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L J Seidman

Publications and source records attributed to L J Seidman.

At least 55 records · Page 3Linked to original sources

Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study.

Substantial evidence suggests that nonpsychotic relatives of schizophrenia patients manifest subtle abnormalities in communication, eye movements, event-related potentials, and neuropsychological processes of attention, reasoning, and memory. We sought to determine whether adult relatives without psychosis or schizophrenia spectrum diagnoses might also have structural brain abnormalities, particularly in subcortical regions found to be impaired in patients with schizophrenia itself. Subjects were six sisters of schizophrenic patients and eleven normal female controls. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images (MRI) of the entire brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter was segmented using a semiautomated intensity contour mapping algorithm. Volumes were adjusted for total brain volumes. Adjusted gray matter subcortical volumes were significantly smaller in relatives than in controls in total hippocampus, right amygdala, right putamen, left thalamus, and brainstem. Relatives had significantly enlarged left and total inferior lateral ventricles. These results, though preliminary, suggest that some never-psychotic relatives of schizophrenic patients have abnormal brain structure. If replicated in a larger sample including both sexes, these results would suggest that the genetic liability to schizophrenia is also expressed as structural brain abnormalities.

Adolescent↗

Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability.

We investigated the hypothesis that different prefrontal brain systems (i.e., dorsal vs. ventral) and sex contribute differentially to cognitive deficit in schizophrenia. Performance was assessed among clinically stable, chronic schizophrenic outpatients and matched normal control subjects on olfactory identification [on the University of Pennsylvania Smell Identification Test (UPSIT)] and on executive functions [using the Wisconsin Card Sorting Test (WCST)]. Patients were impaired on both tests compared to controls, and male schizophrenics were impaired on the WCST compared to female schizophrenics. The pattern of results suggests that gender differences on the UPSIT are mildly accentuated in schizophrenia. The data support our previous study indicating that UPSIT performance is largely independent of the executive or attentional deficits typically associated with schizophrenia, with the exception of verbal ability. Further research with larger samples is required to test the hypothesis that there is a severely impaired subgroup of male patients with diffuse prefrontal dysfunctions.

Adolescent↗

Neuropsychological dysfunction in schizotypal personality disorder: a profile analysis.

In order to examine the neuropsychological profile of schizotypal personality disorder (SPD), we studied a wide array of cognitive functions in 10 right-handed men who met DSM-III-R criteria for SPD and 10 matched normal controls. Cognitive functions included abstraction, verbal and spatial intelligence, memory and learning, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of the normal control group. SPD subjects showed significant decrements in performance on the California Verbal Learning Test, a word-list learning measure which requires semantic clustering for more efficient performance, and on the Wisconsin Card Sort Test, a measure requiring concept formation, abstraction, and mental flexibility. These results suggest possible areas of specific neuropsychological dysfunction in SPD, and are consistent with current hypotheses of left-temporal and prefrontal brain dysfunction in schizophrenia.

Adult↗

Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands.

Some recent studies suggest that men with schizophrenia may have greater neuropsychological deficits than women. It is not known, however, whether similar sex differences may be present in biological relatives of schizophrenic patients. We evaluated neuropsychological functioning of 54 relatives of schizophrenic patients and 72 normal volunteers. It was hypothesized that, if sex differences were present, they would be accounted for largely by deficits in male relatives. We were particularly interested in three neuropsychological functions that we previously identified as putative neuropsychological vulnerability indicators for schizophrenia: (1) abstraction/executive function; (2) verbal memory; and (3) auditory attention. There were significant group x sex interactions for verbal memory and motor function, and trends toward significant interactions for auditory attention and mental control/encoding. However, with the exception of motor function, it was the female relatives who accounted for most of the impairment. A speculative explanation for the findings is that women may have a higher threshold than men for developing schizophrenia. If so, female relatives might be able to withstand greater impairments than men before developing psychotic symptoms. Consequently, in a sample that was limited to non-psychotic relatives--as in the present study--there could be over-representation of both less impaired men and more impaired women. Alternative explanations and limitations of the study are also discussed.

Adolescent↗

A pilot study of neuropsychological function in girls with ADHD.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is known to have neuropsychological consequences that are evident from psychological tests and from measures of school failure. However, most available data are based on studies of boys. Our goal was to assess, in this pilot study, whether ADHD in girls expressed neuropsychological features similar to those found in boys. METHOD: Subjects were 43 girls, aged 6 to 17 years, with DSM-III-R ADHD and 36 comparison girls without ADHD. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Girls with ADHD were significantly more impaired on estimated IQ than comparison girls despite being matched on other demographic variables. Relative to comparison girls, the girls with ADHD were also significantly more impaired on the Freedom From Distractibility subtests of the WISC-R and on arithmetic and reading achievement scores. Although their mean performance on executive function tests was generally poorer than that of control girls, there were no statistically significant differences on these measures. CONCLUSIONS: Girls with ADHD have impairments in some tests of attention and achievement. However, neuropsychological performance on tests of executive function was less impaired than that previously documented in boys with ADHD. If confirmed in a larger sample, these findings suggest that girls with ADHD may be less vulnerable to executive function deficits than boys.

Adolescent↗

Neuropsychological function in homeless mentally ill individuals.

Because little data are available on the neuropsychological functioning of severely and persistently mentally ill (SPMI) persons who are homeless, our primary goal was to describe accurately and extensively the general neuropsychological functioning of a large group of such homeless individuals. In addition, we have sought to examine the relationship between some neuropsychological functions and demographic, illness, and clinical state measures in this population. A 5-hour neuropsychological test battery was administered to 116 SPMI homeless individuals. Neuropsychological, diagnostic, substance abuse, clinical, and psychopathology data were obtained in a standardized manner. SPMI homeless individuals were significantly impaired on a wide range of neuropsychological functions. Specific test performances were most significantly related to precursor variables (level of education and parental socioeconomic status) and state variables (level of psychosis and anticholinergic medication dose). Gender and substance abuse had significant effects limited to sustained attention. Neuropsychological performance was impaired in this sample of homeless SPMI persons. Further research, using profile analysis to directly compare groups composed of homeless persons without psychiatric illness or demographically matched persons of comparable psychiatric status who are not homeless will help clarify the role of homelessness and psychosis on neuropsychological function.

Adult↗

Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients.

OBJECTIVE: The factor structures of individual positive and negative symptoms as well as global ratings were examined in a diagnostically heterogeneous group of subjects. METHOD: Subjects were identified through a clinical and family study of patients with major psychoses at a VA medical center and evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. For the examination of global-level factor structures (N = 630), both principal-component analysis and factor analysis with orthogonal rotation were used. Factor analysis was used for the examination of item-level factor structures as well (N = 549). RESULTS: The principal-component analysis of global ratings revealed three factors: negative symptoms, positive symptoms, and disorganization. The factor analysis of global ratings revealed a negative symptom factor and a positive symptom factor. The item-level factor analysis revealed two negative symptom factors (diminished expression and disordered relating), two positive symptom factors (bizarre delusions and auditory hallucinations), and a disorganization factor. CONCLUSIONS: The generation of additional meaningful factors at the item level suggests that important information about symptoms is lost when only global ratings are viewed. Future work should explore clinical and pathological correlates of the more differentiated item-level symptom dimensions.

Adult↗

MRI brain abnormalities in chronic schizophrenia: one process or more?

It has been suggested that schizophrenia is primarily a prefrontal-temporal-limbic circuitry disorder. Further, it has been argued that primary neurologic vulnerability to the illness is established only during early stages of brain development and is not progressive. We tested the hypothesis of whether brain volume losses in prefrontal and temporal-limbic regions have occurred either before or after brain growth was hypothesized to be complete in schizophrenia. Nineteen chronic schizophrenic patients and 19 age- and sex-matched normal controls underwent magnetic resonance imaging (MRI). All scans were segmented into gray and white matter and cerebrospinal fluid (CSF) compartments for the frontal and temporal lobes and posterior cerebral hemispheres. Multivariate analysis of variance was used to analyze absolute intracranial cerebrum and subregion volumes, i.e., gray, white and CSF, absolute tissue (i.e., gray plus white) volumes, and tissue to intracranial volume (TCV) ratios. Patients showed significant intracranial volume reductions only in the frontal lobes but highly significantly lower TCV ratios (i.e., greater relative tissue loss) in all three major regions. It is suggested that the observed decreases in frontal intracranial volumes reflect a pathologic process in schizophrenia that impacted the frontal regions before brain growth was complete. We hypothesize that the generalized lower patient TCV ratios are attributable to a process that affected the whole cerebrum over a time period after brain volume had reached its maximum levels.

Adult↗

Topographic abnormalities of P3 in schizotypal personality disorder.

Schizotypy, a schizophrenia spectrum disorder, is of interest because schizotypes share traits with schizophrenics, albeit milder, without potential confounds such as chronic neuroleptic treatment and/or hospitalization. Thus, schizotypy may be particularly useful in exploring biological correlates of an underlying schizophrenic predisposition. The P3 event-related potential, which is aberrant in schizophrenia, was measured in 11 male, right-handed, DSM-III-R-defined schizotypes and 11 matched controls while subjects covertly counted 1.5 kHz target tones (15%) in trains of 1 kHz standard tones. Like schizophrenics, schizotypes displayed an asymmetrical P3, with smaller amplitudes over the left temporal lobe. Unlike schizophrenics, schizotypes were not significantly smaller in P3 amplitude over the sagittal midline of the head, although there was a trend towards reduced amplitudes at central and posterior midline sites. Asymmetry of P3 amplitude, with left-sided deficit, may be associated with the schizophrenia diathesis, but overall P3 reductions may be more associated with chronic effects.

Adult↗

Neuropsychological functioning among the elderly nonpsychotic relatives of schizophrenic patients.

In our prior work with a young sample (age < 60), we showed that three neuropsychological functions were impaired among relatives of schizophrenic patients: abstraction, verbal memory, and auditory attention. In the present work we show that these results do not generalize to an older sample aged 60 years and greater. Thus, although we and others have put forth measures of neuropsychological function as indicators of the schizophrenia genotype, the present study suggests that conclusions may be limited to non-elderly samples. Further work is needed to address this issue definitively.

Aged↗

Self-report and observer measures of substance abuse among homeless mentally ill persons in the cross-section and over time.

The comparability of self-report and observer measures of substance abuse among 118 homeless mentally ill persons was assessed using cross-sectional and longitudinal measures. Possible correlates of nondisclosure were identified from demographic variables and clinical indicators. Lifetime abuse reported at baseline was a sensitive predictor of subsequent abuse behavior in the project, but cross-sectional measures based only on self-report or observer ratings failed to identify many abusers. A total of 17% of the subjects never disclosed abuse that was observed during the project. The level of substance abuse is likely to be severely underestimated among homeless mentally ill persons when only one self-report measure is used at just one point in time. This problem can, however, largely be-overcome by incorporating information from observers and from multiple follow-ups or by focusing on lifetime rather than current abuse. We also conclude that underreporting may bias estimates of some correlates of substance abuse.

Adult↗

The '3 Rs' and neuropsychological function in schizophrenia: a test of the matching fallacy in biological relatives.

The 'matching fallacy' suggests that matching schizophrenic patients and normal control subjects on education or IQ may cause systematic mismatching of theoretically expected ability. This study supports a modest version of the matching fallacy effect in nonpsychotic biological relatives of schizophrenic patients. At equivalent levels of education, relatives and control subjects had similar Reading and Spelling scores on the Wide Range Achievement Test-Revised--measures that are largely unimpaired by schizophrenia-related processes. However, relatives showed a deficit in IQ (primarily verbal IQ) compared with what would be predicted from their Reading scores. A similar deficit in Arithmetic scores was found in non-college-educated relatives, but college-educated relatives showed an advantage. We discuss possible implications of the findings with regard to genetic and environmental factors.

Adult↗

No confirmation of Geschwind's hypothesis of associations between reading disability, immune disorders, and motor preference in ADHD.

Geschwind and colleagues have proposed an association among reading disability, immune disorder, and motor preference. Although reading disability commonly overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been previously examined in studies evaluating Geschwind's hypothesis. In this paper we evaluate whether ADHD is associated with either asthma or left motor preference and whether asthma and left motor preference are associated with each other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). Information on reading disability, asthma, and motor preference was obtained in a standardized manner blind to the proband's clinical status. Neither ADHD nor reading disability was associated with either asthma or left motor preference nor was asthma and left motor preference associated with one another. Our results are not consistent with Geschwind's hypothesis linking reading disability, immune disorder, and left motor preference.

Adolescent↗

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis.

Numerous studies suggest that the relatives of schizophrenic patients exhibit neuropsychological impairments that are milder yet similar to those seen among schizophrenic patients. The authors assessed 35 nonpsychotic relatives of schizophrenic patients and 72 normal controls using a clinical and experimental neuropsychological test battery. Three neuropsychological functions met criteria for risk indicators of the schizophrenia genotype: abstraction, verbal memory, and auditory attention. These findings could not be attributed to parental socioeconomic status, education, general visual-spatial ability, or psychopathology. Furthermore, exploratory analyses were performed to determine whether the diagnostic efficiency of the indicators could be adjusted to meet the needs of genetic linkage analyses. These analyses suggest that psychometric considerations may help to create measures for genetic linkage studies.

Adolescent↗

Effects of family history and comorbidity on the neuropsychological performance of children with ADHD: preliminary findings.

OBJECTIVE: Because ADHD is heterogeneous with respect to psychiatric comorbidity, familiality, and learning disabilities, it was hypothesized that such features might influence the severity and pattern of neuropsychological function in ADHD. METHOD: Subjects were 9- to 20-year-old males with DSM-III-R ADHD (n = 65) and normal controls (n = 45). Information on neuropsychological performance was obtained in a standardized manner, blind to the proband's clinical status. RESULTS: ADHD probands were significantly impaired on neuropsychological functions compared with controls irrespective of composite psychiatric comorbidity status, and those with a family history of ADHD were most impaired. ADHD probands with learning disabilities showed a pattern suggestive of reduced motor dominance and extremely slow reading speed. CONCLUSIONS: These results indicate that neuropsychological performance in ADHD is significantly affected by familial status and presence of learning disabilities. The similarity of findings between ADHD children with and without comorbid psychiatric disorders suggests that the neuropsychological impairments in our sample were associated with ADHD. These findings raise the possibility of alterations of cerebral dominance and of frontal networks in ADHD. Further research is needed to replicate these findings in larger samples, to clarify the role of specific comorbid psychiatric disorders, and to assess directly cerebral functioning in subjects with ADHD.

Adolescent↗

Performance of children with ADHD on the Rey-Osterrieth complex figure: a pilot neuropsychological study.

This study evaluates the performance of boys with Attention Deficit Hyperactivity Disorder (ADHD) on the Rey-Osterrieth Complex Figure (ROCF) taking into consideration familiality and comorbid psychiatric and learning disorders (LD). Sixty-five children with ADHD performed at developmentally lower levels of Copy Organization and Recall Style than did 45 controls. ADHD children with LD scored significantly lower on Copy Organization than did ADHD children without LD, whereas psychiatric comorbidity and familiality had no effect. These results suggest that a developmental analysis of the ROCF identifies organizational difficulties associated with ADHD and that these impairments cannot simply be attributed to comorbidities associated with ADHD.

Adolescent↗

Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes?

OBJECTIVE: Numerous studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit psychiatric and other features that discriminate them from normal comparison subjects. These features have been put forth as "spectrum" phenotypes that may be variant manifestations of the schizophrenia genotype. However, most of these studies do not address a key measurement question: does the diagnostic accuracy of these spectrum classifications warrant their use in genetic linkage studies of schizophrenia? METHOD: The authors reviewed 30 studies of putative indicators of the schizophrenic genotype: schizotypal personality disorder, eye tracking dysfunction, attentional impairment, auditory evoked potentials, neurological signs, neuropsychological impairment, and allusive thinking. RESULTS: Although each of 42 measures of these indicators discriminated the relatives of schizophrenic patients from the normal comparison subjects, a diagnostic accuracy analysis suggested that only six of these would improve the informativeness of genetic linkage data. CONCLUSIONS: Many proposed spectrum phenotypes for schizophrenia may not be useful for linkage analysis because of high false positive rates (poor specificity). Future work aimed at describing and developing phenotypes for linkage analysis should assess the diagnostic accuracy of proposed measures.

Attention↗