Pub Date : 2022-04-11DOI: 10.1101/2022.04.04.22273426
M. Jabbi, P. Harvey, R. Kotwicki, C. Nemeroff
Background: Early life adversity such as childhood emotional, physical, and sexual trauma is associated with a plethora of later-life psychiatric and chronic medical conditions, including elevated inflammatory markers. Although previous research suggests a role for chronic inflammatory dysfunctions in several disease etiologies, specific associations between childhood trauma types and later life inflammation and health status are not well understood. Methods: We studied patients (n=280) who were admitted to a psychiatric rehabilitation center. Self-reported histories of childhood emotional, physical, and sexual trauma history were collected. At the time of admission, we also assessed the body mass index (BMI) for each individual and collected blood samples that were used to examine levels of inflammatory marker C-reactive protein (CRP). Results: The prevalence of all three types of abuse was quite high, at 21% or more. 50% of the sample had elevations in CRP, with clinically significant elevations in 26%. We found that compared to a history of emotional or physical abuse, a history of childhood sexual trauma was more specifically associated with elevated CRP. This result held up when controlling for BMI. Limitation: Our sample is relatively young, with an average age of 27.2 years, with a minimal representation of ethnic and racial minority participants. Conclusion: Relative to childhood emotional and physical trauma, childhood sexual trauma may lead to elevated inflammatory responses, which were common overall in the sample. Future studies need to assess the causal link between childhood sexual trauma and poorer health outcomes later in life.
{"title":"Specific Associations Between Type of Childhood Abuse and Elevated C-Reactive Protein in Young Adult Psychiatric Rehabilitation Participants","authors":"M. Jabbi, P. Harvey, R. Kotwicki, C. Nemeroff","doi":"10.1101/2022.04.04.22273426","DOIUrl":"https://doi.org/10.1101/2022.04.04.22273426","url":null,"abstract":"Background: Early life adversity such as childhood emotional, physical, and sexual trauma is associated with a plethora of later-life psychiatric and chronic medical conditions, including elevated inflammatory markers. Although previous research suggests a role for chronic inflammatory dysfunctions in several disease etiologies, specific associations between childhood trauma types and later life inflammation and health status are not well understood. Methods: We studied patients (n=280) who were admitted to a psychiatric rehabilitation center. Self-reported histories of childhood emotional, physical, and sexual trauma history were collected. At the time of admission, we also assessed the body mass index (BMI) for each individual and collected blood samples that were used to examine levels of inflammatory marker C-reactive protein (CRP). Results: The prevalence of all three types of abuse was quite high, at 21% or more. 50% of the sample had elevations in CRP, with clinically significant elevations in 26%. We found that compared to a history of emotional or physical abuse, a history of childhood sexual trauma was more specifically associated with elevated CRP. This result held up when controlling for BMI. Limitation: Our sample is relatively young, with an average age of 27.2 years, with a minimal representation of ethnic and racial minority participants. Conclusion: Relative to childhood emotional and physical trauma, childhood sexual trauma may lead to elevated inflammatory responses, which were common overall in the sample. Future studies need to assess the causal link between childhood sexual trauma and poorer health outcomes later in life.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128776429","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}
This New Drug Application (NDA) was first submitted to the US Food and Drug Administration (FDA) by the Orion Corporation from Finland on January 2, 1998. The final clinical pharmacology review was completed on September 3, 1999. Entacapone is a potent and specific peripheral catechol-O-methyltransferase (COMT) inhibitor. It has been shown to improve the clinical benefits of levodopa plus an aromatic L-amino acid decarboxylase inhibitor (AADC) when given to patients with Parkinson's disease and end-of-dose deterioration in the response to levodopa (the "wearing-off" phenomenon). The drug indication is for Parkinson's disease as an adjunct therapy to levodopa/carbidopa. This is a combination drug with carbidopa (aromatic amino acid decarboxylation inhibitor) and entacapone. It is rapidly absorbed after oral administration of a single dose with peak time generally reached within 1 hour. It is noted that no accumulation of plasma entacapone was detected after 8 daily doses. The maximum daily dose is 2000 mg. In this paper, the clinical pharmacology review of the drug is presented from the perspective of a clinical pharmacologist that reviewed this NDA at the FDA. It should be noted that all the information in this paper is publicly available on the FDA website and in its literature.
{"title":"The Clinical Pharmacology of Entacapone (Comtan®) From the Food and Drug Administration (FDA) Reviewer.","authors":"Sam Habet","doi":"10.1093/ijnp/pyac021","DOIUrl":"https://doi.org/10.1093/ijnp/pyac021","url":null,"abstract":"This New Drug Application (NDA) was first submitted to the US Food and Drug Administration (FDA) by the Orion Corporation from Finland on January 2, 1998. The final clinical pharmacology review was completed on September 3, 1999. Entacapone is a potent and specific peripheral catechol-O-methyltransferase (COMT) inhibitor. It has been shown to improve the clinical benefits of levodopa plus an aromatic L-amino acid decarboxylase inhibitor (AADC) when given to patients with Parkinson's disease and end-of-dose deterioration in the response to levodopa (the \"wearing-off\" phenomenon). The drug indication is for Parkinson's disease as an adjunct therapy to levodopa/carbidopa. This is a combination drug with carbidopa (aromatic amino acid decarboxylation inhibitor) and entacapone. It is rapidly absorbed after oral administration of a single dose with peak time generally reached within 1 hour. It is noted that no accumulation of plasma entacapone was detected after 8 daily doses. The maximum daily dose is 2000 mg. In this paper, the clinical pharmacology review of the drug is presented from the perspective of a clinical pharmacologist that reviewed this NDA at the FDA. It should be noted that all the information in this paper is publicly available on the FDA website and in its literature.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"00 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132291868","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}
A. Daiwile, S. Jayanthi, B. Ladenheim, M. McCoy, Christie Brannock, J. Schroeder, J. Cadet
BACKGROUND Methamphetamine (METH) use disorder (MUD) is prevalent worldwide. There are reports ofsex differences in quantities of drug used and relapses to drug use among individuals with MUD. However, the molecular neurobiology of these potential sex differences remains unknown. METHODS We trained rats to self-administer METH (0. 1 mg/kg/infusion, IV) on a FR-1 schedule for 20 days using two 3-h daily METH sessions separated by 30 min breaks. At the end of self-administration (SA) training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 (WD3) and 30 (WD30). Twenty-four hours later, nucleus accumbens (NAc) was dissected and then used to measure neuropeptide mRNA levels. RESULTS Behavioral results show that male rats increased the number of METH infusions earlier during SA training and took more METH than females. Both male and female rats could be further divided into two phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH SA experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin (Pdyn) and hypocretin/orexin receptors (Hcrtr1/2) than males whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of NAc dynorphin after METH SA. Moreover, there were significant correlations between NAc Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. CONCLUSION Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.
{"title":"Sex differences in escalated methamphetamine self-administration and altered gene expression associated with incubation of methamphetamine seeking.","authors":"A. Daiwile, S. Jayanthi, B. Ladenheim, M. McCoy, Christie Brannock, J. Schroeder, J. Cadet","doi":"10.1093/ijnp/pyz050","DOIUrl":"https://doi.org/10.1093/ijnp/pyz050","url":null,"abstract":"BACKGROUND\u0000Methamphetamine (METH) use disorder (MUD) is prevalent worldwide. There are reports ofsex differences in quantities of drug used and relapses to drug use among individuals with MUD. However, the molecular neurobiology of these potential sex differences remains unknown.\u0000\u0000\u0000METHODS\u0000We trained rats to self-administer METH (0. 1 mg/kg/infusion, IV) on a FR-1 schedule for 20 days using two 3-h daily METH sessions separated by 30 min breaks. At the end of self-administration (SA) training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 (WD3) and 30 (WD30). Twenty-four hours later, nucleus accumbens (NAc) was dissected and then used to measure neuropeptide mRNA levels.\u0000\u0000\u0000RESULTS\u0000Behavioral results show that male rats increased the number of METH infusions earlier during SA training and took more METH than females. Both male and female rats could be further divided into two phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH SA experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin (Pdyn) and hypocretin/orexin receptors (Hcrtr1/2) than males whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of NAc dynorphin after METH SA. Moreover, there were significant correlations between NAc Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats.\u0000\u0000\u0000CONCLUSION\u0000Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131111555","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}
D. Tomasi, C. Wiers, E. Shokri-Kojori, Amna Zehra, Veronica Ramirez, Clara R Freeman, Jamie A. Burns, Christopher Kure Liu, P. Manza, S. W. Kim, Gene-Jack Wang, N. Volkow
BACKGROUND Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. METHODS We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. RESULTS Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. CONCLUSIONS The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.
{"title":"Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity.","authors":"D. Tomasi, C. Wiers, E. Shokri-Kojori, Amna Zehra, Veronica Ramirez, Clara R Freeman, Jamie A. Burns, Christopher Kure Liu, P. Manza, S. W. Kim, Gene-Jack Wang, N. Volkow","doi":"10.1093/ijnp/pyz036","DOIUrl":"https://doi.org/10.1093/ijnp/pyz036","url":null,"abstract":"BACKGROUND\u0000Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated.\u0000\u0000\u0000METHODS\u0000We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT.\u0000\u0000\u0000RESULTS\u0000Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu.\u0000\u0000\u0000CONCLUSIONS\u0000The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116620413","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}
Pub Date : 2014-06-01DOI: 10.1017/S1461145714000091
Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Shih-Heng Chen, Chun-Hsieh Chu, San-Yuan Huang, Nian-Sheng Tzeng, Chen Lin Wang, Liang-Jen Wang, I. Lee, T. Yeh, R. Lu, Yen Kuang Yang, Jau-Shyong Hong
{"title":"Erratum: Genotype variant associated with add-on memantine in bipolar II disorder (International Journal of Neuropsychopharmacology (2014) 17 ( 979))","authors":"Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Shih-Heng Chen, Chun-Hsieh Chu, San-Yuan Huang, Nian-Sheng Tzeng, Chen Lin Wang, Liang-Jen Wang, I. Lee, T. Yeh, R. Lu, Yen Kuang Yang, Jau-Shyong Hong","doi":"10.1017/S1461145714000091","DOIUrl":"https://doi.org/10.1017/S1461145714000091","url":null,"abstract":"","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"20 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120931592","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}
Pub Date : 2013-04-01DOI: 10.1017/S1461145713000114
T. Robbins
![Graphic][1] Peter B. Dews is generally regarded as the ‘father’ of behavioural pharmacology and is especially famous for his early interactions with B. F. Skinner and the introduction of quantitative measurement to the discipline in the 1950s. He was British, being born in Yorkshire, and undertook early medical training at the University of Leeds. He worked under well-known pharmacologists in the UK such as Bain (Leeds), Burn (Oxford) and Gaddum (Manchester) before moving to the US on a Burroughs-Wellcome research fellowship to their facility in New York City where he produced his first major (and most cited) paper (Dews, 1953) on effects of amphetamine, nicotine, cocaine and other drugs on motor activity in mice. He then obtained a PhD at the University of Minnesota and worked at the Mayo Clinic, where he gained his tremendous expertise in statistics. His career took a major step forwards when he moved to Otto Krayer's Department at Harvard, at which point his academic globe-trotting ceased and he spent the rest of his career developing what was to become an eminent laboratory there under his overall direction. His most influential visits to the experimental psychology laboratories at Harvard of Skinner and C. B. Ferster led to the invention of a new paradigm in behavioural pharmacology, which depended on the use of objectively measuring the patterning of operant behaviour over time, … (Email: twr2{at}cam.ac.uk) [1]: /embed/inline-graphic-1.gif
[1] Peter B. Dews通常被认为是行为药理学的“父亲”，尤其以他与B. F. Skinner的早期互动以及在20世纪50年代将定量测量引入该学科而闻名。他是英国人，出生于约克郡，并在利兹大学接受了早期的医学培训。他曾在英国知名药理学家的指导下工作，如贝恩(Bain)(利兹)、伯恩(Burn)(牛津)和加达姆(Gaddum)(曼彻斯特)，之后他以Burroughs-Wellcome的研究奖学金来到美国，在他们位于纽约的机构进行研究，在那里他发表了他的第一篇重要(也是被引用最多的)论文(Dews, 1953)，研究安非他明、尼古丁、可卡因和其他药物对小鼠运动活动的影响。随后，他在明尼苏达大学获得博士学位，并在梅奥诊所工作，在那里他获得了统计学方面的丰富专业知识。当他搬到哈佛大学奥托·克莱耶的系时，他的职业生涯迈出了重要的一步，在这一点上，他停止了学术上的环球旅行，在他的总体指导下，他用余下的职业生涯发展了一个后来成为著名实验室的实验室。他对哈佛大学斯金纳(Skinner)和C. B. Ferster的实验心理学实验室最具影响力的访问导致了行为药理学新范式的发明，该范式依赖于使用客观测量随时间变化的操作性行为模式，[1]:/embed/inline-graphic-1.gif
{"title":"Peter B. Dews (1922–2012)","authors":"T. Robbins","doi":"10.1017/S1461145713000114","DOIUrl":"https://doi.org/10.1017/S1461145713000114","url":null,"abstract":"![Graphic][1] \u0000\u0000Peter B. Dews is generally regarded as the ‘father’ of behavioural pharmacology and is especially famous for his early interactions with B. F. Skinner and the introduction of quantitative measurement to the discipline in the 1950s. He was British, being born in Yorkshire, and undertook early medical training at the University of Leeds. He worked under well-known pharmacologists in the UK such as Bain (Leeds), Burn (Oxford) and Gaddum (Manchester) before moving to the US on a Burroughs-Wellcome research fellowship to their facility in New York City where he produced his first major (and most cited) paper (Dews, 1953) on effects of amphetamine, nicotine, cocaine and other drugs on motor activity in mice. He then obtained a PhD at the University of Minnesota and worked at the Mayo Clinic, where he gained his tremendous expertise in statistics.\u0000\u0000His career took a major step forwards when he moved to Otto Krayer's Department at Harvard, at which point his academic globe-trotting ceased and he spent the rest of his career developing what was to become an eminent laboratory there under his overall direction. His most influential visits to the experimental psychology laboratories at Harvard of Skinner and C. B. Ferster led to the invention of a new paradigm in behavioural pharmacology, which depended on the use of objectively measuring the patterning of operant behaviour over time, … \u0000\u0000(Email: twr2{at}cam.ac.uk)\u0000\u0000 [1]: /embed/inline-graphic-1.gif","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129132772","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}
Pub Date : 2012-05-01DOI: 10.1017/S1461145711001726
C. H. West, J. Weiss
We have read the letter commenting on our article entitled ‘Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum’. We offer the following response. The authors of the letter direct attention to our mean spontaneous firing rate for dopaminergic neurons in the ventral tegmental area (VTA-DA neurons) being lower than typically found and particularly note that we included neurons with firing rates as low as 1.0 Hz. Our mean rates of firing are indeed somewhat lower than often reported by other investigators. We were clearly aware of this, specifically describing in our Methods section that we included slow-firing neurons. Our criteria for DA neurons in the VTA depended upon ( a ) stereotaxic location and then ( b ) the specific wave form of the unit as stated in the Procedure section, which is widely acknowledged for these neurons. Because we were recording multiple neurons in each animal, there was no way to mark individual neurons and identify their locations and/or characteristics histologically; consequently, we included neurons based on waveform. Given these criteria, we saw no basis for discarding neurons because their firing rate was slow and, consequently, such neurons were included. The writers of the letter call attention to an article by Ungless et al. (2004), who described differences between DA and non-DA neurons in the VTA. The writers noted that our mean spontaneous firing rate was closer to that of non-dopaminergic cells than dopaminergic cells. However, the main point of the article by Ungless et al. was that VTA-DA neurons were inhibited by aversive or stressful stimuli whereas non-DA neurons were excited by such stimuli; they reported 10 of 12 DA neurons were inhibited by 10-s foot pinch whereas four of six non-DA neurons were excited by this stimulus. We have examined the …
{"title":"Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum: a reply to Chenu et al. (2011)","authors":"C. H. West, J. Weiss","doi":"10.1017/S1461145711001726","DOIUrl":"https://doi.org/10.1017/S1461145711001726","url":null,"abstract":"We have read the letter commenting on our article entitled ‘Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum’. We offer the following response.\u0000\u0000The authors of the letter direct attention to our mean spontaneous firing rate for dopaminergic neurons in the ventral tegmental area (VTA-DA neurons) being lower than typically found and particularly note that we included neurons with firing rates as low as 1.0 Hz. Our mean rates of firing are indeed somewhat lower than often reported by other investigators. We were clearly aware of this, specifically describing in our Methods section that we included slow-firing neurons. Our criteria for DA neurons in the VTA depended upon ( a ) stereotaxic location and then ( b ) the specific wave form of the unit as stated in the Procedure section, which is widely acknowledged for these neurons. Because we were recording multiple neurons in each animal, there was no way to mark individual neurons and identify their locations and/or characteristics histologically; consequently, we included neurons based on waveform. Given these criteria, we saw no basis for discarding neurons because their firing rate was slow and, consequently, such neurons were included.\u0000\u0000The writers of the letter call attention to an article by Ungless et al. (2004), who described differences between DA and non-DA neurons in the VTA. The writers noted that our mean spontaneous firing rate was closer to that of non-dopaminergic cells than dopaminergic cells. However, the main point of the article by Ungless et al. was that VTA-DA neurons were inhibited by aversive or stressful stimuli whereas non-DA neurons were excited by such stimuli; they reported 10 of 12 DA neurons were inhibited by 10-s foot pinch whereas four of six non-DA neurons were excited by this stimulus. We have examined the …","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126651298","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":"Corrigendum: Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration – CORRIGENDUM","authors":"M. Vicente, H. Zangrossi","doi":"10.1017/S1461145711001143","DOIUrl":"https://doi.org/10.1017/S1461145711001143","url":null,"abstract":"doi: 10.1017/S1461145711000873, Published by Cambridge University Press, 14 June 2011.\u0000\u0000One of the figures published within this paper did …","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128618167","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}
Pub Date : 2012-03-01DOI: 10.1017/S1461145712000089
A. Frazer
It is popularly stated that there is an ‘epidemic’ of obesity, with great concern because of the health problems associated with it. Different classes of psychotropic drugs have been used to decrease appetite and assist with weight loss whereas other psychotherapeutic agents produce weight gain, often significant, as a serious side effect. This month's thematic section contains five articles dealing with eating disorders and obesity. Two are reviews with one being part of the series “evidence-based pharmacotherapy of …” That review primarily covers short-term efficacy of drugs in various eating disorders …
{"title":"Eating Disorders and Obesity","authors":"A. Frazer","doi":"10.1017/S1461145712000089","DOIUrl":"https://doi.org/10.1017/S1461145712000089","url":null,"abstract":"It is popularly stated that there is an ‘epidemic’ of obesity, with great concern because of the health problems associated with it. Different classes of psychotropic drugs have been used to decrease appetite and assist with weight loss whereas other psychotherapeutic agents produce weight gain, often significant, as a serious side effect. This month's thematic section contains five articles dealing with eating disorders and obesity. Two are reviews with one being part of the series “evidence-based pharmacotherapy of …” That review primarily covers short-term efficacy of drugs in various eating disorders …","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130599789","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}
Pub Date : 2011-11-01DOI: 10.1017/S1461145711000964
K. Fountoulakis, H. Möller
Horder et al. (in press) criticize the results of Kirsch et al. (2008) solely on the basis of meta-analytical methodology. In the letter by Matthews (2011) commenting on our paper (Fountoulakis & Moller, 2010) this emphasis on methodological issues is again central. Matthews comments on the method used (pooling drug and placebo arms separately) and on the use of effect size instead of raw HAMD scores. We argue that the problem does not lie in methodological issues. We performed the re-analysis by using simple averaging, weighting by sample size, weighted by the inverse variance and also with precision weighted analysis. The differences in the results of these different approaches were not significant at all although some similarity was shown between the results of precision weighted analysis and those reported by Kirsch et al. Horder et al. are right when suggesting that the 1.80 difference can be derived with the precision weighted analysis method but the effect size with this method is not 0.32 as Kirsch et al. report, but 0.28. So no matter which method is used, it seems that Kirsch et al. had flawed calculations. To say that a method is ‘unusual’ or ‘idiosyncratic’ does not necessarily imply it is inappropriate or false. It is assumed that all trial results belong to a single distribution; that is why a meta-analysis is possible even with a random-effects model. Practically the way one groups and pools arms and trials plays little if any role. That is why ultimately, the correction of the effect size is minimal and all methods give an effect size of 0.28–0.35 and a difference in raw HAMD change from baseline between placebo and active drug of 1.78–2.93 (Table 1). Even the results after simple averaging do not deviate, probably because the number of RCTs is high enough …
{"title":"Antidepressants vs . placebo: not merely a quantitative difference in response","authors":"K. Fountoulakis, H. Möller","doi":"10.1017/S1461145711000964","DOIUrl":"https://doi.org/10.1017/S1461145711000964","url":null,"abstract":"Horder et al. (in press) criticize the results of Kirsch et al. (2008) solely on the basis of meta-analytical methodology. In the letter by Matthews (2011) commenting on our paper (Fountoulakis & Moller, 2010) this emphasis on methodological issues is again central. Matthews comments on the method used (pooling drug and placebo arms separately) and on the use of effect size instead of raw HAMD scores.\u0000\u0000We argue that the problem does not lie in methodological issues. We performed the re-analysis by using simple averaging, weighting by sample size, weighted by the inverse variance and also with precision weighted analysis. The differences in the results of these different approaches were not significant at all although some similarity was shown between the results of precision weighted analysis and those reported by Kirsch et al. Horder et al. are right when suggesting that the 1.80 difference can be derived with the precision weighted analysis method but the effect size with this method is not 0.32 as Kirsch et al. report, but 0.28. So no matter which method is used, it seems that Kirsch et al. had flawed calculations. To say that a method is ‘unusual’ or ‘idiosyncratic’ does not necessarily imply it is inappropriate or false. It is assumed that all trial results belong to a single distribution; that is why a meta-analysis is possible even with a random-effects model. Practically the way one groups and pools arms and trials plays little if any role. That is why ultimately, the correction of the effect size is minimal and all methods give an effect size of 0.28–0.35 and a difference in raw HAMD change from baseline between placebo and active drug of 1.78–2.93 (Table 1). Even the results after simple averaging do not deviate, probably because the number of RCTs is high enough …","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"164 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129342843","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：