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L J Seidman

Publications and source records attributed to L J Seidman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.

BACKGROUND: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.

Adult↗
PubMed1999

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.

BACKGROUND: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS: The data support a hypothesized dysfunction of the ACcd in ADHD.

Adolescent↗
PubMed1999

Treatment of nonpsychotic relatives of patients with schizophrenia: four case studies.

BACKGROUND: Substantial evidence now shows that the genetic vulnerability to schizophrenia can be manifested clinically in first-degree relatives of people with schizophrenia, even without the full manifestations of the disorder. One pattern of problems observed involves the combination of negative symptoms and neuropsychological deficits. We have investigated whether a low dose of a novel antipsychotic medication, risperidone, could attenuate these clinical problems in non-psychotic, first-degree relatives, and report here findings from our first 4 cases. METHODS: Twelve adults who were first-degree relatives of patients with schizophrenia were evaluated for the presence of negative symptoms and neuropsychological deficits (in attention and working memory, long-term verbal memory and executive functions). Four subjects who met our predetermined criteria, and who did not demonstrate medical contraindications, were enrolled in a 6-week trial of risperidone. Clinical and medical measures were assessed before, during and after treatment. Doses of risperidone started at 0.25 mg and were increased to 1.0-2.0 mg/day. RESULTS: These subjects showed substantial reductions in negative symptoms, and one subject showed modest reductions. All four subjects showed substantial improvements on some tests of attention and working memory. Side effects of risperidone were temporary and mainly mild. CONCLUSIONS: These initial findings support two conclusions. First, clinical deficits in non-psychotic first-degree relatives of people with schizophrenia are identifiable, and to a significant extent, reversible. Second, risperidone may eventually serve as an effective treatment for people whose lives are impaired by similar or related problems.

Adult↗
PubMed1999

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Adult↗
PubMed1999

Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging.

BACKGROUND: Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. METHODS: Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. RESULTS: The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and frontoorbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. CONCLUSION: Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.

Adult↗
PubMed1999

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a 4-year follow-up study.

In a prior study of 54 relatives of patients with schizophrenia and 72 control participants, 3 neuropsychological functions met the criteria for risk indicators of the schizophrenia genotype: executive functioning, memory, and auditory attention. In an assessment of the stability of these findings, the sample was reexamined 4 years after the initial assessment. Three test scores were found to differ between groups (Immediate Verbal Memory, Delayed Verbal Memory, and Dichotic Listening Digits Detected) or to show a significant Group x Gender interaction (immediate and delayed verbal and visual memories). None of the test scores showed Group x Time interactions, suggesting that the discriminating power of the tests was stable over time. Evidence for deficits in working memory and rule learning on the object alternation test was also found. These results support the idea that neuropsychological dysfunction among relatives of patients with schizophrenia is a stable trait caused by the familial predisposition to schizophrenia.

Adult↗
PubMed1999

Electrophysiological correlates of language processing in schizotypal personality disorder.

OBJECTIVE: This study examined whether the electrophysiological correlates of language processing found previously to be abnormal in schizophrenia are also abnormal in schizotypal individuals. The authors used the N400 component to evaluate language dysfunction in schizotypal individuals. METHOD: Event-related potentials were recorded in 16 comparison subjects and 17 schizotypal individuals (who met full DSM-III-R criteria) to sentences presented both visually and aurally; half of the sentences ended with an expected word completion (congruent condition), and the other half ended with an unexpected word completion (incongruent condition). RESULTS: In the congruent condition, the N400 amplitude was more negative in individuals with schizotypal personality disorder than in comparison subjects in both the visual and auditory modalities. In addition, in the visual modality, the N400 latency was prolonged in the individuals with schizotypal personality disorder. CONCLUSIONS: The N400 was found to be abnormal in the individuals with schizotypal personality disorder relative to comparison subjects. The abnormality was similar to the abnormality the authors' laboratory reported earlier in schizophrenic subjects, in which the N400 amplitude was found to be more negative in both congruent and incongruent sentence completions. The N400 abnormality is consistent with the inefficient use of context.

Adult↗
PubMed1998

Sex differences in self-reported schizotypal traits in relatives of schizophrenic probands.

We used the Schizotypal Personality Questionnaire to evaluate schizotypal traits in 44 normal volunteers and 40 non-psychotic, biological relatives of schizophrenic probands. Relatives endorsed more cognitive-perceptual traits than did controls; a group-by-sex interaction indicated that male relatives accounted for this difference. Although not statistically significant, a similar pattern was observed for interpersonal traits. Thus, elevated rates of some schizotypal traits appear to be more prominent in male than in female relatives of schizophrenic probands, at least when assessed by self-report. Subscale analysis indicated that differences were accounted for primarily by suspiciousness and ideas of reference, suggesting that paranoid-like phenomena from both the cognitive-perceptual and interpersonal factors may constitute an important dimension of schizotypy in relatives. Unlike previous studies, we did not find any differences in constricted affect or disorganization signs. Interviews and other non-self-report techniques are probably best suited for an assessment of these features, although the question remains as to whether the combination of both approaches might provide some incremental discriminatory power.

Adult↗
PubMed1998

The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study.

The goal of this study was to assess whether degree of information processing load differentially affects vigilance performance in patients with schizophrenia as compared to normal controls or patients with other attentional disorders. We contrasted the performance of clinically stable outpatients with schizophrenia (n = 18), with that of normal controls (n = 17), and adults with developmental attentional/learning disorders (n = 13) on simple and demanding versions of a visual continuous performance test (CPT). Patients with schizophrenia were significantly impaired on both versions of the CPT compared to normal controls, and showed a significant decline in perceptual sensitivity and significantly more omission errors with increased processing demands. Compared to adults with developmental attentional/learning disorders, patients with schizophrenia manifested a tendency toward a decline in perceptual sensitivity. There were no significant differences between groups on a measure of response bias. The data support the hypothesis that patients with schizophrenia have insufficient information processing resources to cope with higher processing demands on effortful attention tasks. Further study comparing schizophrenic patients with patients who have other neuropsychiatric disorders, controlling for severity of illness, is required to determine the specificity of this deficit in schizophrenia.

Adult↗
PubMed1998

Neuropsychological function in adults with attention-deficit hyperactivity disorder.

BACKGROUND: Recent studies indicate that attention-deficit hyperactivity disorder (ADHD) persists into adulthood, but little is known about the neuropsychological features of adult ADHD. Our objective was to assess neuropsychological functioning in adults with ADHD with a battery of executive function tests. METHODS: Subjects were 64 unmedicated adults, 19-59 years of age, with DSM-III-R ADHD of childhood onset who met criteria for ADHD when referred in adulthood and 73 non-ADHD controls of similar age and gender. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Compared with controls, adults with ADHD were significantly impaired on measures of vigilance, semantic encoding for verbal memory, and written arithmetic, irrespective of age, gender, psychiatric comorbidity, or presence of learning disability. Despite comparable educational level and IQ, ADHD adults had a trend to lower occupational attainment and had significantly more academic problems in school. CONCLUSIONS: These executive, attention, and achievement dysfunctions demonstrated in adults with ADHD provide additional support for the validity of the syndrome in adults.

Adult↗
PubMed1998

Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands.

Evidence of subtle neuropsychological deficits in relatives of schizophrenic probands (REL-SZs) suggests that these are risk indicators for schizophrenia, but little is known about whether neuropsychological performance in REL-SZs differs from that in other groups of relatives. We compared neuropsychological function in female REL-SZs (n = 39), relatives of primarily psychotic bipolar disorder probands (REL-BPs; n = 15), and a normal control group (n = 44). After adjustment for expected intellectual ability (based on reading recognition), REL-SZs showed deficits in verbal and visual memory (Wechsler Memory Scale-Revised logical memories, visual reproductions), and auditory attention (dichotic digits) compared with either REL-BPs or control subjects. Memory, but not dichotic listening differences remained significant after adjusting for current IQ; however, average effect sizes after controlling for either reading or IQ were roughly comparable for these three parameters (d = 0.80, 0.71, and 0.69, respectively). REL-BPs and control subjects showed little difference. Although both schizophrenic and bipolar patients often manifest neuropsychological dysfunction, these preliminary findings indicate subtle neuropsychological deficits only in REL-SZs. Such differences suggest different underlying processes; neuropsychological impairment may, in part, reflect an expression of genetic liability to schizophrenia but not bipolar disorder. Replication with a larger REL-BP sample and with male relatives is needed to evaluate the generalizability of the results.

Adolescent↗
PubMed1998

Association of neuropsychological vulnerability markers in relatives of schizophrenic patients.

We investigated the association of neuropsychological risk indicators in a matched sample of first-degree relatives of schizophrenic patients (n = 54) and normal controls (n = 72). We focussed on three functions previously identified in a smaller, initial sample as putative risk indicators of the schizophrenia genotype: abstraction, verbal memory and auditory attention. The expanded sample of relatives displayed significantly lower scores than controls on abstraction, verbal memory and auditory attention. The relatives demonstrated significant intercorrelations among these three functions. The significant correlations among relatives between attention and verbal memory and between attention and abstraction differed significantly from these correlations among controls. We discuss how the use of multiple risk indicators may help us better identify those relatives that carry the schizophrenia genotype.

Adult↗
PubMed1998

Factor structure of the Wisconsin Card Sorting Test: dimensions of deficit in schizophrenia.

The aim of this study was to explore the factorial structure of the Wisconsin Card Sorting Test (WCST) and to identify the dimensions of deficit in schizophrenia. WCST scores in patients with schizophrenia and schizophrenia-related psychosis (n = 292), 1st degree relatives of schizophrenic patients (n = 91), and normal controls (n = 141) were subjected to a principal factor analysis followed by orthogonal rotation. This led to 3 factors, perseveration, failure to maintain set, and idiosyncratic sorting. The detected factor structure was found to be invariant across the schizophrenic and control subsamples. Moreover, it replicated previous findings from 2 smaller samples. Only perseverations and, to a lesser degree, idiosyncratic sorting appeared to differentiate schizophrenic patients from comparisons. Only perseveration had good sensitivity and specificity, as well as the most robust significant correlations with estimates of IQ, attention, and other measures of executive functioning. Thus, perseveration appears to be the most diagnostically useful and characteristic WCST feature of schizophrenia.

Adult↗
PubMed1998

A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands.

This study identified the brain activations associated with auditory vigilance tasks, using functional magnetic resonance imaging. We created auditory continuous performance tests (CPTs) in which a demanding task (working memory task) was made more difficult than a simple vigilance task by increasing working memory and interference filtering demands. Two cohorts of normal male controls performed significantly worse on the working memory CPT than on the vigilance task. Compared to the vigilance task, performance of the working memory task produced significant signal change in lateral and medial prefrontal cortex, precentral cortex, temporal lobe, including insula and hippocampus, parietal-occipital cortex, cingulate, thalamus, and superior colliculus. Performance and degree of activation was associated with an estimate of IQ. Further research should clarify the contributions of working memory and interference filtering to the activated network.

Adult↗
PubMed1998

Are there sex differences in neuropsychological functions among patients with schizophrenia?

OBJECTIVE: Studies of sex differences in neuropsychological performance in schizophrenia report inconsistent results, due in part to methodological artifacts. The study presented here was specifically designed to examine sex differences in neuropsychological performance. It was hypothesized that schizophrenic women would exhibit fewer neuropsychological deficits than schizophrenic men and that their performance would be more similar to that of normal women than schizophrenic men's performance would be to that of normal men. METHOD: Thirty-one outpatients with DSM-III-R-defined schizophrenia were systematically sampled from an extensive service network serving a large urban catchment area for seriously mentally ill persons. Twenty-seven normal comparison subjects were matched within sex on the basis of age, parental socioeconomic status, ethnicity, and handedness. An extensive neuropsychological test battery was administered, and multivariate analysis of variance was used to test for the effects of sex and group and sex-by-group interactions. RESULTS: Male patients were significantly impaired across all functions in comparison with normal male subjects and on tests of attention, verbal memory, and executive functions in comparison with female patients. Female patients performed significantly worse than female normal comparison subjects only on tests of attention, executive functions, visual memory, and motor functions. CONCLUSIONS: The findings suggest that women with schizophrenia may be less vulnerable to particular cognitive deficits, especially those involving verbal processing, than schizophrenic men.

Adult↗
PubMed1998

IQ decline during childhood and adult psychotic symptoms in a community sample: a 19-year longitudinal study.

OBJECTIVE: The goal of this study was to examine cognitive antecedents of psychosis by determining whether variability in IQ during childhood was predictive of psychotic symptoms in adulthood. METHOD: Deviant responder analyses were used to examine prospectively the relationship of IQ at ages 4 and 7 to psychotic symptoms at age 23 in 547 offspring from a community sample (National Collaborative Perinatal Project) that was unselected for psychiatric illness. The authors compared three hypotheses: that 1) low IQ, 2) large IQ fluctuations regardless of direction, or 3) large IQ declines would predict the presence of adult psychotic symptoms. RESULTS: The 10% of individuals with substantially larger than expected IQ declines from age 4 to 7 had a rate of psychotic, but not other psychiatric, symptoms at age 23 that was nearly seven times as high as the rate for other persons. Parental socioeconomic status and IQ at age 7 also predicted adult psychotic symptoms. However, when IQ at age 7, IQ decline between ages 4 and 7, and socioeconomic status were all included in a logistic regression analysis, only IQ decline remained significant. CONCLUSIONS: There is an increased likelihood of developing psychotic symptoms in adulthood for a subgroup of individuals with substantially greater than expected IQ declines during childhood. IQ decline is specific for psychotic symptoms, but follow-up assessment when the study participants are further into the age of risk will be necessary to determine specificity for schizophrenia. The authors discuss the implications of this early cognitive downturn for a neurodevelopmental view of schizophrenia.

Adult↗
PubMed1998

Comparative effects of schizophrenia and temporal lobe epilepsy on memory.

The goal of this study was to further characterize episodic memory functioning in schizophrenia. This study compared verbal and visual learning and memory performance in (1) patients with schizophrenia (N = 35), (2) patients with temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results indicated significant memory impairments in patients with schizophrenia and TLE. "Savings" score measures of memory decay showed that the loss of information in schizophrenia and TLE was approximately equal, and quantitatively mild compared to that found in most neurologic groups with memory disorders. The severe difficulty shown by the schizophrenia group on a task of incidental recall suggested that the absence of instructional set added to a vulnerability to memory deficit. In contrast, relatively mildly impaired performance on paired associate learning suggested that patients with schizophrenia benefited from retrieval cues, multiple trials, and short (nonsupraspan) informational loads. Because patients with schizophrenia consisted of a relatively nonchronic sample with a mean IQ of 99.7, their memory disorder could not be attributed to schizophrenic dementia, nor was it accounted for by other potential confounds. Patients with schizophrenia, even those relatively early in the course of illness, have a mild episodic memory disorder.

Adolescent↗