Faculty Bibliography

Depression frequently is comorbid with a variety of medical illnesses; individuals who have such comorbidities may have increased morbidity and lower functional status. Usual antidepressant treatments can be effective in depressed patients who have comorbid medical illness. These patients, however, experience lower rates of recovery and remission of depressive symptoms and higher rates of relapse during follow-up than seen in patients who have MDD with no medical comorbidity. Comorbid medical illness therefore is a marker of treatment resistance in MDD. Collaborative treatments combining antidepressants, psychotherapy, education, and case management may be effective and could overcome the risk of treatment resistance. Two clinical strategies seem warranted in light of the studies presented here: (1) an increased index of suspicion for depression in medically ill patients, and (2) more intensive antidepressant treatment in depressed patients who have medical comorbidity.

Previous reports of increased rates of cardiovascular risk factors in major depressive disorder (MDD) with anger attacks led the authors to hypothesize that MDD with anger attacks may be associated with brain vascular changes (magnetic resonance imaging white matter hyperintensities [WMHs]). Sixty-five subjects meeting DSM-III-R criteria for major depressive disorder were administered brain magnetic resonance imaging scans at 1.5T to detect T2 WMH. The severity of brain WMH was classified with the Fazekas scale. We used standardized scales to assess melancholic MDD, atypical MDD, and MDD with anger attacks. In logistic regression analyses, MDD with anger attacks was associated with higher severity of subcortical WMH and of total WMH, but not with periventricular WMH. Atypical and melancholic MDD subtypes were not significantly associated with brain WMH. In conclusion, subcortical brain vascular lesions may be more prevalent or severe in MDD with anger attacks.

OBJECTIVE: Depression and anger have been separately associated with cardiovascular risk factors. We investigated if major depressive disorder (MDD) with concomitant anger attacks was associated with cardiovascular risk factors. METHOD: We measured total serum cholesterol, glycemia, resting blood pressure, and smoking parameters in 333 (52.9% women) MDD nonpsychotic outpatients, mean age of 39.4 years. MDD was diagnosed with the Structured Clinical Interview (SCID) in accordance with the Diagnostic and Statistic Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). The presence of anger attacks was established with the Massachusetts General Hospital Anger Attacks Questionnaire. RESULTS: In a logistic regression analysis, anger attacks were independently associated with cholesterol levels > or = 200 mg/dL (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.18-3.94) and years of smoking > 11 (OR, 2.59; 95% CI, 1.32-5.04). CONCLUSIONS: MDD with anger attacks was significantly associated with increased cholesterol levels and years of smoking.

BACKGROUND: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression. METHOD: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness. RESULTS: 117 MDD patients (mean +/- SD age: 43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002). CONCLUSION: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD.

BACKGROUND: Studies investigating the performance of instruments to detect major depressive disorder (MDD) have reported inconsistent results. Subsyndromal depression (SD) has also been associated to increased morbidity, and little is known about its detection in primary care setting. This study aimed to investigate the performance of the Primary Care Evaluation of Mental Disorders (PRIME-MD) to detect MDD and any depression (threshold at SD) in an outpatient unit of a teaching general hospital. METHODS: Nineteen primary care physicians using the PRIME-MD evaluated 577 patients, 240 of them (75% female; mean age, 40.0 +/- 14.4), including all with MDD and a randomly subset of those without MDD, were evaluated by 11 psychiatrists using the Structured Clinical Interview Axis I Disorders, Patient Version (SCIDI/P) for DSM-IV as the standard instrument. RESULTS: The kappa between the PRIME-MD and the SCID was 0.42 for the diagnosis of any depression and 0.32 for MDD. The distribution of the number of depressive symptoms per patient suggested the existence of a continuum between SD and MDD, and a high frequency of subjects with 4-6 symptoms (close to the cutoff for the diagnosis of MDD). LIMITATIONS: The sample has a modest size and is a subset of an original one. CONCLUSION: A continuum between SD and MDD may in part explain the relatively low agreement for the diagnosis of MDD in our sample and possibly in other studies. Studies investigating the performance of screening instruments to detect MDD, should consider the relevance of identifying SD, and the influence of the distribution of the number of depressive symptoms in their results.

BACKGROUND: An increased incidence of brain white-matter hyperintensities has been described in major depressive disorder, butthe impact of such hyperintensities on treatment outcome is still controversial. AIMS: To investigate the relationship of brain white-matter hyperintensities with cardiovascular risk factors and with treatment outcome in younger people with major depressive disorder. METHOD: We assessed brain white-matter hyperintensities and cardiovascular risk factors in 84 people with major depressive disorder prior to initiating antidepressant treatment. We also assessed hyperintensities in 35 matched controls. RESULTS: We found no significant difference in the prevalence of white-matter hyperintensities between the depression and the control groups. Left-hemisphere subcortical hyperintensities correlated with lower rates of treatment response. We found no correlation between global hyperintensity measures and clinical outcome. Brain white-matter hyperintensities correlated with hypertension and age and withtotal cardiovascular risk score. CONCLUSIONS: Subcortical white-matter hyperintensities in the left hemisphere (but notin other brain areas) maybe associated with poor response to antidepressant treatment in major depression.

Both diabetes and depression are highly prevalent. Patients with diabetes experience higher rates of depression compared to the general population. When present, depression is associated with an increase in the morbidity and mortality of diabetes, suggesting the importance of treatment in this population. The objective of the present study was to characterize depressive characteristics in depressed patients with and without comorbid diabetes. Seventeen patients with type 1 or type 2 diabetes were drawn from outpatient clinical trials. Depressed patients without diabetes were identified from the same studies. Unpaired t-tests and multiple chi-square analyses were used to compare demographic and clinical characteristics between the samples. Diabetic patients in our sample were more depressed and reported lower levels of somatic well-being and contentment compared to non-diabetic patients. The samples did not differ significantly along other dimensions of depression, including course of illness, response to previous treatments and comorbid conditions. These findings suggest that depressed diabetic patients are more similar than not to non-diabetic depressed patients, although important differences exist.