Psychiatry and Clinical Neurosciences最新文献

{"title":"Identification of novel genomic loci for anxiety symptoms and extensive genetic overlap with psychiatric disorders.","authors":"Markos Tesfaye, Piotr Jaholkowski, Alexey A Shadrin, Dennis van der Meer, Guy F L Hindley, Børge Holen, Nadine Parker, Pravesh Parekh, Viktoria Birkenæs, Zillur Rahman, Shahram Bahrami, Gleda Kutrolli, Oleksandr Frei, Srdjan Djurovic, Anders M Dale, Olav B Smeland, Kevin S O'Connell, Ole A Andreassen","doi":"10.1111/pcn.13742","DOIUrl":"10.1111/pcn.13742","url":null,"abstract":"<p><strong>Aims: </strong>Anxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders.</p><p><strong>Methods: </strong>We included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders.</p><p><strong>Results: </strong>Anxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>47</mn></mrow> </mfenced> </mrow> </math> , BIP <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>33</mn></mrow> </mfenced> </mrow> </math> , SCZ <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>71</mn></mrow> </mfenced> </mrow> </math> , ADHD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>20</mn></mrow> </mfenced> </mrow> </math> , and ASD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </mfenced> </mrow> </math> . Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways including cell adhesion and neurofibrillary tangle compared with genes annotated to the shared loci.</p><p><strong>Conclusions: </strong>Anxiety is highly polygenic phenotype with extensive genetic overlap with psychiatric disorders, and we identified novel loci for anxiety implicating new molecular pathways. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified molecular underpinnings may lead to potential drug targets.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"783-791"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCN Art Brut Series No. 42, Artwork Description.","authors":"Kenjiro Hosaka","doi":"10.1111/pcn.13771","DOIUrl":"https://doi.org/10.1111/pcn.13771","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"78 12","pages":"833"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When is an MRI-based classification first ready for use in clinical settings?","authors":"Shinsuke Koike","doi":"10.1111/pcn.13750","DOIUrl":"https://doi.org/10.1111/pcn.13750","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"78 12","pages":"731"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocaine and dopamine abuse improved by subthalamic nucleus deep brain stimulation in one Parkinsonian patient.","authors":"Valentin Mira, Christelle Baunez, Alexandre Eusebio, Tatiana Witjas, Eve Benchetrit, Jean-Philippe Azulay","doi":"10.1111/pcn.13738","DOIUrl":"10.1111/pcn.13738","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"829-830"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible association of elevated CSF IL-6 levels with anxiety and frustration in psychiatric disorders.","authors":"Takako Enokida, Kotaro Hattori, Kaori Okabe, Takamasa Noda, Miho Ota, Noriko Sato, Shintaro Ogawa, Megumi Tatsumi, Mikio Hoshino, Hiroshi Kunugi, Kazuyuki Nakagome","doi":"10.1111/pcn.13743","DOIUrl":"10.1111/pcn.13743","url":null,"abstract":"<p><strong>Aim: </strong>Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders.</p><p><strong>Methods: </strong>We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging.</p><p><strong>Results: </strong>Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients.</p><p><strong>Conclusion: </strong>Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"792-799"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and imaging correlates of hyperorality in syndromes associated with frontotemporal lobar degeneration.","authors":"Daniele Altomare, Valeria Bracca, Enrico Premi, Anna Micheli, Maria Sofia Cotelli, Roberto Gasparotti, Antonella Alberici, Barbara Borroni","doi":"10.1111/pcn.13751","DOIUrl":"10.1111/pcn.13751","url":null,"abstract":"<p><strong>Aim: </strong>Empirical research investigating hyperorality in syndromes associated with frontotemporal lobar degeneration (FTLD) is limited. The present study aims to assess and describe hyperorality and its clinical and imaging correlates in patients with FTLD-associated syndromes.</p><p><strong>Methods: </strong>This retrospective longitudinal study included consecutive patients with FTLD who underwent a clinical, cognitive, and behavioral assessment. The presence and severity of hyperorality was assessed using the Frontal Behavior Inventory.</p><p><strong>Results: </strong>A total of 712 patients with FTLD were included in the study. Hyperorality was reported by 29% (204 of 712 [95% CI: 25-32%]) of patients; was more frequent in those with severe dementia than in those with prodromal or mild to moderate dementia (P < 0.05); was associated with younger age (odds ratio [OR] = 0.96 [95% CI: 0.94-0.99]), (P = 0.003) and positive family history for dementia (OR = 2.03 [95% CI: 1.18-3.49], P = 0.010); was overall more probable in the behavioral variant of frontotemporal dementia (bvFTD) and frontotemporal dementia with amyotrophic lateral sclerosis phenotypes, and less probable in other language or motor phenotypes; and was associated with higher severity of neuropsychiatric symptoms (OR = 1.08 [95% CI: 1.06-1.10], P < 0.001) and with the presence of several behavioral symptoms (P < 0.05). Moreover, hyperorality severity increased over time only in patients with bvFTD (β = +0.15, P = 0.011) or semantic variant of primary progressive aphasia (β = +0.34, P = 0.010). Finally, the presence of hyperorality was significantly associated with greater atrophy in the right anterior insula and right orbitofrontal region (false discovery rate-corrected P < 0.05).</p><p><strong>Conclusion: </strong>Hyperorality is common in certain FTLD-associated syndromes. Understanding its correlates can help clinicians define pharmacological and educational interventions and clarify related anatomical circuits.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"818-825"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome sequencing analysis of Japanese autism spectrum disorder trios.","authors":"Sawako Furukawa, Itaru Kushima, Hidekazu Kato, Hiroki Kimura, Yoshihiro Nawa, Branko Aleksic, Masahiro Banno, Maeri Yamamoto, Mariko Uematsu, Yukako Nagasaki, Tomoo Ogi, Norio Ozaki, Masashi Ikeda","doi":"10.1111/pcn.13767","DOIUrl":"https://doi.org/10.1111/pcn.13767","url":null,"abstract":"<p><strong>Aim: </strong>Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous neurodevelopmental disorder with a strong genetic basis. Conducting the first comprehensive whole-genome sequencing (WGS) analysis of Japanese ASD trios, this study aimed to elucidate the clinical significance of pathogenic variants and enhance the understanding of ASD pathogenesis.</p><p><strong>Methods: </strong>WGS was performed on 57 Japanese patients with ASD and their parents, investigating variants ranging from single-nucleotide variants to structural variants (SVs), short tandem repeats (STRs), mitochondrial variants, and polygenic risk score (PRS).</p><p><strong>Results: </strong>Potentially pathogenic variants that could explain observed phenotypes were identified in 18 patients (31.6%) overall and in 10 of 23 patients (43.5%) with comorbid intellectual developmental disorder (IDD). De novo variants in PTEN, CHD7, and HNRNPH2 were identified in patients referred for genetic counseling who exhibited previously reported phenotypes, including one patient with ASD who had profound IDD and macrocephaly with PTEN L320S. Analysis of the AlphaFold3 protein structure indicated potential inhibition of intramolecular interactions within PTEN. SV analysis identified deletions in ARHGAP11B and TMLHE. A pathogenic de novo mitochondrial variant was identified in a patient with ASD who had a history of encephalitis and cognitive decline. GO enrichment analysis of genes with nonsense variants and missense variants (Missense badness, PolyPhen-2, and Constraint >1) showed associations with regulation of growth and ATP-dependent chromatin remodeler activity. No reportable results were obtained in the analysis of STR and PRS.</p><p><strong>Conclusion: </strong>Characterizing the comprehensive genetic architecture and phenotypes of ASD is a fundamental step towards unraveling its complex biology.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal choroid plexus, hippocampus, and lateral ventricles volumes as markers of treatment-resistant major depressive disorder.","authors":"Beatrice Bravi, Marco Paolini, Melania Maccario, Chiara Milano, Laura Raffaelli, Elisa Maria Teresa Melloni, Raffaella Zanardi, Cristina Colombo, Francesco Benedetti","doi":"10.1111/pcn.13764","DOIUrl":"https://doi.org/10.1111/pcn.13764","url":null,"abstract":"<p><strong>Aim: </strong>One-third of patients with major depressive disorder (MDD) do not achieve full remission and have high relapse rates even after treatment, leading to increased medical costs and reduced quality of life and health status. The possible specificity of treatment-resistant depression (TRD) neurobiology is still under investigation, with risk factors such as higher inflammatory markers being identified. Given recent findings on the role of choroid plexus (ChP) in neuroinflammation and hippocampus in treatment response, the aim of the present study was to evaluate inflammatory- and trophic-related differences in these regions along with ventricular volumes among patients with treatment-sensitive depression (TSD), TRD, and healthy controls (HCs).</p><p><strong>Methods: </strong>ChP, hippocampal, and ventricular volumes were assessed in 197 patients with MDD and 58 age- and sex-matched HCs. Volumes were estimated using FreeSurfer 7.2. Treatment resistance status was defined as failure to respond to at least two separate antidepressant treatments. Region of interest volumes were then compared among groups.</p><p><strong>Results: </strong>We found higher ChP volumes in patients with TRD compared with patients with TSD and HCs. Our results also showed lower hippocampal volumes and higher lateral ventricular volumes in TRD compared with both patients without TRD and HCs.</p><p><strong>Conclusions: </strong>These findings corroborate the link between TRD and neuroinflammation, as ChP volume could be considered a putative marker of central immune activity. The lack of significant differences in all of the region of interest volumes between patients with TSD and HCs may highlight the specificity of these features to TRD, possibly providing new insights into the specific neurobiological underpinnings of this condition.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.","authors":"Hang Su, Weichen Song, Qiming Lv, Tianzhen Chen, Xiaotong Li, Xiaomin Xu, Ruihua Li, Qianqian Sun, Sufang Peng, Di Deng, Na Zhong, Yan Zhao, Haifeng Jiang, Jiang Du, Guan Ning Lin, Ti-Fei Yuan, Min Zhao","doi":"10.1111/pcn.13761","DOIUrl":"https://doi.org/10.1111/pcn.13761","url":null,"abstract":"<p><strong>Aim: </strong>Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction.</p><p><strong>Methods: </strong>In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10^-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD.</p><p><strong>Conclusion: </strong>These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonergic underpinnings of obsessive-compulsive disorder: A systematic review and meta-analysis of neuroimaging findings.","authors":"Martin Pastre, Bob-Valéry Occéan, Vincent Boudousq, Ismael Conejero, Pascale Fabbro-Peray, Laurent Collombier, Luc Mallet, Jorge Lopez-Castroman","doi":"10.1111/pcn.13760","DOIUrl":"https://doi.org/10.1111/pcn.13760","url":null,"abstract":"<p><p>Obsessive-compulsive disorder (OCD) is a frequent and disabling condition, with many patients being treatment-resistant. Improved understanding of its neurobiology is vital for better therapies. Evidence is still conflicting regarding specific serotonergic-related dysfunctions in OCD. We systematically reviewed the literature to provide a quantitative assessment of the role of serotonin (5-HT) in patients with untreated OCD through imaging. We searched for neuroimaging studies investigating central 5-HT tonus in unmedicated patients with OCD, excluding studies comprising treated patients to prevent bias from antidepressant-induced changes in serotonergic tonus. We also conducted a meta-analysis using a homogeneous group of positron emission tomography and single photon emission computed tomography articles that compared 5-HT transporter (SERT) and 5-HT2A receptor (HT2AR) binding potential in different brain regions of patients with untreated OCD and healthy controls. The systematic review encompassed 18 articles, with 13 included in the subsequent meta-analysis. Risk of bias was assessed by a revised form of the Newcastle-Ottawa Scale. We provided standardized mean difference (SMD) values for SERT and 5-HT2AR binding potential measures across 15 different brain regions. Patients with OCD showed lower SERT binding potential in the brainstem (SMD = -1.13, 95% CI [-1.81 to -0.46]), midbrain (SMD = -0.54, 95% CI [-0.92 to -0.16]), and thalamus/hypothalamus regions (SMD = -0.58, 95% CI [-0.99 to -0.18]) with neglectable to moderate heterogeneity. By combining results from 2 decades of molecular imaging studies, we show that individuals with OCD exhibit lower SERT binding potential in specific brain regions, providing compelling evidence of a 5-HT system dysfunction. However, the exact mechanisms underlying this phenotype remain elusive. The limitations include heterogeneity across studies in populations, imaging techniques, and radiotracer usage.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}