Depression, deficits in functional capacity, and impaired glycemic control in urban African Americans with type 2 diabetes.

BACKGROUND: Effective depression treatment does not reliably reduce glycosylated hemoglobin (HbA1c) in depressed patients with type 2 diabetes, possibly in part due to deficits in functional capacity, i.e. performance of certain everyday living skills, essential for effective diabetes self-management. We sought to determine: a) the magnitude of deficits in functional capacity among urban, African American (AA) patients with type 2 diabetes, and b) whether these deficits were associated with poorer glycemic control. METHODS: At their initial visit to an inner-city diabetes clinic, 172 AA patients with type 2 diabetes were assessed with a variety of instruments, including the Mini International Neuropsychiatric Interview (MINI) and the UCSD Performance Skills Assessment-Brief (UPSA-B). They then entered a comprehensive diabetes management intervention, whose success was indexed by HbA1c levels at up to four reassessments over a one-year period. A mixed-effects model repeated-measures method was used to predict HbA1c. RESULTS: The prevalence of depression was 19%; the mean UPSA-B score was 81 ± 17. After multivariate adjustment, increased HbA1c levels over time were predicted by the presence of major depression (B = .911, p = .002) and decreasing (worse) scores on the UPSA-B (B = -.016, p = .027), respectively. Further adjustment for increasing the dosage of oral or insulin during the treatment eliminated the association between the UPSA score and HbA1c level (B = -.010, p = .115). CONCLUSIONS: Depression, as well as deficits in functional capacity, predicted reduced effectiveness of a diabetes self-management intervention. Future studies will determine whether interventions targeted at both improve glycemic control.

Dry eye syndrome, posttraumatic stress disorder, and depression in an older male veteran population.

PURPOSE: To evaluate whether veterans with posttraumatic stress disorder (PTSD) or depression have differences in dry eye symptoms and signs compared to a population without these conditions. METHODS: Male patients aged ≥50 years with normal eyelid, conjunctival, and corneal anatomy were recruited from the Miami Veterans Affairs Eye Clinic (N = 248). We compared dry eye symptoms (determined by the Dry Eye Questionnaire 5 [DEQ5] score) to tear film indicators obtained by clinical examination (i.e., tear osmolarity, corneal staining, tear breakup time, Schirmer's, meibomian gland quality, orifice plugging, lid vascularity) between patients with PTSD or depression and those without these conditions. Student's t-tests, χ(2) analyses, and linear and logistic regressions were used to assess differences between the groups. RESULTS: DEQ5 scores were higher in the PTSD (mean = 13.4; standard error [SE] = 1.1; n = 22) and depression (mean = 12.0; SE = 0.8; n = 40) groups compared to the group without these conditions (mean = 9.8; SE = 0.4; n = 186; P < 0.01 and P = 0.02, respectively). More patients in the PTSD and depression groups had severe dry eye symptoms, defined as a DEQ5 score ≥ 12 (77% and 63% vs. 41%; P < 0.01 and P = 0.02, respectively). No significant differences in tear film indicators were found among the three groups. Multivariable logistic regression indicated that a PTSD diagnosis (odds ratio [OR] = 4.08; 95% confidence interval [CI] = 1.10-15.14) and use of selective serotonin reuptake inhibitors (OR = 2.66; 95% CI = 1.01-7.00) were significantly associated with severe symptoms. CONCLUSIONS: Patients with PTSD have ocular surface symptoms that are not solely explained by tear indicators. Identifying underlying conditions associated with ocular discomfort is essential to better understand the mechanisms behind ocular pain in dry eye syndrome.

Decision-making in diabetes mellitus type 1.

Decreased treatment adherence in patients with diabetes mellitus type 1 (type 1 DM) may reflect impairments in decision-making and underlying associated deficits in working memory and executive functioning. Other factors, including comorbid major depression, may also interfere with decision-making. The authors sought to review the clinically relevant characteristics of decision-making in type 1 DM by surveying the literature on decision-making by patients with type 1 DM. Deficiencies in decision-making in patients with type 1 DM or their caregivers contribute to treatment nonadherence and poorer metabolic control. Animal models of type 1 DM reveal deficits in hippocampal-dependent memory tasks, which are reversible with insulin. Neurocognitive studies of patients with type 1 DM reveal lowered performance on ability to apply knowledge to solve problems in a new situation and acquired scholarly knowledge, psychomotor efficiency, cognitive flexibility, visual perception, speed of information-processing, and sustained attention. Other factors that might contribute to poor decision-making in patients with type 1 DM, include "hypoglycemia unawareness" and comorbid major depression (given its increased prevalence in type 1 DM). Future studies utilizing novel treatment strategies to help patients with type 1 DM make better decisions about their disease may improve their glycemic control and quality of life, while minimizing the impact of end-organ disease.

Diagnosis and treatment of depression in patients with congestive heart failure: a review of the literature.

CONTEXT: Major depressive disorder (MDD) can be challenging to diagnose in patients with congestive heart failure, who often suffer from fatigue, insomnia, weight changes, and other neurovegetative symptoms that overlap with those of depression. Pathophysiologic mechanisms (eg, inflammation, autonomic nervous system dysfunction, cardiac arrhythmias, and altered platelet function) connect depression and congestive heart failure. OBJECTIVE: We sought to review the prevalence, diagnosis, neurobiology, and treatment of depression associated with congestive heart failure. DATA SOURCES: A search of all English-language articles between January 2003 and January 2013 was conducted using the search terms congestive heart failure and depression. STUDY SELECTION: We found 1,498 article abstracts and 19 articles (meta-analyses, systematic reviews, and original research articles) that were selected for inclusion, as they contained information about our focus on diagnosis, treatment, and pathophysiology of depression associated with congestive heart failure. The search was augmented with manual review of reference lists of articles from the initial search. Articles selected for review were determined by author consensus. DATA EXTRACTION: The prevalence, diagnosis, neurobiology, and treatment of depression associated with congestive heart failure were reviewed. Particular attention was paid to the safety, efficacy, and tolerability of antidepressant medications commonly used to treat depression and how their side-effect profiles impact the pathophysiology of congestive heart failure. Drug-drug interactions between antidepressant medications and medications used to treat congestive heart failure were examined. RESULTS: MDD is highly prevalent in patients with congestive heart failure. Moreover, the prevalence and severity of depression correlate with the degree of cardiac dysfunction and development of congestive heart failure. Depression increases the risk of congestive heart failure, particularly in those patients with coronary artery disease , and is associated with a poorer quality of life, increased use of health care resources, more frequent adverse clinical events and hospitalizations, and twice the risk of mortality. CONCLUSIONS: At present, limited empirical data exist with regard to treatment of depression in the increasingly large population of patients with congestive heart failure. Evidence reveals that both psychotherapeutic treatment (eg, cognitive-behavioral therapy) and pharmacologic treatment (eg, use of the selective serotonin reuptake inhibitor sertraline) are safe and effective in reducing depression severity in patients with cardiovascular disease. Collaborative care programs featuring interventions that work to improve adherence to medical and psychiatric treatments improve both cardiovascular disease and depression outcomes. Depression rating scales such as the 9-item Patient Health Questionnaire should be used to monitor therapeutic efficacy.

Changes in heart rate variability of depressed patients after electroconvulsive therapy.

Objective. As few, small studies have examined the impact of electroconvulsive therapy (ECT) upon the heart rate variability of patients with major depressive disorder (MDD), we sought to confirm whether ECT-associated improvement in depressive symptoms would be associated with increases in HRV linear and nonlinear parameters. Methods. After providing consent, depressed study participants (n = 21) completed the Beck Depression Index (BDI), and 15-minute Holter monitor recordings, prior to their 1st and 6th ECT treatments. Holter recordings were analyzed for certain HRV indices: root mean square of successive differences (RMSSD), low-frequency component (LF)/high-frequency component (HF) and short-(SD1) versus long-term (SD2) HRV ratios. Results. There were no significant differences in the HRV indices of RMSDD, LF/HF, and SD1/SD2 between the patients who responded, and those who did not, to ECT. Conclusion. In the short term, there appear to be no significant improvement in HRV in ECT-treated patients whose depressive symptoms respond versus those who do not. Future studies will reveal whether diminished depressive symptoms with ECT are reliably associated with improved sympathetic/parasympathetic balance over the long-term, and whether acute changes in sympathetic/parasympathetic balance predict improved mental- and cardiac-related outcomes.

Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine.

In patients at high risk for recurrence of malignant melanoma, interferon-α (IFN-α), a stimulator of innate immunity, appears to induce distinct neurobehavioral symptom dimensions: a mood and anxiety syndrome, and a neurovegetative syndrome, of which the former is responsive to prophylactic administration of paroxetine. We sought to determine whether symptom dimensions (and treatment responsiveness) arise in patients with hepatitis C administered IFN-α and ribavirin. In a randomized, double-blind, 6-month study, 61 patients with hepatitis C eligible for therapy with IFN-α and ribavirin received the antidepressant paroxetine (n=28) or a placebo (n=33). Study medication began 2 weeks before IFN-α/ribavirin therapy. Neuropsychiatric assessments included the 10-item Montgomery-Asberg Depression Rating Scale (MADRS). The items of the MADRS were grouped into depression, anxiety, cognitive dysfunction, and neurovegetative symptom dimensions, and analyzed using a mixed model. By 2 weeks of IFN-α/ribavirin therapy, all four dimensions increased, with the symptom dimensions of anxiety and cognitive dysfunction fluctuating and worsening, respectively, in both groups over time. The depression symptom dimension was significantly lower in the paroxetine treatment group (p=0.04); severity of the neurovegetative symptom dimension was similar in both groups. Similar to patients with malignant melanoma receiving high-dose IFN-α, the depression symptom dimension is more responsive to paroxetine treatment in individuals undergoing concomitant IFN-α/ribavirin therapy. However, the anxiety, cognitive dysfunction, and neurovegetative symptom dimensions appear less responsive to prophylactic paroxetine administration. Different neurobiologic pathways may contribute to the responsiveness of IFN-α-induced symptom dimensions to antidepressant treatment, requiring relevant psychopharmacologic strategies.

The relationship of depression and diabetes: pathophysiological and treatment implications.

Diabetes is a highly prevalent, chronic disease that requires ongoing, multi-specialty medical care combined with patient self-management, family support, and education to prevent or delay end-organ morbidity and mortality. There is clearly an increased prevalence of major depressive disorder, a relatively common and costly central nervous system syndrome, in diabetic patients. During the past two decades, multiple studies reveal that not only are depressive symptoms a risk factor for the development of type 2 diabetes, but they have also been shown to contribute to hyperglycemia, diabetic complications, functional disability and all-cause mortality among diabetic patients. This article reviews studies examining the relationship between depression and diabetes, neurochemical underpinnings of the two disorders, and the diagnosis and treatment of depression associated with diabetes. We examine the validity of rating scales used to diagnose depression in diabetic patients and review the literature on psychotherapeutic and psychopharmacologic management for these patients. The challenges of optimal depression screening and treatment in primary care settings of diabetic patients are currently under close scrutiny, especially regarding their potential impact related to improvements in diabetes-related outcomes and decreased health care costs, be it "depression" or "diabetes" relevant. Much of the current literature regarding the intertwined nature of diabetes and depression is cross-sectional in nature. Future research should focus on longitudinal, prospective studies to determine causal factors. What is clear from the research reviewed in this article is that depression and diabetes should be treated together rather than as isolated diseases. The mind/body dualism is a false dichotomy and a truly team-based approach is necessary to address both issues of depression and diabetes. Collaborative care and the "patient-centered medical home" have emerged as potentially effective interventions to improve quality of care and patient outcomes in patients with depression and medical illnesses such as diabetes.

Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure.

OBJECTIVE: The purpose of this study is to compare the effectiveness of a combined 12-week home-based exercise (EX)/cognitive behavioral therapy (CBT) program (n=18) with CBT alone (n=19), EX alone (n=20), and with usual care (UC, n=17) in stable New York Heart Association Class II to III heart failure (HF) patients diagnosed with depression. METHODS: Depressive symptom severity [Hamilton Rating Scale for Depression (HAM-D)], physical function [6-min walk test (6MWT)], and health-related quality of life (HRQOL) (Minnesota Living with Heart Failure Questionnaire) were evaluated at baseline (T1), after the 12-week intervention/control (T2), and following a 3-month telephone follow-up (T3). A repeated measures analysis of variance was used to determine group differences. Depression severity was dichotomized as minor (HAM-D, 11-14) and moderate-to-major depression (HAM-D, >/=15), and group intervention and control responses were also evaluated on that basis. RESULTS: The greatest reduction in HAM-D scores over time occurred in the EX/CBT group (-10.4) followed by CBT (-9.6), EX (-7.3), and UC (-6.2), but none were statistically significant. The combined group showed a significant increase in 6-min walk distance at 24 weeks (F=13.5, P<.001). Among all groups with moderate-to-major depression, only those in CBT/EX had sustained lower HAM-D scores at 12 and 24 weeks, 6MWT distances were significantly greater at 12 (P=.018) and 24 (P=.013) weeks, and the greatest improvement in HRQOL also occurred. CONCLUSIONS: Interventions designed to improve both physical and psychological symptoms may provide the best method for optimizing functioning and enhancing HRQOL in patients with HF.

Sequential multiple-assignment randomized trial design of neurobehavioral treatment for patients with metastatic malignant melanoma undergoing high-dose interferon-alpha therapy.

BACKGROUND: Interferon-alpha therapy, which is used to treat metastatic malignant melanoma, can cause patients to develop two distinct neurobehavioral symptom complexes: a mood syndrome and a neurovegetative syndrome. Interferon-alpha effects on serotonin metabolism appear to contribute to the mood and anxiety syndrome, while the neurovegetative syndrome appears to be related to interferon-alpha effects on dopamine. PURPOSE: Our goal is to propose a design for utilizing a sequential, multiple assignment, randomized trial design for patients with malignant melanoma to test the relative efficacy of drugs that target serotonin versus dopamine metabolism during 4 weeks of intravenous, then 8 weeks of subcutaneous, interferon-alpha therapy. METHODS: Patients will be offered participation in a double-blinded, randomized, controlled, 14-week trial involving two treatment phases. During the first month of intravenous interferon-alpha therapy, we will test the hypotheses that escitalopram will be more effective in reducing depressed mood, anxiety, and irritability, whereas methylphenidate will be more effective in diminishing interferon-alpha-induced neurovegetative symptoms, such as fatigue and psychomotor slowing. During the next 8 weeks of subcutaneous interferon therapy, participants whose symptoms do not improve significantly will be randomized to the alternate agent alone versus escitalopram and methylphenidate together. RESULTS: We present a prototype for a single-center, sequential, multiple assignment, randomized trial, which seeks to determine the efficacy of sequenced and targeted treatment for the two distinct symptom complexes suffered by patients treated with interferon-alpha. LIMITATIONS: Because we cannot completely control for external factors, a relevant question is whether or not 'short-term' neuropsychiatric interventions can increase the number of interferon-alpha doses tolerated and improve long-term survival. CONCLUSIONS: This sequential, multiple assignment, randomized trial proposes a framework for developing optimal treatment strategies; however, additional studies are needed to determine the best strategy for treating or preventing neurobehavioral symptoms induced by the immunotherapy interferon-alpha.

Stress, depression, and coronary artery disease: modeling comorbidity in female primates.

Depression and coronary heart disease (CHD) are leading contributors to disease burden in women. CHD and depression are comorbid; whether they have common etiology or depression causes CHD is unclear. The underlying pathology of CHD, coronary artery atherosclerosis (CAA), is present decades before CHD, and the temporal relationship between depression and CAA is unclear. The evidence of involvement of depression in early CAA in cynomolgus monkeys, an established model of CAA and depression, is summarized. Like people, monkeys may respond to the stress of low social status with depressive behavior accompanied by perturbations in hypothalamic-pituitary-adrenal (HPA), autonomic nervous system, lipid metabolism, ovarian, and neural serotonergic system function, all of which are associated with exacerbated CAA. The primate data are consistent with the hypothesis that depression may cause CAA, and also with the hypothesis that CAA and depression may be the result of social stress. More study is needed to discriminate between these two possibilities. The primate data paint a compelling picture of depression as a whole-body disease.

Effects of a cognitive stress challenge on myocardial perfusion and plasma cortisol in coronary heart disease patients with depression.

Although it is well established that coronary heart disease (CHD) patients with depression exhibit increased mortality compared with equally ill cardiac patients without depression, the mechanisms mediating this effect remain obscure. Depression is characterized by vulnerability to stress and heightened stress responsiveness, and stress can theoretically act through several biological pathways to contribute to excess mortality from CHD. Mechanisms connecting stress, depression and cardiovascular mortality have not been previously explored in detail. The purpose of this study was to assess the effects of stress and depression on myocardial perfusion and plasma cortisol concentrations in CHD patients. Patients with CHD with and without depression (n = 28) underwent single photon emission computed tomography imaging of myocardial perfusion at rest and during a stressful cognitive challenge. Severity of ischaemia was measured by summing perfusion defect scores across myocardial segments and subtracting out rest from stress scores. Plasma cortisol concentrations were measured at baseline and in response to the stressful challenge. There were no differences in stress-induced myocardial ischaemia or plasma cortisol response to stress between CHD patients with and without depression. Depressed CHD patients with a history of psychological trauma (n = 5) had an increase in stress-induced ischaemia scores [7; standard deviation (SD) = 5] compared with CHD patients with depression without a history of psychological trauma (2 SD = 2) and CHD patients without depression or psychological trauma (1; SD = 2) (F = 8.51; degree of freedom = 2,23; p = 0.007). Eighty per cent of CHD/depression trauma-exposed subjects had stress-induced ischaemia as opposed to 38 per cent of CHD/depression subjects without trauma exposure and 23 per cent of subjects with CHD without depression or trauma. Self-reported nervousness during the cognitive stressor was correlated with stress-induced ischaemia. These preliminary findings suggest that depression with a history of prior exposure to traumatic stress is associated with increased risk for stress-induced cardiovascular ischaemia.

Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

Platelet thromboxane A2 secretion in patients with major depression responsive to electroconvulsive therapy.

OBJECTIVE: To determine a) whether clinical response to electroconvulsive therapy (ECT) is associated with decreased platelet activation in patients with major depressive disorder (MDD) and b) if any medical/demographic characteristics predict response to ECT or changes in platelet activation. Increased platelet activation may underlie the increased risk of coronary artery disease (CAD) in patients with MDD. METHODS: Before their first and sixth ECT treatments, study patients (n = 44) completed the Beck Depression Inventory (BDI) to assess the severity of depressive symptoms. Activity of the platelet thromboxane (TBX) A(2) pathway was assessed by measuring the morning spot urinary concentrations of 11-dehydroxy-thromboxane B(2) (11-D-TBX B(2)), a major metabolite of platelet-derived TBX A(2). RESULTS: Multivariate logistic regression analyses revealed that improvement on the BDI was significantly more likely in patients without a history of hypertension (p = .02) and in patients who were prescribed a greater number of "platelet-altering" medications (p = .03). During a course of ECT, a decrease in urinary 11-D-TBX B(2) was significantly more likely to occur in ECT nonresponders (p = .01) and younger patients (p = .02). CONCLUSIONS: Clinical response to ECT coadministered may not be associated with decreases in platelet-derived TBX. Future studies will confirm which somatic "antidepression" treatments offer optimal thrombovascular benefits for depressed patients with multiple risk factors for, or clinically evident, cerebral disease or CAD.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma.

BACKGROUND: The dexamethasone/corticotropin-releasing factor (CRF) test is considered to be the most sensitive measure of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and has been demonstrated to be altered in patients with major depression (MDD). Although childhood trauma is a demonstrated risk factor for MDD and patients with a history of childhood abuse and MDD demonstrate HPA axis hyperactivity, the dexamethasone/CRF test remains unstudied in this population. We determined the impact of childhood trauma on dexamethasone/CRF test results in patients with MDD. METHODS: Forty-nine healthy men, ages 18-60 years, without mania or psychosis, active substance abuse, or eating disorder and medication-free were recruited into four study groups, including: 1) normal subjects with no childhood abuse history or psychiatric disorder (n = 14); 2) men with childhood abuse histories without current MDD (n = 14); 3) men with childhood abuse histories with current MDD (n = 15); and 4) men with current MDD and no childhood abuse history (n = 6). Plasma adrenocorticotropin (ACTH) and cortisol concentrations were measured in response to dexamethasone/CRF administration. RESULTS: Men with childhood trauma histories exhibited increases in ACTH and cortisol responses to dexamethasone/CRF compared with non-abused men. In particular, abused men with current MDD showed increased responsiveness compared with control subjects and depressed men without childhood abuse experience. Increased response was associated with the severity, duration, and earlier onset of the abuse. The effects were not explained by concurrent posttraumatic stress disorder. CONCLUSIONS: Childhood trauma increases HPA axis activity as measured with the dexamethasone/CRF test in adult men with MDD, potentially reflecting environmental risk for developing depression.

The diagnosis of major depression in patients with cancer: a comparative approach.

Depressive symptoms not only impair quality of life in cancer patients but constitute an independent risk factor for increased mortality. In order to accurately and efficiently identify depression in cancer patients, the authors developed a biostatistical strategy to identify items of the 21-item, observer-rated Hamilton Rating Scale for Depression (Ham-D) that would optimize the diagnosis of depression among cancer patients. Exhibiting a relatively high sensitivity and specificity, our most optimal diagnostic tool contained six Ham-D items (late insomnia, agitation, psychic anxiety, diurnal mood variation, depressed mood, and genital symptoms). This study may serve as a prototype to generate valid instruments accurate for the diagnosis of major depression in other populations of cancer patients.

Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress.

OBJECTIVE: The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress. METHOD: Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test. RESULTS: Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS: Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.

A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. METHOD: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. RESULTS: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. CONCLUSION: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.