Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in the Diabetes Prevention Program.

OBJECTIVE: Antidepressant medication use (ADM) has been shown to predict diabetes. This article assessed the role of inflammatory markers in this relationship within the Diabetes Prevention Program (DPP). METHODS: DPP participants randomized to metformin (MET), life-style intervention (ILS), or placebo (PLB) were assessed for depression (Beck Depression Inventory [BDI]) annually, ADM use semiannually, serum inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6]) at baseline and year 1, and diagnosis of type 2 diabetes mellitus (T2DM) semiannually (for 3.2 years). RESULTS: At baseline (N = 3187), M (SD) body mass index was 34 (6) kg/m and the median (interquartile range) BDI score was 3 (1-7). One hundred eighty-one (5.7%) reported ADM use and 328 (10%) had BDI scores of 11 or higher. CRP and IL-6 levels did not differ by treatment group. Baseline ADM, but not BDI score, was associated with higher levels of baseline CRP adjusted for demographic, anthropometric variables, and other medications (20% higher, p = .01). Year 1 CRP decreased for non-ADM users in the MET (-13.2%) and ILS (-34%) groups and ADM users in the ILS group (-29%). No associations were found with IL-6. CRP and continuous use of ADM predicted incident T2DM in the PLB group. In the ILS group, continuous and intermittent ADM, but not CRP, predicted T2DM. In the MET group, CRP predicted incident T2DM. CRP did not mediate the risk of T2DM with ADM use in any group. CONCLUSIONS: ADM was significantly associated with elevated CRP and incident T2DM. In the PLB group, ADM and CRP independently predicted onset of T2DM; however, CRP did not significantly mediate the effect of ADM.

Program ACTIVE: Cognitive Behavioral Therapy to Treat Depression in Adults With Type 2 Diabetes in Rural Appalachia.

High rates of type 2 diabetes (T2DM) and depression exist in rural Appalachia with limited access to psychotherapeutic treatment. No manualized cognitive behavioral therapy (CBT) treatment materials exist that are culturally tailored for individuals in this region with T2DM. We describe the development of the Program ACTIVE CBT intervention for use with adults with T2DM and depression by mental health providers in rural Appalachia. Qualitative and quantitative methods were used to test the feasibility and acceptability of Program ACTIVE. Intervention materials were rated at the 6th-7th grade reading level. Key informant interviews evaluated materials as culturally sensitive and accessible. Participants indicated high levels of satisfaction with therapy (94%), support from their therapist (86%), and usefulness of therapy and depression improvement (80.3%). Program ACTIVE was found to be a feasible and acceptable culturally tailored manualized CBT treatment for adults with T2DM and depression living in rural Appalachia. Implementation of these materials on a regional scale needs to be assessed.

Depressive symptoms and type 2 diabetes mellitus in rural appalachia: an 18-month follow-up study.

OBJECTIVE: Despite high rates of diabetes and depression in rural areas, limited data exists to document patterns and predictors of depressive symptoms in rural patients with type 2 diabetes (T2DM). The purpose of this study was to assess the rates and predictors of co-morbid depressive symptoms over an 18-month period in a cohort of rural Appalachian adults with T2DM. METHODS: N = 100 adult T2DM patients were recruited from family medicine and endocrinology practices located in the rural Appalachian counties of southeastern Ohio and West Virginia. Data were collected using a longitudinal observational survey design. RESULTS: The sample consisted of predominantly White (93%) females (62%) who were married (71%), completed high school or less (48%), and had a mean age of 60 years (SD 11). Mean BDI score was 14.0 (SD 12) with 27% scoring in the moderate/severe range for depressive symptoms. A majority of patients (77%) reported depressive symptoms, at both time points, with 88% of these reporting consistent depressive symptoms in the year prior to study follow-up. Patients with depressive symptoms at Time 1 and Time 2 did not differ from other groups in the number of treatment strategies or medications used. Predictors of depressive symptoms in this group were increased diabetes treatment complexity (OR = 2.3), lack of home ownership (OR = 11.4), and decreased satisfaction with antidepressant medications (OR = 2.0; χ(2) = 28.9, p < .0001). CONCLUSIONS: Rural T2DM patients reported high rates of repeated depressive symptoms without corresponding rates of depression treatment. These patients may benefit from close monitoring and ongoing adjustment of their treatment for depression and diabetes by primary care providers.

Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings.

Type 2 diabetes (T2D) patients are twice as likely to experience depressive symptoms than people without T2D, resulting in greater economic burden, worse clinical outcomes, and reduced quality of life. Several overlapping pathophysiological processes including hypothalamic-pituitary-adrenal axis hyperactivity, sympathetic nervous system activation, and elevated pro-inflammatory biomarkers are recognized as playing a role between T2D and depressive symptoms. However, other neurobiological mechanisms that may help to further link these comorbidities have not been extensively reviewed. Reduced neuroplasticity in brain regions sensitive to stress (e.g., hippocampus) may be associated with T2D and depressive symptoms. T2D patients demonstrate reduced neuroplasticity including morphological/volumetric abnormalities and subsequent neurocognitive deficits, similar to those reported by patients with depressive symptoms. This review aims to summarize recent studies on morphological/volumetric abnormalities in T2D and correlated neurocognitive deficits. Modifying factors that contribute to reduced neuroplasticity will also be discussed. Integrating reduced neuroplasticity with other biological correlates of T2D and depressive symptoms could enhance future therapeutic interventions and further disentangle the bidirectional associations between these comorbidities.

Emotional reactions to pain predict psychological distress in adult patients with Sickle Cell Disease (SCD).

Differentiating somatic from emotional influences on the experience of chronic pain has been of interest to clinicians and researchers for many years. Although prior research has not well specified these pathways at the anatomical level, some evidence, both theoretical and empirical, suggest that emotional reactions influence the experience of disease and non-disease-related pains. Other studies suggest that treatments directed at negative emotional responses reduce suffering associated with pain. The current study was conducted to explore the influence of emotional reactions to pain as a predictor of psychological distress in a sample of adult Blacks with Sickle Cell Disease (SCD). Using cross-sectional survey data, we evaluated whether negative emotional reactions to the experience of pain were predictive of psychological distress after controlling for the somatic dimension of pain and age in n = 67 Black patients with Sickle Cell Disease (SCD). Results showed that greater negative emotion associated with pain predicted Somatization (p < .01), Anxiety (p < .05), Phobic Anxiety (p < .05), and Psychoticism (p < .05). Increased negative emotion associated with pain was also predictive of the General Symptoms Index (p < .05) and the Positive Symptoms Total from the SCL-90-R (p < .01). We believe the current study demonstrates that negative emotional reactions to the experience of pain in adults with SCD are predictive of psychological distress above and beyond the influences of age and the direct nociceptive experience. We also believe these data to be valuable in conceptualizing the allocation of treatment resources toward a proactive approach with early identification of patients who are responding poorly for the purpose of potentially reducing later psychopathology. A deeper understanding of the ways that subpopulations cope with chronic disease-related pain may produce models that can be ultimately generalized to the consumers of the majority of healthcare resources.

State of the science: depression and type 2 diabetes.

Depression is a significant comorbid condition in diabetes. Individuals with type 2 diabetes (T2DM) are 2 times more likely to experience depression or elevated depressive symptoms compared to those without T2DM. The aims of this state of the science review were to summarize the putative links between diabetes and depression and review empirically supported treatments of depression in diabetes. Findings suggest that a bidirectional association between depression and T2DM exists and that several biological and psychosocial mediators underlie these conditions. Available data indicate that conventional treatments (antidepressant medication, cognitive behavioral therapy, and collaborative care) reduce depression and symptoms of depression; however more controlled studies and development of novel therapies are needed. Glycemic outcomes have most frequently been examined, but findings have been mixed. Self-care and adherence outcomes have been less well studied. Emerging evidence suggests that these outcomes may be important targets for future depression research in T2DM.

Cognitive and Affective Perceptions of Vulnerability as Predictors of Exercise Intentions among People with Type 2 Diabetes.

Most conventional measures of risk perception such as perceived likelihood address largely deliberative or cognitive perceptions of vulnerability. Nevertheless, affective perceptions of vulnerability such as worry may have different antecedents and consequences than do these conventional measures, serve as stronger predictors of behavior, and qualify effects of conventional deliberative risk perceptions on behavior. In this study, we assessed how worry - the most common measure of affective perceptions of vulnerability compared with three conventional measures of risk (absolute risk, comparative risk, and conditional risk) in predicting behavioral intentions. Participants were 83 adults with type 2 diabetes who assessed their risk of heart disease and reported their intentions to increase physical activity (which reduces heart disease risk). As predicted, worry was the only significant predictor of exercise intentions such that higher worry was associated with higher intentions. Importantly, this relationship was stronger among individuals who perceived their absolute risk to be relatively higher and those who perceived their comparative risk to be relatively lower, demonstrating that cognitive and affective perceptions interact. These findings highlight the importance of not conflating affective and cognitive perceptions of vulnerability when assessing perceived risk, and suggest the need for more research on how to best conceptualize perceived risk in different samples and settings.

Diabetes, depressive symptoms, and inflammation in older adults: results from the Health, Aging, and Body Composition Study.

OBJECTIVE: Up-regulated levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) are common to both type 2 diabetes mellitus (T2DM) and elevated depressive symptoms, yet little attention has been given to the biological mechanisms associated with these co-morbidities. This study examined the association between inflammation and both T2DM and elevated depressive symptoms. METHODS: Baseline data were analyzed from 3009 adults, aged 70-79, participating in the Health, Aging, and Body Composition Study. Diabetes was assessed per self-report, medication use, fasting glucose and/or glucose tolerance tests. Elevated depressive symptoms were categorized using the Center for Epidemiologic Studies Depression scale (cut-score≥20). Log-transformed IL-6, TNF-α, and CRP were analyzed using ANCOVA. RESULTS: Participants with T2DM and elevated depressive symptoms (T2DM+DEP n=14) demonstrated significantly (p<.05) higher IL-6 compared to (T2DM Only n=628), (DEP Only n=49), and (No T2DM or DEP n=2067) groups following covariate adjustment. Similarly, participants with T2DM+DEP (n=14) had significantly (p<.05) higher CRP, after covariate adjustment, compared to DEP Only (n=50) and No T2DM or DEP groups (n=2153). No association was observed for TNF-α. CONCLUSIONS: These findings provide evidence that inflammation is associated with T2DM and elevated depressive symptoms. Participants with T2DM+DEP demonstrated the highest IL-6 levels compared to all other groups. Greater CRP levels were also observed in T2DM, but not elevated depressive symptoms, which may suggest that differential associations between T2DM and depressive symptoms exist for various inflammatory markers. Further investigation into these associations could aid in understanding the biological pathways underlying both T2DM and depressive symptoms.

Association of anxiety and depression with pulmonary-specific symptoms in chronic obstructive pulmonary disease.

OBJECTIVES: To examine the association of anxiety and depression with pulmonary-specific symptoms of Chronic Obstructive Pulmonary Disease (COPD), and to determine the extent to which disease severity and functional capacity modify this association. METHOD: Patients (N = 162) enrolled in the INSPIRE-II study, an ongoing randomized, clinical trial of COPD patients and their caregivers who received either telephone-based coping skills training or education and symptom monitoring. Patients completed a psychosocial test battery including: Brief Fatigue Inventory, St. George's Respiratory Questionnaire, UCSD Shortness of Breath Questionnaire, State-Trait Anxiety Inventory, and Beck Depression Inventory. Measures of disease severity and functional capacity (i.e., FEV1 and six-minute walk test) were also obtained. RESULTS: After covariate adjustment, higher anxiety and depression levels were associated with greater fatigue levels (ps < .001, deltaR2 = 0.16 and 0.29, respectively), shortness of breath (ps < .001, deltaR2 = 0.12 and 0.10), and frequency of COPD symptoms (ps < .001, deltaR2 = 0.11 and 0.13). In addition, functional capacity was a moderator of anxiety and pulmonary-specific COPD symptoms. The association between anxiety and shortness of breath (p = 0.009) and frequency of COPD symptoms (p = 0.02) was greater among patients with lower functional capacity. CONCLUSIONS: Anxiety and depression were associated with higher levels of fatigue, shortness of breath, and frequency of COPD symptoms. It is important for clinicians to be aware of the presence of anxiety and depression in COPD patients, which appears to correlate with pulmonary-specific COPD symptoms, especially in patients with lower functional capacity. Prospective design studies are needed to elucidate the causal relationships between anxiety and depression and pulmonary-specific symptoms in COPD patients.

Can lifestyle interventions do more than reduce diabetes risk? Treating depression in adults with type 2 diabetes with exercise and cognitive behavioral therapy.

The epidemic of metabolic syndrome, prediabetes, and type 2 diabetes is global in scope and comprehensive in its impact on individuals, health care systems, and societies. One in four patients with diabetes will experience depression in their lifetime. Comorbid depression is associated with poorer outcomes, greater functional disability, and early mortality. Prior studies have demonstrated beneficial effects of exercise as an efficacious form of treatment for depression in the general population. Few studies have evaluated this strategy in patients with prediabetes or type 2 diabetes. Program ACTIVE (Appalachians Coming Together to Increase Vital Exercise) was designed to treat depression among adults with type 2 diabetes by pairing aerobic activity with individual cognitive behavioral therapy. This combination treatment approach has been shown to be feasible to implement in a rural environment and promising in terms of depression, diabetes, and cardiovascular outcomes. Data from this study suggest that exercise can be used to achieve multiple benefits for adults with type 2 diabetes. Future work to compare this approach to singular treatment strategies for adults at risk for type 2 diabetes is needed.

A Model of Community-Based Behavioral Intervention for Depression in Diabetes: Program ACTIVE.

Depression affects one in four people with diabetes and significantly affects diabetes health. Earlier studies of the treatment of depression have documented that cognitive behavioral therapy (CBT) and exercise have each been found to be effective in treating depression in people with and without diabetes in the context of medical settings. Individuals in rural areas lack regular access to medical centers and require treatment options that may be adapted for local communities. To date, no studies have combined CBT and exercise for people with diabetes. This article presents a translational behavioral depression intervention study designed for individuals with type 2 diabetes in a rural Appalachian region as a model of an interdisciplinary approach to the treatment of depression in diabetes.

Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).

PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.

Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking.

RATIONALE: Compared to men, the smoking behavior of women may be less responsive to nicotine and more responsive to nonpharmacological factors, perhaps including verbal information (e.g., dose instructions). OBJECTIVE: This study compared the influence of the presence vs absence of dose instructions on the subjective and reinforcing effects of nicotine via cigarette smoking in men and women. METHODS: Subjects (n=120) abstained overnight from smoking and were randomly assigned to one of four groups. Half of the subjects received nicotine cigarettes (Quest 1, yield of 0.6 mg), and the other half received denicotinized cigarettes ("denic"; Quest 3, yield of 0.05 mg). Furthermore, half of each subsample was accurately instructed they were receiving a "normal nicotine" or a "no nicotine" cigarette, while the other half received no instructions. Subjects completed baseline measures of craving and mood (positive and negative affect), took two puffs from the cigarette after receiving dose instructions or no instructions, and then rated the cigarette's "reward" value (liking, satisfying) and other characteristics. They also repeated the craving and mood measures. Subjects then smoked more of that same brand ad libitum over the next 30 min to measure reinforcement (puff number and latency to first puff). RESULTS: Overall, nicotine increased reward, other cigarette ratings, and positive affect, but did not affect craving or smoking behavior. However, results varied by sex. Dose instructions enhanced the effects of nicotine on smoking reward and reinforcement in women, while instructions tended to dampen or even reverse these effects of nicotine in men (i.e., interaction of sex x nicotine x instructions). CONCLUSIONS: In women but not in men, the influence of nicotine on smoking reward and reinforcement is enhanced by accurate verbal information about the cigarette's nicotine dose. These results are consistent with the notion that the smoking behavior of women, relative to men, may be more responsive to nonpharmacological factors.

The subjective and reinforcing effects of visual and olfactory stimuli in alcohol drinking.

Nonpharmacological cues associated with drug intake may influence subjective and reinforcing effects of those drugs. Social drinkers (N = 80) participated in 2 sessions in which they rated and then consumed ad lib their preferred beer (with participants blind to brand). Visual and olfactory stimuli were obscured during 1 session (blocked) and not obscured during the other (unblocked). Dependent measures included ratings of "liking", "want another", and "desire to drink"; subjective mood; and ad lib beer consumption (reinforcement). Most ratings and ad lib consumption were lower during the blocked versus the unblocked condition. There were no interactions of blockade condition with sex and no effect of blockade on mood. These findings show that nonpharmacological stimuli associated with alcohol consumption influence alcohol's subjective and reinforcing effects.