Neurology Psychiatry and Brain Research最新文献

{"title":"Changes in inflammation with treatment for bipolar II depression: Pilot trial data on differential effects of psychotherapy and medication","authors":"Jess G. Fiedorowicz ,&nbsp;Jill M. Cyranowski ,&nbsp;Zhuangzhuang Liu ,&nbsp;Holly A. Swartz","doi":"10.1016/j.npbr.2019.07.007","DOIUrl":"10.1016/j.npbr.2019.07.007","url":null,"abstract":"<div><h3>Objectives</h3><p>Limited prospective data, mostly focused on bipolar I disorder, suggests that pro-inflammatory cytokines are elevated in abnormal mood states. We evaluated whether treatment normalizes peripheral markers of inflammation in bipolar II disorder.</p></div><div><h3>Methods</h3><p>Using data from a randomized clinical trial of Interpersonal and Social Rhythm Therapy (IPSRT) + quetiapine vs. IPSRT + placebo for bipolar II depression, we examined whether these treatments for bipolar II depression impact inflammatory cytokines and whether observed changes in cytokines are associated with changes in depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD-17).</p></div><div><h3>Results</h3><p>Cytokine values were available for 33 participants who completed baseline and 20-week follow-up visits. After excluding those with CRP values &gt; = 10 mg/L, there were 27 patients available for analysis (IPSRT + quetiapine N = 10, IPSRT + placebo N = 17). Baseline measure of inflammation did not appear to moderate treatment response, nor was change in HRSD-17 score correlated with changes in cytokines. Those who received IPSRT + quetiapine had significantly greater increases in IL-6 (<em>p</em> = 0.02) and TNF-α (<em>p</em> = 0.04), even after adjusting for changes in body mass index, than the IPSRT alone group. Descriptively, the quetiapine group showed increases in pro-inflammatory and decreases in anti-inflammatory cytokines and the psychotherapy group showed reduced pro-inflammatory cytokines.</p></div><div><h3>Conclusions</h3><p>Despite both groups showing depression improvement, this small study suggests a more pro-inflammatory cytokine profile over time with quetiapine plus psychotherapy compared to psychotherapy alone. Elevated risk of cardiovascular morbidity and mortality among those with bipolar II disorder underscores the importance of delivering treatments that do not exacerbate these risk factors.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 112-118"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37527211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of bipolar I disorder with obsessive compulsive disorder: A clinical study from Pakistan","authors":"Qurat ul ain Khan ,&nbsp;Sana Younus ,&nbsp;Hania Hasan ,&nbsp;Muhammad Zaman Khan","doi":"10.1016/j.npbr.2019.07.003","DOIUrl":"10.1016/j.npbr.2019.07.003","url":null,"abstract":"<div><h3>Background</h3><p>The association and/or comorbidity of bipolar I disorder I (BD I) with obsessive compulsive disorder (OCD) is discussed in the literature. This association is under-recognized in Pakistan causing management problems. This is the first study reporting this association in Pakistan.</p></div><div><h3>Method</h3><p>Retrospective data collection of 500 patients consecutively diagnosed with BD I according to DSM IV-TR was done in inpatient and outpatient settings at a tertiary care setting in Karachi, Pakistan; 469 patients who fulfilled the criteria were included in the study. Patients with BD I with and without OCD were compared for demographics, presenting symptoms, duration of disease, differences in treatment, and other clinical variables.</p></div><div><h3>Results</h3><p>35 (7.5%) of the 469 patients had OCD along with BD I, with more than half having bipolar as the first diagnosis. A majority of the BD I−OCD patients had OCD symptoms during manic phase or in remission, with contamination as the main theme. The BD I−OCD group had a lower level of education, higher divorce rates, a higher incidence of OCD, as well as BD in the family, longer duration of illness, and fewer medical comorbidities.</p></div><div><h3>Limitations</h3><p>This is a retrospective study with patients from both inpatient and outpatient settings from a tertiary care hospital.</p></div><div><h3>Conclusion</h3><p>The association of BD I with OCD needs to be recognized by clinicians, as presentation may be different in this group especially in contextualized settings in Pakistan, where OCD or OCD-like symptoms may be related to BD itself. This finding has important diagnostic and management implications.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 89-92"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83847716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generalized problematic Internet use, depression, and explicit self-esteem: Evidence from the United Arab Emirates","authors":"Zahir Vally","doi":"10.1016/j.npbr.2019.07.002","DOIUrl":"10.1016/j.npbr.2019.07.002","url":null,"abstract":"<div><h3>Background</h3><p>This study estimated the prevalence of generalized problematic Internet use (PIU) in a sample of college-aged young adults resident in the United Arab Emirates. It also assessed associations between PIU, Internet use, and two psychological outcomes, depression and explicit self-esteem.</p></div><div><h3>Methodology</h3><p>The study was cross-sectional. A sample of 706 participants (<em>M</em> = 20.71, <em>SD</em> = 2.13) completed measures of generalized PIU, depression, explicit self-esteem, and a range of demographic variables.</p></div><div><h3>Results</h3><p>PIU was common in this sample, so too was depression, and low self-esteem. PIU did not differ as a result of age, sex, level of education, or marital status. PIU and its factors were consistently predicted by elevated depressive symptoms, increasing duration of daily online time, and diminished ratings of self-esteem.</p></div><div><h3>Conclusion</h3><p>This study serves as the very first estimation of generalized PIU in a sample of young adults resident in this region of the world.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 93-100"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90270521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomanic Tendencies and Lifetime Aggression","authors":"Alan King,&nbsp;Tyler W. Kolander,&nbsp;Jenna Wolff,&nbsp;Matt C. Evans,&nbsp;Ani Mangold","doi":"10.1016/j.npbr.2019.05.008","DOIUrl":"10.1016/j.npbr.2019.05.008","url":null,"abstract":"<div><h3>Background</h3><p>Irritability has been identified a mood-related symptom of the bipolar spectrum disorders, but associations have not been firmly established between (hypo)manic attributes and physical aggression. The Hypomanic Personality Scale (HPS; <span>Eckblad &amp; Chapman, 1986</span>) is a dimensional measure which has been shown in longitudinal studies to predict future bipolar spectrum diagnoses or symptomatology. This study examined relationships between HPS and selected lifetime aggression indicators. HPS factor scores were derived from three different analytic models (<span>Rawlings, Barrantes-Vidal, Claridge, McCreery, &amp; Galanos, 2000</span>; <span>Schalet, Durbin, &amp; Revelle, 2011</span>; &amp; <span>Stanton, McArtor, &amp; Watson, 2017</span>).</p></div><div><h3>Methods</h3><p>College (<em>N</em> = 408) and MTurk (<em>N</em> = 324) samples were examined. The criterion measures provided estimates of the frequency, consequences, and precipitating events of past aggression.</p></div><div><h3>Results</h3><p>HPS associations with the aggression indicators were pervasive and strong (medium to large) in their effect sizes in the MTurk sample. These associations tended to be stronger for the men. The odds of prior lethal threats and/or injuries to other(s) were three to five times higher for respondents in this MTurk sample with an HPS score above 25 as compared to the remaining sample. Factor scores measuring emotional volatility, inflated social confidence, and activation levels were most closely associated with aggressive tendencies. The HPS-20 (<span>Meads &amp; Bentall, 2008</span>) was found to approximate the HPS outcomes.</p></div><div><h3>Limitations</h3><p>This cross-sectional methodology precluded inferences regarding the directionality of the associations. The accuracy of these retrospective self-reports could not be verified.</p></div><div><h3>Conclusions</h3><p>Hypomania appears to be associated with both irritability and self-reported acts of lifetime physical aggression.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 22-31"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.05.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73956288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mediterranean dietary pattern and depression risk: A systematic review","authors":"Areni Altun ,&nbsp;Helen Brown ,&nbsp;Cassandra Szoeke ,&nbsp;Alicia M Goodwill","doi":"10.1016/j.npbr.2019.05.007","DOIUrl":"10.1016/j.npbr.2019.05.007","url":null,"abstract":"<div><h3>Background</h3><p>Depression is a major global health burden and psychiatry requires evidence-based primary prevention and treatment strategies. Evidence suggests that certain dietary patterns, in particular, components of the Mediterranean diet, possess key biological factors associated with abating depressive risk and disease progression. We sought to evaluate the existing evidence regarding the association between the Mediterranean diet and depressive symptoms by conducting a systematic review.</p></div><div><h3>Methods</h3><p>A search of published studies was conducted using the computer databases Medline, Embase, PsychINFO, Scopus and Google Scholar, for articles in the English language published from inception to April 2018. The search strategy applied the following subject headings and keywords: “Mediterranean diet” OR Mediterranean* AND “Major depressive disorder” OR Depress* OR “Negative mood” OR Mood. The NIH quality assessment tool was implemented by reviewers to determine study quality.</p></div><div><h3>Results</h3><p>Results from twenty observational studies and six intervention trials were qualitatively examined. The majority (85%) of observational studies support the evidence that the Mediterranean dietary pattern is associated with reductions in depressive incidence and all intervention studies echoed these findings.</p></div><div><h3>Limitations</h3><p>Methodological disparity in Mediterranean style diets limited comparisons but were overcome by specifying inclusion criteria and compressive appraisal of the data.</p></div><div><h3>Conclusions</h3><p>Modifying diet provides a potential treatment for depression which procures few side effects, lessens disease progression and demonstrates a cost-effective measure that can be implemented globally. Present research has found that more objective measures are necessary to define the Mediterranean diet and highlights the need for longitudinal studies and clinical trials for future research.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 1-10"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.05.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81258679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination effect of Aspirin and N-acetylcysteine against global cerebral ischemic reperfusion injury in rats","authors":"Ravi Chandra Sekhara Reddy Danduga ,&nbsp;Subba Reddy Dondapati ,&nbsp;Phani Kumar Kola ,&nbsp;Sanith Satya Has Kavati ,&nbsp;Meenakshi Seshadri Singapalli","doi":"10.1016/j.npbr.2019.07.006","DOIUrl":"10.1016/j.npbr.2019.07.006","url":null,"abstract":"<div><h3>Aim</h3><p>The study was intended to investigate the combined influence of Aspirin and <em>N</em>-acetylcysteine on global cerebral ischemic reperfusion injury in rats.</p></div><div><h3>Materials and methods</h3><p>The ischemic reperfusion injury was induced by bilateral common carotid artery ligation (BCCA) for 20 min and reperfused for 48 h. The treatment groups Aspirin, <em>N</em>-acetylcysteine and combined treatment groups were administered respective treatments, one week prior to the global ischemia and continued for the next two days. After 24 h of reperfusion, the animals were observed for behavioral assessments and after 48 h, all the animals were sacrificed to estimate oxidative stress parameters, acetylcholinesterase levels, neurochemical analysis in the brain homogenates. The proinflammatory cytokines in serum and histopathological alterations in the cortex and hippocampus (CA1 and CA3) were performed.</p></div><div><h3>Key findings</h3><p>The combined treatment group improved all the behavioral performances in the ischemic reperfuion injured rats than the individual treatment group of animals. Further, decreased the oxidative stress in the combined treatment group than the individual treatment groups. The acetylcholinesterase levels in the brain homogenates and the proinflammatory cytokines in the serum were significantly reduced in the combined treatment group than the individual treatment groups. The neurochemical alterations in the brain were significantly mitigated in the combined treatment group than the individual treatment groups. Further, the neuroprotection of the combined treatment group was confirmed by the histological studies in the cortex and hippocampus (CA1 and CA3).</p></div><div><h3>Significance</h3><p>Hence, the study suggested that the additive effect was observed in the combined treatment group of animals.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 101-111"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88678424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment in patients with treatment resistant schizophrenia: Associations with DRD2, DRD3, HTR2A, BDNF and CYP2D6 genetic polymorphisms","authors":"Dmitriy Sosin ,&nbsp;Dmitriy Ivashchenko ,&nbsp;Zhannet Sozaeva ,&nbsp;Kristina Ryzhikova ,&nbsp;Veronika Fadeeva ,&nbsp;Veronika Chomskaya ,&nbsp;Roman Sheidakov ,&nbsp;Maria Yanushko ,&nbsp;Andrey Otmakhov ,&nbsp;Elena Grishina ,&nbsp;Dmitriy Sychev ,&nbsp;Mikhail Ivanov","doi":"10.1016/j.npbr.2019.06.003","DOIUrl":"10.1016/j.npbr.2019.06.003","url":null,"abstract":"<div><h3>Introduction</h3><p>According to various data, 25–50% of all patients with schizophrenia<span> suffer from treatment resistance. It is believed that patients with treatment-resistant schizophrenia (TRS) have reduced cognitive skills, compared to the patients with a more favourable type of schizophrenia. However, according to some authors, there is limited evidence-based research on this topic at present.</span></p></div><div><h3>Materials and methods</h3><p><span>The total number of patients included 130 patients with a diagnosis of schizophrenia (F20 according to ICD 10). All patients were examined according to the following scales: Positive and Negative Syndrome Scale (PANSS), </span>Global Assessment of Functioning (GAF), Brief Assessment of Cognition in Schizophrenia (BACS).</p></div><div><h3>Results</h3><p>Our results showed that patients with TRS as a whole had worse cognitive functions than nTRS patients (p = 0.357). In the group of patients with TRS, polymorphism <em>CYP2D6*4</em><span> showed an effect on executive functions. Carriers of the heterozygous GA genotype had higher values of executive functions (p = 0.043). No association between the studied gene polymorphic variants and TRS was found in this research.</span></p></div><div><h3>Conclusion</h3><p>The polymorphic variant <em>CYP2D6*4</em><span> showed an effect on cognitive function in the TRS group, regardless of their mental state and the effect of pharmacotherapy. In the future, it will be necessary to conduct larger prospective studies with a greater number of patients and a greater number of polymorphic variants of genes. Further identification of genetic predictors of cognitive impairment<span> will improve researchers’ understanding of their causes and possibly move closer to more targeted therapy for schizophrenia.</span></span></p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 48-55"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78251744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of triiodothyronine on the hippocampal long-term potentiation in an animal model of the Alzheimer's disease: The role of BDNF and reelin","authors":"Sahreh Shabani ,&nbsp;Yaghoob Farbood ,&nbsp;Alireza Sarkaki ,&nbsp;Seyyed Ali Mard ,&nbsp;Akram Ahangarpour ,&nbsp;Layasadat Khorsandi","doi":"10.1016/j.npbr.2019.07.004","DOIUrl":"10.1016/j.npbr.2019.07.004","url":null,"abstract":"<div><p>Converging evidence, propose a close relation between thyroid function and Alzheimer’s disease (AD). We have assessed the effect of subcutaneous and intrahippocampal administrations of triiodothyronine (T3) on the electrophysiological activity (hippocampal long-term potentiation (LTP)), the levels of thyroid hormones (THs) and TSH, the protein expression of BDNF and reelin as well as histological changes in the hippocampus of AD rats. Beta-amyloid (Aβ) plus ibotenic acid (Ibo) were injected intrahippocampally and rats were treated with T3 or saline. The hippocampal levels of THs and the protein expression are measured by ELISA kits and Western blotting method respectively. Results have been shown that T3 (S.C., and I. H), significantly reversed the amplitude and the slope impairment of the DG neurons, induced by Aβ. The hippocampal levels of THs, TSH and two protein expression were significantly decreased (p &lt; 0.001) in AD animals and increased significantly in AD rats that have received T3 (S. C and I. H) (p &lt; 0.01). Formation of amyloid plaques was declined in AD rats treated with T3. In conclusion, both S.C., and I.H. injections of T3 is effective in preventing the disruption of synaptic plasticity induced by Aβ. This positive effect of T3 may be mediated through a regulation of proteins expression and the hippocampal level of THs. The best effect was observed in I.H. microinjection of T3.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 82-88"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77185465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 modulates anxiety and improves autistic like features induced by high fat diet but not valproate","authors":"Mohammed Ali Eshra ,&nbsp;Laila Ahmed Rashed ,&nbsp;Rania Farag A. Eltelbany ,&nbsp;Heba Omar ,&nbsp;Asmaa Mohammed ShamsEldeen","doi":"10.1016/j.npbr.2019.05.006","DOIUrl":"10.1016/j.npbr.2019.05.006","url":null,"abstract":"<div><h3>Background</h3><p>continuous consumption of high-fat diet (HFD) during pregnancy and lactation could alter developmental complexity of higher brain functions and enhance appearance of social withdrawal and anxiety among offsprings. On the contrary, omega-3 fatty acids with its multi-neuro-protective effects could limit oxidative stress production and complications. We aimed to investigate the impact of HFD intake before and during pregnancy till weaning versus prenatal exposure to valproate (as a model of autism) on behavior and brain neurochemistry as well as the possible therapeutic rational of omega-3 intake.</p></div><div><h3>Material and methods</h3><p>After confirmation of G0 day of pregnancy, thirty Sprague–Dawley female rats were divided into: control group fed normal chow (10 kcal% from fat), group II (HFD) mothers supplied with diet of 60 kcal% from fat and group III (HFD-Omega) supplied with 60% HFD enriched with omega-3, group IV (Valp) pregnant females received sodium valproate once i.p, and group V (Valp-Omega) rats received valproate once i.p and diet enriched with omega-3. From day 7 till end of the study, offsprings were subjected to growth, neurodevelopmental assessment and behavioral tests using elevated plus maze and social interaction in open field. Levels of serotonin, GABA, neuropeptide Y, IL-6 and relative gene expression of syntaxin1A and FoxO1 gene were measured.</p></div><div><h3>Results</h3><p>Offsprings born to HFD and Valp-groups demonstrated growth retardation, social withdrawal together with disturbed levels of measured neurotransmitter that were improved in HFD group supplied with omega-3.</p></div><div><h3>Conclusion</h3><p>Omega-3 exhibited to be potential modulator of behavioral changes and autistic-like features induced by HFD.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 11-21"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.05.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73160686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of inflammation modulation on tryptophan and kynurenine pathway regulation in treatment resistant bipolar depression","authors":"Stephen Murata ,&nbsp;Monica Feliz R. Castillo ,&nbsp;Michael Murphy ,&nbsp;Markus Schwarz ,&nbsp;Natalie Moll ,&nbsp;Brendan Martin ,&nbsp;Elif Weidinger ,&nbsp;Bianka Leitner ,&nbsp;Norbert Mueller ,&nbsp;Angelos Halaris","doi":"10.1016/j.npbr.2019.07.001","DOIUrl":"10.1016/j.npbr.2019.07.001","url":null,"abstract":"<div><h3>Background</h3><p>Adjunctive immune-modulation can be safe and effective for treatment-resistant bipolar depression (TRBDD), but molecular work is needed to further characterize the safety and efficacy involved in treatment response and the reversal of treatment resistance. Here we profiled the kynurenine pathway (KP) for biomarkers associated with TRBDD and treatment response to celecoxib (CBX)-augmentation.</p></div><div><h3>Methods</h3><p>47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg twice daily) + CBX (200 mg twice daily), or ESC (10 mg twice daily) + placebo (PBO) (twice daily). Plasma kynurenine pathway (KP) metabolite levels were measured at baseline, week 4, and week 8, and in a healthy control (HC) group of subjects (N = 35) once.</p></div><div><h3>Results</h3><p>Patients receiving ESC + CBX had 4.278 greater odds of responding (<em>p</em> = 0.021) with NNT=3, and 15.300 greater odds of remitting (<em>p</em> &lt; 0.001) with NNT=2, compared with ESC + PBO patients. Study patients exhibited elevated baseline tryptophan (<em>p</em> &lt; 0.001), low kynurenine/tryptophan (<em>p</em> &lt; 0.001), elevated 3-hydryoxykynurenine/kynurenine (adj-<em>p*</em>&lt;0.001), low kynurenic acid/3-hydroxykynurenine, and low picolinic acid/quinolinic acid (<em>p</em> &lt; 0.001) compared to healthy controls. Treatment responders exhibited tryptophan depletion (<em>p</em> = 0.020) without a concomitant change in kynurenine/tryptophan ratio by week 8 (<em>p</em> = 0.163).</p></div><div><h3>Conclusion</h3><p>Clinical response to CBX augmentation is not associated with altered neurotoxic or neuroprotective indices within the time frame of this study. TRBDD revealed alterations in neuroprotective and neurotoxic indices, in the context of low kynurenine/tryptophan and high tryptophan. Treatment responders revealed a depletion in tryptophan by week 8, without concomitant kynurenine pathway (KP) activation.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 65-72"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78461681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}