Pub Date : 2017-10-01DOI: 10.1080/15622975.2016.1252466
J. Ou, Ming Li, Xiao Xiao
Abstract Objectives: Genome-wide association studies (GWAS) followed by independent replications suggest that ZNF804A is a risk gene for schizophrenia (SCZ), considering the substantial genetic overlap between SCZ and major mood disorders (e.g., bipolar disorder (BPD) and major depressive disorder (MDD)). Methods: We collected the data of two ZNF804A single-nucleotide polymorphisms (SNPs rs1344706 and rs7597593) from European and Asian populations to perform systematic meta-analyses with major mood disorders in a total of 65,240 subjects. Results: Meta-analysis showed that rs1344706 and rs7597593 were both associated with major mood disorders as well as diagnosis of either BPD or MDD, although neither of the analyses achieved a genome-wide level of statistical significance. Conclusions: Our data provide evidence for the genetic involvement of ZNF804A SNPs in the susceptibility of major mood disorders, but further replication analyses in larger samples are necessary.
{"title":"The schizophrenia susceptibility gene ZNF804A confers risk of major mood disorders","authors":"J. Ou, Ming Li, Xiao Xiao","doi":"10.1080/15622975.2016.1252466","DOIUrl":"https://doi.org/10.1080/15622975.2016.1252466","url":null,"abstract":"Abstract Objectives: Genome-wide association studies (GWAS) followed by independent replications suggest that ZNF804A is a risk gene for schizophrenia (SCZ), considering the substantial genetic overlap between SCZ and major mood disorders (e.g., bipolar disorder (BPD) and major depressive disorder (MDD)). Methods: We collected the data of two ZNF804A single-nucleotide polymorphisms (SNPs rs1344706 and rs7597593) from European and Asian populations to perform systematic meta-analyses with major mood disorders in a total of 65,240 subjects. Results: Meta-analysis showed that rs1344706 and rs7597593 were both associated with major mood disorders as well as diagnosis of either BPD or MDD, although neither of the analyses achieved a genome-wide level of statistical significance. Conclusions: Our data provide evidence for the genetic involvement of ZNF804A SNPs in the susceptibility of major mood disorders, but further replication analyses in larger samples are necessary.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"34 1","pages":"557 - 562"},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80284784","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 : 2017-10-01DOI: 10.1080/15622975.2016.1237042
Henrik Nørbak-Emig, L. Pinborg, J. Raghava, C. Svarer, W. Baaré, P. Allerup, L. Friberg, E. Rostrup, B. Glenthøj, B. Ebdrup
Abstract Objectives: Long-term dopamine D2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D2/3 receptor binding potentials (BPND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment. Methods: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [123I]epidepride single-photon emission computerised tomography (SPECT), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT. Results: Neither extrastriatal D2/3 receptor BPND at baseline, nor blockade at follow-up, was related to regional cortical volume changes. In post-hoc analyses excluding three patients with cannabis use we found that higher D2/3 receptor occupancy was significantly associated with an increase in right frontal grey matter volume. Conclusions: The present data do not support an association between extrastriatal D2/3 receptor blockade and extrastriatal grey matter loss in the early phases of schizophrenia. Although inconclusive, our exclusion of patients tested positive for cannabis use speaks to keeping attention to potential confounding factors in imaging studies.
{"title":"Extrastriatal dopamine D2/3 receptors and cortical grey matter volumes in antipsychotic-naïve schizophrenia patients before and after initial antipsychotic treatment","authors":"Henrik Nørbak-Emig, L. Pinborg, J. Raghava, C. Svarer, W. Baaré, P. Allerup, L. Friberg, E. Rostrup, B. Glenthøj, B. Ebdrup","doi":"10.1080/15622975.2016.1237042","DOIUrl":"https://doi.org/10.1080/15622975.2016.1237042","url":null,"abstract":"Abstract Objectives: Long-term dopamine D2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D2/3 receptor binding potentials (BPND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment. Methods: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [123I]epidepride single-photon emission computerised tomography (SPECT), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT. Results: Neither extrastriatal D2/3 receptor BPND at baseline, nor blockade at follow-up, was related to regional cortical volume changes. In post-hoc analyses excluding three patients with cannabis use we found that higher D2/3 receptor occupancy was significantly associated with an increase in right frontal grey matter volume. Conclusions: The present data do not support an association between extrastriatal D2/3 receptor blockade and extrastriatal grey matter loss in the early phases of schizophrenia. Although inconclusive, our exclusion of patients tested positive for cannabis use speaks to keeping attention to potential confounding factors in imaging studies.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"14 1","pages":"539 - 549"},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74569486","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 : 2017-08-18DOI: 10.1080/15622975.2016.1252464
V. Galvez, Lucy C. McGuirk, C. Loo
Abstract Objectives: This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). Methods: A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: “ketamine” and “Electroconvulsive Therapy”, from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Results: Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. Conclusions: The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.
{"title":"The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes","authors":"V. Galvez, Lucy C. McGuirk, C. Loo","doi":"10.1080/15622975.2016.1252464","DOIUrl":"https://doi.org/10.1080/15622975.2016.1252464","url":null,"abstract":"Abstract Objectives: This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). Methods: A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: “ketamine” and “Electroconvulsive Therapy”, from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Results: Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. Conclusions: The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"16 1","pages":"424 - 444"},"PeriodicalIF":0.0,"publicationDate":"2017-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86296485","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 : 2017-08-18DOI: 10.3109/15622975.2016.1151075
K. S. MacDowell, A. Sayd, B. García-Bueno, J. Caso, J. Madrigal, J. Leza
Abstract Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.
{"title":"Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex","authors":"K. S. MacDowell, A. Sayd, B. García-Bueno, J. Caso, J. Madrigal, J. Leza","doi":"10.3109/15622975.2016.1151075","DOIUrl":"https://doi.org/10.3109/15622975.2016.1151075","url":null,"abstract":"Abstract Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"179 1","pages":"457 - 470"},"PeriodicalIF":0.0,"publicationDate":"2017-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90602368","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 : 2017-08-18DOI: 10.1080/15622975.2016.1245441
N. Steen, M. Aas, C. Simonsen, I. Dieset, M. Tesli, M. Nerhus, Erlend Gardsjord, R. Mørch, I. Agartz, I. Melle, T. Ueland, O. Spigset, O. Andreassen
Abstract Objectives: Antipsychotics are effective in treating psychosis and mood episodes; however, the effect on cognition is less known. We investigated the association between serum levels of second-generation antipsychotics (SGAs) and cognitive performance in psychosis spectrum disorders in a naturalistic setting. Methods: A total of 495 patients with a DSM-IV Schizophrenia and Other Psychotic Disorders (SCZ, n = 373) or Bipolar Disorder (BD, n = 122) diagnosis treated with olanzapine, quetiapine, aripiprazole or risperidone were tested neuropsychologically with concurrent measurement of the serum concentration of the drug. Linear regression was used for association analyses. Results: Attention was positively associated with the olanzapine concentration (standardised beta (β) coefficient = 0.19, P = .006), and short-term verbal memory and verbal fluency were negatively associated with the quetiapine (β = –0.24, P = .004) and risperidone (β = –0.37, P = .007) concentrations respectively. Conclusions: The present results suggest that SGA serum concentration is associated with better attention (small effect size), and worse verbal memory (small effect size) and verbal fluency (medium effect size). These findings are in line with the notion that SGAs affect aspects of cognitive function, and suggest careful dosing in patients with severe memory and executive problems.
目的:抗精神病药物治疗精神病和情绪发作有效;然而，对认知的影响却鲜为人知。我们在自然环境中研究了第二代抗精神病药物(SGAs)血清水平与精神病谱系障碍患者认知表现之间的关系。方法:采用奥氮平、喹硫平、阿立哌唑或利培酮治疗的495例DSM-IV型精神分裂症及其他精神障碍(SCZ, n = 373)或双相情感障碍(BD, n = 122)患者进行神经心理测试，同时测定药物的血清浓度。关联分析采用线性回归。结果:注意力与奥氮平浓度呈正相关(标准化β (β)系数= 0.19,P = 0.006)，短期言语记忆和言语流畅性分别与喹硫平(β = -0.24, P = 0.004)和利培酮(β = -0.37, P = 0.007)浓度呈负相关。结论:目前的研究结果表明，SGA血清浓度与更好的注意力(小效应量)、更差的言语记忆(小效应量)和言语流畅性(中等效应量)相关。这些发现与SGAs影响认知功能的观点一致，并建议对有严重记忆和执行问题的患者谨慎用药。
{"title":"Serum levels of second-generation antipsychotics are associated with cognitive function in psychotic disorders","authors":"N. Steen, M. Aas, C. Simonsen, I. Dieset, M. Tesli, M. Nerhus, Erlend Gardsjord, R. Mørch, I. Agartz, I. Melle, T. Ueland, O. Spigset, O. Andreassen","doi":"10.1080/15622975.2016.1245441","DOIUrl":"https://doi.org/10.1080/15622975.2016.1245441","url":null,"abstract":"Abstract Objectives: Antipsychotics are effective in treating psychosis and mood episodes; however, the effect on cognition is less known. We investigated the association between serum levels of second-generation antipsychotics (SGAs) and cognitive performance in psychosis spectrum disorders in a naturalistic setting. Methods: A total of 495 patients with a DSM-IV Schizophrenia and Other Psychotic Disorders (SCZ, n = 373) or Bipolar Disorder (BD, n = 122) diagnosis treated with olanzapine, quetiapine, aripiprazole or risperidone were tested neuropsychologically with concurrent measurement of the serum concentration of the drug. Linear regression was used for association analyses. Results: Attention was positively associated with the olanzapine concentration (standardised beta (β) coefficient = 0.19, P = .006), and short-term verbal memory and verbal fluency were negatively associated with the quetiapine (β = –0.24, P = .004) and risperidone (β = –0.37, P = .007) concentrations respectively. Conclusions: The present results suggest that SGA serum concentration is associated with better attention (small effect size), and worse verbal memory (small effect size) and verbal fluency (medium effect size). These findings are in line with the notion that SGAs affect aspects of cognitive function, and suggest careful dosing in patients with severe memory and executive problems.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"7 1","pages":"471 - 482"},"PeriodicalIF":0.0,"publicationDate":"2017-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73015877","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 : 2017-08-18DOI: 10.1080/15622975.2016.1246750
Anne R. Reuter, J. Bumb, Juliane K. Mueller, Cathrin Rohleder, F. Pahlisch, Franziska Hanke, E. Arens, F. Leweke, D. Koethe, E. Schwarz
Abstract Objectives: Binocular depth inversion illusion (BDII) represents an illusion of visual perception that involves higher-order visual and cognitive processes. Its impairment has been linked to psychotic conditions and identified as a marker for at-risk mental states. The endogenous cannabinoid system (ECS) is involved in various neurophysiological processes. One of its key components, anandamide, is involved in the pathophysiology of schizophrenia. Little is known about its impact on BDII alterations. Therefore, we explored associations between BDII and anandamide levels. Methods: BDII was conducted and blood and CSF were taken in 28 first-episode antipsychotic-naïve schizophrenia (SZ) patients and 81 healthy controls (HC). Serum and CSF anandamide levels were determined by high-performance liquid chromatography/mass spectrometry. Results: BDII scores were significantly elevated in SZ versus HC, indicating a disruption of illusionary revision of percepts in SZ. Anandamide levels were significantly higher in CSF of SZ compared to HC, while serum anandamide was not. However, we found specific association differences of anandamide levels and BDII scores between schizophrenia patients and controls in serum. Conclusions: These findings support the hypothesis of an involvement of anandamide in cognitive processes impaired in schizophrenia and are consistent with a protective effect of elevated anandamide levels herein.
{"title":"Association of anandamide with altered binocular depth inversion illusion in schizophrenia","authors":"Anne R. Reuter, J. Bumb, Juliane K. Mueller, Cathrin Rohleder, F. Pahlisch, Franziska Hanke, E. Arens, F. Leweke, D. Koethe, E. Schwarz","doi":"10.1080/15622975.2016.1246750","DOIUrl":"https://doi.org/10.1080/15622975.2016.1246750","url":null,"abstract":"Abstract Objectives: Binocular depth inversion illusion (BDII) represents an illusion of visual perception that involves higher-order visual and cognitive processes. Its impairment has been linked to psychotic conditions and identified as a marker for at-risk mental states. The endogenous cannabinoid system (ECS) is involved in various neurophysiological processes. One of its key components, anandamide, is involved in the pathophysiology of schizophrenia. Little is known about its impact on BDII alterations. Therefore, we explored associations between BDII and anandamide levels. Methods: BDII was conducted and blood and CSF were taken in 28 first-episode antipsychotic-naïve schizophrenia (SZ) patients and 81 healthy controls (HC). Serum and CSF anandamide levels were determined by high-performance liquid chromatography/mass spectrometry. Results: BDII scores were significantly elevated in SZ versus HC, indicating a disruption of illusionary revision of percepts in SZ. Anandamide levels were significantly higher in CSF of SZ compared to HC, while serum anandamide was not. However, we found specific association differences of anandamide levels and BDII scores between schizophrenia patients and controls in serum. Conclusions: These findings support the hypothesis of an involvement of anandamide in cognitive processes impaired in schizophrenia and are consistent with a protective effect of elevated anandamide levels herein.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"48 1","pages":"483 - 488"},"PeriodicalIF":0.0,"publicationDate":"2017-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80177887","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 : 2017-07-04DOI: 10.1080/15622975.2016.1224925
Yu‐Jie Chiou, Tiao-Lai Huang
Abstract Objectives: Brain-derived neurotrophic factors (BDNF) are known to be related to the psychopathology of schizophrenia. However, studies focussing on drug-naïve first-episode schizophrenia are still rare. Methods: Over a 5-year period, we investigated the serum BDNF levels in patients with first-episode drug-naïve schizophrenia and compared them to age- and sex-matched healthy controls. We also explored the association between antipsychotic doses, positive and negative syndrome scale (PANSS) scores, and serum BDNF levels before and after a 4-week antipsychotic treatment. Results: The baseline serum BDNF levels of 34 patients were significantly lower than those of the controls (df = 66, P = .001). Although the PANSS scores of 20 followed-up patients improved significantly after antipsychotic treatment, the elevation of the serum BDNF levels was not statistically significant (P = .386). In addition, Pearson’s correlation test showed significant correlations between pre-treatment negative scale scores and percentage changes in BDNF (P = .002). Conclusions: The peripheral BDNF levels in Taiwanese patients with drug-naïve first-episode schizophrenia, compared with healthy controls, did not elevate after antipsychotic treatment, and pre-treatment negative symptoms played a pivotal role in trajectories of serum BDNF levels. Large samples will be needed in future studies to verify these results.
摘要目的:脑源性神经营养因子(BDNF)与精神分裂症的精神病理有关。然而，专注于drug-naïve首发精神分裂症的研究仍然很少。方法:在5年的时间里，我们调查了首发drug-naïve精神分裂症患者的血清BDNF水平，并将其与年龄和性别匹配的健康对照组进行了比较。我们还探讨了抗精神病药物剂量、阳性和阴性症状量表(PANSS)评分以及抗精神病药物治疗前后血清BDNF水平之间的关系。结果:34例患者血清BDNF基线水平显著低于对照组(df = 66, P = 0.001)。20例随访患者经抗精神病药物治疗后PANSS评分明显改善，但血清BDNF水平升高无统计学意义(P = .386)。此外，Pearson相关检验显示，治疗前负量表评分与BDNF百分比变化呈显著相关(P = 0.002)。结论:台湾地区drug-naïve首发精神分裂症患者抗精神病药物治疗后外周血BDNF水平与健康对照相比没有升高，治疗前阴性症状在血清BDNF水平的变化轨迹中起关键作用。在未来的研究中需要大量的样本来验证这些结果。
{"title":"Serum brain-derived neurotrophic factors in Taiwanese patients with drug-naïve first-episode schizophrenia: Effects of antipsychotics","authors":"Yu‐Jie Chiou, Tiao-Lai Huang","doi":"10.1080/15622975.2016.1224925","DOIUrl":"https://doi.org/10.1080/15622975.2016.1224925","url":null,"abstract":"Abstract Objectives: Brain-derived neurotrophic factors (BDNF) are known to be related to the psychopathology of schizophrenia. However, studies focussing on drug-naïve first-episode schizophrenia are still rare. Methods: Over a 5-year period, we investigated the serum BDNF levels in patients with first-episode drug-naïve schizophrenia and compared them to age- and sex-matched healthy controls. We also explored the association between antipsychotic doses, positive and negative syndrome scale (PANSS) scores, and serum BDNF levels before and after a 4-week antipsychotic treatment. Results: The baseline serum BDNF levels of 34 patients were significantly lower than those of the controls (df = 66, P = .001). Although the PANSS scores of 20 followed-up patients improved significantly after antipsychotic treatment, the elevation of the serum BDNF levels was not statistically significant (P = .386). In addition, Pearson’s correlation test showed significant correlations between pre-treatment negative scale scores and percentage changes in BDNF (P = .002). Conclusions: The peripheral BDNF levels in Taiwanese patients with drug-naïve first-episode schizophrenia, compared with healthy controls, did not elevate after antipsychotic treatment, and pre-treatment negative symptoms played a pivotal role in trajectories of serum BDNF levels. Large samples will be needed in future studies to verify these results.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"29 1","pages":"382 - 391"},"PeriodicalIF":0.0,"publicationDate":"2017-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87638794","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 : 2017-07-04DOI: 10.1080/15622975.2016.1224929
A. Schmitt, D. Martins‐de‐Souza, S. Akbarian, J. Cassoli, H. Ehrenreich, A. Fischer, A. Fonteh, W. Gattaz, M. Gawlik, M. Gerlach, E. Grünblatt, Tobias Halene, A. Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, J. Kornhuber, Theo F. J. Kraus, B. Malchow, J. Nascimento, M. Rossner, M. Schwarz, J. Steiner, L. Talib, F. Thibaut, P. Riederer, P. Falkai
Abstract Objectives: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. Methods: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. Results: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. Conclusions: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.
{"title":"Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms","authors":"A. Schmitt, D. Martins‐de‐Souza, S. Akbarian, J. Cassoli, H. Ehrenreich, A. Fischer, A. Fonteh, W. Gattaz, M. Gawlik, M. Gerlach, E. Grünblatt, Tobias Halene, A. Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, J. Kornhuber, Theo F. J. Kraus, B. Malchow, J. Nascimento, M. Rossner, M. Schwarz, J. Steiner, L. Talib, F. Thibaut, P. Riederer, P. Falkai","doi":"10.1080/15622975.2016.1224929","DOIUrl":"https://doi.org/10.1080/15622975.2016.1224929","url":null,"abstract":"Abstract Objectives: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. Methods: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. Results: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. Conclusions: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"5 1","pages":"330 - 356"},"PeriodicalIF":0.0,"publicationDate":"2017-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85596461","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 : 2017-07-04DOI: 10.1080/15622975.2016.1245443
Sern-Yih Cheah, R. McLeay, L. Wockner, B. Lawford, R. Young, C. P. Morris, J. Voisey
Abstract Objectives: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene. Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia. Results: There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects. Conclusions: Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.
{"title":"Expression and methylation of BDNF in the human brain in schizophrenia","authors":"Sern-Yih Cheah, R. McLeay, L. Wockner, B. Lawford, R. Young, C. P. Morris, J. Voisey","doi":"10.1080/15622975.2016.1245443","DOIUrl":"https://doi.org/10.1080/15622975.2016.1245443","url":null,"abstract":"Abstract Objectives: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene. Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia. Results: There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects. Conclusions: Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"24 1","pages":"392 - 400"},"PeriodicalIF":0.0,"publicationDate":"2017-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75548220","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 : 2017-07-04DOI: 10.3109/15622975.2015.1117654
Chun‐Yuan Lin, Sun-Yuan Liang, Yue-Cune Chang, Shuo-Yen Ting, Ching-Ling Kao, Yu-Hsin Wu, G. Tsai, H. Lane
Abstract Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.
{"title":"Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial","authors":"Chun‐Yuan Lin, Sun-Yuan Liang, Yue-Cune Chang, Shuo-Yen Ting, Ching-Ling Kao, Yu-Hsin Wu, G. Tsai, H. Lane","doi":"10.3109/15622975.2015.1117654","DOIUrl":"https://doi.org/10.3109/15622975.2015.1117654","url":null,"abstract":"Abstract Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.","PeriodicalId":22963,"journal":{"name":"The World Journal of Biological Psychiatry","volume":"43 1","pages":"357 - 368"},"PeriodicalIF":0.0,"publicationDate":"2017-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91191634","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}
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