Subthreshold depression and subjective cognitive complaints in Parkinson's disease.

BACKGROUND AND PURPOSE: Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients. METHODS: Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions. RESULTS: On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients. CONCLUSIONS: SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being.

Biological mechanisms of stroke prevention by physical activity in type 2 diabetes.

The principal modifiable risk factors for stroke are hypertension, diabetes mellitus, hypercholesterolaemia, hyperhomocysteinaemia, smoking and limited physical activity. However, it is not clear whether physical inactivity is a risk factor per se, or because it predisposes to pathological conditions that are risk factors for stroke. The limited availability of effective therapeutic approaches for stroke emphasizes the crucial role of prevention of risk factors. The global burden associated with type 2 diabetes is large and continues to grow. Convincing epidemiologic data support the role of physical activity in preventing type 2 diabetes. The increasing evidence of physical activity in preventing diabetic complications, including stroke, has generated interest in the molecular basis underlying these beneficial effects. The aim of the present review is to discuss the biological mechanisms underlying the effect of physical activity in preventing stroke in type 2 diabetes.

Imipramine treatment of alcoholics with primary depression: A placebo-controlled clinical trial.

BACKGROUND: Depressive disorders are commonly comorbid with alcoholism, particularly in treatment-seeking samples. If antidepressant treatment were safe and improved the treatment outcome in the subset of actively drinking alcoholics with depression, this would be of clinical importance. METHODS: We conducted a randomized, 12-week placebo-controlled trial of imipramine hydrochloride combined with weekly relapse prevention psychotherapy. The subjects were 69 actively drinking alcoholic outpatients with current depressive disorders. The first onset of depression was either antecedent to the abuse of alcohol or occurred during prolonged periods of sobriety. Depression and drinking outcomes at 12 weeks, as well as their relationship, were measured. RESULTS: Imipramine treatment was safe and associated with improvement in depression in both adequately treated and intention-to-treat samples. While there was no overall effect on drinking outcome, patients whose mood improved showed decreased alcohol consumption that was more marked in those treated with imipramine. CONCLUSIONS: Imipramine treatment is effective for primary depression among actively drinking alcoholic outpatients, and may improve alcoholic outcome for those whose depression responds to treatment.

Chronological milestones to guide drug change. When should clinicians switch antidepressants?

BACKGROUND: We attempt to identify the time when patients whose conditions are unimproved while receiving antidepressants are unlikely to respond and should have their treatment changed. METHODS: A total of 593 patients were studied. The course of treatment for patients was examined to determine the weeks at which patients who received drug therapy had a better chance of being rated as responders at the study end (week 6) vs patients who received placebo. RESULTS: At the end of week 3, 19 (32%) of the 59 patients who received drug therapy and 6 (10%) of the 57 patients who received placebo and who never minimally improved were rated as responders at week 6. For those who showed no improvement by week 4, the effects of drug therapy and the placebo were equal. Patients who received drug therapy and whose conditions were unimproved but who had been minimally improved at some point had a superior prognosis with drug therapy vs placebo until week 4. Of those unimproved at week 4 but minimally improved at some point previously, 20 (39%) of the 51 patients who received drug therapy vs 3 (8%) of the 36 patients who received placebo were rated as responders at week 6. Of the 75 patients who minimally improved while receiving drug therapy at the end of week 5, 33 (44%) had a chance of being rated a responder at the end of week 6 vs 9 (26%) of the 35 patients receiving placebo. CONCLUSIONS: Patients tolerant of an adequate dose, whose conditions have never been at least minimally improved by the end of week 4, should have their treatment regimen altered. These patients represented a minority of drug-treated patients in the sample studied (ie, 39/392 [10%]). Patients whose conditions minimally improve at some prior week but not after week 5 should have their treatment changed. Patients whose conditions minimally improve in week 5 should continue treatment until week 6.

Factors associated with premature medication discontinuation among responders to an MAOI or a tricyclic antidepressant.

The charts of 80 outpatients who responded to antidepressants were reviewed to determine if there was a higher rate of premature medication discontinuation with phenelzine than with imipramine. The phenelzine responders had a significantly (p less than .01) higher rate of drug discontinuation, mainly because of side effects. Controlled studies of long-term use are needed to better explain the problem of attrition.

Outcome of cognitive-behavioral therapy for depression: relation to hemispheric dominance for verbal processing.

Unmedicated depressed outpatients were tested on dichotic syllable and complex tone tests prior to receiving 16 weekly sessions of cognitive therapy (n = 31) or 6-12 weeks of placebo treatment (n = 45). Cognitive-therapy responders had twice the right-ear (left hemisphere) advantage for syllables when compared with nonresponders but did not differ from nonresponders on the nonverbal task. The larger right-ear advantage in cognitive-therapy responders was due to better right-ear accuracy; they did not differ from nonresponders in left-ear accuracy. No differences in perceptual asymmetry or accuracy were found between placebo responders and nonresponders. Right-ear accuracy for syllables was the best predictor of response to cognitive therapy in a logistic regression analysis. The findings suggest that greater left-hemisphere advantage for verbal processing is associated with more favorable outcome of cognitive therapy for depression.

Predictors of persistent social impairment among recovered depressed outpatients.

BACKGROUND: Though the social functioning of most depressed outpatients improves with effective treatment, a subgroup may remain impaired after recovering from depression. The purpose of this study was to identify predictors of residual social impairment among patients who recovered from depression. METHODS: These data were obtained from the Treatment of Depression Collaborative Research Program (TDCPR) public access tape. The TDCPR tested the relative efficacy of two psychotehrapies, imipramine, and placebo in major depression. Patients received follow-up assessments after completing the clinical trial. The following assessment instruments were used to assess predictor variables: Social Adjustment Scale II, Personality Assessment Form (PAF), Longitudinal Interval Follow-up Events (LIFE), and the Schedule for Affective Disorders (SADS). RESULTS: Recovered patients who were socially impaired at the end of treatment and six months later, had a higher rate of Intermittent Depression, and reported greater malfunctioning during adolescence than recovered patients whose functioning was unimpaired after treatment and at follow-up. The rates of personality disorders were not significantly different between these groups. LIMITATIONS: These analyses were performed post-hoc and the sample size was small. CONCLUSIONS: A chronic course of depression predicted persistent social maladjustment among patients who recovered from depression for 6 months.

One year clinical and psychosocial outcomes of early-onset chronic depression.

BACKGROUND: Results from short-term treatment studies have demonstrated the efficacy of antidepressant medications for outpatients with early-onset chronic depression. However, scant data exists regarding the long-term outcome of these patients treated for this disorder. METHODS: The author conducted a one-year naturalistic follow-up study of 50 outpatients with early-onset, chronic depression, who were treated in a university-based psychopharmacology research clinic. Assessments were conducted blind to the patients' histories. RESULTS: Forty-eight percent of the total sample reported 9-12 months of sustained euthymia (Months Well). Among the patients who recovered, 50% relapsed. LIMITATIONS: The major limitations of this study were its small sample size and lack of a comparison group. CONCLUSIONS: These results data demonstrate that despite initial response, many outpatients with chronic depression seem to relapse after leaving university-based psychopharmacology centers.

Residual symptoms and social functioning over six-months in recovered outpatients with chronic depression.

BACKGROUND: Scant data exists regarding the global mental health of recovered chronically depressed outpatients. The purpose of this study was to compare the symptoms and functioning of these patients to those found in a normal control group (NCG). METHODS: Social functioning was assessed by the Social Adjustment Scale interview. Symptoms were measured with the Symptom Check List-90. RESULTS: The overall social functioning of recovered females was more impaired than a NCG. Recovered males and females had more psychiatric symptoms than a NCG. LIMITATIONS: The two samples were not demographically similar. CONCLUSIONS: Though the differences in social functioning and symptoms between the recovered patients and NCG's were statistically significant, they were not clinically meaningful. In general, recovered females had a relatively robust level of mental health.

Atypical and non-atypical subtypes of depression: comparison of social functioning, symptoms, course of illness, co-morbidity and demographic features.

BACKGROUND: There are scant data regarding the demographic and psychosocial characteristics of outpatients with Atypical Depression (AD). METHODS: The demographic characteristics, rates of chronic dysphoria, baseline Symptom Check List Revised, and Social Adjustment Scale scores of 320 moderately depressed patients with and without AD were compared. RESULTS: ADs had a higher number of self-reported symptoms, greater impairments in functioning, and higher rates of chronic dysphoria and bipolar II than patients without Atypical Depression (NAD). LIMITATIONS: Variables used in this study were mostly cross-sectional, and the analyses were performed post-hoc. CONCLUSIONS: These data suggest ADs had a more pernicious course of illness than NADs, and that patients with AD were more symptomatic and dysfunctional at admission.

The efficacy of imipramine and psychotherapy in early-onset chronic depression: a reanalysis of the National Institute of Mental health Treatment of Depression Collaborative Research Program.

The authors compared the effectiveness of Cognitive Behavioral Therapy (CBT), Interpersonal Psychotherapy (IPT), Imipramine Clinical Management (ICM) to Placebo Clinical Management (PCM) for outpatients with early-onset chronic depression (N = 65) in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (TDRP). The post-treatment depression scores of the CBT. IPT, and ICM groups were not significantly different from the PCM group. We did not find a relationship between the duration of Major Depression and response to a specific treatment. Studies are needed to determine if combining psychotherapy with medication improves social functioning and enhances the quality of life for patients with chronic depression.

Social functioning and residual symptomatology among outpatients who responded to treatment and recovered from major depression.

It is unclear whether depressed patients who respond to treatment, and subsequently recover, manifest a significant degree of residual symptomatology and enduring psychosocial impairment. The purpose of this study was to compare the social functioning and symptoms of depressed outpatients who responded to acute treatment, and had a sustained recovery from major depression for 6 months, with psychiatrically normal community samples. The sample (n = 48) was drawn from the NIMH Treatment of Depression Collaborative Research Program. The Social Adjustment Scale scores and the Symptom Check List of recovered patients were clinically indistinguishable from the community sample scores. These data suggest that patients who benefit from acute treatment and recover from major depression can expect to achieve a normal level of functioning and symptomatology.

Life satisfaction and psychosocial functioning in chronic depression: effect of acute treatment with antidepressants.

Social functioning was evaluated in 61 chronically depressed adults with early onset. Patients were treated for 6 weeks in a double-blind trial of phenelzine, imipramine, L-deprenyl, or placebo and functioning was reassessed. The posttreatment social functioning of patients who received drug treatment was superior to the placebo group in the following areas: work functioning, house functioning, relationship with relatives, sex frequency and life satisfaction. These results suggest that psychosocial impairment in some chronic depressives may be a sequaela of depression, rather than a global manifestation of characterological pathology.

Somatization as a predictor of medication discontinuation due to adverse events.

Medication discontinuation due to intolerable side-effects remains a significant clinical problem in the treatment of depression. We were unable to locate studies which found predictors of medication cessation due to side-effects. We posited that an identifiable subgroup of medically healthy, depressed adults who discontinued medication because of adverse events would have higher pre-treatment somatic symptoms than patients who completed a course of treatment. The sample (n =940) was drawn from a series of double-blind, placebo-controlled studies of antidepressants (imipramine, phenelelzine, L-deprenyl, mianserin and desipramine). Within the medication group, side-effect dropouts had more somatic symptoms than study completers and those who discontinued treatment for miscellaneous reasons. Within the placebo-treated group, the small number of subject who discontinued treated because of side-effects precluded valid statistical analyses, but the findings were in the same direction as those in the medication group. Clearly, further research is required to determine whether these results, obtained from a series of university-based clinical trials with healthy subjects, are generalizable to patients with significant comorbid medical and/or psychiatric disorders, treated with newer antidepressants agents in a general clinical practice setting.

Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells.

The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of epithelial sodium channel-mediated sodium transport and is involved in the transduction of growth factor-dependent cell survival and proliferation signals. Growing evidence now points to Sgk1 as a key element in the development and/or progression of human cancer. To gain insight into the mechanisms through which Sgk1 regulates cell proliferation, we adopted a proteomic approach to identify up- or downregulated proteins after Sgk1-specific RNA silencing. Among several proteins, the abundance of which was found to be up- or downregulated upon Sgk1 silencing, we focused our attention of RAN-binding protein 1 (RANBP1), a major effector of the GTPase RAN. We report that Sgk1-dependent regulation of RANBP1 has functional consequences on both mitotic microtubule activity and taxol sensitivity of cancer cells.

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1.

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells.

The efficacy of treatments in reducing alcohol consumption: a meta-analysis.

Meta-analysis was used to assess the relative efficacy of various treatments in reducing alcohol consumption over the short-term, 6 months, and 12 months. All the treatments were administered in well-controlled studies. In the short-term and 1-year follow-up studies, patients in the experimental group drank much less than the control group. However, between group consumption differences were negligible in the 6-month studies. When the studies were pooled, regardless of the follow-up assessment periods, the experimental group drank significantly less than the control group. These results suggest that, in general, patients who received experimental treatments consumed much less alcohol than patients in the control groups.

The efficacy of controlled trials of alcohol misuse treatments in maintaining abstinence: a meta-analysis.

Meta-analysis was used to establish the efficacy of various controlled alcohol misuse treatments in maintaining abstinence over short-term, 6-month, and 12-month follow-ups. Effect sizes were measured by odds ratio. Aggregate effect size differences between experimental and control groups were negligible. Only three of 15 studies found a clinically significant difference between treatment abstinence outcomes.

Six month follow-up of early-onset chronic depression.

BACKGROUND: This study sought to characterize the morbidity and treatment behavior of 49 patients with early-onset chronic depression, 6 months after terminating treatment at a university-based psychopharmacology research clinic. METHOD: Patients with and without early-onset chronic depression were selected to participate in a naturalistic follow-up study. Assessments were conducted blind to patients' histories. Patients' depressive symptoms, psychosocial functioning, and post-discharge treatment histories were assessed. RESULTS: After termination, the mean length of recovery for the sample was 3.6 months. When they left the clinic, 78% (38/49) were euthymic. At follow-up, 37% (14/38) of these had relapsed; while 45% (17/38) remained in remission for 6 months. During the follow-up period, 47% of the patients were on antidepressants. Sixty-three percent of the patients who relapsed, or were depressed when they left the clinic, did not enter treatment, 50% of whom cited insufficient resources as the primary reason for not receiving care. CONCLUSIONS: After leaving a depression research clinic, a substantial portion of patients with early-onset chronic depression remained recovered during a 6-month period, but financial impediments prevented a majority of those who did poorly from entering treatment.

Patient factors related to early attrition from an outpatient cocaine research clinic.

The dropout rates among cocaine abusers in outpatient treatment programs have averaged 55%. We sought to find patient predictor variables associated with early attrition. Dropouts were more likely to be African-American or Hispanic-American, younger, with an earlier onset of substance abuse. Among minorities, those with more education were less likely to drop out. Patients who were less educated and smoked or injected cocaine were particularly prone to discontinue treatment prematurely. The implications of these findings, and promising interventions for reducing the dropout problem, are discussed.