Interferon therapy and its association with depressive disorders - A review.

Interferons (IFNs) are important in controlling the innate immune response to viral infections. Besides that, studies have found that IFNs also have antimicrobial, antiproliferative/antitumor and immunomodulatory effects. IFNs are divided into Type I, II and III. Type I IFNs, in particular IFN-α, is an approved treatment for hepatitis C. However, patients developed neuropsychological disorders during treatment. IFN-α induces proinflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), oxidative and nitrative stress that intensifies the body's inflammatory response in the treatment of chronic inflammatory disease. The severity of the immune response is related to behavioral changes in both animal models and humans. Reactive oxygen species (ROS) is important for synaptic plasticity and long-term potentiation (LTP) in the hippocampus. However, excess ROS will generate highly reactive free radicals which may lead to neuronal damage and neurodegeneration. The limbic system regulates memory and emotional response, damage of neurons in this region is correlated with mood disorders. Due to the drawbacks of the treatment, often patients will not complete the treatment sessions, and this affects their recovery process. However, with proper management, this could be avoided. This review briefly describes the different types of IFNs and its pharmacological and clinical usages and a focus on IFN-α and its implications on depression.

Akkermansia muciniphila ameliorates depressive disorders in a murine alcohol-LPS (mALPS) model.

Depression is the most common mental disorder in the world. Recently, an increasing number of studies have reported alcohol-related depression. However, there is no simple, efficient, and time-saving alcohol-related depression animal model yet. Based on the fact that people with alcohol addiction often have impaired gastrointestinal (GI) tract health like dysbiosis, which serves as a primary factor to augment lipopolysaccharides (LPS), we first developed a murine alcohol-LPS model (mALPS), with oral gavage of LPS in acute alcohol treated mice, and successfully observed depression-like symptoms. We found that acute alcohol treatment damaged the intestinal barrier and caused dysbiosis, which further increased the translocation of LPS and neuroinflammatory responses (TNF-α and IL-1ß) and led to abnormal expression of the depression-related genes, i.e. BDND and IDO, reduced the levels of 5-HT and caused depressive behaviors in mice. Probiotic intervention could improve depressive symptoms without notable adverse effects. Akkermansia muciniphila (AKK), one of the next-generation probiotics, has been widely used for the restoration of the intestinal barrier and reduction of inflammation. Here, we found that AKK significantly ameliorated alcohol-related depressive behaviors in a mALPS model, through enhancing the intestinal barrier and maintaining the homeostasis of the gut microbiota. Furthermore, AKK reduced serum LPS, ameliorated neuroinflammation (TNF-α and IL-1ß), normalized the expression of depression-related genes and increased the 5-HT levels in the hippocampus. Our study suggests that AKK supplements will be a promising therapeutic regime for alcohol-associated depression in the future.

Antidepressant medication use and prostate cancer recurrence in men with depressive disorders.

PURPOSE: Whether treating prostate cancer survivors with a depressive disorder with antidepressants can affect their cancer outcomes is unknown. We evaluated the association between antidepressant use and prostate cancer recurrence, in survivors with comorbid depressive disorders. METHODS: We conducted a longitudinal cohort study of 10,017 men with prostate cancer (stages I-II) diagnosed who also had a comorbid depressive disorder followed a maximum of 22 years, and examined rates of biochemical recurrence by antidepressant medication use. We conducted multivariable Cox models based on time-dependent antidepressant drug use status, and examined the risk of biochemical recurrence by cumulative duration of antidepressant use. RESULTS: Of these 10,017 survivors, 1842 (18%) experienced biochemical recurrence over 69,500 person-years of follow-up. The prostate cancer biochemical recurrence rate was greater with antidepressant non-use (31.3/1000 person-years) compared to antidepressant use (23.5/1000 person-years). In Cox proportional hazards multivariable adjusted models, non-use of antidepressants was associated with a 34% increased risk of biochemical recurrence compared to antidepressant use (HR = 1.34, 95% CI: 1.24-1.44). Longer use of antidepressants was associated with a lower biochemical recurrence risk (P trend test < 0.001). CONCLUSION: Untreated depressive disorders in prostate cancer patients may be associated with an increased risk of biochemical recurrence.

Xanthohumol Attenuates Lipopolysaccharide-Induced Depressive Like Behavior in Mice: Involvement of NF-κB/Nrf2 Signaling Pathways.

Depression is the most common psychiatric disorder associated with brain and immune system abnormalities. In recent years, xanthohumol (Xn) a bioactive prenylated flavonoid has received ample attention for its polypharmacological effects, therefore, here we aimed to explore the protective effects of Xn against the LPS-induced depressive-like symptoms mediated by inflammation and oxidative stress. We tested the effect of Xn against LPS-induced behavioural changes in mice by means of forced swimming test (FST), tail suspention test (TST), sucrose preference test (SPT) and open field test (OPT). Examined the neuroinflammation and oxido-nitrosative stress (O&NS) markers and analyze Nrf2 and NF-κB signalling pathways in the hippocampus. Our results indicated that peripheral repeated administration of lipopolysaccharides (LPS) (1 mg/kg, intra peritoneally) induced depressive-like behavior, neuroinflammation and O&NS in mice. Pretreatment with Xn (10 and 20 mg/kg, intra gastrically) reverse the behavioural impairments prophylactically as obvious in the FST and TST without effecting locomotion, however only 20 mg dose improve anhedonic behavior as observed in SPT. Similarly, Xn pretreatment in dose-dependent manner prevented the LPS induced neuro-inflammation and O&NS. Immunofluorescence analysis showed that Xn reduced activated gliosis via attenuation of Iba-1 and GFAP in hippocampus. In addition, Xn considerably reduced the expression of phospho-NF-κB and cleaved caspase-3 while enhanced Nrf2 and HO-1 expression in the hippocampus. To the best of our knowledge, this is the first study to examine the underlying beneficial prophylactic effects of the Xn in neuroinflammation and O&NS mediating depressive-like behaviors.

Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression. Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center. Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25. Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores <60. There was no association between male sex and BIS-11 ≥60 and male sex did not increase the odds of increased scores (OR = 0.66, CI95% 0.25-1.76, p = 0.41). No significant difference was found for macroadenoma, prolactin levels, testosterone levels, hypogonadism, testosterone replacement in men, and increased impulsivity or depression scores. Conclusion: Use of PHQ-9 and BIS-11 is practical for routine screening of depression and ICD during outpatient pituitary clinic visits for patients with pituitary disease both naïve to treatment and during DA therapy. We recommend close follow-up after initiation of DA therapy for younger patients, regardless of dose.

Ginsenoside Rk1 alleviates LPS-induced depression-like behavior in mice by promoting BDNF and suppressing the neuroinflammatory response.

Ginsenoside Rk1, a saponin component produced by heat-processed ginseng, possesses anti-inflammatory and antitumor activities. The aim of our study was to explore the effects of Rk1 on Lipopolysaccharide (LPS)-induced depression-like behavior in mice and to observe its effects on oxidative stress, the inflammatory response and brain-derived neurotrophic factor (BDNF) - tropomyosin-related kinase B (TrkB) signaling. After mice were pretreated with Rk1 (5, 10, and 20 mg/kg), the immobility time in both the forced swimming test (FST) and the tail suspension test (TST) was reduced, suggesting that Rk1 effectively improved depression-like symptoms. Rk1 (10 and 20 mg/kg) and Fluoxetine (Flu, 20 mg/kg) increased the activity of the antioxidant enzyme SOD in the brain and protected against lipid peroxidation. Different concentrations of Rk1 (10 and 20 mg/kg) and Flu significantly decreased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 in serum, while Rk1 (5, 10, and 20 mg/kg) and Flu reduced the concentrations of IL-6 in a dose-dependent manner. Western blot analysis showed that the administration of Rk1 (20 mg/kg) and Flu significantly downregulated the level of Sirt1 and that Rk1 (5, 10, and 20 mg/kg) and Flu inhibited the p-NF-κb/NF-κb and p-IκB-α/IκB-α ratios, which indicated that the neuroprotective effect of Rk1 may be related to the suppression of inflammation. In addition 5, 10 and 20 mg/kg Rk1 significantly attenuated the LPS-induced decreases in BDNF and TrkB. These results indicated that Rk1 acts as an antidepressant through its antioxidant activity, the inhibition of neuroinflammation, and the positive regulation of the BDNF-TrkB pathway. This study may help develop active ginsenoside-based compounds for neurodegenerative diseases.

Transient effects of chemotherapy for testicular cancer on mouse behaviour.

The treatment of testicular cancer includes unilateral orchiectomy and chemotherapy and is curative for most patients. However, observational studies revealed an association with depression, anxiety and cognitive impairment. It is unclear whether these side effects are caused by chemotherapy, hemicastration or the disease itself. The aim of our study was to analyse the behavioural effects of hemicastration and chemotherapy in adult male mice. The animals were randomly divided into four groups - control, chemotherapy, hemicastration and hemicastration with chemotherapy. After chemotherapy that included three cycles of bleomycin, etoposide, cisplatin mice underwent a battery of behavioural tests. To assess the long-term effects animals were tested also 3 months after the end of treatment. Chemotherapy led to lower locomotor- and exploratory activity, higher anxiety-like behaviour and worse spatial memory immediately after treatment. These behavioural effects were not present three months later. Hemicastration had no effect on most of the observed outcomes. In conclusion, adverse behavioural effects induced by chemotherapy in mice are transient and disappear later in life. Further studies are needed to elucidate the mechanisms responsible for the observed effects.

The association of depressive symptoms, personality traits, and sociodemographic factors with health-related quality of life and quality of life in patients with advanced-stage lung cancer: an observational multi-center cohort study.

BACKGROUND: Identification of patient-related factors associated with Health-Related Quality of Life (HRQoL) and Quality of Life (QoL) at the start of treatment may identify patients who are prone to a decrease in HRQoL and/or QoL resulting from chemotherapy. Identification of these factors may offer opportunities to enhance patient care during treatment by adapting communication strategies and directing medical and psychological interventions. The aim was to examine the association of sociodemographic factors, personality traits, and depressive symptoms with HRQoL and QoL in patients with advanced-stage lung cancer at the start of chemotherapy. METHODS: Patients (n = 151) completed the State-Trait Anxiety Inventory (trait anxiety subscale), the Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI), the Center for Epidemiologic Studies Depression (CES-D), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Simple linear regression analyses were performed to select HRQoL and QoL associated factors (a P ≤ 0.10 was used to prevent non-identification of important factors) followed by multiple linear regression analyses (P ≤ 0.05). RESULTS: In the multiple regression analyses, CES-D score (ß = - 0.63 to - 0.53; P-values < 0.001) was most often associated with the WHOQOL-BREF domains and general facet, whereas CES-D score (ß = - 0.67 to - 0.40; P-values < 0.001) and Eastern Cooperative Oncology Group (ECOG) performance status (ß = - 0.30 to - 0.30; P-values < 0.001) were most often associated with the scales of the EORTC QLQ-C30. Personality traits were not related with HRQoL or QoL except for trait anxiety (Role functioning: ß = 0.30; P = 0.02, Environment: ß = - 0.39; P = 0.007) and conscientiousness (Physical health: ß = 0.20; P-value < 0.04). CONCLUSIONS: Higher scores on depressive symptoms and ECOG performance status were related to lower HRQoL and QoL in patients with advanced-stage non-small cell lung cancer. Supportive care interventions aimed at improvement of depressive symptoms and performance score may facilitate an increase of HRQoL and/or QoL during treatment.

Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy.

PURPOSE: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials. METHODS: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years. RESULTS: Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point. CONCLUSION: Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.

Genes Involved in the HPA Axis and the Symptom Cluster of Fatigue, Depressive Symptoms, and Anxiety in Women With Breast Cancer During 18 Months of Adjuvant Therapy.

This study aimed to (1) identify subgroups of women with breast cancer with the psychological symptom cluster (fatigue, depressive symptoms, and anxiety) during the first 18 months of adjuvant therapy and (2) explore associations between demographic and clinical characteristics and variations in genetic polymorphisms related to hypothalamic-pituitary-adrenal (HPA) axis function and predicted symptom trajectory subgroup membership. We obtained symptom data at 4 time points from baseline to 18 months of adjuvant therapy among 292 postmenopausal women with breast cancer. Genetic data were collected in a subgroup at baseline (N = 184). Group-based multitrajectory modeling was used to classify women into subgroups with similar psychological symptom cluster trajectories. Binary logistic regression was used to explore the associations between each genotypic and phenotypic predictor and predicted subgroup membership. Two distinct symptom subgroups (low and high) were identified based on the trajectories of the symptom cluster of fatigue, depressive symptoms, and anxiety over the first 18 months of adjuvant therapy. Women who were younger, less educated, and who received chemotherapy had greater likelihood of being in the high-symptom subgroup. Variation in genes regulating the HPA axis (FKBP5 rs9394309 [odds ratio (OR) = 3.98, p = .015], NR3C2 rs5525 [OR = 2.54, p = .036], and CRHR1 rs12944712 [OR = 3.99, p = .021]) was associated with membership in the high-symptom subgroup. These results may help to identify women with breast cancer who are at increased risk for psychological symptoms, facilitating the development of individualized and preemptive interventions to better manage these symptoms during adjuvant therapy.

Changes in chemotherapy-induced peripheral neuropathy, disturbance in activities of daily living, and depression following chemotherapy in patients with colorectal cancer: A prospective study.

PURPOSE: This study was conducted to identify the changes in oxaliplatin-induced peripheral neuropathy (OIPN), disturbance in activities of daily living (ADL), and depression and their interrelationships during the cancer care trajectory in colorectal cancer patients. METHODS: Eighty-six subjects participated in the study and completed the questionnaire at three time points: pre-chemotherapy, undergoing chemotherapy, and 3 months after the completion of chemotherapy. The assessment tools were Chemotherapy-Induced Peripheral Neuropathy 20 for OIPN, Chemotherapy-Induced Peripheral Neuropathy Assessment Tool to measure disturbances in ADL, and Hospital Anxiety and Depression Scale for depression. Data were analyzed using descriptive statistics and repeated-measures analysis of variance. RESULTS: While undergoing chemotherapy, 37.2% of the patients complained of OIPN and 32.6% exhibited OIPN at 3-month follow-up. Repeated-measures analysis of variance showed a significant increase in OIPN after chemotherapy, which remained high at the 3-month follow-up. The most frequent symptom of OIPN was "tingling feeling in the hand and foot," and the second was "impotence." Disturbance in ADL by OIPN and depression showed similar patterns as OIPN. The mean score for disturbance in ADL of OIPN was 48.58. The mean score was 7.36 for depression, with a prevalence of 23.5%. There were significant correlations among the three variables, suggesting that OIPN may be casual in the OIPN- disturbance in ADL-depression symptom interrelationships. CONCLUSION: These results suggest that chemotherapy is highly associated with OIPN, disturbance in ADL by OIPN, and depression in colorectal cancer patients. Nursing intervention is needed to relieve depression as well as OIPN in patients undergoing chemotherapy.

New-onset insomnia among cancer patients undergoing chemotherapy: prevalence, risk factors, and its correlation with other symptoms.

STUDY OBJECTIVES: Although insomnia is common among cancer patients, its prevalence remains variable, and its risk factors and correlation with other cancer-related symptoms are not fully explored in the literature. This study aims to determine the prevalence and severity of insomnia as well as risk factors and sleep-related symptom clusters in a sample of cancer patients. METHODS: A cross-sectional survey was conducted collecting data from 213 cancer patients undergoing chemotherapy (age = 53.1 ± 11.3 years, 60% female). Insomnia was measured using the Insomnia Severity Index, a sleep log, and Actigraph, while symptoms were assessed using the Memorial Symptom Assessment Scale and the Hospital Anxiety and Depression Scale. Quality of life was measured with the Functional Assessment of Cancer Therapy-General. RESULTS: Of the participants, 42.8% reported insomnia, with 31.9% of those with insomnia reporting severe insomnia. Insomnia occurrence and severity were not correlated with the participants' characteristics, cancer-related or treatment-related factors, only with the participants' anxiety/depression scores. Principal component analysis showed that insomnia, depression, and anxiety formed a symptom cluster (p < 0.001). There was no difference between sleep parameters measured by Actigraphy in insomnia and non-insomnia participants. CONCLUSION: This study demonstrated that the prevalence of insomnia was high and indicated a symptom cluster of insomnia, depression, and anxiety. Therefore, interventions to reduce this symptom cluster may benefit cancer patients who are trying to manage these symptoms.

Investigating Relationship between Pre- and Post- Chemotherapy Cognitive Performance with Levels of Depression and Anxiety in Breast Cancer Patients: A Cross-Sectional Study.

INTRODUCTION: Evidence suggests that cancer and chemotherapy-related cognitive impairments are an important clinical issue that can have a negative impact on the quality of life (QOL) of many cancer patients during and after treatment. The aim of the current study was to investigate the relationship between cognitive performance before and after chemotherapy with levels of depression and anxiety in patients with breast cancer. MATERIALS AND METHODS: This cross-sectional descriptive-analytical study was performed on 100 women with breast cancer in south of Iran. Patients included in the study were evaluated for cognitive performance before chemotherapy and 1, 3, and 6 months after chemotherapy. Patients' cognitive performance was assessed by Mini-Mental State Examination (MMSE). Patients were also assessed for their level of anxiety and depression using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Descriptive tests (percentage, frequency and mean) and ANOVA test used for statistical analysis. RESULTS: Results of ANOVA test showed a significant difference between the cognitive performance of patients with breast cancer at 1, 3, and 6 months after chemotherapy compared to pre- chemotherapy phase. The above test also revealed a significant relationship between cognitive performance of patients and anxiety and depression. CONCLUSION: The results showed that, due to the decrease in cognitive performance and increased anxiety and depression after initiation of chemotherapy in patients with breast cancer, it is necessary to closely monitor the mental and psychological status of these patients by their family and the treatment staffs so that the patient be able to cope with the disease more optimally and to recover.

Inhibition of activated astrocyte ameliorates lipopolysaccharide- induced depressive-like behaviors.

BACKGROUND: Numerous studies indicate that inflammation plays important roles in the development of depression. Astrocytes are crucial regulators of immune response in the central nervous system, and strongly activated by pro-inflammatory cytokines. We hypothesized that inhibition of activated astrocytes contributed to ameliorate depressive-like symptoms. METHODS: This study evaluated the antidepressant-like effect of inhibition of activated astrocytes, by a well-established astrocyte inactivator fluorocitrate (FC), on a lipopolysaccharide (LPS)-induced model of depression. Forced swim test (FST), tail suspension test (TST) and sucrose preference test were used to assess depressive-like behaviors. The expression of fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neuroinflammation were determined in the hippocampus and cortex. RESULTS: The results demonstrated that LPS increased immobility time in the TST and FST, reduced sucrose preference as well. LPS also enhanced the expression of IL-1ß, TNF-α, iNOS and GFAP, accompanying with decreased expression of BDNF in the hippocampus and cortex. Inhibition of activated astrocytes by FC significantly prevented LPS- induced alteration in the FST, TST and sucrose preference test. Moreover, in the hippocampus and cortex, inhibition of activated astrocytes by FC significantly attenuated increases of neuroinflammation and GFAP whereas reversed decrease of BDNF in LPS- challenged depression. CONCLUSIONS: Taken together, the results suggest that inhibition of activated astrocytes ameliorates LPS-induced depressive-like behavior, providing the first evidence that inhibition of activated astrocytes might represent a novel therapeutic target for depression.

Anxiety and depression associated with tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia.

BACKGROUND: ABL tyrosine kinase inhibitors (TKIs) significantly changed the prognosis of patients with chronic myeloid leukemia (CML), and clinical trials demonstrated that TKIs can be discontinued in approximately 50% of patients after a period of deep molecular response (DMR). However, in some patients, TKI discontinuation leads to anxiety and depression. Here, we analysed the incidence of anxiety and depression in patients who stop TKI therapy. METHODS: Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS) in 32 patients with CML. The survey periods were at TKI discontinuation, at 1, 6, 12, and 24 months and at reintroduction of TKIs. The HADS score at the initial TKI discontinuation was compared between patients within and outside clinical trials. Treatment-free remission (TFR) rates outside clinical trials were evaluated. RESULTS: The HADS scores were significantly higher at TKI reintroduction after molecular relapse than at the initial TKI discontinuation (at the initiation of stopping TKIs vs. at reintroduction of TKIs, 8.47 ± 5.53 vs. 1.67 ± 2.26; p = 0.0003). The TFR rate at 12 months after stopping TKIs outside clinical trials was 55.6%. The HADS score at the initial TKI discontinuation did not differ between patients within and outside clinical trials. CONCLUSION: Stopping TKIs outside clinical trials is feasible if the guidelines for stopping are followed and an adequate monitoring system is available. Discontinuation of TKIs requires adequate management of anxiety and depression.

Factors associated with psychological distress amongst outpatient chemotherapy patients: An analysis of depression, anxiety and stress using the DASS-21.

AIM: This study sought to identify clinical, demographic and service-related factors associated with psychological distress amongst outpatient chemotherapy patients. BACKGROUND: Distress in cancer patients leads to increased risk of psychological comorbidity, contributing to sub-optimal treatment adherence and potentially leading to poorer health outcomes. Screening and recognition of distress and risk factors is an important aspect of holistic care within a multidisciplinary team environment. METHODS: Data were obtained via survey and chart review of ambulatory chemotherapy patients at three public tertiary referral hospitals in Perth, Western Australia. The DASS-21 was used to screen for psychological distress. Regression analyses were used to assess the relationship between distress and a range of cancer, socioeconomic and treatment factors. RESULTS: Patients with a Karnofsky Performance Score≤80 (OR 3.8, 95% CI [1.7, 78.7]) and average waiting time (between oncology outpatient appointment and commencement of chemotherapy infusion) >60min (OR 2.4, 95% CI [1.04, 5.5]) were at increased risk of moderate-severe distress. Patients with a household income between $AU 50-75,000 p.a. had a lower risk of distress compared to <$25,000 p.a. (OR 0.05, 95% CI [0.01, 0.52]). On sub-scale analysis, depression and anxiety contributed more to overall distress than the stress subscales. CONCLUSIONS: Performance status, waiting times and household income were key predictors of distress. Findings could assist clinicians to identify higher-risk population subsets that could benefit from targeted screening and additional psychological and social work support. Findings could also assist administrators to consider the contribution of modifiable factors such as waiting times to patient distress.

Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice.

Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a hormone synthesized and secreted by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like effects. In this way, it would be interesting to evaluate the putative antidepressant-like effect of melatonin treatment in an acute inflammation mice model of depression. The present study aimed to investigate the effect of melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior, neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic fator (BDNF) levels. Mice were treated with melatonin (10 mg/kg, i.p.) 30 min before LPS (0.5 mg/kg, i.p.) injection. Twenty-four hours after LPS infusion, mice were submitted to the behavioral tests and, thereafter, biochemical determinations were performed. Melatonin treatment prevented LPS-induced depressive-like behavior in the forced swim and tail suspension tests with no alterations in locomotor activity evaluated in the open field test. Melatonin attenuated LPS-induced increase in tumor necrosis factor-α (TNF-α) and reduction of BDNF levels in the hippocampus. Treatment with melatonin also prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus. In conclusion, the present study suggests that melatonin treatment exerted neuroprotective effects against LPS-induced depressive-like behavior which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.

Chronic corticosterone-induced depression mediates premature aging in rats.

BACKGROUND: Stress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear. METHODS: Rats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days. Age-related indexes were then compared between CORT-treated rats and control rats. RESULTS: CORT induced affective behaviors indicative of depressive-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swimming test. CORT-treated rats exhibited telomere shortening, possibly contributing to decreased telomerase activity and down-regulated expression of telomere-binding factor 2, correlated with enhanced oxidative damage. This was associated with inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2 and glutathione reductase. CORT-treated rats showed degenerated mitochondrial functions represented by decreased adenosine triphosphate production, decreased nicotinamide adenine dinucleotide+ content, and decreased activity of nicotinamide phosphoribosyltransferase. LIMITATIONS: The group sample sizes were small, and only male rats and a single dose level of CORT were used. CONCLUSION: These findings demonstrate that CORT-induced depression may be involved in mediating the pathophysiology of premature aging in rats.

Hearing loss and tinnitus in survivors with chemotherapy-induced neuropathy.

PURPOSE: The purpose of this study was to evaluate for differences in demographic, clinical, and pain characteristics, as well as measures of sensation, balance, perceived stress, symptom burden, and quality of life (QOL) among survivors who received neurotoxic chemotherapy (CTX) and who reported only chemotherapy-induced neuropathy (CIN, n = 217), CIN and hearing loss (CIN/HL, n = 69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n = 85). We hypothesized that as the number of neurotoxicities increased, survivors would have worse outcomes. METHODS: Survivors were recruited from throughout the San Francisco Bay area. Survivors completed self-report questionnaires for pain and other symptoms, stress and QOL. Objective measures were assessed at an in person visit. RESULTS: Compared to survivors with only CIN, survivors with all three neurotoxicities were less likely to be female and less likely to report child care responsibilities. In addition, survivors with all three neurtoxicities had higher worst pain scores, greater loss of protective sensation, and worse timed get up and go scores. These survivors reported higher state anxiety and depression and poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported balance problems), significantly worse outcomes were found for the survivors with CIN/HL and CIN/HL/TIN compared to those with only CIN. CONCLUSIONS: Our findings suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are at increased risk for the most severe symptom burden, significant problems associated with sensory loss and changes in balance, as well as significant decrements in all aspects of QOL.

Association of androgen deprivation therapy and depression in the treatment of prostate cancer: A systematic review and meta-analysis.

BACKGROUND: There is increasing evidence that androgen deprivation therapy (ADT) may be associated with depression. Existing studies have shown conflicting results. METHODS: PubMed, Web of Science, Embase, and PsycINFO were queried on April 5, 2017. Eligible studies were in English and reported depression among individuals with prostate cancer exposed to a course of ADT vs. a lesser-exposed group (e.g., any-ADT vs. no ADT and continuous ADT vs. intermittent ADT). We used the MOOSE statement guidelines and the Cochrane Review Group's data extraction template. Study quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted a random-effects meta-analysis to calculate summary statistic risk ratios (RRs) and 95% CIs. Heterogeneity was quantified using the I2 statistic and prespecified subgroup analysis. Small study effects were evaluated using Begg and Egger statistics. RESULTS: A total of 1,128 studies were initially identified and evaluated. A meta-analysis of 18 studies among 168,756 individuals found that ADT use conferred a 41% increased risk of depression (RR = 1.41; 95% CI: 1.18-1.70; P<0.001). We found a consistent strong statistically significant association when limiting our analysis to studies in localized disease (RR = 1.85; 95% CI: 1.20-2.85; P = 0.005) and those using a clinical diagnosis of depression (RR = 1.19; 95% CI: 1.08-1.32; P = 0.001). We did not find an association for continuous ADT with depression risk compared to intermittent ADT (RR = 1.00; 95% CI: 0.50-1.99; P = 0.992). There was no statistically significant evidence of small study effects. Statistically significant heterogeneity in the full analysis (I2 = 80%; 95% CI: 69-87; P<0.001) resolved when examining studies using a clinical diagnosis of depression (I2 = 16%; 95% CI: 0-60; P = 0.310). CONCLUSION: The currently available evidence suggests that ADT in the treatment of prostate cancer is associated with an increased risk of depression.