Efficacy of perioperatively application of ketamine on postoperative depressive symptoms in adult patients: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Whether ketamine used in the perioperative period reduces the risk of postoperative depressive symptoms remains uncertain. We conducted this systematic review and meta-analysis to evaluate the clinical efficacy of ketamine in adult surgical patients. METHODS: Two investigators independently systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Web of Science, and PsycINFO databases using a combination of relevant Medical Subject Headings terms and free-text keywords from database inception through May 24, 2023. RESULTS: 29 studies encompassing 5327 patients were included. The pooled analysis demonstrated that the ketamine group had no significantly reduced incidence of postoperative depressive mood compared with the control group, with trial sequential analysis (TSA) inconclusive. However, postoperative depression scale scores were significantly decreased in the ketamine group. LIMITATIONS: Most randomized controlled trials of surgical patients have included depression scale scores as the primary outcome. The incidence of postoperative depressive has been assessed as a secondary outcome or has not been assessed. In addition, non-uniform assessment scales have introduced greater heterogeneity. More rigorous methods and higher-quality evidence for further research are needed to better understand the effects of ketamine on perioperative depression in surgical anesthesia. CONCLUSIONS: Current evidence suggests that ketamine cannot significantly decrease the incidence of postoperative depressive mood in adult surgical patients. However, ketamine can reduce postoperative depression scores. PROSPERO registration: CRD42023431566.

Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression.

OBJECTIVE: Previous research has shown that ketamine can improve social functions. In addition, evidence also suggests that ketamine can alleviate pain. Herein, we propose that ketamine-induced improvements in pain and depression are partially mediated by a reduction in pain. We aimed to determine whether improvements in pain-mediated changes in psychological function were associated with ketamine treatment. METHOD: This trial included unipolar or bipolar patients (n = 103) who received 6 intravenous infusions (0.5 mg/kg) of ketamine over 2 weeks. The severity of current depressive symptoms and social function were evaluated by the Montgomery-Åsberg Depression Scale (MADRS), Self-Rating Depression Scale (SDS) and Global Assessment Function (GAF), respectively, at baseline and on day 13 and day 26. At the same time points, the three dimensions of pain, including the sensory index, affective index and present pain intensity (PPI), were measured by the Simple McGill Pain Scale (SF-MPQ). RESULTS: The mixed model results showed that ketamine plays an important role in improving the psychosocial functioning of patients. There was a significant decrease from baseline to the day 13 and day 26, indicating that the pain index of the patient improved significantly. Mediation analysis showed that for SDS score (coef = -5.171, 95 % CI[-6.317, -4.025]) and GAF score (coef = 1.021, 95 % CI[0.848, 1.194]), the overall effect of ketamine was observable. The overall indirect and direct effects of ketamine on social functioning were significant (SDS: direct: coef = -1949 to -2114; total indirect: from 0.594 to 0.664; GAF: from 0.399 to 0.427; total indirect: coef = 0.593 to 0.664). The MADRS total score and emotional index were important mediators of the association between ketamine treatment and improvements in subjective and objective social functioning. CONCLUSION: Depressive symptom severity and the affective index of pain partially mediated improvements in social function after six repeated ketamine treatments among patients with bipolar or unipolar depressive disorder.

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.

The Role of Natural Products in Treatment of Depressive Disorder.

Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's life. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic- pituitary-adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.

Protective effect of Myrcia pubipetala Miq. against the alterations in oxidative stress parameters in an animal model of depression induced by corticosterone.

Depression is a debilitating disorder in humans that significantly affects quality of life. As such, alternative therapies are highly sought after by patients seeking treatment for depression. Experimentally, the chronic administration of corticosterone (CORT) in rodents has been reported to promote depressive-like behaviors. Herein, animals received saline or CORT for 21 days and, during the last 7 days, they were treated with the crude hydroalcoholic extract (CHE) of Myrcia pubipetala Miq (50, 100 or 150 mg/Kg), or vehicle (distilled water), by oral route. After 24 h, animals were subjected to the open field (OFT) and forced swimming tests (FST), and then sacrificed for the removal of the hippocampus and cerebral cortex for biochemical analysis. Results showed enhanced catalase (CAT) and superoxide dismutase (SOD) activities, as well as an elevated formation of thiobarbituric acid reactive substances (TBARS), in the cerebral cortex of CORT-treated mice. The chronic administration of the CHE (100 and 150 mg/Kg) reduced TBARS and the increased total sulfhydryl content, and also reversed the increase in TBARS induced by CORT. In the hippocampus, CORT increased CAT and SOD activities and reduced glutathione peroxidase (GSH-Px) (C) activity, while Myrcia pubipetala Miq. CHE (100 and 150 mg/Kg) increased GSH-Px activity when administered alone and reversed decreased GSH-Px (100 and 150 mg/Kg) activity when given during CORT administration. Neither CORT administration nor CHE treatment significantly altered the immobility time of the animals in FST and no changes were observed in the locomotor activity of the animals in the OFT. Findings indicate that the CHE of Myrcia pubipetala Miq. exerts antioxidant effects in the cerebral cortex and hippocampus of mice induced to depression by CORT. Since phenolic compounds are reported to have antioxidant effects in this species, the effects of the CHE may be, at least in part, mediated by the presence of these compounds in Myrcia extract.

Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response.

Parkinson's disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson's disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lack of characterization of the extent of behavioral deficits and of the neuronal loss/neurotransmitter system in unilateral lesion mouse models. In this study, we present an extensive behavioral and histological characterization of a unilateral intrastriatal 6-OHDA mouse model. Our results indicate significant alterations in balance and fine motor coordination, voluntary locomotion, and in the asymmetry's degree of forelimb use in 6-OHDA lesioned animals, accompanied by a decrease in self-care and motivational behavior, common features of depressive-like symptomatology. These results were accompanied by a decrease in tyrosine hydroxylase (TH)-labelling and dopamine levels within the nigrostriatal pathway. Additionally, we also identify a marked astrocytic reaction, as well as proliferative and reactive microglia in lesioned areas. These results confirm the use of unilateral intrastriatal 6-OHDA mice for the generation of a mild model of nigrostriatal degeneration and further evidences the recapitulation of key aspects of PD, thereby being suitable for future studies beholding new therapeutical interventions for this disease.

Age effects on treatment patterns in 138,097 patients with unipolar depression followed in general practices in Germany.

BACKGROUND: Risk factors and comorbidities associated with depression vary with age and must be considered when selecting appropriate anti-depressant medication for patients. Studies are lacking which focus both on treatments prescribed and include a broad age spectrum. The goal of this study was to investigate whether age of patients at diagnosis impact the type of antidepressant drug class prescribed. METHODS: This retrospective cohort study based on the Disease Analyzer database (IQVIA) included 138,097 patients with depression followed in 1188 general practices from date of first depression diagnosis given between 2015 and 2018 (index date). Patients aged 18-30, 31-65 and > 65 were compared in homogeneous groups based on gender and insurance type. Odds ratios adjusted by gender, insurance type, treatment site and Charlson-Comorbidity-Index were used to assess the difference in probability of receiving prescription for antidepressant drug classes as well as individual treatment drugs by age group. RESULTS: The cohort included 13,553 (9.8%), 82,524 (59.8%) and 42,020 (30.4%) patients aged 18-30 years (young), 31-65 years (middle-aged) and >65 years (older). Less than half of patients received anti-depressant medication, with 4717 (34.8%) aged 18-30, 35,014 (42.4%) aged 31-65, and 20,294 (48.3%) aged 65 or older receiving at least one anti-depressant medication. Tri- and tetra-cyclic mediations were prescribed to 65.8% of patients aged >65, and 59.0% of patients aged 31-65. Selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) were prescribed to 55.5% of patients. Older patients showed an increased probability (OR: 1.3 [1.26-1.34 95% CI], p < 0.0001) for tri- and tetra-cyclic medication, while younger patients showed an increased probability for SSRIs and SNRIs (OR: 1.23 [1.16-1.30 95% CI], p < 0.0001). CONCLUSION: Age-related differences in anti-depressant medication prescription were shown, with older patients above 65 years predominantly receiving tri- and tetra-cyclic medication, while younger patients aged 18-30 received SSRIs more frequently. Further studies with homogeneous groups relating to comorbidity profile and disease severity are needed to fully understand age effects on treatment patterns.

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.

Do ß-Blockers Cause Depression?: Systematic Review and Meta-Analysis of Psychiatric Adverse Events During ß-Blocker Therapy.

[Figure: see text].

Chronically infused angiotensin II induces depressive-like behavior via microglia activation.

Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. However, there is no animal study showing the direct relationship between ANGII and depression. To address this issue, ANGII-containing osmotic pumps were implanted into adult male C57BL/6 mice subcutaneously for subacute (7 days) and chronic (at least 21 days) periods and behavioral and molecular analyses were conducted. Chronic infusion of ANGII into mice induced depressive-like behaviors, including the tail suspension test and forced swimming test, which were reversed by imipramine. Chronic infusion of ANGII also induced microglial activation in the hippocampus with increase of Il-1ß mRNA and decrease of Arg1 mRNA. In addition, chronic ANGII infusion activated the hypothalamic-pituitary-adrenal axis (HPA axis) and resulted in decreased hippocampal glucocorticoid receptor level. However, subacute ANGII infusion did not induce significant molecular and behavioral changes in mice compared to that of control. The molecular and behavioral changes by chronic ANGII infusion were reversed by co-treatment of minocycline or telmisartan. In addition, ANGII treatment also induced the pro-inflammatory changes in BV-2 microglial cells. Our results indicate that ANGII can induce depressive-like behaviors via microglial activation in the hippocampus and HPA axis hyperactivation in mice. These might suggest possible mechanism on depressive symptom in chronic hypertensive state.

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.

Stress, inflammation, depression, and dementia associated with phosphate toxicity.

Depression and dementia are predicted to increase within aging global populations. Pathophysiological effects of phosphate toxicity, dysregulated amounts of accumulated phosphorus in body tissue, are under-investigated in association with stress, inflammation, depression, and dementia. A comparative analysis of concepts in cited sources from the research literature was used to synthesize novel themes exploring the disease-oriented neuroscience effects of phosphate toxicity. Phosphate toxicity is associated with activation of cellular stress response systems and inflammation. Cortisol released by the hypothalamic-pituitary-adrenal axis responds to stress and inflammation associated with phosphate toxicity and depression. In a reciprocal interaction, phosphate toxicity is capable of harming adrenal gland function, possibly leading to adrenal insufficiency and depression. Furthermore, Alzheimer's disease is associated with hyperphosphorylated tau which self-assembles into neurofibrillary tangles from excessive amounts of phosphate in the brain and central nervous system. Future research should investigate dietary phosphate modification to reduce potential pathophysiological effects of phosphate toxicity in stress, inflammation, depression, and cognitive decline which affects global populations.

Antihypertensive Drugs and Risk of Depression: A Nationwide Population-Based Study.

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and ß-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 ß-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.

Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of Coronavirus Disease-2019: Psychopharmacological Interactions and Neuropsychiatric Sequelae.

BACKGROUND: Chloroquine and hydroxychloroquine are among several experimental treatments being investigated in the urgent response to the coronavirus disease-2019. With increased use of these medications, physicians need to become knowledgeable of these drugs' neuropsychiatric side effects and interactions with psychiatric medications. OBJECTIVE: Clarify evidence base regarding the psychiatric side effects and psychiatric drug interactions of chloroquine and hydroxychloroquine. METHODS: A literature review was performed in PubMed from 1950 to 2020 regarding psychiatric topics and targeted pharmacological properties of chloroquine and hydroxychloroquine. RESULTS: First, chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications, and psychiatric medications that interfere with CYP2D6 or CYP3A4 activity could alter chloroquine and hydroxychloroquine levels. Second, they may prolong the QT interval, warranting caution with concomitant prescription of other QT prolonging agents. Finally, neuropsychiatric side effects are very uncommon but possible and include a potentially prolonged phenomenon of "psychosis after chloroquine." Hydroxychloroquine has less information available about its neuropsychiatric side effects than chloroquine, with psychosis literature limited to several case reports. Weak evidence suggests a possible association of hydroxychloroquine exposure and increased suicidal ideation. It is not clear whether patients with psychiatric illness are more vulnerable to neuropsychiatric sequela of these medications; however, overdose of these medications by suicidal patients has high risk of mortality. CONCLUSION: The risk of neuropsychiatric side effects of chloroquine and hydroxychloroquine when used for coronavirus disease-2019 treatment is not known. Best practice may include suicide risk assessment for patients treated with hydroxychloroquine. However, delirium is expected to be a more likely etiology of neuropsychiatric symptoms in critically ill patients treated for coronavirus disease-2019, and adjustment disorder is a much more likely etiology of anxiety and depression symptoms than the side effects of chloroquine or hydroxychloroquine.

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.