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Biomedical subjects

V I Reus

Publications and source records attributed to V I Reus.

At least 19 recordsLinked to original sources
PubMed1999

Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women.

BACKGROUND: Estrogen replacement therapy (ERT) may delay dementia-related cognitive decline in post-menopausal women, but few studies have longitudinally examined this relationship and none has controlled for baseline functioning or concurrent medication. METHODS: We report the results of a 1-year retrospective longitudinal study examining cognitive functioning in female estrogen and nonestrogen users (n = 3128) who presented to the state of California memory disorder clinics in a naturalistic multisite study of senile dementia, Alzheimer's type (SDAT), and other cognitive impairments. RESULTS: At baseline, estrogen users had significantly lower rates of SDAT diagnoses (possible and probable) than nonestrogen users, and significantly higher rates of the lesser diagnoses of "cognitive impairment" and "no dementia." ERT was significantly associated with higher cognitive functioning at baseline and at 1 year follow-up (n = 358). Nonestrogen users deteriorated significantly from baseline to follow-up; estrogen users did not. Results were similar in groups matched on baseline Blessed-Roth Dementia Rating Scale (BRDRS) ratings (n = 32) and in a variety of subpopulations. CONCLUSIONS: These findings are consistent with estrogen acting as a protective factor against cognitive deterioration in post-menopausal women with SDAT and other cognitive impairments, and may suggest an increased effect in earlier stages of cognitive impairment.

Aged↗
PubMed1999

Antiglucocorticoid treatment of depression: double-blind ketoconazole.

BACKGROUND: Hypercortisolemia is frequently observed in major depression but its pathophysiologic significance is unknown. In patients in whom hypercortisolism contributes to depressive symptomatology, antiglucocorticoid agents should have antidepressant effects. METHODS: Twenty medication-free depressed patients (eight of whom were hypercortisolemic and twelve of whom were not) received either the cortisol biosynthesis inhibitor, ketoconazole (400-800 mg/d p.o.) or placebo for 4 weeks in a double-blind manner, and behavioral ratings were performed weekly. RESULTS: Ketoconazole, compared to placebo, was associated with improvements in depression ratings in the hypercortisolemic, but not in the non-hypercortisolemic patients. The hormonal changes seen (decreased dehydroepiandrosterone and testosterone levels and increased pregnenolone and pregnenolone-sulfate levels) are consistent with enzymatic blockade of C17,20-lyase, 11-hydroxylase, and 17-hydroxylase. Ketoconazole was generally well tolerated with no occurrence of significant side effects or laboratory abnormalities. CONCLUSIONS: This small-scale double-blind study suggests that antiglucocorticoids have antidepressant activity in hypercortisolemic depressed patients. The data are consistent with a causal role of adrenocortical dysfunction in some depressed patients and suggest the need for larger-scale trials.

Adult↗
PubMed1999

Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: an initial screen for bipolar disorder loci on chromosome 18.

Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at approximately 6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I-susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.

Bipolar Disorder↗
PubMed1999

Double-blind treatment of major depression with dehydroepiandrosterone.

OBJECTIVE: This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans. METHOD: Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, received either DHEA (maximum dose = 90 mg/day) or placebo for 6 weeks in a double-blind manner and were rated at baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone. RESULTS: DHEA was associated with a significantly greater decrease in Hamilton depression scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms. CONCLUSIONS: These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.

Adult↗
PubMed1998

Cortisol and response to dexamethasone as predictors of withdrawal distress and abstinence success in smokers.

BACKGROUND: Glucocorticoids have been linked to self-administration of a wide range of drugs in animals and are increased endogenously by chronic nicotine intake. Corticosteroids have also been shown to regulate nicotine receptor sensitivity and to be involved in behavioral sensitization to nicotine. METHODS: Cortisol levels and cortisol suppression in response to dexamethasone were measured in a sample of smokers participating in a smoking cessation treatment trial. RESULTS: Cortisol levels dropped significantly during the early quitting process (2 weeks post-quit) and returned to a level below baseline 1 month post-quit. The magnitude of the initial drop in cortisol was strongly related to post-quit distress and marginally predictive of abstinence. Neither baseline nor post-quit changes in percent cortisol suppression after dexamethasone were related to abstinence success or withdrawal distress. CONCLUSIONS: Withdrawal from cigarette smoking is marked by a reduction in cortisol levels that appears to be related to the degree of distress experienced during the early quitting period. Further work is needed to determine whether withdrawal-related cortisol changes or distress are predictive of abstinence success.

Adult↗
PubMed1998

Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.

BACKGROUND: A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence. METHODS: This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date. RESULTS: Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men. CONCLUSIONS: Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.

Adult↗
PubMed1998

Mapping genes for psychiatric disorders and behavioral traits.

In the past year, findings from genetic studies in non-human organisms have yielded a number of exciting insights regarding the genetic basis of complex behaviors. Although there were encouraging developments in the genetic study of human behavioral traits, particularly those involved with cognitive function, there was relatively little progress in genetic mapping of the most common psychiatric phenotypes.

Animals↗
PubMed1998

Selective alteration of personality and social behavior by serotonergic intervention.

OBJECTIVE: The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans. METHOD: A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N = 26), or placebo (N = 25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment. RESULTS: Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment. CONCLUSIONS: Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.

Adult↗
PubMed1997

Glucocorticoid medication, memory and steroid psychosis in medical illness.

Steroid psychosis, including associated cognitive changes, is infrequent with short-term low-dose GC treatment, especially if only major objectively discernible effects are assessed. With long-term or high-dose treatment, however, or if milder subjectively discernible symptoms are also assessed, the incidence may be quite high. In lupus cerebritis, the differentiation between cognitive difficulties secondary to the underlying illness, which might warrant more aggressive GC treatment, versus those secondary to GC treatment itself, which might warrant dosage reduction, may be problematic, but certain guidelines have been proposed. Although GCs are widely prescribed and represent a clinically important class of medication, their deleterious effects may also be considerable. Glucocorticoids have prominent effects on central nervous system biochemistry and electrophysiology, and recent reports suggest they make certain hippocampal neurons more vulnerable to a variety of metabolic insults. Indeed, the clinical literature reviewed here is consistent with a disruption of hippocampus-dependent memory function (perhaps in conjunction with other areas of dysfunction), although in most cases the disruption is relatively mild and, in the vast majority, if not all cases, is reversible. From a clinical prospective, it is important to discuss potential neuropsychiatric side effects with patients before prescribing GC treatment. A greater understanding of the risk factors for experiencing SP and of its underlying mechanisms will lead to more informed clinical decision making and to a greater understanding of the role exogenous, and perhaps endogenous, GCs play in human cognition and behavior.

Adult↗
PubMed1997

Dehydroepiandrosterone (DHEA) treatment of depression.

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Aged↗
PubMed1997

Antiglucocorticoid treatments in psychiatry.

A confluence of evidence indicates that alterations in hypothalamic-pituitary-adrenal regulation can have profound effects on the symptom picture of psychiatric illnesses and that therapeutic interventions directly targeted at corticosteroid metabolism may have clinical benefit. This paper reviews the varying lines of inference that support such a hypothesis and reviews work by our group and others utilizing the cortisol synthesis inhibitor, ketoconazole and, more recently, dehydroepiandrosterone (DHEA), as potential novel mood-altering agents. The data thus far suggest that antiglucocorticoid drug treatment may be useful in certain subgroups of depressed patients and may offer a theoretical rationale for alternative drug design.

Dehydroepiandrosterone↗
PubMed1996

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Bipolar Disorder↗
PubMed1996

Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population.

Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis.

Adult↗
PubMed1996

An approach to investigating linkage for bipolar disorder using large Costa Rican pedigrees.

Despite the evidence that major gene effects exist for bipolar disorder (BP), efforts to map BP loci have so far been unsuccessful. A strategy for mapping BP loci is described, focused on investigation of large pedigrees from a genetically homogenous population, that of Costa Rica. This approach is based on the use of a conservative definition of the BP phenotype in preparation for whole genome screening with polymorphic markers. Linkage simulation analyses are utilized to indicate the probability of detecting evidence suggestive of linkage, using these pedigrees. These analyses are performed under a series of single locus models, ranging from recessive to nearly dominant, utilizing both lod score and affected pedigree member analyses. Additional calculations demonstrate that with any of the models employed, most of the information for linkage derives from affected rather than unaffected individuals.

Bipolar Disorder↗
PubMed1996

Management of treatment-resistant unipolar and chronically depressed patients.

The majority of depressed patients presenting as treatment refractory will respond to a properly chosen new medication or to a previous agent administered correctly. Drug combinations are less frequently required than current practice would indicate, and their usage depends at present more on clinical experience than scientific fact. Educating the patient about the series of options available, and the sequence in which they will be undertaken, and imbuing the enterprise with hopeful optimism are essential ingredients to ultimate success.

Antidepressive Agents↗
PubMed1996

Mood management and nicotine gum in smoking treatment: a therapeutic contact and placebo-controlled study.

Earlier research indicated that a 10-session mood management (MM) intervention was more effective than a 5-session standard intervention for smokers with a history of major depressive disorder (MDD). In a 2 x 2 factorial design, the present study compared MM intervention to a contact-equivalent health education intervention (HE) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD. Participants were 201 smokers, 22% with a history of MDD. Contrary to the earlier findings, the MM and HE interventions produced similar abstinence rates: 2 mg gum was no more effective than placebo. History-positive participants had a greater increase in mood disturbance after the quit attempt. Independent of depression diagnosis, increases in negative mood immediately after quitting predicted smoking. No treatment differences were found in trends over time for measures of mood, withdrawal symptoms, pleasant activities and events, self-efficacy, and optimism and pessimism. History-positive smokers may be best treated by interventions providing additional support and contact, independent of therapeutic content.

Adult↗