Biomedical subjects

Prabha Siddarth

Publications and source records attributed to Prabha Siddarth.

At least 19 recordsLinked to original sources

PubMed2006

PET of brain amyloid and tau in mild cognitive impairment.

BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.

Aged↗

PubMed2006

Hippocampal volume in childhood complex partial seizures.

PURPOSE: This study compared hippocampal volume in children with cryptogenic epilepsy, all of whom had complex partial seizures (CPS), and age and gender matched normal children controlling for between group differences in IQ and demographic variables (e.g., age, gender, ethnicity, socioeconomic status). It also examined the relationship between hippocampal volumes and seizure variables in the patients. METHODS: Using quantitative magnetic resonance imaging (MRI), we compared the hippocampal volumes of 19 medically treated children with CPS, aged 6-14 years, to 21 age and gender matched normal children. RESULTS: The children with CPS had significantly smaller total hippocampal volumes than the normal children. This finding was accounted for primarily by significantly smaller anterior hippocampal volumes. Within the CPS group, smaller total and posterior hippocampus volumes were significantly associated with longer duration of illness. Anterior hippocampal volumes, however, were unrelated to seizure variables. CONCLUSIONS: These findings imply impaired development of the hippocampus, particularly the anterior hippocampus, and a differential effect of the underlying illness and on-going seizures on hippocampal development in medically controlled pediatric CPS.

Adolescent↗

PubMed2006

Thought disorder: A developmental disability in pediatric epilepsy.

This study compared thought disorder (i.e., impaired use of language to formulate and organize thoughts) in 93 children with complex partial seizures (CPSs) and 56 children with primary generalized epilepsy with absence (PGE) and its relationship to age, seizure, cognitive, and linguistic variables. By the use of psychopathology, social competence, academic achievement, and school problem measures, the functional implications of thought disorder in these two groups were compared. When demographic variables were controlled for, there were no significant differences in thought disorder scores between the CPS and PGE groups. However, the profile of age, gender, seizure, and cognitive variables related to thought disorder differed in the CPS and PGE groups. Within each group, different aspects of thought disorder were associated with different seizure variables. Thought disorder was related to psychopathology, school problems, decreased academic achievement, and poor peer interaction in the CPS group, but with school problems in the PGE group. These findings suggest that CPS and PGE affect the normal maturation of children's discourse skills, albeit through different mechanisms. The relationship of thought disorder to behavioral, academic, and social problems implies that these discourse deficits are one component of the developmental disabilities or comorbidities associated with pediatric CPS and PGE.

Adolescent↗

PubMed2006

Serotonin 1A receptors in the living brain of Alzheimer's disease patients.

4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT(1A)) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT(1A) receptor densities in the living brains of Alzheimer's disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6), and controls (n = 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 +/- 0.07; ADs 1.18 +/- 0.26) and also in raphe nuclei (controls 0.63 +/- 0.09; ADs 0.37 +/- 0.20). When volume losses are included, 5-HT(1A) losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT(1A) receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT(1A) receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-d-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 +/- 0.04, ADs 0.72 +/- 0.04; posterior cingulate gyrus: controls 1.05 +/- 0.09, ADs 0.79 +/- 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same subjects. The in vivo observations were confirmed independently by in vitro digital autoradiography with 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile on brain tissue specimens from two ADs and three nondemented subjects.

Alzheimer Disease↗

PubMed2006

Perceived loss of memory ability and cerebral metabolic decline in persons with the apolipoprotein E-IV genetic risk for Alzheimer disease.

CONTEXT: Concerns about age-related memory loss are greater in persons who have the apolipoprotein E-IV (APOE4) genetic risk for Alzheimer disease, but the correlation between the degree of concerns and future cerebral metabolic decline is unknown. OBJECTIVE: To investigate whether the degree of self-perceived memory loss is associated with regional cerebral metabolic decline. DESIGN: Longitudinal study. SETTING: Aging and Memory Research Center, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. PARTICIPANTS: Thirty right-handed, cognitively intact, middle-aged and older adults (age range, 50-82 years) with age-associated memory complaints, 14 of whom were carriers of the apolipoprotein E-IV allele, were recruited for longitudinal study. MAIN OUTCOME MEASURES: At baseline, we administered a standardized neuropsychological battery and assessed self-appraisal of memory functioning using the Memory Functioning Questionnaire, which yields 4 factor scores indicating frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use. Regional cerebral glucose metabolism was determined using fluorodeoxyglucose F18-positron emission tomography at baseline and after 2 years. RESULTS: At baseline, APOE4 carriers and noncarriers did not differ significantly on objective memory measures or on Memory Functioning Questionnaire factor scores. However, the factor score for frequency of forgetting significantly correlated with global cerebral metabolic decline in all subjects regardless of APOE4 genetic risk (P = .01). By contrast, the factor score for mnemonics use significantly correlated with metabolic decline in the temporal regions in APOE4 carriers but not in noncarriers (P = .03). CONCLUSIONS: The degree of perceived memory loss correlates with subsequent global cerebral metabolic decline for APOE4 carriers and noncarriers; hence, memory complaints may reflect underlying cerebral metabolic changes. Compensatory strategies, as reflected by more frequent mnemonics use in APOE4 carriers, may reflect underlying metabolic changes in the brain regions associated with prodromal Alzheimer disease. Self-reported mnemonics use may be helpful in identifying persons for clinical monitoring.

Aged↗

PubMed2006

Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.

OBJECTIVE: The authors evaluated the potential of methylphenidate to accelerate and enhance antidepressant response to citalopram in elderly depressed patients. METHODS: Sixteen outpatients with major depression were treated in a 10-week double-blind trial. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. RESULTS: An accelerated response was observed by week 3 in five subjects receiving citalopram (CIT)+methylphenidate (MPH) and in none of those receiving CIT+placebo (PBO). Subjects receiving citalopram and methylphenidate showed a significant improvement in depressive symptoms compared with those on citalopram and placebo. CONCLUSION: Combined treatment with citalopram and methylphenidate appears to be a viable strategy for accelerating and enhancing antidepressant response in elderly depressed patients limited by tolerability and safety.

Aged↗

PubMed2006

Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints. METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures. CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

Adult↗

PubMed2005

Abnormal development of the anterior cingulate in childhood-onset schizophrenia: a preliminary quantitative MRI study.

The anterior cingulate is a key component of neural networks subserving attention and emotion regulation, functions often impaired in patients with psychosis. The study aimed to examine anterior cingulate volumes and sulcal morphology in a group of patients with childhood-onset schizophrenia (COS) compared with controls. Brain magnetic resonance imaging (MRI) scans were obtained in 13 COS and 18 matched control children, ages 6-17 years. Volume measures for the anterior cingulate gyrus (ACG) were obtained through manual labeling. A determination of cingulate sulcal pattern (single or double) was made for each hemisphere. The COS group had a reduced leftward skew of the double cingulate sulcal pattern, and absence of the normal left>right ACG volume asymmetry. The right ACG was larger in the COS than in controls. The schizophrenic children showed decreases in all ACG volumes with age, while the controls showed increases or no change. The data suggest that significant cingulate abnormalities may result from deviations in progressive neurodevelopmental processes, beginning before birth and continuing through childhood and adolescence, in persons who develop schizophrenia. These structural differences may relate to the well-described cognitive deficits these children display, and to the cardinal symptoms of schizophrenia.

Adolescent↗

PubMed2005

Object naming and semantic fluency among individuals with genetic risk for Alzheimer's disease.

OBJECTIVES: This study longitudinally examined the object naming and semantic fluency of individuals who are at risk for developing Alzheimer's disease (AD) by virtue of having APOE-4 or a family history of AD. METHODS: A total of 108 participants (40 with a family history of AD and 43 with APOE-4) completed the Boston Naming Test and the Animal Naming task at initial assessment and after two years. RESULTS: At baseline, object naming was significantly lower for those with both risk factors, F(2, 99) = 5.72, p < 0.01, but those with either risk factor had significantly lower scores at follow-up, F(2, 99) = 3.41, p < 0.05. Semantic fluency (animal naming) was reduced among subjects with the APOE-4 allele at baseline, F(1, 100) = 4.02, p < 0.05, but it was not associated with either risk factor at follow-up. CONCLUSIONS: These deficits may be associated with a prodromal risk for AD and may serve as pre-symptomatic markers for the development of AD.

Aged↗

PubMed2005

Estrogen use and brain metabolic change in postmenopausal women.

OBJECTIVE: We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD: Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously reported to decline in older persons at risk for Alzheimer's disease (AD) (posterior cingulate and lateral temporal cortex). RESULTS: Region of interest (ROI) analysis at baseline showed no regional differences between women estrogen users and non users. ROI follow-up analysis revealed that women non-users declined significantly in the posterior cingulate cortex (P= 0.04). Statistical parametric mapping (SPM) analysis confirmed a significant decrease in metabolism of the posterior cingulate cortex among non-users at 2-year follow-up (P = 0.004). In contrast, women estrogen users did not exhibit significant metabolic change in the posterior cingulate. CONCLUSIONS: Estrogen use may preserve regional cerebral metabolism and protect against metabolic decline in postmenopausal women, especially in posterior cingulate cortex, the region of the brain found to decline in the earliest stages of AD.

Aged↗

PubMed2005

Social competence in pediatric epilepsy: insights into underlying mechanisms.

This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 children with complex partial seizures (CPS) and 62 with absence epilepsy (CAE) of average intelligence with scores of 91 healthy children. It also examined the role of seizure-related, cognitive, behavioral, linguistic, social communication, and demographic variables on these measures. When differences in cognitive, linguistic, and demographic variables were controlled for, the CPS and CAE groups had significantly lower scores in the school, but not in the social interaction and activities domains compared with the healthy control group. Among the patients, lower Full Scale IQ externalizing behaviors, disruptive disorders, minority status, and impaired social communication, but not seizure variables, predicted lower social competence scores. These findings demonstrate the importance of controlling for cognitive, behavioral, and demographic variables in social competence studies of children with CPS and CAE and the need to assess cognition and behavior when parents report school and social problems in these children.

Achievement↗

PubMed2005

Age of first onset major depression in Chinese Americans.

Using data from the Chinese American Epidemiological Study, risk for experiencing an initial episode of major depression across the life course was examined. Data were collected on 1,747 U.S.-born and foreign-born Chinese Americans (ages 18-65 years). Results suggest that Chinese American women did not evidence higher risk than Chinese American men for experiencing a 1st major depressive episode. Risk for experiencing a 1st depressive episode decreased as length of residence in the United States increased. Although those who immigrated at younger ages evidenced greater overall risk, those who came at later ages were more likely to become depressed at or soon after arrival. Competing theories of acculturation-related risk are discussed and directions for future research are proposed.

Adolescent↗

PubMed2005

Depression and anxiety disorders in pediatric epilepsy.

PURPOSE: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure-related, cognitive, linguistic, family history, social competence, and demographic variables. METHODS: A structured psychiatric interview, mood self-report scales, as well as cognitive and language testing were administered to 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral information on each child through a structured psychiatric interview and behavior checklist. RESULTS: Significantly more patients had affective and anxiety disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal group, but none had made a suicide attempt. Anxiety disorder was the most frequent diagnosis among the patients with a diagnosis of affective or anxiety disorders, and combined affective/anxiety and disruptive disorder diagnoses, in those with suicidal ideation. Only 33% received some form of mental health service. Age, verbal IQ, school problems, and seizure type were related to the presence of a diagnosis of affective or anxiety disorder, and duration of illness, to suicidal ideation. CONCLUSIONS: These findings together with the high rate of unmet mental health underscore the importance of early detection and treatment of anxiety disorders and suicidal ideation children with CPSs and CAE.

Adolescent↗

PubMed2005

Similar neurocognitive performance of adults with and without a history of parental Alzheimer's disease: a pilot study.

The first reported 20-year prospective follow-up of middle-aged children of Alzheimer patients failed to find statistically significant neurocognitive decline. Because that report did not include a comparison group, the current study compared the 20-year follow-up scores with scores obtained on the same 8 measures by an age-comparable sample of healthy adults without a family history of Alzheimer's disease. Both were convenience samples (n = 24). Statistical analyses (correcting for age) yielded no significant group differences in neurocognitive scores but did show a significantly higher mean score for the comparison group on the Mini-Mental State Examination (29.5 vs 28.8, P = .003, controlling for age). Even though this finding suggests that adult children of a parent with Alzheimer's disease performed well on a limited neurocognitive battery and on the Mini-Mental State Examination, the findings are preliminary and require confirmation on large representative samples with appropriate controls and long-term follow-up.

Aged↗

PubMed2004

Thought disorder and nucleus accumbens in childhood: a structural MRI study.

Thought disorder has been described as a hallmark feature in both adult and childhood-onset schizophrenia. The nucleus accumbens (NAc) has been repeatedly proposed as a critical station for modulating gating of information flow and processing of information within the thalamocortical circuitry. The aim of the present study was to investigate the relationship of thought disorder measures, which were administered to 12 children with schizophrenia and 15 healthy age-matched controls, and NAc volumes obtained from high-resolution volumetric magnetic resonance imaging analyses. The propensity for specific thought disorder features was significantly related to NAc volumes, despite no statistically significant differences in the NAc volumes of children with schizophrenia and normal children. Smaller left NAc volumes were significantly related to poor on-line revision of linguistic errors in word choice, syntax and reference. On the other hand, underuse of on-line repair of errors in planning and organizing thinking was significantly associated with decreased right NAc volumes. The results of this pilot study suggest that the NAc is implicated in specific thought patterns of childhood. They also suggest that subcortical function in the NAc might reflect hemispheric specialization patterns with left lateralization for revision of linguistic errors and right lateralization for repair strategies involved in the organization of thinking.

Child↗

PubMed2004

Psychopathology and pediatric complex partial seizures: seizure-related, cognitive, and linguistic variables.

PURPOSE: This study examined the role of cognition, language, seizure-related, and demographic variables in the psychopathology of children with complex partial seizure disorder (CPS) of average intelligence. METHODS: One-hundred one CPS and 102 normal children, aged 5.1 to 16.9 years, had a structured psychiatric interview and cognitive and language testing. Parents provided demographic, perinatal, and seizure-related information, as well as behavioral information through the Child Behavior Checklist (CBCL) and a structured psychiatric interview about the child. RESULTS: Significantly more CPS patients had psychopathology, cognitive deficits, and linguistic deficits than did those in the normal group. Among the patients, Verbal IQ predicted the presence of a psychiatric diagnosis, as well as CBCL scores in the borderline/clinical range. Seizure, linguistic, and demographic variables were unrelated to psychopathology. The cognitive and linguistic deficits of the CPS group, however, were predicted by seizure factors (e.g., prolonged seizures/febrile convulsions; seizure frequency/number of antiepileptic drugs) and demographic factors (e.g., minority status). CONCLUSIONS: Because subtle verbal cognitive deficits predict behavioral disturbances in pediatric CPSs, the study's findings highlight the importance of assessing behavior, cognition, and language in these children. They also underscore the negative impact of prolonged seizures, febrile convulsions, seizure frequency, and antiepileptic drug polytherapy on cognition and language in pediatric CPSs.

Adolescent↗

PubMed2003

Differential associations of sex and D2 dopamine receptor (DRD2) genotype with negative affect and other substance abuse risk markers in children of alcoholics.

Children of alcoholics have increased risk for substance abuse problems. Self-medication of negative affect may be one developmental path to future substance abuse. Because the 146 young (adolescent) children of alcoholics in the current sample had not used enough abused substances to study substance use directly, the relation of substance abuse risk markers to negative affect was assessed. Because the D2 dopamine receptor (DRD2) A1 allele has been associated with alcoholism and other substance use disorders, negative affect, measured by the Beck Depression Inventory (BDI), was determined in four groups of children: boys and girls with the A1+ allele (A1A1 and A1A2 genotypes) and with the A1- allele (A2A2 genotype). The other risk markers were stress, low amplitude of the P300 evoked potential, poor visuospatial functioning, novelty seeking (NS), and harm avoidance (HA). Stress was correlated with BDI scores in all groups. In contrast, low P300 was associated with BDI scores only in boys with the A1+ allele (P = .04), NS was associated with BDI scores only in girls with the A1+ allele (P = .02), and HA was associated with BDI scores only in boys with the A1- allele (P = .01). In addition, boys with the A1+ allele had lower BDI (P = .05) and HA (P = .005) scores than the respective scores for boys with the A1- allele. Girls with the A1- allele had lower HA scores compared with scores for boys with the A1- allele (P = .02). Girls with the A1+ allele had lower visuospatial functioning than that of boys with the A1+ allele (P<.001). Results indicate that both sex and DRD2 genotype modify associations between negative affect and other substance abuse risk markers.

Adolescent↗

PubMed2003

Behavioral disorders in pediatric epilepsy: unmet psychiatric need.

PURPOSE: This study examined the relation between psychiatric diagnosis and mental health services in children with epilepsy and the associated demographic, cognitive, linguistic, behavioral, and seizure-related variables. METHODS: The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), the Child Behavior Checklist, the Test of Language Development, and the Wechsler Intelligence Scale for Children-Revised (WISC-R) were administered to 114 children, aged 5 to 16 years, with either complex partial seizures (CPS) or primary generalized with absence (PGE, petit mal). A Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis and information regarding mental health services were derived from the K-SADS. RESULTS: Although approximately 60% of the subjects had a DSM-IV psychiatric diagnosis, >60% received no mental health treatment. Absence of mental health care was associated with younger age, less parental education, limited number of antiepileptic drugs (AEDs; i.e., one or none), and higher verbal IQ. In addition, children with PGE and a single psychiatric diagnosis were less likely to have a history of mental health treatment. CONCLUSIONS: This is the first study to demonstrate unmet mental health need in a large sample of children with CPS and PGE. The study's findings suggest that parents and clinicians should be aware of the mental health needs of children with epilepsy, particularly if they have one or more of the identified risk factors.

Adolescent↗