Predictors of fatigue in cancer patients before and after chemotherapy.

Fatigue is a debilitating and common condition in cancer patients. This study examined pretreatment predictors of fatigue before chemotherapy and also assessed whether these could prospectively predict fatigue posttreatment. A total of 100 patients completed questionnaires assessing psychological factors, physical activity and sleep. A subsample of 26 participants wore actigraphs to objectively assess sleep/wake and activity/rest. Fatigue was measured pretreatment and posttreatment and at follow-up several months later. Greater pretreatment pain, depression, stress and sleep disruption significantly predicted greater fatigue before chemotherapy, explaining 55 percent of the variance. Pretreatment fatigue significantly predicted post-treatment fatigue. No other significant prospective predictors of posttreatment fatigue emerged.

C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy.

Heightened inflammatory activity has been proposed as a mechanism for the development of cancer-related fatigue (CRF), a common and distressing condition that can negatively affect quality of life. Inflammation is also implicated in the pathogenesis of depression, and depression is a strong predictor of CRF. Thus, the role of the pro-inflammatory cytokine network in CRF may be mediated by depression or both conditions may share similar underlying physiological processes. The current study investigated associations between fatigue, depression and inflammatory cytokine (IFN-γ, IL-6, TNF-α) and CRP concentrations, as well as kynurenine pathway (KP) activation, in 61 breast cancer patients prior to chemotherapy. Changes in inflammatory markers and KP activation over time were also explored, and associations with changes in fatigue and depression were examined. Higher levels of CRP were significantly correlated with fatigue and depression before chemotherapy; nevertheless, CRP predicted fatigue independently of depression. Although greater kynurenine concentrations were associated with increased immune activation, there was no evidence that the KP played a role in fatigue or depression. Furthermore, no relationships emerged between either fatigue or depression and IFN-γ, IL-6, or TNF-α before chemotherapy. Nevertheless, kynurenine levels pre- and post-treatment significantly predicted changes in depression, suggesting that heightened KP activation may contribute to depressive symptoms in patients treated for cancer. In addition, IL-6 significantly covaried with fatigue. These preliminary findings provide some support for the idea that low-grade inflammation contributes to the development of CRF, independently of depression; however, there was no evidence that this is mediated by KP activity.

The widely-used anti-viral drug interferon-alpha induces depressive- and anxiogenic-like effects in healthy rats.

Interferon-alpha (IFN-alpha) is a naturally occurring human cytokine that is a key therapy in the treatment of several viral diseases and cancers. However, treatment can produce significant neuropsychiatric and neurotoxic adverse events, including depression and anxiety. Here we investigated the effects of a clinically-comparable treatment regime of IFN-alpha on depressive- and anxiety-like behaviour in rats; and also examined frontal-cortical and hippocampal BDNF levels. Rats treated with IFN-alpha for four weeks showed significant increases in depressive- and anxiety-like behaviour. Further experimental investigation revealed that hedonic dysregulation (stronger preference for a sweet solution) did not emerge until the second week of treatment, and became more persistent as treatment progressed. No significant IFN-alpha-induced changes in BDNF levels were found. These results indicate that the affective deficits seen in patients may be modelled in healthy animals. This model may represent a novel tool to investigate the extent of and mechanisms underlying the IFN-alpha psychiatric syndrome.

Reliability and validity of the Hospital Anxiety and Depression Scale and the Beck Depression Inventory (Full and FastScreen scales) in detecting depression in persons with hepatitis C.

BACKGROUND: We examined the performance the Beck Depression Inventory (BDI) and its short form (BDI-FS) and the Hospital Anxiety and Depression Scale depression (HADS-D) and anxiety (HADS-A) subscales in detecting depression in a group of patients with hepatitis C. METHODS: SCID-CV was used to establish DSM-IV diagnosis. Sensitivity, specificity, positive and negative predictive values were used to assess test performance and Cohen's Kappa to measure agreement with DSM diagnosis. RESULTS: Twenty-five of 88 participants had a DSM-IV depressive diagnosis. There was considerable non-overlap between 'caseness' on the BDI and HADS (Kappa=0.44). The HADS depression subscale had poor sensitivity (52%) and poor agreement with clinical diagnosis (Kappa=0.35). The full BDI had a sensitivity of 88% and a Kappa of 0.54 against a sensitivity of 84% and Kappa of 0.42 for the short form. The HADS anxiety subscale predicted depression as well as the depression subscale (sensitivity 88%, Kappa 0.47). CONCLUSIONS: Neither the BDI nor the HADS agrees well with the clinical diagnosis of depressive disorder, nor do they agree well with one another. The anxiety subscale of the HADS appears to measure depression at least as well as the depressive subscale.

Depression and anxiety in patients with hepatitis C: prevalence, detection rates and risk factors.

OBJECTIVE: We examined a group of patients awaiting interferon treatment for hepatitis C to estimate the prevalence and detection rates of and risk factors for mood disorders. METHODS: The Structured Clinical Interview for DSM-IV Axis I Disorders: Clinician Version was used to detect psychiatric disorder. Self-completion instruments were used to rate symptom severity, subjective cognitive function, work and social adjustment, stigma, acceptance of illness and treatment satisfaction. RESULTS: The 90 participants included 23 women (26%); 33 (37%) had contracted hepatitis C iatrogenically, 42 (47%) through injecting drug use and the remainder (17%) were of unknown origin. There was a 28% 1-month prevalence of depressive disorders, 72% of whom were previously undiagnosed, and a 24% prevalence of anxiety disorders, 86% previously undiagnosed. Current methadone maintenance was strongly associated with risk of depression (odds ratio, 5.0; 95% CI, 1.08-23.0). After adjustment for age and sex, depression was associated with poorer work and social adjustment, lower acceptance of illness, higher illness stigma, poorer reported thinking and concentration, and higher levels of subjective physical symptoms (all P < .05). Anxiety disorders were uncorrelated with any risk factor. CONCLUSIONS: Depression and anxiety have high prevalences in hepatitis C, and are largely undetected and treated. Depression, but not anxiety, is associated with adverse experiences of illness.