The Relationship between Neurobiological Function and Inflammation in Depressed Children and Adolescents: A Scoping Review.

INTRODUCTION: Neurobiological dysfunction is associated with depression in children and adolescents. While research in adult depression suggests that inflammation may underlie the association between depression and brain alterations, it is unclear if altered levels of inflammatory markers provoke neurobiological dysfunction in early-onset depression. The aim of this scoping review was to provide an overview of existing literature investigating the potential interaction between neurobiological function and inflammation in depressed children and adolescents. METHODS: Systematic searches were conducted in six databases. Primary research studies that included measures of both neurobiological functioning and inflammation among children (≤18 years) with a diagnosis of depression were included. RESULTS: Four studies (240 participants; mean age 16.0 ± 0.6 years, 62% female) meeting inclusion criteria were identified. Studies primarily examined the inflammatory markers interleukin 6, tumor necrosis factor alpha, C-reactive protein, and interleukin 1 beta. Exploratory whole brain imaging and analysis as well as region of interest approaches focused on the anterior cingulate cortex, basal ganglia, and white matter tracts were conducted. Most studies found correlations between neurobiological function and inflammatory markers; however, depressive symptoms were not observed to moderate these effects. CONCLUSIONS: A small number of highly heterogeneous studies indicate that depression may not modulate the association between altered inflammation and neurobiological dysfunction in children and adolescents. Replication in larger samples using consistent methodological approaches (focus on specific inflammatory markers, examine certain brain areas) is needed to advance the knowledge of potential neuro-immune interactions early in the course of depression.

Changes in SLITRK1 Level in the Amygdala Mediate Chronic Neuropathic Pain-Induced Anxio-Depressive Behaviors in Mice.

BACKGROUND: Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD. METHODS: A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1. RESULTS: Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin. CONCLUSION: Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.

Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice.

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.

Depressive symptoms among cancer patients: Variation by gender, cancer type, and social engagement.

Prior literature has documented an association between cancer and depressive symptoms. There has been a limited understanding about whether the association between cancer and depressive symptoms varies by gender and whether social engagement moderates this association. Using seven waves of the Korean Longitudinal Study of Ageing (N = 10,055), we examine the association between cancer and depressive symptoms among middle- and older-aged adults in Korea. We conduct fixed-effects regression models to account for unobserved characteristics of individuals that may confound this association. We first investigate whether the association between cancer and depressive symptom differs by gender. We distinguish among cancer types to assess potentially distinctive mental health consequences of different types of cancer. Then, we explore whether social engagement moderates the cancer-depressive symptoms association. Naive OLS models yielded significant associations between cancer and depressive symptoms for both men and women. However, our preferred fixed effects estimates revealed that the association was statistically significant only for men, and not for women. This association was especially pronounced for lung cancer. We also found that one's level of social engagement including informal connections and formal social activities moderates the link between cancer and depressive symptoms. Cancer is not only a leading cause of death, but also a serious threat to one's mental health. This study sheds light on gender differences in psychological reactions to cancer among Korean adults. Findings of this study hold important implications for programs aiming to improve the mental health and quality of life of cancer patients.

Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.

The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1.

Intranasal treatment of lixisenatide attenuated emotional and olfactory symptoms via CREB-mediated adult neurogenesis in mouse depression model.

Convergent lines of evidence indicate a striking correlation between olfactory deficits and depressive symptoms. However, the effectiveness of intranasal treatment of antidepressant or other neurotrophic agents remains poorly understanding. Here in this study, we created depression mouse model and explored the antidepressant effects of GLP-1 analog lixisenatide (LXT) with intranasal treatment. Consecutive intranasal treatment of LXT remarkably reduced the depressive and anxiety behaviors. Meanwhile, it also improved the olfactory memory and olfactory sensitivity. Immunofluorescent analysis demonstrated the LXT improved the adult neurogenesis in olfactory system and hippocampus. Inhibition of adult neurogenesis with TMZ caused the compromised effects of LXT in improving emotional and olfactory functions, suggesting the vital role of adult neurogenesis in LXT induced depression therapeutic effects. Treatment of LXT resulted in the increased phosphorylation of CREB protein in hippocampal tissue, indicating CREB plays important roles in antidepressant effects of LXT intranasal treatment. Inhibiting CREB with chemical approach decreased effects of LXT in reserving depression induced emotional and olfactory functions. In conclusion, our study suggests intranasal treatment of LXT could be a potential antidepressant to improve the olfactory functions as well as the emotional behaviors.

Childhood trauma and dysregulation of multiple biological stress systems in adulthood: Results from the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between CT and separate and cumulative activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), remains inconclusive. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA, n = 2778), we determined whether self-reported CT (as assessed by the Childhood Trauma Interview) was associated with separate and cumulative markers of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), the immune-inflammatory system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period) in adulthood. RESULTS: Almost all individuals with CT (n = 1330) had either current or remitted depressive and/or anxiety disorder (88.6%). Total-sample analyses showed little evidence for CT being significantly associated with the separate or cumulative stress systems' activity in adulthood. These findings were true for individuals with and without depressive and/or anxiety disorders. To maximize contrast, individuals with severe CT were compared to healthy controls without CT. This yielded slight, but significantly higher levels of cortisol awakening response (AUCg, ß = .088, p = .007; AUCi, ß = .084, p = .010), cumulative HPA-axis markers (ß = .115, p = .001), C-reactive protein (ß = .055, p = .032), interleukin-6 (ß = .053, p = .038), cumulative inflammation (ß = .060, p = .020), and cumulative markers across all systems (ß = .125, p = .0003) for those with severe CT, partially explained by higher rates of smoking, body mass index, and chronic diseases. CONCLUSION: While our findings do not provide conclusive evidence on CT directly dysregulating stress systems, individuals with severe CT showed slight indications of dysregulations, partially explained by an unhealthy lifestyle and poorer health.

Longitudinal proneuroactive and neuroactive steroid profiles in medication-free women with, without and at-risk for perinatal depression: A liquid chromatography-tandem mass spectrometry analysis.

BACKGROUND: Neuroactive steroids (NAS) are derivatives of cholesterol or steroidal precursors made in the gonads, adrenal gland, placenta and brain. We characterized longitudinal plasma proneuroactive and NAS in healthy perinatal comparison women (HPCW), women at-risk for perinatal depression (AR-PND), and women with PND with/without comorbid anxiety. We hypothesized that AR-PND women who either did or did not go on to develop PND would have elevated NAS concentrations as compared to HPCW and that NAS would be correlated to depressive and anxiety symptoms. METHODS: A prospective cohort study evaluated 75 medication-free perinatal women (HPCW, n = 30; AR-PND, n = 19; PND, n = 26). Standardized depression and anxiety assessments and blood samples were completed across 5 visits. Structured Clinical Interviews for DSM-IV TR Disorders were administered at study entry and exit. Plasma pregnenolone, progesterone, 5α- and 5ß-dihydroprogesterone, pregnanolone, allopregnanolone, deoxycorticosterone and tetrahydrodeoxycorticosterone were quantified by liquid chromatography-tandem mass spectrometry. Longitudinal relationships between risk-group, depression and anxiety symptoms, and NAS concentrations were analyzed using generalized estimating equations to control for repeated measures correlations. RESULTS: Perinatal 5α-dihydroprogesterone, 5ß-dihydroprogesterone, allopregnanolone, deoxycorticosterone, and tetrahydrodeoxycorticosterone concentrations were higher in AR-PND and PND women compared to HPCW (ß = 3.57 ± 1.40 and ß = 2.11 ± 1.12, p = 0.03; ß = 0.18 ± 0.06 and ß = 0.03 ± 0.05, p = 0.02; ß = 1.06 ± 0.42 and ß = 1.19 ± 0.47, p = 0.01; ß = 0.17 ± 0.07 and ß = 0.11 ± 0.06, p = 0.05; ß = 0.03 ± 0.01 and ß = 0.03 ± 0.01, p = 0.05, respectively). Perinatal allopregnanolone, 5α-dihydroprogesterone and tetrahydrodeoxycorticosterone were positively associated with HAM-D17 (all p < 0.02). HAM-A was positively associated with 5α- and 5ß-dihydroprogesterone, pregnanolone, allopregnanolone, deoxycorticosterone and tetrahydrodeoxycorticosterone (all p < 0.05). A history of depression was associated with increased 5α-dihydroprogesterone (2.20 ± 1.09, p = 0.05), deoxycorticosterone (0.13 ± 0.06, p = 0.03) and tetrahydrodeoxycorticosterone (0.03 ± 0.01, p = 0.02). CONCLUSION: To our knowledge, this study represents the largest prospective study of 5-α and 5-ß reductase products of progesterone and deoxycorticosterone in HPCW and women AR-PND. Data suggest that PND is associated with both a reduction of progesterone to 5ß-dihydroprogesterone, 5α-dihydroprogesterone, and allopregnanolone, and the 21-hydroxylation to deoxycorticosterone and tetrahydrodeoxycorticosterone. The shift towards 5α-dihydroprogesterone, deoxycorticosterone and tetrahydrodeoxycorticosterone was associated with a history of depression, a significant risk factor for PND.

Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: Evidence from inflammation and oxidative stress.

OBJECTIVE: The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. MATERIALS AND METHODS: The animals were allocated to five groups (n = 10 in each) and treated by: (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. RESULTS: LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (SOD), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. CONCLUSION: It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.

La relación entre la obesidad y estados depresivos / The relationship between obesity and depressive states

La depresión y la obesidad son patologías altamente prevalentes y corresponden a los principales problemas de salud pública. Estas patologías tienen un gran impacto en la morbilidad y mortalidad de los pacientes y afectan la salud y el bienestar de quienes las padecen, así como también afectan en el aspecto socioeconómico consecuencia del deterioro funcional y el gasto de recursos en salud ocasionados. Resultados de estudios epidemiológicos, ensayos clínicos y meta-análisis apoyan la asociación entre los estados depresivos y la obesidad, ya que ambos ocurren conjuntamente en todas las razas de poblaciones evaluadas. El objetivo es abordar la evidencia con respecto a 4 aspectos: (1) obesidad y respuesta a los antidepresivos, (2) trastornos depresivos y su impacto sobre la progresión de la obesidad, (3) tratamiento de la obesidad y el impacto sobre los resultados entre pacientes con trastornos depresivos, (4) el tratamiento de los trastornos depresivos y su impacto sobre los resultados de la obesidad. La evidencia existente apoya la asociación entre obesidad y los resultados adversos para la salud en individuos con trastornos depresivos. Además, destaca el concepto que el tratamiento de una de las dos enfermedades (obesidad o trastornos depresivos) es relevante para mejorar el curso de la otra patología. Puede ser beneficioso explorar dirigidamente la presencia de un trastorno depresivo en sujetos con sobrepeso u obesidad, así como el aumento de peso en personas con depresión. Conocer el efecto de los fármacos antidepresivos sobre el peso corporal es también relevante para facilitar la adherencia al tratamiento en el largo plazo.

Depression and obesity are highly prevalent illness and a mayor public health concern. These diseases have a great impact on morbidity and mortality of patients and affect the health and well-being of those who suffer them, as well as being affected in the socioeconomic aspect as a result of the functional deterioration and the spending of resources. Results of epidemiological studies, clinical trials and meta-analysis support the association between mood disorders and obesity, since both occur together in all the populations evaluated. The objective is to address the evidence regarding four aspects: (1) obesity and response to antidepressants, (2) depressive disorders and their effect on the progression of obesity, (3) treatment of obesity and the effect on outcomes among patients with depressive disorders, (4) the treatment of depressive disorders and their effect on obesity outcomes. Existing evidence supports the association between obesity and adverse health outcomes in individuals with depressive disorders. In addition, it highlights the concept that the treatment of one of the two diseases (obesity or depressive disorders) is relevant to improve the course of the other disease. It may be beneficial to explore the presence of a depressive disorders in overweight or obese subjects, as well as weight gain in subjects with depression. Knowing the effect of antidepressant drugs on body weight is relevant to facilitate adherence to long-term treatment.

Under-treated depression negatively impacts lifestyle behaviors, participation and health-related quality of life among older people with multiple sclerosis.

PURPOSE: To what extent depression may negatively impact successful aging with multiple sclerosis (MS) is not known. We examined the impact of depression/depressive symptoms on lifestyle choices (diet, exercise, smoking and alcohol), participation and health-related quality of life (HRQoL) among older people living with MS (n = 742). METHODS: Based on self-reported depression diagnosis and scores on the Hospital Anxiety and Depression Scale, we divided the sample into four groups: 1. No depression diagnosis and low symptoms (n = 412), 2. Diagnosed with depression and low symptoms (n = 103), 3. Diagnosed with depression and high symptoms (n = 87), and 4. No depression diagnosis and high symptoms (n = 140). We used regression modelling to predict outcomes, controlling for age, MS disease duration, type of MS at initial diagnosis and disability. RESULTS: A high proportion (44.5%) reported either being diagnosed with depression, having high levels of symptoms or both. Only 12.1% reported that they were prescribed anti-depressants and 13.6% utilized psychosocial services. Compared to those with depression who had low symptoms, respondents who had high depressive symptoms (n = 227) were more likely to be non-exercisers (OR 1.85, 95%CI 1.02-3.34, p = 0.042), consume a poor diet (OR 2.12, 95%CI 1.27-3.52, p = 0.004), have the lowest levels of participation (OR 3.36, 95%CI 1.74-6.49, p = 0.0003) and report the poorest HRQoL (OR 1.95, 95%CI 1.17-3.26, p = 0.011). Men and people experiencing higher levels of disability and fatigue were at greater risk of having high symptoms and being undiagnosed. CONCLUSION: Undiagnosed and under-treated depression is common among older people living with MS and adversely impacts health choices.

Paclitaxel Induces Sex-biased Behavioral Deficits and Changes in Gene Expression in Mouse Prefrontal Cortex.

Paclitaxel (PTX) is one of the most commonly used chemotherapeutic agents for various cancer diseases. Despite its advantages, PTX also causes behavioral deficits related to nervous-system dysfunction, such as neuropathic pain, depression, anxiety, and cognitive impairments. The prefrontal cortex (PFC) is one of the areas that is susceptible to adverse effects of chemotherapeutic agents. Therefore, the present study was designed to examine sex-biased behavioral deficits and whole-transcriptome changes in gene expression in the PFC of mice treated with vehicle or PTX. In this study, PTX (4 mg/kg) was injected intraperitoneally four times in mice every other day. Three weeks later, both PTX-treated male and female mice developed mechanical pain hypersensitivities, as indicated by increased paw withdrawal responses to 0.16-g von Frey filaments. Additionally, PTX-treated mice exhibited depression-like symptoms, as they exhibited increased immobility times in the forced swim test. PTX also induced cognitive impairment, as demonstrated via results of a novel object recognition (NOR) test and anxiety-like behavior in an elevated plus-maze test in male mice, but not in female mice. RNA sequencing and in-depth gene expression analysis of the PFC in paired vehicle and PTX-treated mice showed that PTX induced 1755 differentially expressed genes in the PFCs of male and female mice. Quantitative real-time RT-PCR verified that some gene expressions in the medial PFC (mPFC) were related to neurotransmission. In conclusion, this study identified a sex-biased effect of PTX on PFC function and gene expression, which provides a foundation for future studies to explore the precise mechanisms of PTX-induced behavioral deficits.

Association between medicated obstructive pulmonary disease, depression and subjective health: results from the population-based Gutenberg Health Study.

Medicated obstructive pulmonary disease (asthma or COPD) has been associated with depression. Yet, there is little knowledge of the interplay of contributing social, biological, behavioral and psychological factors in the community. The study was conducted: (1) To determine the prevalence of depression in participants with medicated COPD or asthma from the general population, (2) to identify underlying social, biological, behavioral and psychological factors and (3) to determine the contribution of obstructive pulmonary disease and depression to subjective health. The population-based sample of 15.010 study participants (35-74 years) from the Gutenberg Health Study (GHS) was queried according to a medical diagnosis of obstructive pulmonary disease, defined as medicated COPD or asthma, and comorbid disorders. Demographic, behavioral and psychological factors were assessed by self-report; lung function (FEV1; FCV) was measured by spirometry. 307 men (4.3%) and 396 women (5.6%) reported a medical diagnosis of COPD or asthma. The prevalence of depression (PHQ-9 > = 10) was twice as high (16.2% vs. 7.5%) compared to participants without obstructive pulmonary disease. Participants with obstructive pulmonary disease were older, had a lower SES, more comorbid diseases and cardiovascular risk factors, higher distress and took more psychotropic medication. In multivariable logistic regression analyses, obstructive pulmonary disease was associated with a 71% increase of depression (OR = 1.71; 95% CI = 1.30 to 2.24). Additional contributors were FEV1 (1.18; 95% CI = 1.05 to 1.32) and dyspnea (NYHA > = 1) (2.19; 1.82 to 2.64), sex (women) (OR = 1.73; 95% CI 1.41 to 2.12), lower SES (OR = 0.98; 95%CI = 0.96 to 0.99). Lack of active sports OR = 0.79; 95% CI 0.68 to 0.92), obesity (OR 1.27; 95% CI 1.07 to 1.50), smoking (OR = 1.26; 95% CI 1.06 to 1.49) and dyslipidemia (OR = 1.35; 95% CI 1.15 to 1.57) also increased the risk of depression. Additional psychological risks were social phobia, type D, low social support, loneliness and life events in the past 12 months. In multivariable linear regression analyses, obstructive pulmonary disease and depression independently contributed to reduced subjective health in addition to sedentary behavior, smoking and comorbid somatic and mental disorders. These findings provide evidence that COPD and asthma are associated with depression in the community. Complex underlying demographic, medical and psychosocial variables have been identified which may justify an integrative treatment approach. Promoting health behavior (smoking cessation, exercising, weight reduction) and social integration may not only improve the somatic course of the disease, but also mental health. Mental health treatment may also improve health behavior and subjective health.

Neurobiological mechanisms underlying sex-related differences in stress-related disorders: Effects of neuroactive steroids on the hippocampus.

Men and women differ in their vulnerability to a variety of stress-related illnesses, but the underlying neurobiological mechanisms are not well understood. This is likely due to a comparative dearth of neurobiological studies that assess male and female rodents at the same time, while human neuroimaging studies often don't model sex as a variable of interest. These sex differences are often attributed to the actions of sex hormones, i.e. estrogens, progestogens and androgens. In this review, we summarize the results on sex hormone actions in the hippocampus and seek to bridge the gap between animal models and findings in humans. However, while effects of sex hormones on the hippocampus are largely consistent in animals and humans, methodological differences challenge the comparability of animal and human studies on stress effects. We summarise our current understanding of the neurobiological mechanisms that underlie sex-related differences in behavior and discuss implications for stress-related illnesses.

Alteration of oxidative stress markers and behavior of rats in a novel model of depression.

Emotional stress is considered a serious pathogenetic factor of depression. In this study an ultrasound model of emotional stress developed in our laboratory was applied. It is characterized by the use of ultrasound as the stressor agent. Animals are triggered not by any organic or physical disturbances but by the perception of adverse information. This type of stress can induce depressive-like behavioral changes in rodents, manifested by decreased sucrose preference and increased time of immobility in a forced swim test. Ultrasound stress also increased the levels of oxidative stress markers. This is important, as stress has an established association with increased oxidative processes in the central nervous system. Total glutathione and carbonyl protein content were selected as relevant brain markers, as glutathione plays a critical role in cellular defensive mechanisms during oxidative stress and the level of protein carbonyls can be a measure of global protein oxidation. We demonstrated that two weeks of chronic exposure to ultrasound was enough to cause depressive-like behavioral changes in rats. Increased levels of oxidative stress markers in the hippocampus and prefrontal cortex were also observed after two weeks of such stress. The current study has two goals: the first is to study the relationship of depression and oxidative stress; the second is an additional validation of our approach to modeling stress­induced depressive-like states in rats. The present data further support the validity of the ultrasound model by expanding information related to the influence of ultrasound stress on behavioral and physiological parameters, which are of great importance in the development of stress-induced depression. A time correlation between the onset of symptoms and a change in the level of oxidative stress markers in the brain is also demonstrated.

Influence of depressive feelings in the brain processing of women with fibromyalgia: An EEG study.

Depression is one of the most common mental health problems which affects more than 10% of the global population. The prevalence of this disorder is higher in fibromyalgia patients. However, the influence of the combination of depression and fibromyalgia in the brain processing is poorly understood.To explore the modifications of EEG power spectrum in women with fibromyalgia when depressive feelings are elicited.Twenty eight women with fibromyalgia participated in this cross-sectional study. They were classified as women with depression or women without depression according to the score in the Geriatric Depression Scale. This questionnaire was used to elicit depression symptoms during the EEG recording. Analyses were performed with the standardized LOw Resolution Electric Tomography (sLORETA) software. Power spectrum were compared in the following frequency bands: delta, theta, alpha-1, alpha-2, beta-1, beta-2, and beta-3.Fibromyalgia patients with untreated depression showed a hypoactivation of the left hemisphere when compared with fibromyalgia patients without depression. In addition, when compared fibromyalgia patients without depression and women with both fibromyalgia and depression who were taking antidepressant medications, differences in EEG power spectrum in the studied frequency bands were not found.The current study contributes to the understanding on the influence of the combination of fibromyalgia and depression in the brain activity patterns. Patients with untreated depression showed a hypoactivation of the left hemisphere while eliciting depression symptoms. However, further research is needed, antidepressant medication might reduce the differences between patients with depression and those who do not suffer from depression symptoms.

Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life.

OBJECTIVE: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. METHODS: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t = -0.553, df = 542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATPmax]; t = 0.804, df = 553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D ≥16) at follow-up (ΔATPmax: odds ratio = 2.63, χ2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ2 = 5.79, df =1; p = 0.016). CONCLUSION: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with LLD.