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Biomedical subjects

Mark A Riddle

Publications and source records attributed to Mark A Riddle.

At least 19 recordsLinked to original sources
PubMed2007

Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of obsessive-compulsive disorder.

Our objective in this study was to determine whether symptoms of obsessive-compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD. Psychiatrists or psychologists interviewed 221 subjects using the Lifetime Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS-LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories from the Y-BOCS using exploratory factor analysis to identify latent symptom dimensions. The relationship between these symptom dimensions and clinical characteristics and familiality was investigated. A four-factor model emerged as the best classification of OCD symptoms in the Y-BOCS. These factors were labeled Pure Obsessions, Contamination, Symmetry/Order, and Hoarding. The contamination factor was least likely to be associated with other Axis I disorders. Whereas no significant relationship was found between the factor scores of probands and the presence of OCD in their first-degree relatives, the Symmetry/Order and Hoarding factors did breed true. Hoarding was found to predict poorer treatment response. A four-factor classification of OCD features best describes the symptom patterns of a sample of patients with OCD. There were specific clinical correlates for these factors, and significant intrafamilial sib-sib correlations were found for the Symmetry/Order and Hoarding factors.

Adult↗
PubMed2006

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

BACKGROUND: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. METHODS: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. RESULTS: After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). CONCLUSIONS: Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

Comorbidity↗
PubMed2006

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, hoarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks; and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. Hoarding in relatives was associated with indecision in probands, independently of proband hoarding status. The findings suggest that hoarding behavior may help differentiate a distinct clinical subgroup of people with OCD and may aggregate in some OCD families. Indecision may be a risk factor for hoarding in these families.

Adolescent↗
PubMed2006

The OCD collaborative genetics study: methods and sample description.

Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository. In this initial report, we describe the methods of the study and present clinical characteristics of affected individuals for researchers interested in this valuable resource for genetic studies of OCD. The project clinically evaluated and collected blood specimens from 238 families containing 299 OCD-affected sibling pairs and their parents, and additional affected relative pairs, for a genome-wide linkage study. Of the 999 individuals interviewed to date, 624 were diagnosed with "definite" OCD. The mean age of subjects was 36 years (range 7-95). The majority of affected individuals (66%) were female. The mean age at onset of obsessive-compulsive symptoms was 9.5 years. Specific mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in female cases, whereas tics, Tourette disorder, and alcohol dependence were more prevalent in male cases. Compared to "definite" cases of OCD, "probable" cases (n = 82) had, on average, later age at onset of obsessive-compulsive symptoms, lower severity score, and fewer numbers of different categories of obsessions and compulsions, and they were less likely to have received treatment for their symptoms.

Adolescent↗
PubMed2006

Somatic symptoms in children and adolescents with anxiety disorders.

OBJECTIVE: To evaluate the prevalence of somatic symptoms (SSs) in children and adolescents with anxiety disorders; the relationship between SSs and anxiety severity, impairment, and child global functioning; and the impact of fluvoxamine (FLV) versus pill placebo (PBO) on reducing SSs. METHOD: As part of a double-blind, placebo-controlled trial, 128 children (mean age, 10.8 years; range, 6-17) with DSM-IV anxiety disorders (i.e., social, separation, and generalized anxiety) were assessed by expert clinicians on 16 SSs using the Pediatric Anxiety Rating Scale. RESULTS: The most common SSs at baseline were restlessness (74%), stomachaches (70%), blushing (51%), palpitations (48%), muscle tension (45%), sweating (45%), and trembling/shaking (43%). Older children (age 12 and older) reported more SSs than younger children, boys and girls reported similar numbers of SSs, and SSs were higher among children with than without generalized anxiety disorder. SSs were significantly and positively correlated with anxiety severity, impairment, and global functioning. Pre-/postreductions in SSs were statistically significant in both PBO and FLV conditions; however, FLV was superior to PBO in reducing SSs. CONCLUSIONS: SSs are highly prevalent among children and adolescents with anxiety disorders and are associated with greater anxiety severity and impairment. Treatment with FLV was effective in reducing rather than increasing SSs. The high rates of SSs in youths with each of the three anxiety disorders suggest a re-evaluation of SSs in the DSM-IV diagnostic criteria for the most common anxiety disorders among children and adolescents.

Adolescent↗
PubMed2004

The interface between publicly funded and industry-funded research in pediatric psychopharmacology: opportunities for integration and collaboration.

Pediatric psychopharmacology research is undergoing a major expansion consequent to increasing use of psychotropic medications in children and recent legislative incentives to industry. In this rapidly changing context, the interface between publicly and privately funded research needs to be reconsidered to integrate activities and avoid unnecessary duplication of efforts. Once, by default, the almost exclusive domain of public research, child research is now increasingly funded by industry. There are, however, important issues unlikely to be addressed through private funding for which public support is needed, such as direct comparisons between active medications, between pharmacological and psychosocial interventions, or between combined and single treatment modalities; development of effective treatment strategies for patients unresponsive to first-line treatments; development of better research methods to assess efficacy and safety; identification of moderators and mechanisms of treatment response; and impact of treatment on illness course and prognosis. Industry-sponsored research is limited by the restricted access to proprietary databases, which impedes independent analyses and meta-analyses. Translation of basic neuroscience discoveries into treatment applications for children with mental illness is a critical area of inquiry that can benefit from integration of efforts and collaborations among academia, government, and industry.

Adolescent↗
PubMed2004

Neuroimaging correlates of anxiety after pediatric traumatic brain injury.

BACKGROUND: Anxiety disorders are common after traumatic brain injury (TBI). Data on the neural correlates of these conditions are lacking. This study examines the relationship between brain damage, particularly to the orbitofrontal cortex (OFC) and temporal lobe, and anxiety symptoms and disorders. METHODS: Ninety-five children and adolescents were followed for one year postinjury. Preinjury and one-year postinjury anxiety status were obtained from the parent. Magnetic resonance imaging was performed to evaluate brain lesions. The primary analysis used regression models to determine relationships between brain lesions and anxiety outcomes. As a secondary analysis, previously reported posttraumatic stress disorder (PTSD) data were reanalyzed using similar methods for purposes of comparison. RESULTS: The primary analysis showed that greater volume and number of OFC lesions correlated with decreased risk for anxiety, whereas lesions in other brain areas did not correlate with anxiety. Consistent with prior data, the secondary analysis showed an inverse correlation between OFC damage and PTSD; temporal lobe damage was positively correlated with PTSD. CONCLUSIONS: After pediatric TBI, greater damage to the OFC is associated with decreased risk for anxiety outcomes. Similar to adult data, these findings implicate OFC dysfunction in childhood anxiety. Temporal lobe damage did not correlate with anxiety, in contrast to the findings for PTSD.

Adolescent↗
PubMed2004

Clinical correlates of recurrent major depression in obsessive-compulsive disorder.

Major depressive disorder is the most frequent comorbid condition in obsessive-compulsive disorder (OCD). This study investigated factors associated with the development of recurrent major depressive disorder (RDD) in patients with OCD. Eighty OCD cases and 73 control probands were examined by psychiatrists or clinical psychologists using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials and made final consensus diagnoses using DSM-IV criteria. Family history of OCD and RDD, additional comorbid disorders, OCD symptoms and illness severity were compared between persons with OCD alone (n = 21) and OCD with RDD (n = 41). Compared to OCD probands without RDD, OCD probands with RDD had earlier age at first diagnosis, more severe obsessive-compulsive symptoms, and were more likely to have a family history of RDD. Social phobia, separation anxiety disorder, and body dysmorphic disorder occurred more frequently in the comorbid group. In a multiple logistic regression model, only early age of OCD diagnosis was significantly associated with RDD. Early age at onset of OCD increases the risk of depressive disorder in individuals with OCD.

Adult↗
PubMed2004

Olanzapine-induced diabetes in a seven-year-old boy.

The atypical antipsychotics have been recognized to induce diabetes mellitus and ketoacidosis in the adult psychiatric population. This report notes the onset of weight gain, diabetes, and apparent ketosis in a prepubertal boy diagnosed with bipolar disorder and treated with olanzapine. The hyperglycemia rapidly normalized after discontinuation of the olanzapine. Within 2 years, the diabetes recurred. In spite of the normalization of blood-glucose levels, urine ketone tests remained positive and were explained by the fact that patients taking valproic acid may have a false-positive urine test for ketones. Regular monitoring of glucose should be considered in children and adolescents who gain weight while treated with atypical antipsychotics.

Antipsychotic Agents↗
PubMed2004

Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology.

OBJECTIVE: To improve the gathering of adverse events (AEs) in pediatric psychopharmacology by examining the value and acceptability of increasingly detailed elicitation methods. METHOD: Trained clinicians administered the Safety Monitoring Uniform Report Form (SMURF) to 59 parents and outpatients (mean age +/- SD = 11.9 +/- 3.2 years) in treatment, with 36% on stimulants, 29% on selective serotonin reuptake inhibitor drugs, 10% on both, and 25% on other drug combinations. The SMURF included a brief general inquiry, a drug-specific inquiry, and a comprehensive body system review (BSR). RESULTS: SMURF administration took 24.6 +/- 13.9 minutes (median, 21). The BSR took 15.5 +/- 8.1 minutes (median, 14) longer (p < .0001) than the general inquiry (4.3 +/- 5.4 minutes) and the drug-specific inquiry (4.2 +/- 2.9 minutes). The general inquiry elicited 48 AEs, the drug-specific inquiry elicited 16 additional AEs, and the BSR 129 additional AEs. Of all the clinically relevant AEs elicited by the SMURF (n = 36), 19 (53%) were elicited by the BSR. The BSR length and detail were acceptable to parents but not to clinicians. CONCLUSIONS: The BSR elicited additional clinically significant AEs that had been missed with less detailed methods. Parents, but not clinicians, rated satisfaction and acceptability of the BSR as good.

Adolescent↗
PubMed2003

Psychotropic practice patterns for youth: a 10-year perspective.

OBJECTIVE: To examine changes in the full spectrum of psychotropic medication treatment for youths from 1987 to 1996. METHODS: A population-based analysis of community treatment data on nearly 900,000 youths enrolled in 2 US health care systems included (1) computerized Medicaid data from 2 states (a midwestern state and a mid-Atlantic state) composed of outpatient prescription claims and enrollment records and (2) computerized prescription dispensing records from a group-model health maintenance organization. Ten 1-year cross-sectional data sets from 1987 through 1996 were analyzed. RESULTS: Total psychotropic medication prevalence for youths increased 2- to 3-fold and included most classes of medication. The rapid growth since 1991 of alpha-agonists, neuroleptics, and "mood stabilizer" anticonvulsants was particularly notable. The 1996 prevalence of any psychotropic medication among youths younger than 20 years was remarkably similar (5.9%-6.3%) across all 3 sites, with stimulants and antidepressants consistently ranked first and second. Medicaid rates almost always exceeded health maintenance organization rates by large margins, particularly for alpha-agonists, neuroleptics, "mood stabilizer" anticonvulsants, and lithium. Youths in health maintenance organizations had rates similar to Medicaid-insured youths for antidepressants and hypnotics. Over the decade, there was a proportional increase in females receiving stimulants and in males receiving antidepressants, particularly for the 10- to 14-year-old group. The prevalence ratios of whites to African Americans narrowed substantially in 1 Medicaid site. CONCLUSIONS: Youth psychotropic treatment utilization during the 1990s nearly reached adult utilization rates. Youth findings can be used to accurately assess the duration of treatment and unforeseen practice pattern changes, and to identify safety concerns.

Adolescent↗
PubMed2003

Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders.

OBJECTIVE: To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. METHOD: The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. RESULTS: No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement. CONCLUSIONS: In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.

Adolescent↗
PubMed2003

How can we improve the assessment of safety in child and adolescent psychopharmacology?

OBJECTIVE: To identify approaches to improving methods for assessing tolerability and safety of psychotropic medications in children and adolescents. METHOD: Strengths and limitations of current methodology were reviewed and possible alternatives examined. RESULTS: Research on the validity of safety evaluation has been extremely limited. No evidence-based "gold standard" exists. Clinical trials remain the best design to establish causality, but sample size limitations prevent the detection of infrequent, though serious, adverse events. Other designs, such as cohort and case-control studies, and approaches, such as mining of large databases, must be considered. CONCLUSION: The current lack of methodological standardization across studies prevents generalizations and meta-analyses. Because the issues relevant to drug safety are diverse, a variety of methodological approaches and instruments are needed. It is, however, possible to adopt standard basic definitions of adverse events, degree of severity, ascertainment methods, and recording procedures, as a common "core," to which more specific assessment instruments can be added. Systematic empirical testing and validation of safety methodology is needed.

Adolescent↗
PubMed2003

Review of safety assessment methods used in pediatric psychopharmacology.

OBJECTIVE: Elicitation is an essential and critical step in ascertaining adverse events (AEs). This report reviews elicitation methods used in published clinical trials of psychopharmacological agents in children. METHOD: Pediatric psychopharmacology reports were reviewed for safety methods in the Medline database. Studies were included if they were published 1980 or later, provided data on AEs, and described the ascertainment methodology used for determining them. RESULTS: A review of 196 pediatric psychopharmacology articles depicting safety assessments in clinical studies over the past 22 years revealed that there was no common method used for eliciting or reporting AE data. CONCLUSION: The current inconsistency in safety data ascertainment is a major limitation that likely impairs the ability to promptly and accurately identify drug-induced AEs. Research on how best to standardize safety methods should be considered a priority in pediatric psychopharmacology.

Adolescent↗
PubMed2003

Developing methodologies for monitoring long-term safety of psychotropic medications in children: report on the NIMH conference, September 25, 2000.

OBJECTIVE: To improve the methods for long-term assessment of drug-associated side effects and advance knowledge of the safety profile of psychotropic medications in children and adolescents. METHOD: A multidisciplinary, interactive workshop was hosted by the National Institute of Mental Health (NIMH) and the Research Units on Pediatric Psychopharmacology network. Participants were experts in child and adolescent psychiatry, psychopharmacology, pharmacoepidemiology, and statistics from academia, the pharmaceutical industry, the Food and Drug Administration (FDA), and the NIMH. Evaluation of drug safety was examined from five perspectives: research design and methods, industry, regulatory requirements, bioethics, and practice settings. For each of these areas, special emphasis was placed on identifying barriers and generating solutions. RESULTS: A major obstacle is the lack of standardization of the methods used for collecting safety data. The limitations of both randomized clinical trials and passive postmarketing surveillance in assessing long-term safety were recognized. The need to consider alternative approaches, such as registries and trend analysis of population-based databases, was highlighted. Recommendations were proposed together with possible approaches to implementation. CONCLUSIONS: A concerted effort by academic researchers, industry, FDA, practitioners, and NIMH is needed to standardize methods and lay the foundations for systematic research on the long-term safety of psychotropic medications in children.

Adolescent↗
PubMed2003

The relevance of prolonged QTc measurement to pediatric psychopharmacology.

OBJECTIVE: To consider the relevance of prolonged QTc (QT interval corrected for rate) to pediatric psychopharmacology. METHOD: The authors reviewed publications on QTc prolongation and publications on sudden death in Medline from 1968 to November 2002. RESULTS: The search yielded more than 20,000 publications. Review manuscripts with clinical recommendations outnumber the few pediatric studies of QTc duration during treatment. Most reviews have been published in the past 5 years, during a time when the Food and Drug Administration restricted five psychotropic medications because of QTc prolongation (sertindole: not approved; thioridazine, mesoridazine, and droperidol: black-box warning; and ziprasidone: bolded warning) and nine somatic medications because of QTc prolongation. CONCLUSION: Pretreatment screening, careful selection of psychotropic and/or somatic medication combinations, and recognition of QTc prolongation in electrocardiographic tracings during treatment with medications that prolong QTc are important components of clinical practice.

Adolescent↗