- Development and persistence of suspected neuropathic pain after total knee arthroplasty in individuals with osteoarthritis. [Journal Article]
- PM RPM R 2018 Feb 13
- CONCLUSIONS: Although 14% of individuals with knee OA had suspected neuropathic pain that persisted 6-months post-TKA and those with suspected neuropathic pain had higher levels of pain, catastrophizing, and depression, the clinical identification of neuropathic pain remains enigmatic. Preoperative suspected neuropathic pain, as measured by S-LANSS, may have limited prognostic value for post-TKA outcomes.
- Quantitative Proteomic Analysis Reveals Synaptic Dysfunction in the Amygdala of Rats Susceptible to Chronic Mild Stress. [Journal Article]
- NNeuroscience 2018 Feb 13
- The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild...
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2,562 quantified proteins, 102 were differentially expressed. Several proteins that might be associated with the stress insusceptibility/susceptibility difference, including synapse-related proteins, were identified in the amygdala. Immunoblot analysis identified changes in VGluT1, NMDA GluN2A and GluN2B and AMPA GluA1 receptors, and PSD-95, suggesting that CMS perturbs glutamatergic transmission in the amygdala. Changes in these regulatory and structural proteins provide insight into the molecular mechanisms underlying the abnormal synaptic morphological and functional plasticity in the amygdalae of stress-susceptible rats. Interestingly, the expression level of CaMKIIβ, potentially involved in regulation of glutamatergic transmission, was significantly increased in the susceptible group. Subsequent in vitro experimentation showed that overexpression of CaMKIIβ increased the expression of PSD-95 and GluA1 in cultured hippocampal neurons. This result suggested that CaMKIIβ functions upstream from PSD-95 and GluA1 to affect LTP-based postsynaptic functional plasticity in the amygdalae of susceptible rats. Therefore, amygdalar CaMKIIβ is a potential antidepressant target. Collectively, our findings contribute to a better understanding of amygdalar synaptic plasticity in depression.
- Increased CD4 counts, pain and depression are correlates of lower sleep quality in treated HIV positive patients with low baseline CD4 counts. [Journal Article]
- BBBrain Behav Immun 2018 Feb 13
- Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has be...
Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has been associated with CD4+ effector T cells being more spontaneously activated in chronically treated patients. This cross-sectional study investigated whether subjective sleep quality was associated with CD4+ T lymphocyte reconstitution in treated South African HIV+ patients. One hundred and thirty-nine treated HIV+ patients (109 F, age average (SD)= 43 (9)) were recruited from Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa. Participants completed questionnaires evaluating their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck Depression Inventory). Univariate and multivariate analyses were run to determine the correlates of sleep quality in this population. Patients had been on antiretroviral treatment for about 4 years and had increased their CD4 counts from a median at baseline of 82 cells/µL to 467 cells/µL. They had overall poor sleep quality (average (SD) PSQI=7.7 (± 5), 61% reporting PSQI>5, a marker of lower sleep quality), 41% had clinical depression (average (SD) BDI=17 (± 12)) and 55% reported pain. In two separate multivariate analyses, both the overall CD4 count increase from baseline (p=0.0006) and higher current CD4 counts (p=0.0007) were associated with worse sleep quality, when adjusting for depression severity (p<0.001), daytime sleepiness (p=0.01) and the presence of pain (p<0.01). In this cohort of treated South African HIV positive patients, poor sleep quality was associated with higher current CD4 counts, when adjusting for depression severity, daytime sleepiness and pain. Further studies should investigate the temporal relationship between HIV-related poor sleep quality and underlying immune activation.
- TNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. [Journal Article]
- BBBrain Behav Immun 2018 Feb 13
- Recovery from major depressive disorder is difficult, particularly in patients who are refractory to antidepressant treatments. To examine factors that regulate recovery, we developed a prolonged lea...
Recovery from major depressive disorder is difficult, particularly in patients who are refractory to antidepressant treatments. To examine factors that regulate recovery, we developed a prolonged learned helplessness depression model in mice. After the induction of learned helplessness, mice were separated into groups that recovered or did not recover within 4 weeks. Comparisons were made between groups in hippocampal proteins, inflammatory cytokines, and blood brain barrier (BBB) permeability. Compared with mice that recovered and control mice, non-recovered mice displaying prolonged learned helplessness had greater hippocampal activation of glycogen synthase kinase-3 (GSK3), higher levels of tumor necrosis factor-α (TNFα), interleukin-17A, and interleukin-23, increased permeability of the blood brain barrier (BBB), and lower levels of the BBB tight junction proteins occludin, ZO1, and claudin-5. Treatment with the GSK3 inhibitor TDZD-8 reduced inflammatory cytokine levels, increased tight junction protein levels, and reversed impaired recovery from learned helplessness, demonstrating that prolonged learned helplessness is reversible and is maintained by abnormally active GSK3. In non-recovered mice with prolonged learned helpless, stimulation of sphingosine 1-phosphate receptors by Fingolimod or administration of the TNFα inhibitor etanercept repaired the BBB and reversed impaired recovery from prolonged learned helplessness. Thus, disrupted BBB integrity mediated in part by TNFα contributes to blocking recovery from prolonged learned helplessness depression-like behavior. Overall, this report describes a new model of prolonged depression-like behavior and demonstrates that stress-induced GSK3 activation contributes to disruption of BBB integrity mediated by inflammation, particularly TNFα, which contributes to impaired recovery from prolonged learned helplessness.
- Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice. [Journal Article]
- BBBehav Brain Res 2018 Feb 13
- Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the h...
Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice. VOR (25 mg/kg; intraperitoneal) and fluoxetine (FLX) (15 mg/kg; oral) treatments were provided to CORT administered mice. At the end of dosing schedule, neurobehavioral tests were conducted; followed by mechanistic evaluation through biochemical analysis, RTPCR and western blot in serum and hippocampus. Neurobehavioral tests revealed the development of anxiety/depressive-like behavior in CORT mice as compared to the vehicle control. Depressive-mice showed concomitant HPA axis dysregulation as observed from the significant increase in serum CORT and ACTH. Chronic CORT administration was found to significantly increase hippocampal malondialdehyde (MDA) and iNOS levels while lowering glutathione (GSH) content, as compared to vehicle control. VOR treatment, in a similar manner to the classical antidepressant FLX, significantly ameliorated anxiety/depressive-like behavior along with HPA axis alterations induced by CORT. The antidepressant-like ability of drug treatments against chronic CORT induced stress model, as revealed in our study, may be due to their potential to mitigate inflammatory damage and oxidative stress via modulation of hippocampal NF-κB p65, COX-2, HDAC2 and phosphorylated JNK levels.
- Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole. [Review]
- ATActa Trop 2018 Feb 13
- Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioec...
Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease. However, BNZ has exhibited insufficient activity in the chronic phase of Chagas disease, required administration in large doses, prolonged treatment, and shown a high incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal cord depression), toxicity, and low solubility in water. As an antidote, pharmaceutical technologies have been introduced that can improve BNZ's solubility and dissolution, as well as reduce side effects in light of its bioavailability, all of which can enhance therapy for Chagas disease. In response to that trend, by conducting a literature review, we sought to identify current pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas disease. Documented techniques include emulsion and microemulsion formation, solutions, parenteral formulas, micronization, and drug delivery systems supported by the development of nanoparticles and cyclodextrins, solid dispersions, and the use of metal-organic frameworks as innovative excipients. Such technologies increase the water solubility of BNZ by 4-25-fold on dissolution and an 85% release with efficacy in only a few minutes, as recorded during a viability experiment with nanoparticle suspensions. That experiment demonstrated the need for a lower concentration of BNZ to kill 50% of trypomastigote forms of T. cruzi, described in terms of the formation of BNZ-cyclodextrin complexes, and modulating and vectoring of the antichagasic by using metal-organic frameworks. Altogether, the promising results of research identified can enable strategies to improve solubility and efficacy of BNZ, as well as therapy for Chagas disease.
- Real-life closeness of social media contacts and depressive symptoms among university students. [Journal Article]
- JAJ Am Coll Health 2018 Feb 16; :0
- CONCLUSIONS: Having no in-person relationship with SM contacts is associated with increased depressive symptoms; however, having close in-person relationships with SM contacts is associated with decreased depressive symptoms.
- Optimal Items for Assessing Sluggish Cognitive Tempo in Children Across Mother, Father, and Teacher Ratings. [Journal Article]
- JCJ Clin Child Adolesc Psychol 2018 Feb 16; :1-15
- A recent meta-analysis identified optimal items for assessing sluggish cognitive tempo (SCT) as distinct from attention deficit/hyperactivity disorder inattention (ADHD-IN), and a preliminary study w...
A recent meta-analysis identified optimal items for assessing sluggish cognitive tempo (SCT) as distinct from attention deficit/hyperactivity disorder inattention (ADHD-IN), and a preliminary study with teacher ratings of children in the United States found strong support for the convergent and discriminant validity of 15 SCT items. The current study evaluated whether the same 15 SCT items demonstrated convergent and discriminant validity from ADHD-IN in a large, community-based sample of children in Spain, and whether validity results were replicated across mother, father, and teacher ratings. Mothers, fathers, and teachers completed measures of SCT, ADHD-IN, ADHD-hyperactivity/impulsivity, oppositional defiant disorder, limited prosocial emotions, anxiety, depression, shyness, peer rejection, social impairment, and academic impairment on 2,142 Spanish children (49.49% girls; ages 8-13). The 15 SCT symptoms demonstrated convergent validity along with discriminant validity with ADHD-IN across all three informants. The SCT symptom ratings also showed measurement invariance across the informants. In addition, SCT and ADHD-IN factors had different and unique associations with the other symptom and impairment factors. The 15 SCT symptoms identified in this study-consistent across mother, father, and teacher ratings-appear appropriate to serve as a standard symptom set for assessing SCT in children. Use of a common set of symptoms in future studies will advance our understanding of the SCT construct, including its etiology and developmental progression, associations with ADHD and other psychopathologies, links to impairment, and implications for clinical intervention.
- Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. [Review]
- DADepress Anxiety 2018 Feb 16
- The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that ra...
The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that randomly assigned patients (N = 2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill placebo condition. Findings demonstrated moderate placebo-controlled effects of CBT on target disorder symptoms (Hedges' g = 0.56), and small to moderate effects on other anxiety symptoms (Hedges' g = 0.38), depression (Hedges' g = 0.31), and quality of life (Hedges' g = 0.30). Response rates in CBT compared to placebo were associated with an odds ratio of 2.97. Effects on the target disorder were significantly stronger for completer samples than intent-to-treat samples, and for individuals compared to group CBT in SAD and PTSD studies. Large effect sizes were found for OCD, GAD, and acute stress disorder, and small to moderate effect sizes were found for PTSD, SAD, and PD. In PTSD studies, dropout rates were greater in CBT (29.0%) compared to placebo (17.2%), but no difference in dropout was found across other disorders. Interventions primarily using exposure strategies had larger effect sizes than those using cognitive or cognitive and behavioral techniques, though this difference did not reach significance. Findings demonstrate that CBT is a moderately efficacious treatment for anxiety disorders when compared to placebo. More effective treatments are especially needed for PTSD, SAD, and PD.
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- Duration of maternal mental health-related outcomes after an infant's death: A retrospective matched cohort study using linkable administrative data. [Journal Article]
- DADepress Anxiety 2018 Feb 16
- CONCLUSIONS: Elevated rates of depression, anxiety, and psychotropic medication use after the death of a child end within 1 year of the child's death.