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Biomedical subjects

Robert L Findling

Publications and source records attributed to Robert L Findling.

At least 37 records · Page 2Linked to original sources

Prefrontal activation during verbal fluency tests in schizophrenia--a near-infrared spectroscopy (NIRS) study.

Letter- or semantically-cued verbal fluency tests (VFT) induce different, but overlapping activities in the prefrontal cortex (PFC) in healthy subjects. Functional differences between letter and semantic VFT may be important in elucidating the nature of language-related problems in schizophrenia since more profound impairment in semantically-cued retrieval may be suggestive of semantic system dysfunction specific to this disorder. However, the functional differences between the letter vs. semantic VFT on prefrontal metabolism in the subjects with schizophrenia have not been described. In the present study, we used near-infrared spectroscopy (NIRS) to assess hemoglobin concentration changes in the bilateral PFCs in subjects and controls. Sixteen subjects with schizophrenia and 19 healthy controls performed letter and semantic VFTs. Prefrontal hemodynamic changes were simultaneously monitored by NIRS. While healthy subjects performed both tasks equivalently, the subjects with schizophrenia showed more compromised performance in the semantic VFTs compared to the letter VFTs. NIRS measurement revealed that the pattern of PFC activation was greater during the letter VFT when compared to the semantic VFT in the healthy subjects, suggesting more prominent PFC involvement in letter-cued retrieval. In contrast, the subjects with schizophrenia showed the opposite pattern of activation, implying that the semantic mode of lexical access might impose greater cognitive demands on the PFC. The present study is the first to detect abnormal patterns of PFC activation in adults with schizophrenia in response to the distinct cognitive demands associated with letter and semantic VFT.

Adult↗

Update on the treatment of bipolar disorder in children and adolescents.

As the phenomenology of pediatric bipolar disorder has become better delineated, clinicians are now able to more accurately assess and treat young people suffering from this condition. For pediatric patients with bipolar I disorder and symptoms of mania, medication monotherapy has been shown to lead to symptom amelioration. However, this treatment modality oftentimes does not lead to full symptom remission. In an attempt to address this observation, combination treatment strategies have recently been investigated. Recently, a maintenance study has shown that in youths who achieved remission on a combination of lithium and divalproate therapy, either of these agents alone was equally effective as a treatment strategy. In youths identified as being at genetic high risk for bipolarity who also had problematic affective symptomatology, treatment with divalproate was not found to be superior to placebo; however, those with the greatest degree of genetic risk for familial psychopathology remained in the trial longer than those with more modest amounts of familial psychopathology. These data suggest that intervention in youths with only one affected parent may not be a rational prevention strategy for pharmacological intervention in bipolar disorder, and that cohorts more genetically at risk may be a more appropriate group for preventative pharmacotherapy.

Adolescent↗

Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children.

OBJECTIVE: To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR(R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). STUDY DESIGN: Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. RESULTS: Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. CONCLUSIONS: Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of </= 30 mg/day in otherwise healthy children.

Amphetamines↗

Treatment guidelines for children and adolescents with bipolar disorder.

Clinicians who treat children and adolescents with bipolar disorder desperately need current treatment guidelines. These guidelines were developed by expert consensus and a review of the extant literature about the diagnosis and treatment of pediatric bipolar disorders. The four sections of these guidelines include diagnosis, comorbidity, acute treatment, and maintenance treatment. These guidelines are not intended to serve as an absolute standard of medical or psychological care but rather to serve as clinically useful guidelines for evaluation and treatment that can be used in the care of children and adolescents with bipolar disorder. These guidelines are subject to change as our evidence base increases and practice patterns evolve.

Adolescent↗

Risperidone in children with disruptive behavior disorders and subaverage intelligence: a 1-year, open-label study of 504 patients.

OBJECTIVE: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. METHOD: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. RESULTS: Seventy-three percent of the 504 patients enrolled completed the study. The mean +/- SE dose of risperidone was 1.6 +/- 0.0 mg/day. The most common adverse events were somnolence (30%), rhinitis (27%), and headache (22%). The incidence of movement disorders was low, and mean Extrapyramidal Symptom Rating Scale scores decreased during risperidone treatment. No clinically significant changes in mean laboratory values were noted, except for a transient increase in serum prolactin levels. Scores on the Nisonger Child Behavior Rating Form Conduct Problem Scale improved significantly as early as week 1, and improvement was maintained throughout the trial (p < .001 at each time point). Significant improvements were noted on positive social behavior and other Nisonger Child Behavior Rating Form subscales, Aberrant Behavior Checklist, Clinical Global Impressions scale, and tests of patients' cognitive function (each p < .001). CONCLUSIONS: Risperidone was well tolerated and effective in the long-term treatment of disruptive behavior disorders in children with subaverage intelligence.

Adolescent↗

Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder.

OBJECTIVE: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy. METHOD: Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures. RESULTS: Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72). CONCLUSIONS: DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy.

Adolescent↗

A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder.

OBJECTIVE: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. RESULTS: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. CONCLUSIONS: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.

Acute Disease↗

Early symptoms of mania and the role of parental risk.

OBJECTIVES: The objectives of this study were to: (i) describe the phenomenology of youths diagnosed with subsyndromal bipolar disorders; (ii) describe the phenomenology of youngsters who are the children of bipolar parents, who are also experiencing subsyndromal symptoms of bipolar disorder (patients with 'cyclotaxia'); and (iii) explore which symptoms may be most useful in identifying youths with cyclotaxia. METHODS: Four hundred outpatients between the ages of 5 and 17 years received a diagnostic assessment and psychometric questionnaires pertaining to mood symptomatology and psychosocial functioning. Parental diagnostic information was also obtained. Children and adolescents were assigned to one of three diagnostic groups: a 'syndromal bipolar disorder (BP)' group (n = 118), a 'sub-syndromal bipolar (SUB-BP)' group (n = 75), or a 'non-bipolar (NON-BP)' group (n = 207). In addition, based on parental diagnoses, youths were assigned to either a high genetic risk group (n = 167) or a low genetic risk group (n = 233). RESULTS: Youths with subsyndromal bipolar disorders were found to have intermediate degrees of manic symptoms than youths with bipolar disorder and youths without a bipolar diagnosis. Offspring of parents having a bipolar disorder were more likely to show symptoms of hypomania and mania than youths without a bipolar parent. Youths at genetic risk for developing a bipolar disorder were not found to be at higher risk for having a diagnosis of attention-deficit hyperactivity disorder or a disruptive behavior disorder. Finally, results suggest that elevated mood with irritability and rapid mood fluctuations are the key distinguishing characteristics of 'cyclotaxia'. CONCLUSIONS: There exists a group of youngsters who are the offspring of a parent/parents with a bipolar disorder who do not suffer from BP 1 or BP 2, yet have elevated mood symptoms and psychosocial dysfunction. As a result of these observations, treatment studies are needed for youths with 'cyclotaxia'.

Adolescent↗

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents.

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.

Adolescent↗

Comparing diagnostic checklists for pediatric bipolar disorder in academic and community mental health settings.

OBJECTIVES: To compare six promising mania measures, the Parent Mood Disorder Questionnaire (P-MDQ), the Adolescent self-report MDQ, the 10-item short form of the Parent General Behavior Inventory (PGBI-SF10), the 28-item Adolescent General Behavior Inventory (AGBI), the Parent Young Mania Rating Scale (P-YMRS), and the adolescent YMRS, in a demographically diverse outpatient sample. METHODS: Participants were 262 outpatients (including 164 males and 131 African-Americans) presenting to either an academic medical center (n = 153) or a community mental health center (n = 109). Diagnoses were based on semi-structured interviews with the parent and then youth sequentially. RESULTS: Ninety youths (34%) met criteria for a bipolar spectrum disorder. Parent measures yielded Areas Under the Receiver Operating Curve (AUROC) values of 0.81 for the PGBI-SF10 to 0.66 for the P-YMRS. Adolescent report measures performed significantly less well, with AUROCs ranging from 0.65 to 0.50. There were no significant differences in the diagnostic performance of the measures across the sites or by racial groups, although the reliability of measures tended to be lower in the urban community mental health site. The PGBI-SF10 made a significant contribution to logistic regression models examining all combinations of the instruments. The P-MDQ added information in the younger age group, and no measure improved classification of bipolar cases after controlling for the PGBI-SF10 in the older age group. DISCUSSION: Results replicate previous findings that, in decreasing order of efficiency, the PGBI-SF10, P-MDQ, and P-YMRS significantly discriminate bipolar from non-bipolar cases in youths aged 5-18; and they appear robust in a demographically diverse community setting. Adolescent self-report measures are significantly less efficient, sometimes performing no better than chance at detecting bipolar cases.

Academic Medical Centers↗

A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder.

OBJECTIVE: The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder. METHOD: A 20-month, double-blind, parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex. Sixty patients were randomly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type (bipolar I versus bipolar II disorder). RESULTS: Of the 254 patients enrolled in the open-label acute stabilization phase, 76% discontinued the study prematurely (poor adherence: 28%; nonresponse: 26% [of whom 74% remained depressed and 26% remained in a hypomanic/manic/mixed episode], intolerable side effects: 19%). Of the 60 patients (24%) randomly assigned to double-blind maintenance monotherapy, 53% relapsed (59% into depression and 41% into a hypomanic/manic/mixed episode), 22% completed the study, 10% had intolerable side effects, and 10% were poorly adherent. The rates of relapse into any mood episode for those given lithium versus divalproex were 56% and 50%, respectively; the rates were 34% and 29% for a depressive relapse and 19% and 22% for a hypomania/mania relapse. There were no significant differences in time to relapse. The proportion discontinuing prematurely because of side effects was 16% for lithium and 4% for divalproex. CONCLUSIONS: The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder.

Adolescent↗

Toward an evidence-based assessment of pediatric bipolar disorder.

This article outlines a provisional evidence-based approach to the assessment of pediatric bipolar disorder (PBD). Public attention to PBD and the rate of diagnosis have both increased substantially in the past decade. Accurate diagnosis is crucial to avoid harm due to mislabeling or unnecessary medication exposure. Because there are no proven efficacious or effective treatments for PBD, the role of assessment is heightened to demonstrate efficacy in individual cases as well as to identify cases for participation in clinical trials. This review discusses (a) the state of psychopathology research regarding PBD; (b) the likely base rate of PBD in multiple clinical settings; (c) the diagnostic value of family history; (d) challenges to differential diagnosis, including comorbidity and symptom overlap with other diagnoses, shortcomings in contemporary assessment methods, and the cyclical nature of PBD; (e) practical methods for improving diagnosis, focusing on the most discriminative symptoms, extending the temporal window of assessment to capture mood changes, and using screening tools within an actuarial framework; and (f) monitoring response to treatment using a variety of assessment methods. Twelve recommendations are offered to move toward an evidence-based assessment model for PBD.

Bipolar Disorder↗

Gender differences in criminality: bipolar disorder with co-occurring substance abuse.

Outpatient interviews to collect criminal history data were conducted with 55 women and 77 men who had the dual diagnosis of rapid-cycling bipolar disorder with co-morbid substance abuse disorders (DD-RCBD), to ascertain gender-related similarities and differences. Fifty-three percent of women and 79 percent of men reported that they had been charged with a crime, and nearly half of those charged had been incarcerated. Men with DD-RCBD were more likely to have committed a felony and had a trend of committing more misdemeanors. Although women with DD-RCBD were less likely to have a criminal history than their male counterparts, they were far more likely to have a criminal history than were women in the general population. Implications from this pilot study include the need for earlier identification of bipolar disorder and for the increased availability of psychiatric and substance abuse services within correctional facilities.

Bipolar Disorder↗

Use of antipsychotics in children and adolescents.

The comparable efficacy and improved safety of the atypical antipsychotics compared with the traditional antipsychotic agents in the treatment of schizophrenia and other disorders in adults have prompted the use of these agents in children and adolescents. The atypical antipsychotics are increasingly being used in children and adolescents with a variety of different psychiatric diagnoses, including schizophrenia, bipolar disorder, autism/pervasive developmental disorders, conduct disorder, depression, anxiety disorders, tic disorders, delirium, and eating disorders. Unfortunately, clinical use of these agents in pediatric patients has far exceeded the limited evidence from randomized controlled trials. This article reviews the available evidence from the published literature on the use of the atypical antipsychotics in children and adolescents with schizophrenia, bipolar disorder, and maladaptive aggression associated with autism/pervasive developmental disorders and conduct disorder/disruptive behavior disorders.

Adolescent↗

Pharmacologic treatment of behavioral symptoms in autism and pervasive developmental disorders.

Autism and other pervasive developmental disorders (PDDs) are associated with various dysfunctional and problematic behaviors, in addition to the core features of language and social skills dysfunction that define these conditions. Although there is currently no pharmacologic cure for the core features of PDDs, some of the behavioral symptoms may be treated pharmacologically. In addition to relieving some of the daily stress in the lives of patients and their families, improvement of these behavioral symptoms, which include hyperactivity, aggression, tantrums, and self-injury, removes some of the hindrances to other rehabilitative efforts. This article discusses the efficacy and tolerability of various medications and alternative interventions in addressing the symptoms of autism and other PDDs.

Adrenergic alpha-Agonists↗

Mood state at study entry as predictor of the polarity of relapse in bipolar disorder.

Of the placebo-controlled maintenance studies conducted in bipolar disorder, few have enrolled patients who present depressed. In fact, only lithium and lamotrigine have been studied over the long term with placebo-controlled designs in recently manic and recently depressed bipolar patients. Given the magnitude of the unmet medical need and the data suggesting that symptomatic patients with bipolar disorder spend the majority of their time depressed, this is unfortunate. Our review of the pre-lithium literature and more recent publications suggests that mood state at study entry predicts the polarity of relapse and the response to treatment. Accordingly, a need exists to enroll recently depressed patients in maintenance studies to elucidate the complete spectrum of efficacy of putative mood stabilizers and improve the long-term treatment of bipolar depression. Patients presenting depressed for a maintenance study tend to relapse into depression; those presenting manic, into hypomania/mania/mixed states. This is particularly true during the first several months of the randomized treatment. The polarity of the index episode tends to predict the polarity of relapse into a subsequent episode in a ratio of about 2:1 to 3:1. We conclude that putative mood stabilizers must be tested in recently manic and recently depressed patients to determine their spectrum of prophylactic efficacy.

Affect↗