Depression and multiple sclerosis: a potential way to understand the biology of major depressive illness.
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Biomedical subjects
Publications and source records attributed to Russell T Joffe.
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BACKGROUND: There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years. METHOD: Detailed life-charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow-up was examined. RESULTS: Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups. CONCLUSIONS: Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.
OBJECTIVE: There are few data addressing the effect of alcohol consumption on response to antidepressants among nonalcoholics with depression. Similarly, the effect of antidepressant treatment on alcohol consumption in this group is not yet understood. This study focuses on changes in depressive symptoms and alcohol consumption in response to treatment with desipramine. METHOD: Twenty-seven nonalcoholic outpatients with major depression (as determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Version) completed measures of depression (that is, the 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory) and alcohol consumption at intake and after 5 weeks of open treatment with desipramine. Subjects were characterized as minimal or mild-to-moderate drinkers. RESULTS: There was no significant difference between the groups with respect to effectiveness of antidepressant treatment. Analysis for repeated measures demonstrated that alcohol consumption with desipramine was significantly lower after treatment than at intake (F = 4.8, df 23:2, P < 0.01). Further, carbohydrate consumption was also significantly lower after treatment than at intake (F = 4.4, df 23:2, P < 0.05). CONCLUSIONS: Desipramine treatment appeared to result in decreases in alcohol consumption in nonalcoholic patients with depression. Further research is needed to elucidate the effect of alcohol consumption on the course and outcome of major depressive illness among nonalcoholics as well as the effect of antidepressant medication on alcohol consumption in this population.
Substitution of T4 with T3 for T4 replacement in patients with hypothyroidism was undertaken using a randomized placebo controlled study design. Forty individuals were included who had depressive symptoms on stable doses of levothyroxine. Combined T4 plus T3 did not have a significantly different effect on mood and well-being scores than did T4 alone.
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Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.
Endocrine disorders are associated with significant psychiatric morbidity. Psychiatric symptoms may manifest as discreet psychiatric syndromes or, more commonly, with a heterogenous group of nonspecific symptoms. Research is needed to understand the relations between hormone excess or deficiency and alterations of mood, cognition, and perception. It is important for clinicians to carefully screen for psychiatric morbidity in patients who present with endocrine disorders. Moreover, patients who appear to present with primary psychiatric syndromes should be carefully evaluated by physical examination and biochemical screening when appropriate to exclude the presence of an underlying endocrine disorder.
OBJECTIVES: Few studies have examined the question of how personality features impact outcome in bipolar disorder (BD), though results from extant work and studies in major depressive disorder suggest that personality features are important in predicting outcome. The primary purpose of this paper was to examine the impact of DSM-IV personality disorder symptoms on long-term clinical outcome in BD. METHODS: The study used a 'life-charting' approach in which 87 BD patients were followed regularly and treated according to published guidelines. Outcome was determined by examining symptoms over the most recent year of follow-up and personality symptoms were assessed with the Structured Clinical Interview for DSM-IV (SCID-II) instrument at entry into the life-charting study. RESULTS: Patients with better outcomes had fewer personality disorder symptoms in seven out of 10 disorder categories and Cluster A personality disorder symptoms best distinguished euthymic and symptomatic patients. CONCLUSIONS: These results raise important questions about the mechanisms linking personality pathology and outcome in BD, and argue that conceptual models concerning personality pathology and BD need to be further developed. Treatment implications of our results, such as need for psychosocial interventions and treatment algorithms, are also described.
BACKGROUND: Many patients with bipolar disorder (BD) do not regain full function following an acute illness episode, but the extent to which this impairment is the result of persistent symptoms has not been well established. This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospectively followed for an average of 3 years. METHODS: Detailed life charting data from 138 patients with BD were reviewed. Patients were categorized into euthymic, subsyndromal or syndromal groups according to the clinical state during their most recent year of follow-up. The three groups were then examined with respect to comorbidity, function and treatment received. RESULTS: Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders, and were more likely to have increased rates of eating disorders as well. Patients with subsyndromal symptoms had lower global assessment of function (GAF) scores than euthymic patients, and had as many clinic contacts and medication trials as patients with full episodes of illness. CONCLUSIONS: Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning.
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OBJECTIVE: The treatment of bipolar depression is a significant clinical problem that remains understudied. The role for antidepressant (AD) agents vs. mood stabilizers has been particularly problematic to ascertain. METHOD: Detailed life charting data from 42 patients with 67 depressive episodes were reviewed. Response rates and rates of switch into mania were compared based on the preceding mood state and on whether an AD or mood stabilizing (MS) agent was added following onset of depression. RESULTS: Patients who became depressed following a period of euthymia were more likely to respond to treatment (62.5%) than patients who became depressed following a period of mania or hypomania (27.9%). The ratio of response to switch for previously euthymic patients was particularly favorable. CONCLUSION: Mood state prior to onset of depression in bipolar disorder appears to be an important clinical variable that may guide both choice of treatment administered and expectation of outcome to treatment.
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