Prabha Siddarth - Academia.edu (original) (raw)

Papers by Prabha Siddarth

Research paper thumbnail of Associations Between Cytokines and Cortical Thickness in Patients with Late-Life Depression

The American Journal of Geriatric Psychiatry, 2019

Introduction: Psychotic features are more prevalent in older adults with depression than in young... more Introduction: Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods: This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results: NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r =-0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between-0.11 and 0.1). The correlations between HCC and i) IADL performance (r =-0.04) and ii) general functioning (r =-0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and nonpsychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions: This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context.

Research paper thumbnail of Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2012

Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective ... more Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective diagnostic and therapeutic strategies. Carrying the ε4 allele of the apolipoprotein E gene (APOE4) and having a family history of the disease are two such factors, with family history risk reflecting additional yet unknown or rarely studied genetic and perhaps nongenetic risks. Our aim was to determine the influence of APOE genotype and family history status on cognitive performance in healthy individuals. Longitudinal study. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. Seventy-two cognitively healthy middle-aged and older people (mean age ± SD: 62 ± 9 years). Neuropsychological examinations at baseline and after 2 years. Subjects with a family history of AD had lower baseline scores in processing speed, executive functioning, memory encoding, and delayed memory when compared with those without a family history. The family history risk facto...

Research paper thumbnail of Dealing with epilepsy: Parents speak up

Epilepsy & Behavior, 2008

In this study, focus groups were used to examine parents' attitudes toward mental health services... more In this study, focus groups were used to examine parents' attitudes toward mental health services, use of mental health and other services, as well as service-related and other challenges encountered by parents of children with epilepsy. Both quantitative and qualitative analytic approaches were used to analyze the transcripts of 36 parents grouped into six focus groups by socioeconomic status (SES) (high, low) and ethnicity (African-American, Caucasian, Hispanic). The quantitative analyses demonstrated that, irrespective of SES and ethnicity, the parents were highly aware of their children's behavioral, emotional, and cognitive difficulties and the lack of knowledge about epilepsy among medical, educational, and mental health professionals. The higher-SES parents were significantly more concerned about inadequate educational services and the need for medical services, but less concerned about mental health and medical service use than the lower-SES parents. Insufficient knowledge about epilepsy and about services, parent emotional difficulties, and use of educational services differed significantly by ethnicity. The qualitative analyses highlighted the parents' concerns regarding misconceptions about epilepsy and the stigma toward mental health care among the African-American and Hispanic parents. These findings suggest the need for accessible and better-quality mental health, educational, and medical services for children with epilepsy irrespective of SES and ethnicity. They also underscore the importance of educating parents, service providers, and the general public about epilepsy.

Research paper thumbnail of Pediatric psychogenic nonepileptic seizures: A study of assessment tools

Epilepsy & Behavior, 2010

The goal of this study was to identify assessment tools and associated behavioral domains that di... more The goal of this study was to identify assessment tools and associated behavioral domains that differentiate children with psychogenic nonepileptic seizures (PNES) from those with epilepsy. A sample of 24 children with PNES (mean age 14.0 years, 14 female), 24 children with epilepsy (mean age 13.6 years, 13 female), and their parents were recruited from five epilepsy centers in the United States. Participants completed a battery of behavioral questionnaires including somatization, anxiety, and functional disability symptoms. Children with PNES had significantly higher scores on the Childhood Somatization and Functional Disability Inventories, and their parents reported more somatic problems on the Child Behavior Checklist (CBCL). Depression, anxiety, and alexithymia instruments did not differentiate the groups. Measures of somatization and functional disability may be promising tools for differentiating the behavioral profile of PNES from that of epilepsy. Increased somatic awareness and perceived disability emphasize the similarity of PNES to other pediatric somatoform disorders.

Research paper thumbnail of Amygdala volume and psychopathology in childhood complex partial seizures

Epilepsy & Behavior, 2008

Purpose-This study compared amygdala volume in children with cryptogenic epilepsy, who had comple... more Purpose-This study compared amygdala volume in children with cryptogenic epilepsy, who had complex partial seizures (CPS), with age and gender matched normal children. It also examined the relationship of amygdala volumes with seizure variables and the presence of psychopathology in the patients.

Research paper thumbnail of Social competence in pediatric epilepsy: insights into underlying mechanisms

Epilepsy & Behavior, 2005

This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 c... more 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.

Research paper thumbnail of Thought disorder: A developmental disability in pediatric epilepsy

Epilepsy & Behavior, 2006

This study compared thought disorder (i.e., impaired use of language to formulate and organize th... more 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.

Research paper thumbnail of Suicidality and brain volumes in pediatric epilepsy

Epilepsy & Behavior, 2010

This study examined the relationship between suicidal ideation and frontotemporal volumes, partic... more This study examined the relationship between suicidal ideation and frontotemporal volumes, particularly orbital frontal gyrus volume, in 51 subjects with epilepsy with a mean age of 9.8 (2.1) years. Structured psychiatric interviews of the children and parents provided information on suicidal behavior and DSM-IV diagnoses. Tissue of 1.5-T MRI scans was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. The 11 subjects with epilepsy with suicidal ideation had significantly smaller right orbital frontal gyrus white matter volumes and larger left temporal lobe gray matter volumes than the 40 children without suicidal thoughts. Given the role of the orbital frontal gyrus in both emotional regulation and epilepsy, these findings highlight the biological underpinnings of suicidal ideation in pediatric epilepsy.

Research paper thumbnail of Cognition, academic achievement, language, and psychopathology in pediatric chronic epilepsy: Short-term outcomes

Epilepsy & Behavior, 2010

Children with epilepsy and control children were followed over a two year interval. Comorbidities... more Children with epilepsy and control children were followed over a two year interval. Comorbidities of epilepsy, often defined as problems related to IQ, academic achievement, language, and psychopathology, were evaluated prospectively. It was hypothesized that over time a) the presence of comorbidities would predict worse outcomes, and b) epilepsy variables would negatively impact comorbidities. The study included 39 children with complex partial seizures (CPS), 25 children childhood absence epilepsy (CAE), and 27 healthy children, aged 7.6-16.1 years. The findings were notable for stability over the interval in all three groups. Additionally, baseline seizure variables and change over the interval appear to play a role in IQ and math achievement scores of children with epilepsy with average IQ and in the reading achievement scores of those with below average IQ. However, seizures variables at baseline and follow-up were not predictors of DSM-IV diagnoses, depression, anxiety or behavioral problems.

Research paper thumbnail of Language and brain volumes in children with epilepsy

Epilepsy & Behavior, 2010

This study compared the relationship of language skill with fronto-temporal volumes in 69 medical... more This study compared the relationship of language skill with fronto-temporal volumes in 69 medically treated epilepsy subjects and 34 healthy children, aged 6.1-16.6 years. It also determined if the patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions. The children underwent language testing and magnetic resonance imaging scans at 1.5 Tesla. Brain tissue was segmented and fronto-temporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.

Research paper thumbnail of Amygdala volumes in childhood absence epilepsy

Epilepsy & Behavior, 2009

Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity... more Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.

Research paper thumbnail of Frontal and temporal volumes in children with epilepsy

Epilepsy & Behavior, 2007

This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have... more This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have smaller total brain, frontal, and temporal lobe volumes than normal children and how this is related to seizure, cognitive, psychiatric, and demographic variables. Fortyfour children with CPS and 38 normal children, aged 5-16 years, underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, frontal parcellation, and temporal lobe volumes were computed. Other than significantly larger temporal lobe white matter volumes in the CPS group, there were no significant differences in brain volumes between the CPS and normal groups. Earlier onset, longer duration of illness, younger chronological age, and presence of a psychiatric diagnosis were significantly related to smaller frontotemporal volumes in subjects with CPS. Although these findings suggest that CPS might affect development of the temporal and frontal regions, we are unable to rule out the possibility that smaller frontotemporal volumes might predispose children to CPS. These findings highlight the need to control for seizure, cognitive, psychiatric, and demographic variables in studies of frontotemporal volumes in pediatric CPS.

Research paper thumbnail of Obstacles to mental health care in pediatric epilepsy: Insight from parents

Epilepsy & Behavior, 2009

This exploratory study compared the responses of 20 Caucasian and 20 Hispanic mothers of children... more This exploratory study compared the responses of 20 Caucasian and 20 Hispanic mothers of children with epilepsy about possible obstacles to mental health care (MHC) for their children before and after they read a brochure on the neurobehavioral comorbidities of epilepsy. The intervention significantly increased the mothers' knowledge of the behavior and cognitive comorbidities of pediatric epilepsy and their treatment. Baseline differences in the attitude toward MHC and the stigma of epilepsy between Hispanic and Caucasian mothers were no longer apparent after the intervention. Irrespective of ethnicity, the mothers also became significantly more aware that their children did not want to have epilepsy-related behavior and learning difficulties. Efficient use of time spent in doctors' waiting rooms to educate parents about the neurobehavioral comorbidities of epilepsy can address the lack-of-knowledge barrier to MHC. However, the study's findings suggested a need to determine if there are specific obstacles to MHC in pediatric epilepsy.

Research paper thumbnail of Thought disorder and frontotemporal volumes in pediatric epilepsy

Epilepsy & Behavior, 2008

The aim of this study was to determine if volumes of frontotemporal regions associated with langu... more The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5-16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl's gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl's gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.

Research paper thumbnail of Childhood absence epilepsy: Behavioral, cognitive, and linguistic comorbidities

Epilepsia, 2008

Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absen... more Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE. Methods: Sixty-nine CAE children aged 9.6 (SD ¼ 2.49) years and 103 age-and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL). Results: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems. Conclusions: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

Research paper thumbnail of Psychopathology and Pediatric Complex Partial Seizures: Seizure-related, Cognitive, and Linguistic Variables

Epilepsia, 2004

Purpose: This study examined the role of cognition, language, seizure-related, and demographic va... more 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.

Research paper thumbnail of Behavioral Disorders in Pediatric Epilepsy: Unmet Psychiatric Need

Epilepsia, 2003

This study examined the relation between psychiatric diagnosis and mental health services in chil... more 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. 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. 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. 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.

Research paper thumbnail of Language in pediatric epilepsy

Epilepsia, 2009

Purpose: This study examined the severity and range of linguistic impairments in young, intermedi... more Purpose: This study examined the severity and range of linguistic impairments in young, intermediate, and adolescent youth with epilepsy and how these deficits were associated with illness effects, nonverbal intelligence, psychopathology, and reading. Methods: Tests of language, intelligence, achievement, and structured psychiatric interviews were administered to 182 epilepsy youth, aged 6.3-8.1, 9.1-11.7, and 13.0-15.2 years, as well as to 102 age-and gender-matched normal children. Parents provided demographic, seizure-related, and behavioral information on their children. Results: Significantly more epilepsy subjects had language scores 1 standard deviation (SD) below average than the age-matched control groups did. The intermediate and adolescent epilepsy groups also had significantly lower mean language scores compared to their matched controls. The older compared to the younger epilepsy groups had more language impairment and a wider range of linguistic deficits. Longer duration of illness, childhood absence epilepsy, psychiatric diagnosis, and socioeconomic status were associated with linguistic deficits in the young group. Prolonged seizures, lower Performance IQ, and minority status predicted low language scores in the intermediate epilepsy group. In the adolescent group, language impairment was associated with poor seizure control, decreased Performance IQ, and lower socioeconomic status. Linguistic and reading deficits were significantly related in each epilepsy group. Conclusions: The age-related increase in linguistic impairment, different profiles of predictors in each age group, and the relationship of linguistic deficits with poor reading skills have important clinical, developmental, theoretical, and academic implications.

Research paper thumbnail of Depression and Anxiety Disorders in Pediatric Epilepsy

Epilepsia, 2005

Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children ... more 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.

Research paper thumbnail of Frontal and temporal volumes in Childhood Absence Epilepsy

Epilepsia, 2009

Purpose: This study compared frontotemporal brain volumes in children with childhood absence epil... more Purpose: This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age-and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. Methods: Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child.

Research paper thumbnail of Associations Between Cytokines and Cortical Thickness in Patients with Late-Life Depression

The American Journal of Geriatric Psychiatry, 2019

Introduction: Psychotic features are more prevalent in older adults with depression than in young... more Introduction: Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods: This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results: NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r =-0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between-0.11 and 0.1). The correlations between HCC and i) IADL performance (r =-0.04) and ii) general functioning (r =-0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and nonpsychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions: This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context.

Research paper thumbnail of Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2012

Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective ... more Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective diagnostic and therapeutic strategies. Carrying the ε4 allele of the apolipoprotein E gene (APOE4) and having a family history of the disease are two such factors, with family history risk reflecting additional yet unknown or rarely studied genetic and perhaps nongenetic risks. Our aim was to determine the influence of APOE genotype and family history status on cognitive performance in healthy individuals. Longitudinal study. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. Seventy-two cognitively healthy middle-aged and older people (mean age ± SD: 62 ± 9 years). Neuropsychological examinations at baseline and after 2 years. Subjects with a family history of AD had lower baseline scores in processing speed, executive functioning, memory encoding, and delayed memory when compared with those without a family history. The family history risk facto...

Research paper thumbnail of Dealing with epilepsy: Parents speak up

Epilepsy & Behavior, 2008

In this study, focus groups were used to examine parents' attitudes toward mental health services... more In this study, focus groups were used to examine parents' attitudes toward mental health services, use of mental health and other services, as well as service-related and other challenges encountered by parents of children with epilepsy. Both quantitative and qualitative analytic approaches were used to analyze the transcripts of 36 parents grouped into six focus groups by socioeconomic status (SES) (high, low) and ethnicity (African-American, Caucasian, Hispanic). The quantitative analyses demonstrated that, irrespective of SES and ethnicity, the parents were highly aware of their children's behavioral, emotional, and cognitive difficulties and the lack of knowledge about epilepsy among medical, educational, and mental health professionals. The higher-SES parents were significantly more concerned about inadequate educational services and the need for medical services, but less concerned about mental health and medical service use than the lower-SES parents. Insufficient knowledge about epilepsy and about services, parent emotional difficulties, and use of educational services differed significantly by ethnicity. The qualitative analyses highlighted the parents' concerns regarding misconceptions about epilepsy and the stigma toward mental health care among the African-American and Hispanic parents. These findings suggest the need for accessible and better-quality mental health, educational, and medical services for children with epilepsy irrespective of SES and ethnicity. They also underscore the importance of educating parents, service providers, and the general public about epilepsy.

Research paper thumbnail of Pediatric psychogenic nonepileptic seizures: A study of assessment tools

Epilepsy & Behavior, 2010

The goal of this study was to identify assessment tools and associated behavioral domains that di... more The goal of this study was to identify assessment tools and associated behavioral domains that differentiate children with psychogenic nonepileptic seizures (PNES) from those with epilepsy. A sample of 24 children with PNES (mean age 14.0 years, 14 female), 24 children with epilepsy (mean age 13.6 years, 13 female), and their parents were recruited from five epilepsy centers in the United States. Participants completed a battery of behavioral questionnaires including somatization, anxiety, and functional disability symptoms. Children with PNES had significantly higher scores on the Childhood Somatization and Functional Disability Inventories, and their parents reported more somatic problems on the Child Behavior Checklist (CBCL). Depression, anxiety, and alexithymia instruments did not differentiate the groups. Measures of somatization and functional disability may be promising tools for differentiating the behavioral profile of PNES from that of epilepsy. Increased somatic awareness and perceived disability emphasize the similarity of PNES to other pediatric somatoform disorders.

Research paper thumbnail of Amygdala volume and psychopathology in childhood complex partial seizures

Epilepsy & Behavior, 2008

Purpose-This study compared amygdala volume in children with cryptogenic epilepsy, who had comple... more Purpose-This study compared amygdala volume in children with cryptogenic epilepsy, who had complex partial seizures (CPS), with age and gender matched normal children. It also examined the relationship of amygdala volumes with seizure variables and the presence of psychopathology in the patients.

Research paper thumbnail of Social competence in pediatric epilepsy: insights into underlying mechanisms

Epilepsy & Behavior, 2005

This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 c... more 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.

Research paper thumbnail of Thought disorder: A developmental disability in pediatric epilepsy

Epilepsy & Behavior, 2006

This study compared thought disorder (i.e., impaired use of language to formulate and organize th... more 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.

Research paper thumbnail of Suicidality and brain volumes in pediatric epilepsy

Epilepsy & Behavior, 2010

This study examined the relationship between suicidal ideation and frontotemporal volumes, partic... more This study examined the relationship between suicidal ideation and frontotemporal volumes, particularly orbital frontal gyrus volume, in 51 subjects with epilepsy with a mean age of 9.8 (2.1) years. Structured psychiatric interviews of the children and parents provided information on suicidal behavior and DSM-IV diagnoses. Tissue of 1.5-T MRI scans was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. The 11 subjects with epilepsy with suicidal ideation had significantly smaller right orbital frontal gyrus white matter volumes and larger left temporal lobe gray matter volumes than the 40 children without suicidal thoughts. Given the role of the orbital frontal gyrus in both emotional regulation and epilepsy, these findings highlight the biological underpinnings of suicidal ideation in pediatric epilepsy.

Research paper thumbnail of Cognition, academic achievement, language, and psychopathology in pediatric chronic epilepsy: Short-term outcomes

Epilepsy & Behavior, 2010

Children with epilepsy and control children were followed over a two year interval. Comorbidities... more Children with epilepsy and control children were followed over a two year interval. Comorbidities of epilepsy, often defined as problems related to IQ, academic achievement, language, and psychopathology, were evaluated prospectively. It was hypothesized that over time a) the presence of comorbidities would predict worse outcomes, and b) epilepsy variables would negatively impact comorbidities. The study included 39 children with complex partial seizures (CPS), 25 children childhood absence epilepsy (CAE), and 27 healthy children, aged 7.6-16.1 years. The findings were notable for stability over the interval in all three groups. Additionally, baseline seizure variables and change over the interval appear to play a role in IQ and math achievement scores of children with epilepsy with average IQ and in the reading achievement scores of those with below average IQ. However, seizures variables at baseline and follow-up were not predictors of DSM-IV diagnoses, depression, anxiety or behavioral problems.

Research paper thumbnail of Language and brain volumes in children with epilepsy

Epilepsy & Behavior, 2010

This study compared the relationship of language skill with fronto-temporal volumes in 69 medical... more This study compared the relationship of language skill with fronto-temporal volumes in 69 medically treated epilepsy subjects and 34 healthy children, aged 6.1-16.6 years. It also determined if the patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions. The children underwent language testing and magnetic resonance imaging scans at 1.5 Tesla. Brain tissue was segmented and fronto-temporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.

Research paper thumbnail of Amygdala volumes in childhood absence epilepsy

Epilepsy & Behavior, 2009

Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity... more Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.

Research paper thumbnail of Frontal and temporal volumes in children with epilepsy

Epilepsy & Behavior, 2007

This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have... more This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have smaller total brain, frontal, and temporal lobe volumes than normal children and how this is related to seizure, cognitive, psychiatric, and demographic variables. Fortyfour children with CPS and 38 normal children, aged 5-16 years, underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, frontal parcellation, and temporal lobe volumes were computed. Other than significantly larger temporal lobe white matter volumes in the CPS group, there were no significant differences in brain volumes between the CPS and normal groups. Earlier onset, longer duration of illness, younger chronological age, and presence of a psychiatric diagnosis were significantly related to smaller frontotemporal volumes in subjects with CPS. Although these findings suggest that CPS might affect development of the temporal and frontal regions, we are unable to rule out the possibility that smaller frontotemporal volumes might predispose children to CPS. These findings highlight the need to control for seizure, cognitive, psychiatric, and demographic variables in studies of frontotemporal volumes in pediatric CPS.

Research paper thumbnail of Obstacles to mental health care in pediatric epilepsy: Insight from parents

Epilepsy & Behavior, 2009

This exploratory study compared the responses of 20 Caucasian and 20 Hispanic mothers of children... more This exploratory study compared the responses of 20 Caucasian and 20 Hispanic mothers of children with epilepsy about possible obstacles to mental health care (MHC) for their children before and after they read a brochure on the neurobehavioral comorbidities of epilepsy. The intervention significantly increased the mothers' knowledge of the behavior and cognitive comorbidities of pediatric epilepsy and their treatment. Baseline differences in the attitude toward MHC and the stigma of epilepsy between Hispanic and Caucasian mothers were no longer apparent after the intervention. Irrespective of ethnicity, the mothers also became significantly more aware that their children did not want to have epilepsy-related behavior and learning difficulties. Efficient use of time spent in doctors' waiting rooms to educate parents about the neurobehavioral comorbidities of epilepsy can address the lack-of-knowledge barrier to MHC. However, the study's findings suggested a need to determine if there are specific obstacles to MHC in pediatric epilepsy.

Research paper thumbnail of Thought disorder and frontotemporal volumes in pediatric epilepsy

Epilepsy & Behavior, 2008

The aim of this study was to determine if volumes of frontotemporal regions associated with langu... more The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5-16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl's gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl's gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.

Research paper thumbnail of Childhood absence epilepsy: Behavioral, cognitive, and linguistic comorbidities

Epilepsia, 2008

Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absen... more Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE. Methods: Sixty-nine CAE children aged 9.6 (SD ¼ 2.49) years and 103 age-and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL). Results: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems. Conclusions: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

Research paper thumbnail of Psychopathology and Pediatric Complex Partial Seizures: Seizure-related, Cognitive, and Linguistic Variables

Epilepsia, 2004

Purpose: This study examined the role of cognition, language, seizure-related, and demographic va... more 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.

Research paper thumbnail of Behavioral Disorders in Pediatric Epilepsy: Unmet Psychiatric Need

Epilepsia, 2003

This study examined the relation between psychiatric diagnosis and mental health services in chil... more 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. 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. 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. 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.

Research paper thumbnail of Language in pediatric epilepsy

Epilepsia, 2009

Purpose: This study examined the severity and range of linguistic impairments in young, intermedi... more Purpose: This study examined the severity and range of linguistic impairments in young, intermediate, and adolescent youth with epilepsy and how these deficits were associated with illness effects, nonverbal intelligence, psychopathology, and reading. Methods: Tests of language, intelligence, achievement, and structured psychiatric interviews were administered to 182 epilepsy youth, aged 6.3-8.1, 9.1-11.7, and 13.0-15.2 years, as well as to 102 age-and gender-matched normal children. Parents provided demographic, seizure-related, and behavioral information on their children. Results: Significantly more epilepsy subjects had language scores 1 standard deviation (SD) below average than the age-matched control groups did. The intermediate and adolescent epilepsy groups also had significantly lower mean language scores compared to their matched controls. The older compared to the younger epilepsy groups had more language impairment and a wider range of linguistic deficits. Longer duration of illness, childhood absence epilepsy, psychiatric diagnosis, and socioeconomic status were associated with linguistic deficits in the young group. Prolonged seizures, lower Performance IQ, and minority status predicted low language scores in the intermediate epilepsy group. In the adolescent group, language impairment was associated with poor seizure control, decreased Performance IQ, and lower socioeconomic status. Linguistic and reading deficits were significantly related in each epilepsy group. Conclusions: The age-related increase in linguistic impairment, different profiles of predictors in each age group, and the relationship of linguistic deficits with poor reading skills have important clinical, developmental, theoretical, and academic implications.

Research paper thumbnail of Depression and Anxiety Disorders in Pediatric Epilepsy

Epilepsia, 2005

Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children ... more 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.

Research paper thumbnail of Frontal and temporal volumes in Childhood Absence Epilepsy

Epilepsia, 2009

Purpose: This study compared frontotemporal brain volumes in children with childhood absence epil... more Purpose: This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age-and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. Methods: Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child.