Biomedical subjects

Larry J Seidman

Publications and source records attributed to Larry J Seidman.

At least 37 records · Page 2Linked to original sources

PubMed2006

Decreased volume of left and total anterior insular lobule in schizophrenia.

The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.

Adolescent↗

PubMed2006

Real-world cognitive--and metacognitive--dysfunction in schizophrenia: a new approach for measuring (and remediating) more "right stuff".

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established by now, the overlap is far from complete. Moreover, little is known about the potential mechanisms that bridge between cognition and functional outcome. The aim of this article is to aid in closing this gap by presenting a novel, more ecologically valid approach for neuropsychological assessment. The new approach is motivated by the view that metacognitive processes of self-monitoring and self-regulation are fundamental determinants of competent functioning in the real world. The new approach incorporates experimental psychological concepts and paradigms used to study metacognition into current standard neuropsychological assessment procedures. Preliminary empirical data that support and demonstrate the utility of the new approach for assessment, as well as remediation efforts, in schizophrenia are presented and discussed.

Cognition Disorders↗

PubMed2006

Neuropsychological functioning in girls with attention-deficit/hyperactivity disorder with and without learning disabilities.

The authors' goal was to assess neuropsychological performance in girls with attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls without ADHD, ages 6-17 years. Neuropsychological performance was measured in a standardized manner, blind to clinical status. LD was defined by a combined regression-based and low-achievement classification. ADHD was associated with modest, but significant, neuropsychological impairment, as measured with an aggregate measure of performance and with the Stroop Color-Word Test, independent of age, social class, IQ, and psychiatric comorbidity. Neuropsychological deficits were most pronounced in girls with both ADHD and an LD and in those without medications. These results extend to females the previously documented association of LDs with neuropsychological functioning in males with ADHD.

Adolescent↗

PubMed2006

Intellectual decline in schizophrenia: evidence from a prospective birth cohort 28 year follow-up study.

It is well established that IQ is lower among persons with schizophrenia than in the general population. However, it remains unclear if there is deterioration beyond a premorbid deficit. In order to assess the question of IQ deterioration, we assessed persons pre- and-post psychosis, comparing those who developed schizophrenia with those who did not. Twenty six patients with schizophrenia and 59 normal controls, evaluated at age 7 in the prospective, longitudinal, National Collaborative Perinatal Project (NCPP), were re-tested approximately 28 years later. We assessed change in an estimate of IQ based on the Vocabulary and Block Design tests from the Wechsler intelligence scales. Persons who later developed schizophrenia were significantly impaired on IQ compared to controls at age 7, especially on measures of attention. At age 35, persons with schizophrenia demonstrated significant impairment and deterioration on both IQ sub-tests compared to controls. Because impairment occurs by early childhood and subsequent deterioration occurs at an unknown period, designs with more frequent assessment of IQ through the premorbid, prodromal and early phases of illness are required to identify the key period of decline. Future research on this sample will evaluate the prospective roles of family history and perinatal complications on cognition, and assess the specificity of these findings.

Achievement↗

PubMed2006

Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder.

OBJECTIVE: The association between deficits in executive functioning and functional outcomes was examined among adults with attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were adults who did (N=213) and did not (N=145) meet DSM-IV criteria for ADHD. The authors defined having deficits in executive functioning as having at least two measures of executive functioning with scores 1.5 standard deviations below those of matched comparison subjects. RESULTS: Significantly more adults with ADHD had deficits of executive functioning than comparison subjects. Deficits of executive functioning were associated with lower academic achievement, irrespective of ADHD status. Subjects with ADHD with deficits of executive functioning had a significantly lower socioeconomic status and a significant functional morbidity beyond the diagnosis of ADHD alone. CONCLUSIONS: Psychometrically defined deficits of executive functioning may help identify a subgroup of adults with ADHD at high risk for occupational and academic underachievement. More efforts are needed to identify cost-effective approaches to screen individuals with ADHD for deficits of executive functioning.

Accidents, Traffic↗

PubMed2006

Sex differences in language dysfunction in schizophrenia.

OBJECTIVE: Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified. METHOD: Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar. RESULTS: Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas. CONCLUSIONS: Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing.

Adult↗

PubMed2006

Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia.

BACKGROUND: Evaluation of individuals at high genetic risk of schizophrenia is a powerful method for identifying precursors of the illness. AIMS: To identify aspects of personality, psychopathology and social development that differentiate high-risk and control individuals. METHOD: Adolescent and young-adult first-degree relatives (n=35) of people with schizophrenia or schizoaffective disorder and a control group (n=55) were compared on 36 measures at baseline of a longitudinal study. Measures differentiating high-risk and control participants were related to four genetic loading indices. RESULTS: High-risk participants older than 17 years showed more physical anhedonia, less positive involvement with peers and more problems with peers, siblings and the opposite gender. Older high-risk individuals also were less cooperative, less self-directed and less reward-dependent. Problems with peers and the opposite gender, as well as reward dependence, were related linearly to genetic loading. CONCLUSIONS: Alterations in personality traits and social development are present in high-risk individuals, and may be markers for genetic liability toward the illness.

Adolescent↗

PubMed2005

Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder.

INTRODUCTION: Schizotypal personality disorder (SPD) shares with schizophrenia many biological features, yet little is known about the clinical characteristics of persons diagnosed with this disorder. This report describes the clinical, cognitive and socio-occupational characteristics of a community sample of subjects diagnosed with SPD. METHOD: Sixty-four male and 40 female neuroleptic-naive DSM-IV SPD subjects and 59 male and 51 female comparison subjects were recruited from the community for a total sample of 214 subjects. Demographic and cognitive differences between groups and, within the SPD group, the effect of gender on clinical features, such as the SPD criteria, SAPS, SANS, Schizotypal Personality Questionnaire, and co-morbidity, were examined using ANOVA and Chi-square distributions. RESULTS: SPD subjects, in contrast to comparison subjects, had significantly lower socio-economic status, poorer social relationships and skills, and lower vocabulary scores. Furthermore, SPD subjects demonstrated more impairment on Vocabulary scores than on Block Design, as measured by the WAIS-R, a pattern not seen in comparison subjects. In the SPD cohort, positive symptoms predominated and nearly half were co-morbid for major depression. With respect to gender, male SPD subjects, compared with female SPD subjects, evinced significantly more negative symptoms, fewer friends, had more odd speech, and were more likely to also suffer from paranoid and narcissistic personality disorders. In contrast to male SPD subjects, female SPD subjects perceived themselves to be more disorganized. CONCLUSIONS: SPD subjects, similar to schizophrenics, are impaired socially, occupationally, and cognitively, particularly in the area of verbal measures. Moreover, male SPD subjects may be more severely affected than female SPD subjects across multiple domains of functioning.

Adolescent↗

PubMed2005

Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging.

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.

Adult↗

PubMed2005

Neuropsychological functioning in youth with bipolar disorder.

BACKGROUND: Little is known about the neuropsychological status of youth with bipolar disorder (BPD) or whether cognitive deficits in this population are accounted for by comorbidity with attention deficit/hyperactivity disorder (ADHD). We compared neuropsychological and academic functioning of youth with and without DSM-IV BPD, controlling for effects of comorbid ADHD. METHODS: Fifty-seven youth with BPD and 46 healthy control subjects were assessed on a battery of clinical neuropsychological measures including subtests from the Wechsler Intelligence Scales for Children and Adults (Third Editions), the Stroop, the Wisconsin Card Sorting Test, the Rey-Osterreith Complex Figure, an auditory working memory Continuous Performance Test, a measure of verbal learning, and the Wide Range Achievement Test-Third Edition. RESULTS: Bipolar disorder was associated with impairments on subtests reflecting sustained attention, working memory, and processing speed after controlling for ADHD. Additionally, decrements of moderate effect sizes were found for measures of interference control, abstract problem solving, and verbal learning but did not meet criteria for statistical significance. CONCLUSIONS: After controlling for ADHD, youth with BPD show neuropsychological deficits similar to impairments found in adults with the disorder. Further studies are needed to understand the clinical implications of these impairments as well as their role in the underlying risk for pediatric BPD.

Adolescent↗

PubMed2005

Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis.

BACKGROUND: Neurocognitive deficits are severe in first-episode psychosis. METHODS: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests. RESULTS: Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol. CONCLUSIONS: Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.

Adult↗

PubMed2005

Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study.

BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.

Adolescent↗

PubMed2005

Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions.

Over the past few decades, functional neuroimaging techniques have begun to provide unprecedented windows on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) and the neural effects of medications used to treat the disorder. Convergent data from neuroimaging, neuropsychological, genetics, and neurochemical studies have implicated dysfunction of fronto-striatal structures (lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate, and putamen) as likely contributing to the pathophysiology of ADHD. This review 1) provides an overview of the main imaging techniques being used to study ADHD; 2) discusses their relative strengths and weaknesses, highlighting how they can complement one another; 3) shows how the functional imaging literature, which has built on the structural imaging data, is now being used to test focused hypotheses regarding the neurobiological substrate of ADHD; and 4) suggests guidelines for improving future functional imaging studies. Although at present there are no accepted uses for functional imaging in diagnosing ADHD, this article mentions possible future clinical uses of imaging in ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Attention-deficit/hyperactivity disorder endophenotypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder with a multifactorial pattern of inheritance. For complex conditions such as this, biologically based phenotypes that lie in the pathway from genes to behavior may provide a more powerful target for molecular genetic studies than the disorder as a whole. Although their use in ADHD is relatively new, such "endophenotypes" have aided the clarification of the etiology and pathophysiology of several other conditions in medicine and psychiatry. In this article, we review existing data on potential endophenotypes for ADHD, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement. Neuropsychological impairments, as well as measures from neuroimaging and electrophysiological paradigms, show correlations with ADHD and evidence of heritability, but the familial or genetic overlap between these constructs and ADHD remains unclear. We conclude that these endophenotypes will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.

Adoption↗

PubMed2005

MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability.

We revisit here a surface assisted parcellation (SAP) system of the human cerebellar cortex originally described in Makris, N., Hodge, S.M., Haselgrove, C., Kennedy, D.N., Dale, A., Fischl, B., Rosen, B.R., Harris, G., Caviness, V.S., Jr., Schmahmann, J.D., 2003. Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15, 584-599. This system preserves the topographic and morphologic uniqueness of the individual cerebellum and allows for volumetric analysis and representation of multimodal structural and functional data on the cerebellar cortex. This methodology integrates features of automated routines of the program FreeSurfer as well as semi-automated and manual procedures of the program Cardviews to create 64 cerebellar parcellation units based on fissure information and anatomical landmarks of the cerebellar surface. Using this technique, we undertook the parcellation of ten cerebella by two independent raters. The reliability of the resulting parcellation units (64 total) was high, with an average Intraclass Correlation Coefficient (ICC) of 0.724 in the vermis and 0.853 in the hemispheres. Clusters of parcellation units were then created, based on lobar and connectivity data and functional hypotheses. These 36 clusters, when treated as anatomical units, had an average ICC of 0.933. Whereas the individual units provide a high level of detail and anatomical specificity, the clusters add flexibility to the analysis by providing higher reliability.

Algorithms↗

PubMed2005

The effect of working memory performance on functional MRI in schizophrenia.

INTRODUCTION: Studies of prefrontal cortical (PFC) function in schizophrenia have been inconsistent, with studies showing both increased and decreased PFC activation compared to healthy controls. Discrepant findings may be due to task performance effects or demographic differences between samples. We report functional magnetic resonance imaging (fMRI) data comparing subjects with schizophrenia and healthy controls performing a 2-back working memory (WM) task, addressing the effects of task performance. METHODS: Twenty-two controls and 14 patients with DSM-IV schizophrenia, scanned on a Siemens 1.5 T scanner, performed a visual letter 2-back task and control task (CPT-X) during fMRI. Data were analyzed using Statistical Parametric Mapping (SPM)-99. RESULTS: After statistical adjustment for performance differences, persons with schizophrenia showed significantly greater activation than controls in the right medial frontal gyrus and left inferior parietal lobule/medial temporal gyrus region (BA 39/40), and a trend toward greater activation in the left ventrolateral PFC. This pattern was also observed in demographically matched subgroups of participants. CONCLUSIONS: Data are consistent with findings reported in recent studies showing increased PFC and parietal activation in schizophrenia when the effects of reduced WM task performance in patients with schizophrenia are addressed. Further studies are needed to clarify the pathophysiological basis of WM load sensitivity in schizophrenia and its relationship to genes.

Adult↗

PubMed2005

A comparative profile analysis of neuropsychological function in men and women with schizotypal personality disorder.

The purpose of this study was to compare the cognitive profiles of men and women with clinically defined schizotypal personality disorder (SPD). We examined the neuropsychological profile of SPD in 26 right-handed females and 31 right-handed males who met DSM-IV criteria for SPD, and matched comparison subjects. Cognitive performance was assessed on measures of abstraction, verbal and spatial intelligence, learning and memory, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of comparison groups matched for sex, age, handedness, ethnicity and parental SES. Overall, SPD subjects showed mild, general decrements in performance in most cognitive domains. However, unlike male SPD subjects, female SPDs did not show relative deficits in verbal learning and abstraction. The results suggest a less severe pattern of cognitive deficits in women with SPD compared to men, consistent with hypotheses of gender differences in cognitive function in schizophrenia.

Adult↗

PubMed2005

The neuropsychological basis of competence to consent in first-episode schizophrenia: a pilot metacognitive study.

BACKGROUND: This study was designed to explore the neuropsychological basis of competence to consent to treatment in first-episode schizophrenia by evaluating its differential and joint links with cognitive versus metacognitive performance. METHODS: Twenty-one first-episode patients were assessed with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and a metacognitive version of the Wisconsin Card Sorting Test (WCST). In addition to the standard administration of the WCST, subjects were also asked to rate their level of confidence in the correctness of each sort (prior to getting the feedback) and to choose whether they wanted each sort to be "counted" toward their overall performance score on the test. Each "ventured" sort received a bonus of 10 cents if correct but an equal penalty if wrong. RESULTS: Compromised capacity to consent was more strongly related to deficits at the metacognitive level than to cognitive deficits per se. Moreover, prediction of competence to consent significantly improved when adding the new, free-choice metacognitive measures to the conventional WCST measures but not the other way around. CONCLUSIONS: These preliminary results suggest that metacognition plays a fundamental role in capacity to consent, which might be at least equally important for decision-making competence as cognitive deficits per se.

Adult↗