PubMed Health⌕ Search

Biomedical subjects

Mani N Pavuluri

Publications and source records attributed to Mani N Pavuluri.

15 recordsLinked to original sources
PubMed2007

Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients: effect of treatment with mood stabilizing drugs.

Pediatric bipolar disorder (PBD) is a major public health concern, however, its neurobiology is poorly understood. We, therefore, studied the role of protein kinase C (PKC) in the pathophysiology of bipolar illness. We determined PKC activity and immunolabeling of various PKC isozymes (i.e., PKC alpha, PKC betaI, PKC betaII, and PKC delta) in the cytosol and membrane fractions of platelets obtained from PBD patients and normal control subjects. PKC activity and PKC isozymes were also determined after 8 weeks of pharmacotherapy of PBD patients (n=16) with mood stabilizers. PKC activity and the protein expression of PKC betaI and betaII, but not PKC alpha or PKC delta, were significantly decreased in both membrane as well as cytosol fractions of platelets obtained from medication-free PBD patients compared with normal control subjects. Eight weeks of pharmacotherapy resulted in significantly increased PKC activity but no significant changes in any of the PKC isozymes in PBD patients. These results indicate that decreases of specific PKC isozymes and decreased PKC activity may be associated with the pathophysiology of PBD and that pharmacotherapy with mood stabilizing drugs results in an increase and normalization of PKC activity along with improvement in clinical symptoms.

Adolescent↗
PubMed2006

Affective neural circuitry during facial emotion processing in pediatric bipolar disorder.

BACKGROUND: Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. METHODS: Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. RESULTS: In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in right pregenual anterior cingulate, amygdala, and paralimbic cortex. Bipolar patients also showed reduced activation of visual areas in occipital cortex together with greater activation in higher-order visual perceptual areas, including superior temporal sulcus and fusiform gyrus with angry faces and posterior parietal cortex with happy faces. CONCLUSIONS: Findings document a disturbance in affective neurocircuitry in pediatric bipolar disorder. Reduced activation in ventrolateral prefrontal cortex might reflect diminished top-down control that leads to the observed exaggerated activation in amygdala and paralimbic areas. Changes in occipital areas might represent an effort to gate sensory input when affective responses to the faces could not be successfully modulated. Disturbances in affect processing circuitry could contribute to emotional dysregulation and social cognitive difficulties in bipolar youth.

Adolescent↗
PubMed2006

Biological risk factors in pediatric bipolar disorder.

BACKGROUND: The current study attempted to determine whether neurodevelopmental and acquired brain abnormalities are more common in pediatric bipolar disorder (PBD). METHODS: The study sample consisted of 98 subjects with a mean age of 11.5 +/- 3.3 years comprising three demographically matched groups: healthy controls (HC, n = 28), subjects with bipolar disorder - Type I (PBD, n = 37), and bipolar disorder - Type I combined with attention deficit hyperactivity disorder (PBD+ADHD, n = 33). Family history of PBD was determined using the Family History Screen. Additional measures were administered to assess the history on perinatal risk, development milestones, serious physical illnesses, and head injury. RESULTS: Logistic regression showed that that family history and perinatal risk factors predicted the diagnosis of PBD. PBD diagnosis was 15 times higher among those with a family history of BD. Second, for every additional perinatal risk factor such as prenatal exposure to drugs or birth complications, the risk of having a PBD diagnosis increased more than six-fold. CONCLUSIONS: Having a positive familial history of BD in a first degree relative and perinatal insults may elevate the risk for developing PBD. Presence of these risk factors, especially in the context of clinical signs of affect dysregulation, should alert clinicians to screen for PBD.

Adolescent↗
PubMed2006

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.

Adolescent↗
PubMed2006

A one-year open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset bipolar disorder.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of risperidone augmentation of lithium in preschool-onset bipolar disorder (BD) among youth who insufficiently respond to lithium monotherapy. METHOD: Thirty-eight subjects between the ages of 4 and 17 years (mean age = 11.37 +/- 3.8 years) with onset of BD in preschool years (manic or mixed episode) entered this 12-month trial. All subjects received lithium monotherapy. Patients who failed to adequately respond to lithium monotherapy after 8 weeks and those who relapsed after an initial response were given risperidone augmentation for up to 11 months. The Young Mania Rating Scale (YMRS) was the primary outcome measure. Response was defined as a > or =50% decrease from baseline. Additional data were collected on diagnostic comorbidity, family history, number of hospitalizations, perinatal risk factors, history of physical or sexual abuse, Child Depression Rating Scale-Revised (CDRS-R), Clinical Global Impression (CGI) scale for BD (CGI-BP), Children's Global Assessment Scale (C-GAS), and adverse medication effects. RESULTS: Of the 38 subjects treated with lithium monotherapy, 17 responded, whereas 21 required augmentation with risperidone. Response rate in the youths treated with lithium + risperidone was 85.7% (n = 18/21). Significant predictors of inadequate response to lithium monotherapy requiring augmentation were: (1) attention-deficit/hyperactivity disorder (ADHD), (2) severity at baseline, (3) history of sexual or physical abuse, and (4) preschool age. Combination treatment of lithium and risperidone was found to be safe and well tolerated. CONCLUSIONS: A substantial proportion of youth with a history of preschool-onset BD treated with lithium were either nonresponders or partial responders. Subsequent augmentation of lithium with risperidone in these cases was well tolerated and efficacious. Potential predictors of lithium nonresponse identified in this study may guide the choice of medications earlier in the treatment process.

Adolescent↗
PubMed2006

Child mania rating scale: development, reliability, and validity.

OBJECTIVE: To develop a reliable and valid parent-report screening instrument for mania, based on DSM-IVsymptoms. METHOD: A 21-item Child Mania Rating Scale-Parent version (CMRS-P) was completed by parents of 150 children (42.3% female) ages 10.3 +/- 2.9 years (healthy controls = 50; bipolar disorder = 50; attention-deficit/hyperactivity disorder [ADHD] = 50). The Washington University Schedule for Affective Disorders and Schizophrenia was used to determine DSM-IV diagnosis. The Young Mania Rating Scale, Schedule for Affective Disorders and Schizophrenia Mania Rating Scale, Child Behavior Checklist, and Child Depression Inventory were completed to estimate the construct validity of the measure. RESULTS: Exploratory and confirmatory factor analysis of the CMRS-P indicated that the scale was unidimensional. The internal consistency and retest reliability were both 0.96. Convergence of the CMRS-P with the Washington University Schedule for Affective Disorders and Schizophrenia mania module, the Schedule for Affective Disorders and Schizophrenia Mania Rating Scale, and the Young Mania Rating Scale was excellent (.78-.83). The scale did not correlate as strongly with the Conners parent-rated ADHD scale, the Child Behavior Checklist -Attention Problems and Aggressive Behavior subscales, or the child self-report Child Depression Inventory (.29-.51). Criterion validity was demonstrated in analysis of receiver operating characteristics curves, which showed excellent sensitivity and specificity in differentiating children with mania from either healthy controls or children with ADHD (areas under the curve of.91 to.96). CONCLUSION: The CMRS-P is a promising parent-report scale that can be used in screening for pediatric mania.

Adolescent↗
PubMed2006

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients.

OBJECTIVE: A systematic evaluation of neuropsychological functioning in individuals with pediatric bipolar disorder is necessary to clarify the types of cognitive deficits that are associated with acutely ill and euthymic phases of the disorder and the effects of medication on these deficits. METHOD: Unmedicated (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were matched on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. A computerized neurocognitive battery and standardized neuropsychological tests were administered to assess attention, executive function, working memory, verbal memory, visual memory, visuospatial perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder, regardless of medication and illness status, showed impairments in the domains of attention, executive functioning, working memory, and verbal learning compared to healthy individuals. Also, bipolar subjects with comorbid attention deficit hyperactivity disorder (ADHD) performed worse on tasks assessing attention and executive function than patients with bipolar disorder alone. CONCLUSIONS: The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.

Adolescent↗
PubMed2005

Pediatric bipolar disorder: a review of the past 10 years.

OBJECTIVE: To review the literature of the past decade covering the epidemiology, clinical characteristics, assessment, longitudinal course, biological and psychosocial correlates, and treatment and prevention of pediatric bipolar disorder (BD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Pediatric BD is increasingly recognized, and there are several prevailing views on core features of this disorder. The incidence and prevalence of the disorder and the associated comorbidities vary according to study setting and criteria used. This disorder is highly recurrent and accompanied by substantial psychiatric and psychosocial morbidity. Familial studies, including "top down" (offspring of parents with BD) and "bottom up" (relatives of youths with BD) studies indicate that pediatric BD is aggregated in families with adult or later-onset BD and suggest the existence of genetic predisposition. Greater understanding of the risk factors for early onset BD and recognition of the phenomenology of prodromal symptoms offers hope for early identification and prevention. Neuroimaging studies indicate frontotemporal and frontostriatal pathology, but none of these findings seems to be disorder specific. Combination pharmacotherapies appear promising, and the field awaits further short- and long-term randomized, placebo-controlled trials. Preliminary studies of various psychotherapies, including psychoeducation strategies tailored specifically for BD in youths, look encouraging. CONCLUSIONS: Considerable advances have been made in our knowledge of pediatric BD; however, differing viewpoints on the clinical presentation of BD in children are the rule. Phenomenological and longitudinal studies and biological validation using genetic, neurochemical, neurophysiological, and neuroimaging methods may strengthen our understanding of the phenocopy. Randomized, controlled treatment studies for the acute and maintenance treatment of BD disorder are warranted.

Adolescent↗
PubMed2005

Divalproex sodium for pediatric mixed mania: a 6-month prospective trial.

OBJECTIVE: This prospective 6-month open trial examined the effectiveness and safety of divalproex sodium (DVPX) in pediatric mixed mania. METHOD: Thirty-four subjects with a mean age of 12.3 (SD = 3.7) years, DSM-IV diagnosis of a current mixed episode and a baseline Young Mania Rating Scale (YMRS) score >20 were treated with DVPX monotherapy. The primary outcome measures were the YMRS and the Child Depression Rating Scale-Revised. Secondary measures were the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) and the Children's Global Assessment of Functioning Scale (C-GAS). Measures of safety and tolerability were also administered. RESULTS: Effect size (Cohen's d) based on change scores from baseline was 2.9 for the YMRS and 1.23 for the CDRS-R. Response rate (> or =50% change from baseline YMRS score and < or =40 score on CDRS-R at the end of study) was 73.5%. The remission rate (> or =50% change from baseline on YMRS, < or =40 on CDRS-R, CGI-BP-Improvement subscale of < or =2, and > or =51 CGAS score) was 52.9%. Significant improvements (p < 0.001) from baseline were seen for mean scores on all outcome measures (i.e., YMRS, CGI-BP, CDRS-R, and C-GAS). DVPX was safe and well tolerated with no serious adverse events during the 6-month trial. CONCLUSION: This study provides evidence for the effectiveness and safety of DVPX in the treatment of pediatric mixed mania over a 6-month period. Placebo-controlled, randomized trials involving larger samples will ultimately shed light on the efficacy of this agent.

Adolescent↗
PubMed2004

Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania.

OBJECTIVE: This prospective 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus risperidone (Li+Risp). METHODS: Thirty-seven (37) subjects aged 5 and 18 (age=12.1+/-3.5 years) with DSM IV current mixed or manic episode and Young Mania Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and tolerability. RESULTS: Effect sizes (Cohen's d) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates (>or=50% change from baseline YMRS score at the end of study) were 80% for DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated. Significant improvements (p<0.001) from baseline were seen for mean scores on all efficacy measures, i.e., YMRS, CGI-BP, and CDRS-R. There were no significant group differences in safety or tolerability, and no serious adverse events during the 6-month trial. CONCLUSION: Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder.

Adolescent↗
PubMed2004

Psychotic symptoms in pediatric bipolar disorder.

BACKGROUND: There is under-recognition or misdiagnosis of pediatric bipolar disorder with psychotic features. It is of major public health importance to recognize psychosis in bipolar disorder. METHOD: Original research on phenomenological description of psychosis and external validators including family history, longitudinal course and treatment effects are systematically reviewed. Age differences, sampling, and interview methods of the studies on pediatric bipolar disorder that reported psychotic features are compared. Critical differentiating features between pediatric bipolar disorder and pediatric schizophrenia are summarized given the presence of overlapping psychotic features. RESULTS: Prevalence of psychotic features in pediatric bipolar disorder ranged from 16 to 87.5% based on age and methodological differences. The most common psychotic features are mood congruent delusions, mainly grandiose delusions. Psychotic features appear in the context of affective symptoms in pediatric bipolar disorder as opposed to schizophrenia where psychotic symptoms are independent of them. Family history of affective psychosis aggregated in probands with bipolar disorder. LIMITATIONS: There is discrepancy in clinical appraisal of what constitutes psychosis and pediatric bipolar disorder, apart from the differences in methodology and nature of the samples. CONCLUSION: Clinicians must be vigilant in identifying psychosis in pediatric bipolar disorder, especially when there is a positive family history of psychosis.

Adolescent↗
PubMed2004

Child- and family-focused cognitive-behavioral therapy for pediatric bipolar disorder: development and preliminary results.

OBJECTIVE: To describe child- and family-focused cognitive-behavioral therapy (CFF-CBT), a new developmentally sensitive psychosocial intervention for pediatric bipolar disorder (PBD) that is intended for use along with medication. CFF-CBT integrates principles of family-focused therapy with those of CBT. The theoretical framework is based on (1). the specific problems of children and families coping with bipolar disorder, (2). a biological theory of excessive reactivity, and (3). the role of environmental stressors in outcome. CFF-CBT actively engages parents and children over 12 hour-long sessions. METHOD: An exploratory investigation was conducted to determine the feasibility of CFF-CBT. Participants included 34 patients with PBD (mean age 11.33 years, SD = 3.06) who were treated with CFF-CBT plus medication in a specialty clinic. Treatment integrity, adherence, and parent satisfaction were assessed. Symptom severity and functioning were evaluated before and after treatment using the severity scales of the Clinical Global Impression Scales for Bipolar Disorder (CGI-BP) and the Children's Global Assessment Scale (CGAS) respectively. RESULTS: On completion of therapy, patients with PBD showed significant reductions in severity scores on all CGI-BP scales and significantly higher CGAS scores compared to pretreatment results. High levels of treatment integrity, adherence, and satisfaction were achieved. CONCLUSIONS: CFF-CBT has a strong theoretical and conceptual foundation and represents a promising approach to the treatment of PBD. Preliminary results support the potential feasibility of the intervention.

Adaptation, Psychological↗
PubMed2004

A pharmacotherapy algorithm for stabilization and maintenance of pediatric bipolar disorder.

OBJECTIVE: To assess the feasibility and effectiveness of an evidence-based pharmacotherapy algorithm in the treatment of pediatric bipolar disorder. METHOD: The study reports the results of a study of 64 bipolar type I subjects who were treated according to an algorithm developed in our specialty clinic. All subjects had been diagnosed using the Washington University in St. Louis Schedule for Affective Disorders and Schizophrenia. Subjects scored an average of 28 (+/- 4) on the baseline Young Mania Rating Scale. All subjects were assessed over an 18-month period. In addition, we were able to match 17 of the 64 subjects in the algorithm sample for gender, age, ethnicity, socioeconomic status, and diagnosis with an equal number of subjects in a psychopharmacology clinic who received treatment as usual. RESULTS: Prescribing clinicians were able to implement primary and secondary strategies, including detailed tactics of medication choices in the algorithm group. Growth curve analysis of the total algorithm group showed strong and significant improvement in symptoms. Analyses of the matched groups also showed strong effects for the treatment algorithm over treatment as usual. Treatment adherence and family satisfaction were higher in the algorithm group. CONCLUSION: An evidence-based, problem-solving pharmacotherapy algorithm is feasible and may be associated with better outcomes in the treatment of pediatric bipolar disorder. Randomized trials will be necessary to gather additional support for the algorithm's effectiveness.

Algorithms↗
PubMed2002

Anxiety and fear. Discriminant validity in the child and adolescent practitioner's perspective.

OBJECTIVE: We assessed the ability of child and adolescent practitioners to discriminate between anxiety items from the Revised Children's Manifest Anxiety Scale (RCMAS) and fear items from the Fear Survey Schedule for Children-Revised (FSSC-R). In addition, we examined the effects age, gender, nationality, and therapeutic orientation on discrimination ability. METHOD: Child and adolescent psychiatrists and psychologists from two university hospitals in Australia and the USA completed a questionnaire comprised of items randomly chosen from the RCMAS and the FSSC-R. Clinicians rated each item on the extent to which the item represented the construct of anxiety or fear, using a 7-point Likert-type scale. RESULTS: Clinicians were more accurate in their perceptions of anxiety than in their perceptions of fear. Clinicians with a psychodynamic orientation were more likely to perceive an item as describing anxiety, and were less likely to identify fear. There was a significant interaction between age, scale and perception, with the youngest clinicians showing the greatest perceptual differentiation between the fear and anxiety items. CONCLUSIONS: The results suggest a need to develop common terminology among researchers and clinicians, develop scales with items specific to the pathology they intend to measure, and consider the variables influencing the clinicians rating them.

Adolescent↗