hyperactivity disorder (ADHD) were recruited from pediatric and behavioral health clinics for a genetic study. Concurrent comorbidity was assessed to characterize the clinical profile of this cohort.MethodsSubjects 6 to 18 years were diagnosed with the Schedule for Affective Disorders & Schizophrenia for School aged Children (K-SADS-P IVR).ResultsThe most prevalent diagnoses co-occurring with ADHD were Oppositional Defiant Disorder (ODD) (40.6%), Minor Depression/Dysthymia (MDDD) (21.6%), and Generalized Anxiety Disorder (GAD) (15.2%). In Inattentive ADHD (n = 106), 20.8% had MDDD, 20.8% ODD, and 18.6% GAD; in Hyperactive ADHD (n = 31) 41.9% had ODD, 22.2% GAD, and 19.4% MDDD. In Combined ADHD, (n = 203), 50.7% had ODD, 22.7% MDDD and 12.4% GAD. MDDD and GAD were equally prevalent in the ADHD subtypes but, ODD was significantly more common among Combined and Hyperactive ADHD compared to Inattentive ADHD. The data suggested a subsample of Irritable prepubertal children exhibiting a diagnostic triad of ODD, Combined ADHD, and MDDD may account for the over diagnosing of Bipolar Disorder.ConclusionAlmost 2/3rd of ADHD children have impairing comorbid diagnoses; Hyperactive ADHD represents less than 10% of an ADHD sample; ODD is primarily associated with Hyperactive and Combined ADHD; and, MDDD may be a significant morbidity for ADHD youths from clinical samples.

MAOIs in adolescent major depression unresponsive to tricyclic antidepressants.

Abstract Many adolescents with major depressive disorder have at most partial response to standard tricyclic antidepressants despite appropriate dosage and adequate length of treatment. This paper reports a series of 23 such adolescents who were treated with monoamine oxidase inhibitors (MAOIs). Seventy-four percent of this group achieved good or fair antidepressant response, 57% had both good or fair response and continued dietary compliance. There were few serious side effects. Special attention must be paid to subject selection for treatment with MAOIs because of the risk of impulsive or accidental dietary transgression. This retrospective chart review strongly suggests the need for controlled studies of MAOI treatment in adolescents with tricyclic antidepressant refractory major depression.

Taxonicity of adolescent melancholia: a categorical or dimensional construct?

A taxometric analysis was conducted to test the hypothesis that the latent structure of melancholia in adolescents is categorical. Two taxometric procedures were used: Mean Above Minus Below a Cut (MAMBAC) and Maximum Covariance (MAXCOV) analyses. Participants were 378 adolescents presenting for a depression evaluation. Indicators of melancholia were constructed using items from the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS) and the Beck Depression Inventory (BDI). The indicators of melancholia were consistent with a categorical latent variable. The findings suggest that the latent structure of melancholia in adolescents is similar to its previously identified categorical structure in adults. Implications for clinical research are discussed.

ADHD latent class clusters: DSM-IV subtypes and comorbidity

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6-18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding.

Nocturnal enuresis: a suggestive endophenotype marker for a subgroup of inattentive attention-deficit/hyperactivity disorder.

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) and enuresis co-occur at a higher rate than expected; the cause for this is unclear. STUDY DESIGN Diagnostic and demographic variables were compared in 344 children ages 6 to 12 years, with and without enuresis, recruited in an ADHD genetic study. Sleep variables were investigated in a subgroup of 44 enuretic children with age- and sex-matched nonenuretic controls. The association of enuresis with single nucleotide polymorphisms located in regions reported in linkage with enuresis was explored. RESULTS The prevalence rate of nocturnal enuresis was 16.9% for the entire cohort. There were no differences in sex, age, socioeconomic status, intelligence quotient, medication treatment, or comorbidities. The enuresis group had a higher likelihood of inattentive symptoms than the nonenuretic group. Night wakings and ability of children to wake themselves in the morning were both significantly decreased in children with enuresis compared with control children in the Child Sleep Habits Questionnaire Night Wakings subscale. No significant association was found with chromosomal regions previously reported in linkage with enuresis. CONCLUSIONS Deficits in arousal may contribute to both enuresis and inattentive ADHD. Nocturnal enuresis may be a useful clinical marker in identifying a subgroup of the inattentive phenotype in ADHD genetic studies.

What Can ADHD without Comorbidity Teach Us about Comorbidity

Neuropsychiatric comorbidity in ADHD is frequent, impairing and poorly understood. In this report, characteristics of comorbid and comorbid-free ADHD subjects are investigated in an attempt to identify differences that could potentially advance our understanding of risk factors. In a clinically-referred ADHD cohort of 449 youths (ages 6-18), age, gender, IQ, SES and ADHD symptoms were compared among ADHD comorbid free subjects and ADHD with internalizing and externalizing disorders. Logistic regression analyses were also carried out to investigate the relationship between comorbidity and parental psychiatric status. Age range was younger in the ADHD without comorbidity and older in ADHD+internalizing disorders. No significant difference in IQ or SES was found among ADHD comorbid and comorbid-free groups. ADHD with internalizing disorder has a significantly greater association with paternal psychiatric conditions. After matching by age, gender, IQ and SES, ADHD with externalizing disorders had significantly higher total ADHD, hyperactivity/impulsivity score and single item score of difficulty awaiting turn than ADHD without comorbidity and ADHD with internalizing disorders. Older age ranges, ADHD symptom severity and parental psychopathology may be risk factors for comorbidity.

Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in adra1a

Objectives Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common developmental disorder. Although a few confirmed associations have emerged from candidate gene studies, these have shown the same limitations that have become evident in the study of other complex diseases, often with inconsistent and nonreplicated results across different studies. Methods In this report, 27 ADHD candidate genes were explored in greater depth using high-density tag single nucleotide polymorphism (SNP) genotyping. Association with 557 SNPs was tested using the transmission disequilibrium test in 270 nuclear pedigrees selected from an ongoing ADHD genetic study that includes all disease subtypes. Results SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed. Conclusion The strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block. Some of the SNPs in HTR2A and COMT have already been reported by others, whereas other SNPs will need confirmation in independent samples.