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Sanjiv Kumra

Publications and source records attributed to Sanjiv Kumra.

13 recordsLinked to original sources
PubMed2006

Decision-making impairments in adolescents with early-onset schizophrenia.

Adolescence is a time of vulnerability for risk-taking behaviors. This is particularly true of adolescents with schizophrenia who present with high rates of substance use as compared to the general population. Using the Iowa Gambling Task (IGT), the authors compared decision-making processes in adolescents with early-onset schizophrenia (onset of psychosis by age 18) to that of healthy volunteers. Fifteen adolescents with schizophrenia (aged 12-21 years) and 25 demographically similar healthy volunteers were administered the IGT. Overall, adolescents with schizophrenia performed significantly worse on the IGT than healthy adolescents as measured by a significant group by block interaction. Post-hoc testing revealed that adolescents with schizophrenia performed more poorly than healthy adolescents during the last two blocks of the task. Mathematical modeling further indicated that adolescents with schizophrenia allocated significantly more attention to monetary gains than losses encountered during the task, suggesting a hypersensitivity to rewards and relative insensitivity to future consequences. This is similar to what has been reported for adults with externalizing forms of psychopathology, such as those who abuse substances. These findings have potential implications for understanding the increased vulnerability for the development of substance abuse in adolescents with schizophrenia.

Adolescent↗
PubMed2006

Deficits in memory strategy use are related to verbal memory impairments in adolescents with schizophrenia-spectrum disorders.

OBJECTIVE: To assess the nature of learning and verbal memory deficits in adolescents with schizophrenia-spectrum disorders (SzS) (i.e., schizophrenia, schizoaffective disorder, and schizophreniform disorder). METHOD: Sixty patients with SzS (mean age=16.1 years, S.D. = 2.2) and 60 age- and gender-matched diagnosis-free healthy volunteers were assessed using the California Verbal Learning Test (CVLT). Planned analyses were conducted to assess the following aspects of memory: span of apprehension, verbal learning, short-term and long-term memory, rate of forgetting, interference, and organizational strategies. Adolescents with schizophrenia (Sz) were compared to those with schizoaffective disorder (SzA). Second, patients' test profiles were compared to those of controls. Relationships between initial learning and overall verbal learning with organizational strategy were explored. RESULTS: Neurocognitive profiles did not significantly differ between Sz and SzA participants. Patients performed significantly worse than healthy comparison subjects on measures of span of apprehension, verbal learning, short- and long-term memory, and organizational strategies after adjusting for differences in premorbid intelligence. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. CONCLUSIONS: Adolescents with SzS are characterized by significant verbal memory dysfunction similar to what has been observed in adults with first-episode schizophrenia. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate dysfunction of the dorsolateral prefrontal cortex as a contributor to verbal memory deficits in adolescents with SzS.

Adolescent↗
PubMed2006

Treatment-refractory schizophrenia in children and adolescents: an update on clozapine and other pharmacologic interventions.

Treatment-refractory early-onset schizophrenia is a rare but severe form of the disorder associated with poor premorbid function and long-term disability. The currently available evidence suggests that clozapine remains the most efficacious treatment for the amelioration of both positive and negative symptoms of the disorder and problematic aggressive behaviors. Clozapine use in children and adolescents, however, is limited by its association with hematologic adverse events and an increased frequency of seizure activity. Further studies are needed to examine the usefulness of antipsychotic combinations and of augmentation therapies to antipsychotic medications in order to treat persistent residual psychotic symptoms in children and adolescents who have schizophrenia and who have not responded to several sequential trials of antipsychotic monotherapy.

Adolescent↗
PubMed2006

Ethical and practical considerations in the management of incidental findings in pediatric MRI studies.

OBJECTIVE: The authors examined the ethical and practical management issues resulting from the detection of incidental abnormal findings on magnetic resonance imaging (MRI) research studies in healthy pediatric volunteers. METHOD: A retrospective examination of the findings from 60 clinical reports of research MRI scans from a cohort of healthy pediatric volunteers (ages 10-21) was conducted. RESULTS: A neuroradiologist noted incidental abnormalities in 8 (13%) of 60 subjects. Of these eight children, three (5%) adolescents were found to have abnormalities (possible tumor, possible vascular malformation, and unidentified bright object in white matter, respectively) that were judged to require further diagnostic workup. In the first two cases, follow-up MRI ruled out the possibility of a tumor or vascular malformation. In the third case, a follow-up MRI 24 months later found that the white matter abnormality remained stable and was thus deemed to be of no clinical significance. CONCLUSIONS: In healthy children who are participating in research MRI protocols, it is ethically difficult to determine whether films should be read clinically. Based on this retrospective analysis, there would have been no risk(s) associated with not reading the films. In contrast, considerable anxiety was generated as a consequence of having the scans clinically read by a neuroradiologist because of the reporting of incidental abnormalities that later turned out to be false positives. Also, the detection of no abnormality on a research-quality scan could imply erroneously to some subjects that no abnormality was present, which may have been falsely reassuring.

Adolescent↗
PubMed2005

Early-onset schizophrenia is associated with impaired adolescent development of attentional capacity using the identical pairs continuous performance test.

The authors examined performance on the Continuous Performance Test-Identical Pairs "numbers" task in adolescents with schizophrenia (n=59) and healthy controls (n=55). Adjusting for an estimate of premorbid intelligence and socioeconomic status, patients performed worse than normal controls on all three d' conditions (2-digit, 3-digit, 4-digit). However, there was a significant group-by-age-by-condition interaction (F[4,100]=4.69, p<.01) indicating an interaction between development and disease state. At the simplest level of the task (2-digit) the difference between patients with schizophrenia and controls was evident at all ages; while for the more difficult levels of the task (3-digit, 4-digit), differences between groups gradually increased across the tested age span (10 to 20 years of age). Premorbid social isolation was associated with worse attentional performance in patients, suggesting a relationship and continuity with negative symptoms. These data suggest that attentional differences in adolescents with schizophrenia are better captured by different tasks at different ages. The discrepant findings of attentional impairments reported in the literature for adolescents with schizophrenia could reflect the underlying etiological complexity of the disorder that may have a variable impact on involved brain regions and neurocognitive functioning.

Adolescent↗
PubMed2005

Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates.

BACKGROUND: Neurocognitive impairments have been documented in adolescents with early-onset schizophrenia (EOS; onset by age 18) and are important treatment targets. Information concerning the severity, pattern, and clinical correlates of these deficits in EOS remains limited. METHODS: Tests assessing motor skills, attention, memory, visuospatial abilities and executive functioning were administered to 54 clinically stabilized adolescents with EOS and 52 age- and sex-matched healthy controls. Childhood-onset patients (onset by age 13) were compared to those with an adolescent onset of illness. Patients' neurocognitive profiles were compared to those of controls. Relationships between neurocognitive deficits and demographic and clinical characteristics were explored. RESULTS: Neurocognitive profiles did not differ between childhood- and adolescent-onset participants. Patients showed a generalized neurocognitive deficit of 2.0 SDs compared to controls, with relative deficit in executive functioning and relative sparing of language and visuospatial abilities. Degree of generalized neurocognitive impairment was associated with premorbid adjustment and negative symptom severity (Adjusted R(2) = .39). CONCLUSIONS: Results document both a significant generalized deficit and a relative deficit of executive functioning in adolescents with EOS. The overall pattern is similar to that observed in severely ill first-episode adult patients. The impairments across multiple neurocognitive domains suggest widespread brain dysfunction in EOS.

Adolescent↗
PubMed2005

Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study.

BACKGROUND: The purpose of this study was to explore whether there are white matter (WM) abnormalities in children with attention-deficit/hyperactivity disorder (ADHD) using diffusion tensor imaging. Based upon the literature, we predicted decreased fractional anisotropy (FA) findings in the frontal and cerebellar regions. METHODS: Eighteen patients with ADHD and 15 age- and gender-matched healthy volunteers received DTI assessments. Fractional anisotropy maps of WM were compared between groups with a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Children with ADHD had decreased FA in areas that have been implicated in the pathophysiology of ADHD: right premotor, right striatal, right cerebral peduncle, left middle cerebellar peduncle, left cerebellum, and left parieto-occipital areas. CONCLUSIONS: These preliminary data support the hypothesis that alterations in brain WM integrity in frontal and cerebellar regions occur in ADHD. The pattern of decreased FA might implicate the corticopontocerebellar circuit in the pathophysiology of ADHD.

Anisotropy↗
PubMed2005

Clozapine: its impact on aggressive behavior among children and adolescents with schizophrenia.

OBJECTIVE: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.x) at Bronx Children's Psychiatric Center. METHOD: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of emergency oral and injectable medications and the frequency of seclusion events 3 months immediately before and from 12 to 24 weeks of clozapine treatment (when optimal clozapine levels were achieved) were compared. RESULTS: Twenty clozapine-treated children (mean +/- SD dose at week 24, 476 +/- 119 mg) were included. A statistically significant decrease in the frequency of the administration of emergency oral medications, the administration of emergency injectable medications, and seclusion events was found in adolescents during weeks 12 to 24 of clozapine treatment compared with their baseline condition before clozapine initiation. CONCLUSIONS: These preliminary data indicate the benefits of clozapine treatment in adolescents with treatment-refractory schizophrenia for aggressive behaviors. Although open data limit conclusions from this study, it is important that there was a clinically significant improvement in aggressive behaviors that enabled patients to be discharged to a less restrictive setting. Additional controlled clinical trials of clozapine are needed in treatment-refractory children and adolescents.

Adolescent↗
PubMed2005

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study.

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.

Adolescent↗
PubMed2005

Hematological adverse events in clozapine-treated children and adolescents.

OBJECTIVE: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. METHOD: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and agranulocytosis (HAEs) development was determined for 172 eligible patients (mean age at clozapine initiation, 15.03 +/- 2.13 years) with a median observation period of 8 months. RESULTS: Neutropenia (absolute neutrophil count <1,500/mm) developed in 23 (13%) patients and agranulocytosis (absolute neutrophil count <500/mm) in one (0.6%) patient. The cumulative probability of developing an initial HAE at 1 year of clozapine treatment was 16.1% (95% confidence interval 9.7%-22.5%). Eleven (48%) of 24 patients who developed an HAE were successfully rechallenged on clozapine. Eight (5%) of 172 patients from this sample eventually discontinued clozapine because of an HAE (one agranulocytosis, seven neutropenia). CONCLUSIONS: The occurrence of HAEs is a significant risk associated with the administration of clozapine. However, in this sample, few children actually discontinued therapy because of an HAE and the incidence of agranulocytosis does not appear higher than what has been reported in the adult literature.

Adolescent↗
PubMed2005

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study.

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.

Adult↗
PubMed2004

Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study.

BACKGROUND: Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. METHODS: Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). RESULTS: Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. CONCLUSIONS: These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia.

Adolescent↗