The Effectiveness of Cognitive Behavioral Therapy and Emotional Freedom Techniques in Reducing Depression and Anxiety Among Adults: A Pilot Study.
Integr Med (Encinitas). 2016 Apr ;15(2):27-34. PMID: 27330487
Hannah Chatwin, Peta Stapleton, Brett Porter, Sharon Devine, Terri Sheldon
CONTEXT: The World Health Organization (WHO) places major depressive disorder (MDD), or depression, as the fourth leading cause of disability worldwide. Some studies have found that cognitive behavioral therapy (CBT) represents the most superior approach in treating mild to severe symptoms. Recent literature has indicated a number of limitations to this therapeutic approach. An approach that has received increasing attention within the literature is the emotional freedom technique (EFT).
OBJECTIVE: The current pilot study aimed to evaluate the effectiveness of CBT and EFT in the treatment of depression and comorbid anxiety.
DESIGN: The research team designed a pilot study structured as a randomized, controlled trial with 2 intervention arms.
SETTING: The study took place at Bond University in Gold Coast, Queensland, Australia.
PARTICIPANTS: Participants (n = 10) were local community members who had screened positive for a primary diagnosis of MDD.
INTERVENTION: Participants were randomly assigned to an 8-wk CBT or EFT treatment program, the intervention groups. A sample of individuals from the community was assessed for comparative purposes (control group) (n = 57).
OUTCOME MEASURES: Pre- and postintervention, all participants were interviewed using the Mini-International Neuropsychiatric Interview (MINI) 6.0, and they completed the following validated questionnaires: (1) the Beck Depression Inventory, second edition (BDI-2) and (2) the Depression, Anxiety, and Stress Scales (DASS-21).
RESULTS: Findings revealed that both treatment approaches produced significant reductions in depressive symptoms, with the CBT group reporting a significant reduction postintervention, which was not maintained with time. The EFT group reported a delayed effect involving a significant reduction in symptoms at the 3- and 6-mo follow-ups only. Examination of the individual cases revealed clinically significant improvements in anxiety across both interventions.
CONCLUSIONS: Overall, the findings provide evidence to suggest that EFT might be an effective treatment strategy worthy of further investigation.
Article Published Date : Mar 31, 2016
Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial.
J Child Psychol Psychiatry. 2015 May ;56(5):509-20. Epub 2014 Aug 22. PMID: 25146492
Adrian Raine, Jill Portnoy, Jianghong Liu, Tashneem Mahoomed, Joseph R Hibbeln
BACKGROUND: While limited evidence suggests that omega-3 supplementation may reduce antisocial behavior in children, studies have not reported on posttreatment follow-up and most treatment periods have been of short duration. This study tests the hypothesis that omega-3 supplementation over 6 months will reduce behavior problems in children both at the end of treatment and at 6 months post treatment.
METHODS: In this randomized, double-blind, placebo-controlled, stratified, parallel-group trial, a community sample of 8-16 year old children were randomized into a treatment group (N = 100) and a placebo-control group (N = 100). The supplementation consisted of a fruit drink containing 1 g/day of omega-3 or a placebo consisting of the same fruit drink without omega-3. Participants, caregivers, and research assistants were blinded to group assignment. The primary outcome measures of externalizing and internalizing behavior problems were reported by both caregivers and their children in a laboratory setting at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months post treatment), together with the secondary outcome measures of parental antisocial behavior. Data were analyzed on an intention-to-treat basis including all participants.
TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/ct2/show/NCT02016079?term=mauritius&rank=2 RESULTS: Significant group × time interactions were observed with the treatment group showing long-term improvements in child behavior problems. The average posttreatment effect size was d = -.59. Effects were documented for parent reports, but with the exception of proactive and reactive aggression, child-report data were nonsignificant. Parents whose children took omega-3 showed significant posttreatment reductions in their own antisocial and aggressive behavior. This improvement in caregiver behavior partly mediated the improvements observed in child behavior.
CONCLUSIONS: Findings provide initial evidence that omega-3 supplementation can produce sustained reductions in externalizing and internalizing behavior problems. Results are the first to report improvements in caregiver behavior, and to establish this improvement as a part-mechanism for the efficacy of omega-3.
Article Published Date : Apr 30, 2015
Meditation experts try Virtual Reality Mindfulness: A pilot study evaluation of the feasibility and acceptability of Virtual Reality to facilitate mindfulness practice in people attending a Mindfulness conference.
PLoS One. 2017;12(11):e0187777
Authors: Navarro-Haro MV, López-Del-Hoyo Y, Campos D, Linehan MM, Hoffman HG, García-Palacios A, Modrego-Alarcón M, Borao L, García-Campayo J
Regular mindfulness practice benefits people both mentally and physically, but many populations who could benefit do not practice mindfulness. Virtual Reality (VR) is a new technology that helps capture participants' attention and gives users the illusion of "being there" in the 3D computer generated environment, facilitating sense of presence. By limiting distractions from the real world, increasing sense of presence and giving people an interesting place to go to practice mindfulness, Virtual Reality may facilitate mindfulness practice. Traditional Dialectical Behavioral Therapy (DBT®) mindfulness skills training was specifically designed for clinical treatment of people who have trouble focusing attention, however severe patients often show difficulties or lack of motivation to practice mindfulness during the training. The present pilot study explored whether a sample of mindfulness experts would find useful and recommend a new VR Dialectical Behavioral Therapy (DBT®) mindfulness skills training technique and whether they would show any benefit. Forty four participants attending a mindfulness conference put on an Oculus Rift DK2 Virtual Reality helmet and floated down a calm 3D computer generated virtual river while listening to digitized DBT® mindfulness skills training instructions. On subjective questionnaires completed by the participants before and after the VR DBT® mindfulness skills training session, participants reported increases/improvements in state of mindfulness, and reductions in negative emotional states. After VR, participants reported significantly less sadness, anger, and anxiety, and reported being significantly more relaxed. Participants reported a moderate to strong illusion of going inside the 3D computer generated world (i.e., moderate to high "presence" in VR) and showed high acceptance of VR as a technique to practice mindfulness. These results show encouraging preliminary evidence of the feasibility and acceptability of using VR to practice mindfulness based on clinical expert feedback. VR is a technology with potential to increase computerized dissemination of DBT® skills training modules. Future research is warranted.
PMID: 29166665 [PubMed - in process]
Risk of Diabetes Mellitus Among Medicaid Beneficiaries in Hawaii.
Prev Chronic Dis. 2017 Nov 22;14:E116
Authors: Li D, Chinn CC, Fernandes R, Wang CMB, Smith MD, Ozaki RR
INTRODUCTION: Medicaid is the largest primary health insurance for low-income populations in the United States, and it provides comprehensive benefits to cover treatment and services costs for chronic diseases, including diabetes. The standardized per capita spending on diabetes by Medicare beneficiaries enrolled in the fee-for-service program in Hawaii increased from 2012 to 2015. We examined the difference in odds of diabetes between Medicaid and non-Medicaid populations in major racial/ethnic groups in Hawaii.
METHODS: We used data from 2013 through 2015 from the Hawaii Behavioral Risk Factor Surveillance System in this cross-sectional study to compare the difference in risk for self-reported diabetes between Medicaid (n = 1,889) and non-Medicaid (n = 17,207) beneficiaries. We used multivariate logistic regression models that could accommodate the complex sampling design to examine the difference in odds of diabetes between the 2 populations.
RESULTS: In Hawaii, the Medicaid population was younger, was less educated, had more health impairments, and was more likely to be obese and Native Hawaiian/Other Pacific Islander (NH/OPI) than the non-Medicaid population. The unadjusted prevalence of diabetes in the Medicaid population in Hawaii was higher than that for the non-Medicaid population (10.3% vs 8.9%, P = .02). After adjusting for confounding variables, the odds of diabetes in the Medicaid population was still significantly higher than those in the non-Medicaid population (adjusted odds ratio [AOR] = 1.75; 95% confidence interval [CI], 1.33-2.31). Adjusted analysis stratified by race/ethnicity showed that non-Hispanic Asian (AOR = 2.23; 95% CI, 1.31-3.78) and NH/OPI (AOR = 3.17; 95% CI, 1.05-9.54) Medicaid beneficiaries had significantly higher odds of diabetes than their non-Medicaid counterparts.
CONCLUSION: The odds of diabetes was significantly higher among the Hawaii Medicaid population than among the non-Medicaid population. Diabetes prevention programs should address the challenges and barriers that the Medicaid population faces. Our findings can be used to promote culturally competent diabetes education programs.
PMID: 29166251 [PubMed - in process]
The gamma-aminobutyric acid-B receptor (GABAB)encephalitis:Clinical manifestations and response to immunotherapy.
Int J Neurosci. 2017 Nov 22;:1-21
Authors: Cui J, Bu H, He J, Zhao Z, Han W, Gao R, Li X, Li Q, Guo X, Zou Y
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyse the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes.
METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated.
RESULTS: Seven of the eleven patients were males, and a mean age at presentation of 63 years (range: 47-79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11), fever (3/11). GABA-B receptor antibody was positive in serum and/or CSF in 11 patients. Small-cell lung cancer was detected in 5 patients. EEG monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in 5 patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (case 8,9) with tumors had a poor one, one patient (case 10) died of status epilepticus.
CONCLUSION: Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.
PMID: 29166136 [PubMed - as supplied by publisher]
[Healthier after Psychotherapy? Analysis of Claims Data (Lower Saxony, Germany) on Sickness Absence Duration before and after Outpatient Psychotherapy].
Psychother Psychosom Med Psychol. 2017 Nov 17;:
Authors: Epping J, de Zwaan M, Geyer S
Introduction In employed populations sickness absence can be used as a good indicator of health status. In the present study, it was examined how periods of sickness absence are developing within one year before and after psychotherapy under comparison of three types of psychotherapy (behavior therapy, psychodynamic psychotherapy, and psychoanalysis), all fully covered by statutory health insurance. Methods and data The analyses were performed with pseudonymized claims data from the AOK Niedersachsen, a statutory health insurance (N=2,900,065 insured). Certified sickness absences before and after psychotherapy were examined for 9,916 patients. Parallelized controls were used to build a comparison of the length of sickness absences. Analyses were performed separately for women and for men. Results Within one year before starting psychotherapy, patients had longer sickness absences than controls on average. There was a reduction in the length of sickness absence of 20 days (median) within one year before to 12 days (median) within one year after the psychotherapy. The obtained differences between types of psychotherapy were considerable. Discussion Differences in terms of sickness absences may in part be explained by socio-demographic differences. Patients who underwent psychoanalysis were younger and had higher educational levels. However, it remains unclear why the differences of sickness absence periods were that high. It has to be discussed whether self-selection of patients with better health into psychoanalysis had occurred. Conclusions Patients undergoing psychoanalysis differ from patients who underwent other types of psychotherapy in terms of their duration of sickness absence as well as socio-demographic profile. Thus, due to differences in the composition of patients future research in psychotherapy will have to differentiate by type of psychotherapy.
PMID: 29165722 [PubMed - as supplied by publisher]
Effects of pharmacologic and nonpharmacologic interventions on insomnia symptoms and subjective sleep quality in women with hot flashes: A pooled analysis of individual participant data from 4 MsFLASH trials.
Sleep. 2017 Nov 20;:
Authors: Guthrie KA, Larson JC, Ensrud KE, Anderson GL, Carpenter JS, Freeman EW, Joffe H, LaCroix AZ, Manson JE, Morin CM, Newton KM, Otte J, Reed SD, McCurry SM
Study Objectives: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCT) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects relative to control in women with comparably severe insomnia symptoms and VMS.
Methods: We analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) >12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included: Escitalopram 10-20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8-12 weeks of treatment.
Results: CBT-I produced the greatest reduction in ISI from baseline relative to control at -5.2 points (95% CI -7.0 to -3.4). Effects on ISI were similar for exercise at -2.1 and venlafaxine at -2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at -2.7 points (-3.9 to -1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol and venlafaxine. Omega-3 supplements did not improve insomnia symptoms.
Conclusions: This study's findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS.
ClinicalTrials.gov Identifiers: NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), NCT01418209 (MsFLASH 03) and NCT01936441 (MsFLASH 04).
PMID: 29165623 [PubMed - as supplied by publisher]
Recent trends in tobacco use and new insights into strategies to reduce use and improve treatment.
Nicotine Tob Res. 2017 Nov 18;:
Authors: Hitsman B
PMID: 29165622 [PubMed - as supplied by publisher]
Metabolic Syndrome and Cardiovascular Risk in People Treated with Long-Acting Injectable Antipsychotics.
Endocr Metab Immune Disord Drug Targets. 2017 Nov 20;:
Authors: Sanchez-Martinez V, Romero-Rubio D, Abad-Perez MJ, Descalzo-Cabades MA, Alonso-Gutierrez S, Salazar-Fraile J, Montagud V, Facila L
BACKGROUND: People with schizophrenia and other severe mental disorders have an increased mortality mainly attributed to natural causes, specifically cardiovascular disease and cancer. The metabolic syndrome and the Framingham Risk Score are epidemiologic tools related to long-term cardiovascular disease risk and they are increased in people with severe mental disorders. This increase has been attributed both to the disorder itself and to the use of antipsychotic drugs.
OBJECTIVE: To quantify the cardiovascular risk in a group of people treated with long-acting injectable antipsychotics.
METHODS: This is a cross-sectional study developed in an outpatient mental health clinic in which the prevalence of metabolic syndrome was estimated and the cardiovascular risk was measured using the Framingham Risk Score. All the analyses were separated by gender.
RESULTS: 130 people (81 men) were recruited. According to the International Diabetes Federation criteria, 60 participants (46,2%) had metabolic syndrome. The individual criterion most often met in both genders was obesity. The mean Framingham Risk Score for the sample was moderate, 7,7 (SD: 6,3). For women, the risk was lower (mean 5,7, SD: 4,9) than for men (mean=9, SD: 6,7). There were no significant differences in the prevalence of metabolic syndrome and Framingham Risk Scores by long-acting injectable antipsychotic or years of treatment.
CONCLUSION: The prevalence of metabolic syndrome and the cardiovascular risk are high in people with psychosis treated with long acting injectable antipsychotics. To better address this vulnerability, the recommendations involve both behavioral and pharmacological interventions.
PMID: 29165095 [PubMed - as supplied by publisher]
Role of flunarizine hydrochloride in secondary brain injury following intracerebral hemorrhage in rats.
Int J Immunopathol Pharmacol. 2017 Nov 01;:394632017742224
Authors: Niu J, Hu R
This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.
PMID: 29164980 [PubMed - as supplied by publisher]
Psychosis as a sequelae of paraneoplastic syndrome in Small- Cell Lung Carcinoma: A psycho-neuroendocrine interface.
Clin Schizophr Relat Psychoses. 2017 Nov 22;:
Authors: Wilkins CM, Johnson VL, Fargason RE, Birur B
In 2013 more than 150,000 Americans died from all types of lung cancer. Small cell lung cancer (SCLC) represents about 13% of all lung cancers and is notoriously associated with paraneoplastic syndromes (PNS). Here we present an interesting case of psychosis associated with one such PNS-- ectopic Cushing syndrome of SCLC. A 56 year old African-American male with no prior psychiatric history who was diagnosed with SCLC two months prior, presented to the ER for treatment of a right arm laceration he sustained while fighting off attackers, with high concern these individuals may have been part of hallucinatory experiences and well-systematized persecutory delusions regarding his wife. Physical assessment was notable for Cushingoid symptoms. Initial results of serum ACTH and cortisol were 221pg/ml (10-50pg/ml) and 37.1 mcg/dl (10-20mcg/dl) respectively. For psychosis, patient was started on Olanzapine which was titrated from 5 to final dose of 10mg nightly. Since patient was not a surgical candidate, he was treated with metyrapone 250 mg BID and radiation therapy was continued throughout hospitalization. Serum Cortisol level decreased steadily after initiation of metyrapone and psychotic symptoms dramatically reduced on olanzapine, metyrapone, and radiation therapy with apparently resolved persecutory delusions at discharge. This case broadens the available literature and provides data on successful symptomatic treatment with olanzapine while biological treatments of the underlying condition were beginning to take effect. As SCLC remains an important cause of morbidity and mortality in the US, it is imperative that physicians be aware of paraneoplastic syndromes and their psychiatric sequelae.
PMID: 29164929 [PubMed - as supplied by publisher]
A Case of a Patient with Residual Symptoms of Schizophrenia who Relapsed Following Treatment with the Topical Corticosteroid, Clobetasol: A Review of its Risk of Systemic Absorption and Possibility of Exacerbating Psychosis.
Clin Schizophr Relat Psychoses. 2017 Nov 22;:
Authors: Spiegel DR, Arsani U, Le S
Almost fifty percent of patients with schizophrenia experience some type of dermatitis. The standard treatment for dermatitis is a topical corticosteroid. Despite their demonstrated effectiveness, topical corticosteroids are associated with various side effects that may limit their use. These include generalized adverse effects from systemic absorption, such as suppression of the hypothalamic-pituitary-adrenal axis. While dose-related, oral corticosteroid-induced psychiatric symptoms, such as psychosis, are well documented, the literature is devoid of cases of topical corticosteroids precipitating psychosis. We present a case of a patient with schizophrenia who developed morphea. She was liberally treated with the potent topical corticosteroid clobetasol, possibly resulting in a "supraphysiologic exposure." Subsequently, our patient developed an exacerbation of activephase symptoms of schizophrenia. After clobetasol administration was reduced, these active phase symptoms dissipated.
PMID: 29164927 [PubMed - as supplied by publisher]
Who benefits from adolescent sleep interventions? Moderators of treatment efficacy in a randomized controlled trial of a cognitive-behavioral and mindfulness-based group sleep intervention for at-risk adolescents.
J Child Psychol Psychiatry. 2017 Nov 22;:
Authors: Blake MJ, Blake LM, Schwartz O, Raniti M, Waloszek JM, Murray G, Simmons JG, Landau E, Dahl RE, McMakin DL, Dudgeon P, Trinder J, Allen NB
BACKGROUND: The aim of this study was to test moderators of therapeutic improvement in an adolescent cognitive-behavioral and mindfulness-based group sleep intervention. Specifically, we examined whether the effects of the program on postintervention sleep outcomes were dependent on participant gender and/or measures of sleep duration, anxiety, depression, and self-efficacy prior to the interventions.
METHOD: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 59.34%; mean age = 14.48 years, range 12.04-16.31 years) who had elevated levels of sleep problems and anxiety symptoms. Participants were randomized into either a group sleep improvement intervention (n = 63) or group active control 'study skills' intervention (n = 60). The sleep intervention ('Sleep SENSE') was cognitive behavioral in approach, incorporating sleep education, sleep hygiene, stimulus control, and cognitive restructuring, but also had added anxiety-reducing, mindfulness, and motivational interviewing elements. Components of the active control intervention ('Study SENSE') included personal organization, persuasive writing, critical reading, referencing, memorization, and note taking. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Children's Anxiety Scale (SCAS), Center for Epidemiologic Studies Depression Scale (CES-D), and General Self-Efficacy Scale (GSE) and wore an actigraph and completed a sleep diary for five school nights prior to the interventions. Sleep assessments were repeated at postintervention. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001177842; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12612001177842&isBasic=True).
RESULTS: The results showed that compared with the active control intervention, the effect of the sleep intervention on self-reported sleep quality (PSQI global score) at postintervention was statistically significant among adolescents with relatively moderate to high SCAS, CES-D, and GSE prior to the intervention, but not among adolescents with relatively low SCAS, CES-D, and GSE prior to the intervention. The results were consistent across genders. However, the effects of the sleep intervention on actigraphy-measured sleep onset latency and sleep diary-measured sleep efficiency at postintervention were not dependent on actigraphy-measured total sleep time, SCAS, CES-D, or GSE prior to the intervention.
CONCLUSIONS: This study provides evidence that some sleep benefits of adolescent cognitive-behavioral sleep interventions are greatest among those with higher levels of anxiety and depressive symptoms, suggesting that this may be an especially propitious group to whom intervention efforts could be targeted. Furthermore, adolescents with lower levels of self-efficacy may need further targeted support (e.g. additional motivational interviewing) to help them reach treatment goals.
PMID: 29164609 [PubMed - as supplied by publisher]
Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features.
J Mol Neurosci. 2017 Nov 21;:
Authors: Calabrò M, Porcelli S, Crisafulli C, Wang SM, Lee SJ, Han C, Patkar AA, Masand PS, Albani D, Raimondi I, Forloni G, Bin S, Cristalli C, Mantovani V, Pae CU, Serretti A
Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.
PMID: 29164477 [PubMed - as supplied by publisher]
Priorities for Advancing Research on Youth with Autism Spectrum Disorder and Co-occurring Anxiety.
J Autism Dev Disord. 2017 Nov 21;:
Authors: Vasa RA, Keefer A, Reaven J, South M, White SW
Research on anxiety disorders in youth with autism spectrum disorder (ASD) has burgeoned in the past two decades. Yet, critical gaps exist with respect to measuring and treating anxiety in this population. This study used the nominal group technique to identify the most important research priorities on co-occurring anxiety in ASD. An international group of researchers and clinicians with experience in ASD and anxiety participated in the process. Topics ranked as most important focused on understanding how ASD symptoms affect treatment response, implementing treatments in real world settings, developing methods to disentangle overlapping symptoms between anxiety and ASD, and developing objective measures to assess anxiety. Collectively, these priorities can lead to collaborative studies to accelerate research in the field.
PMID: 29164436 [PubMed - as supplied by publisher]
Delayed Development of Feeding Skills in Children with Feeding Difficulties-Cross-sectional Study in a Brazilian Reference Center.
Front Pediatr. 2017;5:229
Authors: Ramos CC, Maximino P, Machado RHV, Bozzini AB, Ribeiro LW, Fisberg M
Background: Delays in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere in the development of feeding skills (FS); and-therefore-in the success of the process of feeding a child. Children with feeding difficulties (FD) commonly present inadequacy of FS.
Objectives: Assessment of five FS in Brazilian children with FD, and search of associations with types of FD.
Methods: Cross-sectional study with 70 children below 10 years old. Data were obtained from medical records: age, gender, age at texture transitions, feeding phase (breastfeeding, weaning to solids or full solids) at first complaint; characteristics of the meal (duration, environment, and shared meals with adults), self-feeding practices, use of feeding equipment and bottle, mouthing, feeding position and FD diagnosis. Skills were categorized according to standards for age. Chi-Square, Anova Test (or non-parametric equivalent) and Multinomial logistic regression tests were used, with a significance level of 5%.
Results: There was no difference in FS (p > 0.05) or in the number of FS inadequateness (p = 0.84) according to FD diagnosis. The majority (94%) of children presented at least one delayed development of FS; 1/3 presented delays in more than half of the FS. The most prevalent inadequacies in FS were inadequate feeding position (73.5%), prolonged bottle feeding (56.9%), and inadequate self-feeding practices (37.9%). Feeding complaints first appeared at 10.9 ± 11.4 months, and picky eating was the most prevalent type of FD (37.1%). Most children were fed in inadequate environments (55.2%), without the company of adults (78%). Transition to solid foods occurred at 16 ± 5.6 months. Multinomial logistic regression showed no difference in likelihood of presenting any type of FD compared to picky eating, according to FS. Age at texture transition both from breastfeeding to complementary feeding (p = 0.95), and from complementary feeding to solid foods (p = 0.43) did not vary according to FD diagnosis.
Conclusion: FS development or number of FS inadequateness did not vary according to FD diagnosis. Identification of these inadequacies could help the discussion for multi-professional treatment of patients with FD.
PMID: 29164081 [PubMed]
Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1.
Front Pediatr. 2017;5:227
Authors: Torres Nupan MM, Velez Van Meerbeke A, López Cabra CA, Herrera Gomez PM
Aim: The last systematic review of research on the behavior of children with neurofibromatosis type 1 (NF1) was in 2012. Since then, several important findings have been published. Therefore, the study aim was to synthesize recent relevant work related to this issue.
Method: We conducted a systematic review of the literature. Relevant articles were identified using the electronic databases PubMed, PsycINFO, and Scopus and a manual search of references lists. Thirty of 156 articles identified met the inclusion criteria. A quality evaluation of the articles was performed and the information was synthesized using a narrative approach.
Results: Compared with controls, children and adolescents with NF1 present significant alterations in language, reading, visuospatial skills, motor function, executive function, attention, behavior, emotion, and social skills. The prevalence of attention-deficit/hyperactivity disorder (ADHD) is important and can affect cognition and executive function variables. A high prevalence of autistic traits and autistic spectrum disorder were reported. The benefits of using statins to treat cognitive deficits are unclear. However, children with NF1 and ADHD seem to benefit from methylphenidate treatment. The presence of hyperintensities in brain magnetic resonance imaging data seem to be related to poor cognitive performance. Analysis of these lesions could help to predict cognitive alterations in children with NF1.
Interpretation: There has been important progress to evaluate cognitive characteristics of children with NF1 and to determine the physiological mechanisms of the concomitant disorders. However, discrepancies in relation to intelligence, learning disabilities, attention deficits, and treatment remain. Further investigations on this topic are recommended.
PMID: 29164079 [PubMed]
Cognitive therapy and eye movement desensitization and reprocessing for reducing psychopathology among disaster-bereaved individuals: study protocol for a randomized controlled trial.
Eur J Psychotraumatol. 2017;8(1):1388710
Authors: Lenferink LIM, Piersma E, de Keijser J, Smid GE, Boelen PA
Background: Confrontation with a traumatic (e.g. disaster-related) loss is a risk factor for the development of psychopathology, including symptoms of prolonged grief (PG), posttraumatic stress (PTS), and depression. Although interventions have been developed for reducing post-loss psychopathology, more research into the effectiveness of treatment is needed to improve care for bereaved persons. Cognitive therapy (CT) and eye movement desensitization and reprocessing (EMDR) have been shown to be effective in trauma-exposed populations. We hypothesize that CT and EMDR are also effective in reducing symptoms among people exposed to traumatic loss. Objective: In this article we describe the rationale of a randomized controlled trial (RCT) to examine (1) treatment effects of CT and EMDR for reducing PG, PTS, and depression among traumatically bereaved people, and (2) the associations between improvements in PG, PTS, and depression symptoms on the one hand and tentative mechanisms of change, including a sense of unrealness, negative cognitions, avoidance behaviour, and intrusive memories, on the other hand. Method: A two-armed (intervention versus waiting list controls) RCT will be conducted. Participants will be asked to fill in questionnaires prior to treatment, during treatment, and one, 12, and 24 weeks post-treatment. Potential participants are people who have lost one or multiple significant other(s) in the Ukrainian plane disaster in 2014 with clinically significant levels of self-rated PG, PTS, and/or depression. Multiple regression, including analysis of covariance, and multilevel regression analyses will be used. Discussion: There is a need for treatment for psychopathology following traumatic loss. Strengths of this study are the development of a treatment that targets grief and trauma-related complaints and the examination of potential mechanisms of change in CT and EMDR. Bereaved people, clinicians, and researchers could benefit from the results of this study.
PMID: 29163863 [PubMed]
Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats.
Oxid Med Cell Longev. 2017;2017:8510761
Authors: Navarro-Cruz AR, Ramírez Y Ayala R, Ochoa-Velasco C, Brambila E, Avila-Sosa R, Pérez-Fernández S, Morales-Medina JC, Aguilar-Alonso P
The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.
PMID: 29163756 [PubMed - in process]
The Mechanisms Underlying Changes in Broad Dimensions of Psychopathology During Cognitive Behavioral Therapy for Social Anxiety Disorder.
J Clin Med Res. 2017 Dec;9(12):1019-1021
Authors: Ogawa S, Imai R, Suzuki M, Furukawa TA, Akechi T
Background: Social anxiety disorder (SAD) patients commonly have broad dimensions of psychopathology. This study investigated the relationship between a wide range of psychopathology and attention or cognitions during cognitive behavioral therapy (CBT) for SAD.
Methods: We treated 96 SAD patients with group CBT. Using multiple regression analysis, we examined the associations between the changes in broad dimensions of psychopathology and the changes in self-focused attention or maladaptive cognitions in the course of CBT.
Results: The reduction in self-focused attention was related to the decreases in somatization, obsessive-compulsive, interpersonal sensitivity, anxiety, phobic anxiety, and global severity index. The reduction in maladaptive cognitions was associated with decreases in interpersonal sensitivity, depression, and global severity index.
Conclusions: The present study suggests that changes in self-focused attention and maladaptive cognitions may predict broad dimensions of psychopathology changes in SAD patients over the course of CBT. For the purpose of improving a wide range of psychiatric symptoms with SAD patients in CBT, it may be useful to decrease self-focus attention and maladaptive cognitions.
PMID: 29163737 [PubMed]
A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson's Disease.
Front Psychiatry. 2017;8:214
Authors: Sauvaget A, Jiménez-Murcia S, Fernández-Aranda F, Granero R, Grall-Bronnec M, Victorri-Vigneau C, Bulteau S, Derkinderen P, Vanelle JM, Hakansson A, Mestre-Bach G, Steward T, Menchón JM
The administration of dopaminergic medication to treat the symptoms of Parkinson's disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions.
PMID: 29163234 [PubMed]
Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats.
Front Physiol. 2017;8:897
Authors: Diao HL, Xue Y, Han XH, Wang SY, Liu C, Chen WF, Chen L
The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST) showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.
PMID: 29163226 [PubMed]
The Modulatory Properties of Chronic Antidepressant Drugs Treatment on the Brain Chemokine - Chemokine Receptor Network: A Molecular Study in an Animal Model of Depression.
Front Pharmacol. 2017;8:779
Authors: Trojan E, Ślusarczyk J, Chamera K, Kotarska K, Głombik K, Kubera M, Basta-Kaim A
An increasing number of studies indicate that the chemokine system may be the third major communication system of the brain. Therefore, the role of the chemokine system in the development of brain disorders, including depression, has been recently proposed. However, little is known about the impact of the administration of various antidepressant drugs on the brain chemokine - chemokine receptor axis. In the present study, we used an animal model of depression based on the prenatal stress procedure. We determined whether chronic treatment with tianeptine, venlafaxine, or fluoxetine influenced the evoked by prenatal stress procedure changes in the mRNA and protein levels of the homeostatic chemokines, CXCL12 (SDF-1α), CX3CL1 (fractalkine) and their receptors, in the hippocampus and frontal cortex. Moreover, the impact of mentioned antidepressants on the TGF-β, a molecular pathway related to fractalkine receptor (CX3CR1), was explored. We found that prenatal stress caused anxiety and depressive-like disturbances in adult offspring rats, which were normalized by chronic antidepressant treatment. Furthermore, we showed the stress-evoked CXCL12 upregulation while CXCR4 downregulation in hippocampus and frontal cortex. CXCR7 expression was enhanced in frontal cortex but not hippocampus. Furthermore, the levels of CX3CL1 and CX3CR1 were diminished by prenatal stress in the both examined brain areas. The mentioned changes were normalized with various potency by chronic administration of tested antidepressants. All drugs in hippocampus, while tianeptine and venlafaxine in frontal cortex normalized the CXCL12 level in prenatally stressed offspring. Moreover, in hippocampus only fluoxetine enhanced CXCR4 level, while fluoxetine and tianeptine diminished CXCR7 level in frontal cortex. Additionally, the diminished by prenatal stress levels of CX3CL1 and CX3CR1 in the both examined brain areas were normalized by chronic tianeptine and partially fluoxetine administration. Tianeptine modulate also brain TGF-β signaling in the prenatal stress-induced animal model of depression. Our results provide new evidence that not only prenatal stress-induced behavioral disturbances but also changes of CXCL12 and their receptor and at less extend in CX3CL1-CX3CR1 expression may be normalized by chronic antidepressant drug treatment. In particular, the effect on the CXCL12 and their CXCR4 and CXCR7 receptors requires additional studies to elucidate the possible biological consequences.
PMID: 29163165 [PubMed]
Transcranial Random Noise Stimulation Does Not Improve Behavioral and Neurophysiological Measures in Patients with Subacute Vegetative-Unresponsive Wakefulness State (VS-UWS).
Front Hum Neurosci. 2017;11:524
Authors: Mancuso M, Abbruzzese L, Canova S, Landi G, Rossi S, Santarnecchi E
Background: The absence of efficient treatments capable to promote central nervous system recovery in patients in vegetative state (VS) due to a severe acquired brain injury highlights the need of exploring alternative neuromodulatory treatments that can lead to neurobehavioral gains. Some encouraging preliminary observations suggest that transcranial direct current stimulation could be effective in disorders of consciousness (DoC) patients, especially when applied on the dorsolateral prefrontal cortex (DLPFC) in patients with minimally conscious state (MCS) but not in those with VS. Objective: The primary aim of the present study was to verify if the application of transcranial random noise stimulation (tRNS) on the DLPFC might favor improvements of consciousness recovery in subacute VS-UWS. Methods: Nine patients with DoC due to traumatic brain injury (n = 1), anoxia (n = 3), and vascular damage (n = 5), have undergone a randomized, double-blind, sham-controlled, neuromodulatory trial with tRNS of bilateral DLPFC. All patients were in a post-acute phase and the DoC onset ranged from 30 days to 4 months. The diagnosis of DoC was based on internationally established criteria from the Multi-Society Task Force on PVS, and classified as VS or MCS using the JFK Coma Recovery Scale-Revised scores (CRS-R). We used CRS-R, Synek Scale, Ad-Hoc semi-quantitative scale and the Clinical Global Impression-Improvement scale to measure behavioral and electrophysiological changes during tRNS intervention. All patients were also treated with daily conventional rehabilitation treatment. Results: No significant differences emerged between active and sham groups regarding improvements of level of consciousness, as well as on electroencephalographic data. Only one patient showed emergence from VS-UWS, evolving from VS to MCS after the tRNS stimulation, at a distance of 3 weeks from the enrolment into the study. Conclusion: Repeated applications of tRNS of the DLPFC, even if applied in a subacute phase of VS-UWS state, did not modify behavioral and neurophysiological outcomes differently than sham stimulation.
PMID: 29163104 [PubMed]
The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.
Front Behav Neurosci. 2017;11:218
Authors: Manfré G, Clemensson EKH, Kyriakou EI, Clemensson LE, van der Harst JE, Homberg JR, Nguyen HP
Rationale: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype. Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping. Methods: Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance. Results: BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected. Conclusions: The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.
PMID: 29163089 [PubMed]
Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life.
Front Behav Neurosci. 2017;11:214
Authors: Abbas Z, Sweet A, Hernandez G, Arvanitogiannis A
Background: The psychostimulant methylphenidate (MPH) is known to temporarily reduce impulsive choice and promote self-control. What is not sufficiently understood is how repeated treatment with MPH affects impulsive choice in the long run, and whether any such effect is contingent on exposure at certain developmental stages. Methods: Using an animal model for impulsive choice, we examined first whether giving MPH through early adolescence alters delay discounting, an operational measure of impulsive choice, later in adulthood. We then tested whether equivalent long-term effects are observed if exposure to the drug occurred during adulthood. Starting on postnatal day 25 or postnatal day 60, male rats received one of a range of doses of MPH for 10 consecutive days. Twenty-six days later, all rats were trained to choose between a lever that produced a small immediate reward and a lever that produced a large reward after a range of delays. Results: Rats showed a long-term decrease in the selection of the delayed larger reward when treated with moderate doses of MPH during early adolescence, but not when treated with the lower or higher doses. In contrast, no differences were observed in the selection of the delayed larger reward in animals that were treated with various doses of MPH during adulthood. Conclusions: Our findings suggest effects of MPH on impulsive choice that are contingent on dosage and on the developmental period of exposure. When administered during adolescence, moderate doses of MPH increase impulsive choice long after the end of treatment, whereas these same doses administered during adulthood were without effect.
PMID: 29163086 [PubMed]
From Structure to Behavior in Basolateral Amygdala-Hippocampus Circuits.
Front Neural Circuits. 2017;11:86
Authors: Yang Y, Wang JZ
Emotion influences various cognitive processes, including learning and memory. The amygdala is specialized for input and processing of emotion, while the hippocampus is essential for declarative or episodic memory. During emotional reactions, these two brain regions interact to translate the emotion into particular outcomes. Here, we briefly introduce the anatomy and functions of amygdala and hippocampus, and then present behavioral, electrophysiological, optogenetic and biochemical evidence from recent studies to illustrate how amygdala and hippocampus work synergistically to form long-term memory. With recent technological advances, the causal investigations of specific neural circuit between amygdala and hippocampus will help us understand the brain mechanisms of emotion-regulated memories and improve clinical treatment of emotion-associated memory disorders in patients.
PMID: 29163066 [PubMed - in process]
Study of Sex Differences in Duloxetine Efficacy for Depression in Transgenic Mouse Models.
Front Cell Neurosci. 2017;11:344
Authors: Xu Y, Ma L, Jiang W, Li Y, Wang G, Li R
Clinical evidences show sex differences in risk of developing depressive disorders as well as effect of antidepressants in depression treatment. However, whether such a sex-dependent risk of depression and efficacy of antidepressants is dependent on endogenous estrogen level remain elusive. The aim of this study is to explore the molecular mechanisms of sex differences in antidepressant duloxetine. In the present study, we used genetic knockout or overexpression estrogen-synthesizing enzyme aromatase (Ar) gene as models for endogenous estrogen deficiency and elevation endogenous estrogen, respectively, to examine the anti-depressive efficacy of duloxetine in males and females by force swimming test (FST). We also measured the sex-specific effect of duloxetine on dopamine and serotonin (5-HT) metabolisms in frontal cortex and hippocampus (HPC). Elevation of brain endogenous estrogen in male and female mice showed a reduction of immobility time in FST compared to control mice. Estrogen deficiency in females showed poor response to duloxetine treatment compared to sex-matched wildtype (WT) or aromatase transgenic mice. In contrast, male mice with estrogen deficiency showed same anti-depressive response to duloxetine treatments as aromatase transgenic mice. Our data showed that the sex different effect of endogenous estrogen on duloxetine-induced anti-depressive behavioral change is associated with brain region-specific changes of dopamine (DA) and 5-HT system. Endogenous estrogen exerts antidepressant effects in both males and females. Lacking of endogenous estrogen reduced antidepressive effect of duloxetine in females only. The endogenous estrogen level alters 5-HT system in female mainly, while both DA and 5-HT metabolisms were regulated by endogenous estrogen levels after duloxetine administration.
PMID: 29163055 [PubMed]
Combination Therapy in Fragile X Syndrome; Possibilities and Pitfalls Illustrated by Targeting the mGluR5 and GABA Pathway Simultaneously.
Front Mol Neurosci. 2017;10:368
Authors: Zeidler S, de Boer H, Hukema RK, Willemsen R
Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability and autism. The disorder is characterized by altered synaptic plasticity in the brain. Synaptic plasticity is tightly regulated by a complex balance of different synaptic pathways. In FXS, various synaptic pathways are disrupted, including the excitatory metabotropic glutamate receptor 5 (mGluR5) and the inhibitory γ-aminobutyric acid (GABA) pathways. Targeting each of these pathways individually, has demonstrated beneficial effects in animal models, but not in patients with FXS. This lack of translation might be due to oversimplification of the disease mechanisms when targeting only one affected pathway, in spite of the complexity of the many pathways implicated in FXS. In this report we outline the hypothesis that targeting more than one pathway simultaneously, a combination therapy, might improve treatment effects in FXS. In addition, we present a glance of the first results of chronic combination therapy on social behavior in Fmr1 KO mice. In contrast to what we expected, targeting both the mGluR5 and the GABAergic pathways simultaneously did not result in a synergistic effect, but in a slight worsening of the social behavior phenotype. This does implicate that both pathways are interconnected and important for social behavior. Our results underline the tremendous fine-tuning that is needed to reach the excitatory-inhibitory balance in the synapse in relation to social behavior. We believe that alternative strategies focused on combination therapy should be further explored, including targeting pathways in different cellular compartments or cell-types.
PMID: 29163043 [PubMed]
Three Dimensional Honeycomb Patterned Fibrinogen Based Nanofibers Induce Substantial Osteogenic Response of Mesenchymal Stem Cells.
Sci Rep. 2017 Nov 21;7(1):15947
Authors: Nedjari S, Awaja F, Altankov G
Stem cells therapy offers a viable alternative for treatment of bone disorders to the conventional bone grafting. However clinical therapies are still hindered by the insufficient knowledge on the conditions that maximize stem cells differentiation. Hereby, we introduce a novel 3D honeycomb architecture scaffold that strongly support osteogenic differentiation of human adipose derived mesenchymal stem cells (ADMSCs). The scaffold is based on electrospun hybrid nanofibers consisting of poly (L-lactide ε-caprolactone) and fibrinogen (PLCL/FBG). Classical fibers orientations, random or aligned were also produced and studied for comparison. The overall morphology of ADMSC's generally followed the nanofibers orientation and dimensionality developing regular focal adhesions and direction-dependent actin cytoskeleton bundles. However, there was an initial tendency for cells rounding on honeycomb scaffolds before ADMSCs formed a distinct bridging network. This specific cells organization appeared to have significant impact on the differentiation potential of ADMSCs towards osteogenic lineage, as indicated by the alkaline phosphatase production, calcium deposition and specific genes expression. Collectively, it was observed synergistic effect of nanofibers with honeycomb architecture on the behavior of ADMSCs entering osteogenic path of differentiation which outlines the potential benefits from insertion of such bioinspired geometrical cues within scaffolds for bone tissue engineering.
PMID: 29162855 [PubMed - in process]
TrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response.
Nat Commun. 2017 Nov 21;8(1):1668
Authors: Ma Z, Zang T, Birnbaum SG, Wang Z, Johnson JE, Zhang CL, Parada LF
Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at the cellular level to sustain this anti-depressive function for prolonged periods remains unclear. Here we report that ketamine accelerates differentiation of doublecortin-positive adult hippocampal neural progenitors into functionally mature neurons. This process requires TrkB-dependent ERK pathway activation. Genetic ablation of TrkB in neural stem/progenitor cells, or pharmacologic disruption of ERK signaling, or inhibition of adult neurogenesis, each blocks the ketamine-induced behavioral responses. Conversely, enhanced ERK activity via Nf1 gene deletion extends the response and rescues both neurogenic and behavioral deficits in mice lacking TrkB. Thus, TrkB-dependent neuronal differentiation is involved in the sustained antidepressant effects of ketamine.
PMID: 29162814 [PubMed - in process]
Renal damage in the metabolic syndrome (MetSx): Disorders implicated.
Eur J Pharmacol. 2017 Nov 18;:
Authors: Joyce T, Irasema CY, Natalia MT, Jose PC
The prevalence of metabolic syndrome is increasing worldwide and has become a risk factor for the development of chronic kidney disease. The complex linkage between metabolic syndrome and chronic kidney disease is under research and the factors involved beyond the biological pathogenesis include demographic, sociological and psychological factors that are related to the metabolic syndrome prevalence. The social context of disease causation is as relevant to today's clinical scientist and practitioner as biomarker-directed risk stratification and therapy. The aim of this review is to compare the criteria for diagnosis among different international health organizations, identifying all factors that contribute to the development of this association between metabolic syndrome and chronic kidney disease, and categorizing them by those that could be useful for preventive strategies. In addition, patients with metabolic syndrome have microvascular disease characterized by microalbuminuria, decreased glomerular filtration rate, tubular atrophy, interstitial fibrosis, and glomerulosclerosis. These effects may be due to insulin resistance, hypertension, dyslipidemias, activation of inflammatory processes, fibrotic, dysbiosis and generation of oxidative stress; which cause an imbalance in the main vasoactive factors and thus endothelial dysfunction, deteriorating the renal function. Furthermore, since unhealthy eating habits and a sedentary lifestyle are among the strongest risk factors related to these diseases, lifestyle interventions programs have been recommended for facilitating positive changes in behavior at the individual level. However, further research is needed to promote multiple social, economic and political transformations, shifting the intervention emphasis from individual education, counseling, regimens and medications to community, national and global institutions.
PMID: 29162432 [PubMed - as supplied by publisher]
Can Mindfulness Training Improve Medication Adherence? Integrative Review of the Current Evidence and Proposed Conceptual Model.
Explore (NY). 2017 Oct 23;:
Authors: Salmoirago-Blotcher E, Carey MP
Medication adherence is a complex, multi-determined behavior that is often influenced by system- (e.g., cost), drug- (e.g., regimen complexity), and patient-related (e.g., depression) factors. System-level approaches (e.g., making medications more affordable) are critically important but do not address patient-level factors that can undermine adherence. In this paper, we identify patient-level determinants of non-adherence and discuss whether mindfulness-training approaches that target these determinants can help to improve adherence to medical treatment. We highlight two chronic medical conditions (viz., heart failure and HIV) where poor adherence is a significant concern, and examine the evidence regarding the use of mindfulness interventions to improve medication adherence in these two conditions. We also discuss the theoretical underpinnings of mindfulness training with respect to medication adherence, and conclude by suggesting directions for future research.
PMID: 29162428 [PubMed - as supplied by publisher]
A new approach for the determination of ECAP thresholds.
Cochlear Implants Int. 2017 Nov 22;:1-11
Authors: Hoth S, Spitzer P, Praetorius M
BACKGROUND: Electrically evoked compound action potentials (ECAPs) of the auditory nerve are routinely recorded for testing the cochlear implant integrity and its functional connection to the auditory system. The response thresholds derived from ECAP recordings are widely used as a helpful guide in the fitting of the dynamic range of electric stimulation, although they may not always predict the behavioral thresholds of individuals well. Conventionally, this threshold is based on the identification of a minimum N peak and maximum P peak and linear extrapolation of the resulting amplitude growth function (AGF). As an alternative, a new procedure involving numeric signal processing and requiring less user intervention is presented here. Data acquisition: In 12 adults implanted with MED-EL FLEX28 electrodes, two series of ECAPs were recorded immediately after implantation: (i) a full profile involving all 12 channels across the whole stimulus range in steps of 200 current units and (ii) a high resolution section (20 records in the immediate neighborhood of the threshold) of the AGF in one selected channel. Data treatment: It was observed that N and P wave latencies do not depend on stimulus intensity. Fixed time windows were hence defined for stimulus plus noise and noise alone regions. In these windows, the variance of the compound signal representing response and noise is extracted, whereas the noise variance is extracted from the tail of the curve following this time window. The base line is corrected by fitting an exponential function to reduce stimulus or amplifier artifacts. The response threshold is then derived from the response to noise ratio which should exceed the limit of 6 dB.
RESULTS: The ECAP thresholds obtained from the new procedure coincide well with those determined by the conventional linear extrapolation of the AGF and they correlate to a greater degree with psychometric thresholds than the existing approach.
CONCLUSIONS: The new ECAP algorithm looks promising and may reduce the need for user intervention in determining thresholds.
PMID: 29161976 [PubMed - as supplied by publisher]
Barriers to and Facilitators of Help-Seeking Behavior Among Men Who Experience Sexual Violence.
Am J Mens Health. 2017 Nov 01;:1557988317740665
Authors: Donne MD, DeLuca J, Pleskach P, Bromson C, Mosley MP, Perez ET, Mathews SG, Stephenson R, Frye V
Research on sexual violence and related support services access has mainly focused on female victims; there is still a remarkable lack of research on men who experience sexual violence. Research demonstrates that people who both self-identify as men and are members of sexual-orientation minority populations are at higher risk of sexual violence. They are also less likely to either report or seek support services related to such experiences. The present study is an exploratory one aimed at filling the gap in the literature and better understanding how men, both straight and gay as well as cisgender and transgender, conceptualize, understand, and seek help related to sexual violence. A sample of 32 men was recruited on-line and participated in either a one-on-one in-depth interview ( N = 19) or one of two focus group discussions ( N = 13). All interviews and groups were audiotaped, professionally transcribed and coded using NVivo 9 qualitative software. The present analysis focused on barriers to and facilitators of support service access. Emergent and cross-cutting themes were identified and presented, with an emphasis on understanding what factors may prevent disclosure of a sexual violence experience and facilitate seeking support services and/or professional help. Through this analysis, the research team aims to add knowledge to inform the development of tools to increase service access and receipt, for use by both researchers and service professionals. Although this study contributes to the understanding of the issue of men's experiences of sexual violence, more research with diverse populations is needed.
PMID: 29161934 [PubMed - as supplied by publisher]