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Biomedical subjects

I M Lesser

Publications and source records attributed to I M Lesser.

At least 19 recordsLinked to original sources
PubMed1997

Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects.

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.

Adult↗
PubMed1997

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Aged↗
PubMed1997

Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors.

BACKGROUND: Patients with frontotemporal dementia (FTD) present initially with primarily behavioral rather than cognitive symptoms. Decreased serotonin receptor binding has been reported in the frontal lobes, temporal lobes, and hypothalamus in autopsy-proven FTD cases. This study tests the hypothesis that many of the behavioral symptoms of FTD (including disinhibition, depressive symptoms, carbohydrate craving, and compulsions) will respond to serotonin selective reuptake inhibitors (SSRIs). METHOD: Eleven subjects meeting the Lund-Manchester clinical, neuropsychological, and neuroimaging criteria for FTD were treated with SSRIs (fluoxetine, sertraline, or paroxetine). After 3 months, treatment responses for disinhibition, depressive symptoms, carbohydrate craving, and compulsions were evaluated prospectively without placebo control. RESULTS: After treatment, disinhibition, depressive symptoms, carbohydrate craving, and compulsions all showed improvement in at least half the subjects in which they had been present. One subject stopped sertraline treatment because of diarrhea, while another stopped paroxetine treatment due to increased anxiety. The presence of individual behavioral symptoms and also the response of each symptom to SSRIs were unrelated to cognitive impairment as measured by baseline Mini-Mental Status Examination (.07 < or = p < or = 1.00) [corrected]. CONCLUSION: The behavioral symptoms of FTD may improve after treatment with SSRIs. Future neurochemical studies and controlled pharmacologic trials may improve available treatments.

1-Naphthylamine↗
PubMed1996

Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms.

Depressed outpatients having primarily psychological or vegetative symptoms, as defined by the factor analytically developed Hamilton Depression Scale superfactors described by Rhoades and Overall (1983), were compared with similarly aged normal controls on a comprehensive neuropsychological battery. The vegetative group evidenced poorer performance than controls on several measures associated with right hemisphere functioning and on a task associated with executive functioning. In contrast, the psychological group did not significantly differ from controls on any measure, and had significantly better performance than the vegetative group on several tasks. These findings suggest that neuropsychological deficits associated with depression may be limited to those patients with primarily vegetative symptoms.

Aged↗
PubMed1996

Cognition and white matter hyperintensities in older depressed patients.

OBJECTIVE: The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. METHOD: Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. RESULTS: The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. CONCLUSIONS: Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.

Age Factors↗
PubMed1996

The evolving science of pharmacogenetics: clinical and ethnic perspectives.

The field of pharmacogenetics has witnessed remarkable progress during the past several decades. Clinical observations of severe toxic reactions and findings of dramatic interindividual as well as cross-ethnic differences in response to therapeutic agents have been instrumental in fostering advances of the field. Research on cytochrome P450 isozymes may be of particular importance to the field of psychiatry, because most psychotropics depend on these enzymes for their biotransformation. This article traces the progress of research in this area and highlights the importance of clinical and cross-ethnic observations in providing the impetus and direction for the field. Knowledge derived from this line of research is likely to make important contributions toward establishment of rational guidelines for psychopharmacotherapy. In addition, research on these enzymes may also have profound implications in regard to the pathogenesis of a number of major disorders, including several types of commonly encountered cancers, as well as neuropsychiatric problems, including Parkinson's disease, tardive dyskinesia, addiction, and drug-induced neurotoxicity.

Cytochrome P-450 Enzyme System↗
PubMed1996

Brain imaging, antidepressants, and ethnicity: preliminary observations.

Magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropylene amine oxime (HMPAO) evaluations were completed on African-American and Caucasian depressed patients prior to their participation in an antidepressant medication trial. The degree of white matter hyperintensities (WMH), ventricle-to-brain ratio (VBR), and uptake of HMPAO did not vary significantly between the groups. After 1 week of placebo run-in, patients received paroxetine in an 8-week, open-label, flexible-dose trial. Final dosages and side effects were similar between groups. There was a trend for the Caucasian patients to have a better treatment response, but the relatively small sample size makes this finding tentative. In general, there were no major differences in either baseline neuroimaging findings or response to paroxetine between these two ethnic groups.

Black or African American↗
PubMed1994

Reduction of cerebral blood flow in older depressed patients.

BACKGROUND: We investigated regional cerebral blood flow in older, drug-free depressed patients and examined factors that might be related to rCBF. METHODS: We studied 39 physically healthy depressed patients over the age of 50 years and 20 psychiatrically healthy control subjects. Regional cerebral blood flow was measured with single photon emission computed tomography, using both xenon 133 (to quantify regional cerebral blood flow) and 99mTc-hexamethylpropylene amine oxime (to make regional comparisons). From magnetic resonance imaging, we derived a semiquantitative measure of areas of white matter hyperintensity and a ventricle-to-brain ratio. RESULTS: Patients exhibited a global reduction in regional cerebral blood flow compared with controls, with the orbital frontal and inferior temporal areas affected bilaterally. Regional cerebral blood flow was also reduced in higher brain slices in the right but not the left hemisphere. Significant predictors of lowered regional cerebral blood flow were being depressed, being male, and having a greater ventricle-to-brain ratio. There appeared to be a subgroup of patients who demonstrated large areas of white matter hyperintensity and low regional cerebral blood flow. CONCLUSIONS: Cerebral blood flow was lower in older, medication-free depressed patients than in age-matched control subjects, involved the orbital frontal and anterior temporal regions, and was more reduced in the right hemisphere.

Age Factors↗
PubMed1993

Wisconsin Card Sorting Test performance in healthy, older adults: relationship to age, sex, education, and IQ.

We obtained Wisconsin Card Sorting Test (WCST) scores on 91 (35 male and 56 female) healthy, well-educated individuals aged 45 to 83. Women scored better than men on six WCST scores (categories, errors, perseverative responses, % perseverative errors, % conceptual level responses, and trials to first category), while subjects with more than 16 years of education outscored those limited to high school education on four measures (perseverative responses, errors, % perseverative errors, % conceptual level responses). Individuals older than 70 years of age scored less well than younger subjects on only two indices (errors, % conceptual level responses). Full Scale IQ was not related to WCST scores. Our findings suggest that WCST scores should be interpreted within the context of patient gender, education, and age.

Age Factors↗
PubMed1993

Brain imaging in late-life schizophrenia and related psychoses.

Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenia-like symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuro-imaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with age-matched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

Aged↗
PubMed1992

Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect.

The clinical significance of white-matter lesions (WMLs) detected by computed tomography and magnetic resonance imaging in healthy elderly subjects has been controversial, with some studies reporting associated deficits in cognition and others failing to document cognitive disturbance. In our sample of 100 healthy elderly individuals, almost half (n = 46) had no WMLs, approximately one fourth had minimal (less than or equal to 1 cm2; n = 27) or moderate (greater than 1 cm2 but less than or equal to 10 cm2; n = 21) WML areas, and six subjects had large WML areas (greater than 10 cm2). Substantial disturbances in basic attention and selected frontal lobe skills were detected in the six subjects with the large WML areas. These findings suggest that a "threshold" of WML area must be present before cognitive deficits are observed. Surprisingly, no significant relationships between duration of hypertension or cholesterol levels and WMLs were detected, suggesting that factors other than vascular disturbances are involved in the origin of at least some WMLs.

Aged↗
PubMed1992

Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia.

OBJECTIVE: The authors' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week, fixed-dose, double-blind, placebo-controlled, dose-response study of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic attacks, avoidance behavior, generalized anxiety, and global response. Blood samples were collected throughout the study and analyzed for alprazolam and other benzodiazepines. RESULTS: Patient compliance with the protocol was judged to be good on the basis of plasma concentrations. According to logistic regression analysis, the relationships between plasma alprazolam concentration and response, as reflected by number of panic attacks reported, phobia ratings, physicians' and patients' ratings of global improvement, and the emergence of side effects, were significant. However, there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms. CONCLUSIONS: The authors conclude that plasma concentration of alprazolam is related to treatment response, particularly in panic attacks. The alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals, highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects.

Adult↗
PubMed1992

A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Adolescent↗
PubMed1991

Brain injury and cognitive function in late-onset psychotic depression.

Fourteen patients who developed a psychotic depression after age 45 were compared with 72 non-psychiatrically ill elderly control subjects using neuroimaging and neuropsychological (NP) tests. Despite the fact that the patients were not studied if they had an obvious dementia or neurological disease, structural brain abnormalities were found in approximately two-thirds of patients and in less than 10% of controls. The most common abnormality, subcortical white matter (WM) lesions, was thought to be vascular in etiology. Also, tumor and primary degenerative dementia were found more frequently in the patients. Compared to an age-, sex-, and education-matched control group, the patients performed more poorly on NP tests of frontal lobe, memory, and visual spatial abilities. Diagnostic evaluation of the patient with late-onset psychotic depression should include computed tomography or magnetic resonance imaging as structural brain abnormalities are common in these patients.

Age of Onset↗