Molecular Psychiatry最新文献

{"title":"Projection-specific circuits of retrosplenial cortex with differential contributions to spatial cognition","authors":"Xiaoxiao Lin, Ali Ghafuri, Xiaojun Chen, Musab Kazmi, Douglas A. Nitz, Xiangmin Xu","doi":"10.1038/s41380-024-02819-8","DOIUrl":"https://doi.org/10.1038/s41380-024-02819-8","url":null,"abstract":"<p>Retrosplenial cortex (RSC) is a brain region involved in neuropsychiatric and neurodegenerative disorders. It has reciprocal connections with a diverse set of cortical and subcortical brain regions, but the afferent structure and behavioral function of circuits defined by its projection-specific sub-populations have yet to be determined. The corticocortical connections between RSC and secondary motor cortex (M2), as well as corticothalamic connections between RSC and anterodorsal thalamus (AD) have been hypothesized to function as semi-independent, but parallel pathways that impact spatial information processing in distinct ways. We used retrograde and anterograde viral tracers and monosynaptic retrograde rabies virus to quantitatively characterize and compare the afferent and efferent distributions of retrosplenial neuron sub-populations projecting to M2 and AD. AD-projecting and M2-projecting RSC neurons overlap in their collateral projections to other brain regions, but not in their projections to M2 and AD, respectively. Compared with AD-projecting RSC neurons, M2-projecting RSC neurons received much greater afferent input from the dorsal subiculum, AD, lateral dorsal and lateral posterior thalamus, and somatosensory cortex. AD-projecting RSC neurons received greater input from the anterior cingulate cortex and medial septum. We performed chemogenetic inhibition of M2- and AD-projecting RSC neurons and examined its impact on object-location memory, object-recognition, open-field exploration, and place-action association. Our findings indicate that inhibition of M2-projecting RSC neurons impairs object location memory as well as place-action association, while the RSC to AD pathway impacts only object-location memory. The findings indicate that RSC is composed of semi-independent circuits distinguishable by their afferent/efferent distributions and differing in the cognitive functions to which they contribute.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"80 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies","authors":"R. Scott Mackin, Emma Rhodes, Michelle Kassel, Maria Kryza-Lacombe, Emily Burns, David Bickford, Ruth Morin, Duygu Tosun, Susan Landau, Meryl A. Butters, Paul Aisen, Rema Raman, Andrew J. Saykin, Arthur Toga, Robert Koeppe, Clifford Jack, Michael W. Weiner, Craig Nelson, Philip S. Insel","doi":"10.1038/s41380-024-02677-4","DOIUrl":"https://doi.org/10.1038/s41380-024-02677-4","url":null,"abstract":"<p>This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve. Twenty-one percent of LLD and ND participants were Aβ positive and the groups did not differ on white matter hyperintensity volume (WMH (logscale); β = 0.12, <i>p</i> = 0.28). Compared to ND, the LLD group exhibited significantly lower bilateral volume in the lateral orbitofrontal cortex, hippocampus, accumbens area, superior temporal lobe, temporal pole, and amygdala after multiple comparison correction (<i>p</i> &lt; 0.009 for all). Cortico-limbic volumes significantly improved classification of LLD beyond demographic characteristics, Aβ status, and WMH (AUC_Vol = 0.71, AUC_WMH, _Aβ = 0.62, AUC difference, 0.09 [0.03 to 0.15]). LLD exhibited poorer performance on measures of global cognition, set shifting, and verbal learning and memory relative to ND. Cognitive function was positively associated with cortico-limbic volumes and these relationships did not differ by group. Secondary analyses with an ND sample additionally matched for Mild Cognitive Impairment (MCI) diagnosis showed a similar but attenuated pattern of volume abnormalities. Overall, our results support LLD as being associated with cortico-limbic volume abnormalities that are distinct from Aβ and white matter pathologies and that these volume abnormalities are important factors associated with cognitive dysfunction in LLD.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"94 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals","authors":"Lorielle M. F. Dietze, Sean R. McWhinney, Pauline Favre, Christoph Abé, Nina Alexander, Carlotta Barkhau, Francesco Benedetti, Michael Berk, Erlend Bøen, Birgitte Boye, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Sean P. Carruthers, Emily L. V. Corkum, Udo Dannlowski, Ana M. Díaz-Zuluaga, Katharina Dohm, Torbjørn Elvsåshagen, Kira Flinkenflügel, Lydia Fortea, Lisa S. Furlong, Benjamin I. Goldstein, Dominik Grotegerd, Marius Gruber, Bartholomeus C. M. Haarman, Fleur M. Howells, Neda Jahanshad, Hamidreza Jamalabadi, Andreas Jansen, James A. Karantonis, Kody G. Kennedy, Tilo T. J. Kircher, Anna Luisa Klahn, Peter Kochunov, Anna Kraus, Mikael Landén, Carlos López-Jaramillo, Bradley J. MacIntosh, Elena Mazza, Colm McDonald, Andrew M. McIntosh, Hannah Meinert, Susanne Meinert, Elisa M. T. Melloni, Philip B. Mitchell, Igor Nenadić, Nils Opel, Mary Phillips, Camille Piguet, Mircea Polosan, Edith Pomarol-Clotet, Arnaud Pouchon, Joaquim Radua, Gloria Roberts, Alex J. Ross, Susan L. Rossell, Raymond Salvador, Kang Sim, Jair C. Soares, Giovana B. Zunta-Soares, Frederike Stein, Benjamin Straube, Chao Suo, Lea Teutenberg, Florian Thomas-Odenthal, Sophia I. Thomopoulos, Paula Usemann, Tamsyn E. Van Rheenen, Amelia Versace, Eduard Vieta, Enric Vilajosana, Benson Mwangi, Wei Wen, Heather C. Whalley, Mon-Ju Wu, Ole A. Andreassen, Christopher R. K. Ching, Paul M. Thompson, Josselin Houenou, Tomas Hajek","doi":"10.1038/s41380-024-02784-2","DOIUrl":"https://doi.org/10.1038/s41380-024-02784-2","url":null,"abstract":"<p>Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal <i>stratum</i>. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"108 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attention and executive delays in early childhood: a meta-analysis of neurodevelopmental conditions","authors":"Dabin Lee, Kelsie A. Boulton, Carter Sun, Natalie L. Phillips, Martha Munro, Fiona Kumfor, Eleni A. Demetriou, Adam J. Guastella","doi":"10.1038/s41380-024-02802-3","DOIUrl":"https://doi.org/10.1038/s41380-024-02802-3","url":null,"abstract":"<p>The objective of this review was to evaluate attention and executive function performance in children with neurodevelopmental conditions across the first 5 years of life, compared to neurotypical peers. MEDLINE, EMBASE, and PsycINFO databases were searched until June 30, 2023, and studies comparing attention or executive function between children with (or at risk for) neurodevelopmental conditions and neurotypical (or low risk) peers, 0 to 5 years old, were included. Of the 4338 studies identified, 111 studies with 12292 participants were included in the meta-analysis. The qualitative analysis of brain development included 5 studies. Primary outcomes were the standardised mean difference (Hedges’ g) in attention and executive function between groups. Meta-regressions examined moderating effects of age, biological sex, diagnosis, and measure type. Children with neurodevelopmental conditions showed small delays in attention (<i>n</i> = 49 studies, <i>k</i> = 251 outcomes, <i>g</i> = 0.36, 95% CI 0.23-0.48, <i>p</i> &lt; 0.001) and moderate delays in executive function (<i>n</i> = 64 studies, <i>k</i> = 368 outcomes, <i>g</i> = 0.64,95% CI 0.53–0.76, <i>p</i> &lt; 0.001). Attention and executive function delays could not be identified in the first year (equivalence tests, <i>p</i> &lt; 0.001), small to moderate delays were found in toddlerhood and moderate delays by preschool. Delays identified were largely transdiagnostic, although there was some evidence of diagnosis-specific delays for attention and moderation by measure type (informant rating vs performance-based vs physiological). Qualitative analysis described how delays were underpinned by a divergence of brain development in medial prefrontal regions. These findings highlight the potential of using attention and executive measures to detect delay and to intervene in neurodevelopmental conditions early in life.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"145 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal and common risk pathways linking childhood maltreatment to later intimate partner violence victimization","authors":"Patrizia Pezzoli, Jean-Baptiste Pingault, Thalia C. Eley, Eamon McCrory, Essi Viding","doi":"10.1038/s41380-024-02813-0","DOIUrl":"https://doi.org/10.1038/s41380-024-02813-0","url":null,"abstract":"<p>Childhood maltreatment and intimate partner violence (IPV) victimization are major psychiatric risk factors. Maltreatment substantially increases the likelihood of subsequent IPV victimization, but what drives this association is poorly understood. We analyzed retrospective self-reports of maltreatment and IPV victimization in 12,794 participants (58% women, 42% men) from the Twins Early Development Study at ages 21 and 26 using quantitative genetic methods. We estimated the etiological influences common to maltreatment and IPV, and the effect of maltreatment on IPV beyond such common influences. Participants who reported childhood maltreatment ( ~ 7% of the sample) were 3 times more likely than their peers to also report IPV victimization at age 21, 4 times more likely at 26. The association between maltreatment and IPV was mostly due to environmental influences shared by co-twins (42–43%) and genetic influences (30–33%), as well as nonshared environmental influences (25–27%). The association between maltreatment and IPV was similar for women and men, but its etiology partly differed by sex. Maltreatment had a moderate effect on IPV in phenotypic models (<i>β</i> = 0.25–0.30), decreasing to a small-to-moderate range in causally informative models accounting for their common etiology (<i>β</i> = 0.15–0.21). Risk factors common to maltreatment and IPV victimization are largely familial in origin, environmental and genetic. Even considering common risk factors, experiencing maltreatment may be causally related to subsequent IPV victimization. Interventions promoting safe intimate relationships among young adults exposed to maltreatment are warranted and should address family-level environmental risk and individual-level risk shaped by genetics.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"20 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.","authors":"Rachel A Hill, Andrew Gibbons, Wittaya Suwakulsiri, Angela Taseska, Hayley Darke, Atul Malhotra, Hnin Yee, Michael Fahey, Rod W Hunt, Izaak Lim, Kirsten Palmer, Suresh Sundram","doi":"10.1038/s41380-024-02808-x","DOIUrl":"https://doi.org/10.1038/s41380-024-02808-x","url":null,"abstract":"<p><p>Maternal infections during pregnancy can increase the risk to offspring of developing a neurodevelopmental disorder. Given the global prevalence and severity of infection with Severe Acute Respiratory Syndrome related Coronavirus 2 (SARS-CoV-2), the objective of this study was to determine if in utero exposure to severe maternal SARS-CoV-2 infection alters infant neurodevelopmental outcomes at 12 months and to identify potential biological markers of adverse infant outcomes. Mother-infant dyads exposed to severe SARS-CoV-2 infection (requiring hospitalization) during pregnancy and age and sociodemographic matched control dyads were recruited from Monash Medical Centre, Australia in 2021/22 and prospectively assessed over 12 months. Maternal serum cytokine levels and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at birth. DNA methylation was assessed from infant buccal swabs at birth (Illumina EPIC BeadChip). Infant neurodevelopmental outcomes at 12 months were assessed using the Ages and Stages Questionnaire (ASQ-3). Mothers exposed to severe SARS-CoV-2 exhibited elevated serum IL-6 and IL-17A and higher EPDS scores than controls at birth. Infants exposed to severe SARS-CoV-2 in utero demonstrated over 3000 significant differentially methylated sites within their genomes compared to non-exposed (adjusted p-value < 0.05), including genes highly relevant to ASD and synaptic pathways. At 12 months, severe SARS-CoV-2 exposed infants scored lower on the ASQ-3 than non-exposed infants, and communication and problem-solving scores negatively correlated with maternal IL-6 levels at birth. DNA methylation changes therefore unveil potential mechanisms linking infection exposure to delayed neurodevelopment and maternal serum IL-6 levels may be a potential biomarker of child developmental delay. Mothers exposed to severe SARS-CoV-2 infections show elevated pro-inflammatory cytokines. Infants exposed in utero to severe SARS-CoV-2 infection show altered DNA methylation at birth and delayed development at 12 months of age. Created in Biorender.com.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke","authors":"Friederike A. Arlt, Pia S. Sperber, Regina von Rennenberg, Pimrapat Gebert, Bianca Teegen, Marios K. Georgakis, Rong Fang, Anna Dewenter, Michael Görtler, Gabor C. Petzold, Silke Wunderlich, Inga Zerr, Martin Dichgans, Harald Prüss, Matthias Endres","doi":"10.1038/s41380-024-02744-w","DOIUrl":"https://doi.org/10.1038/s41380-024-02744-w","url":null,"abstract":"<p>Patients suffering from strokes are at increased risk of developing post-stroke dementia. Serum anti-NMDA receptor autoantibodies (NMDAR1-abs) have been associated with unfavorable post-stroke outcomes. However, their effect on specific cognitive domains remains unclear. We used data from the prospective multicenter DZNE—mechanisms after stroke (DEMDAS) cohort, and measured NMDAR1-abs in serum at baseline. Cognitive function was assessed with a comprehensive neuropsychological test battery at 6- and 12-months follow-up. We employed crude and stepwise confounder adjusted linear and logistic regression models as well as generalized estimating equation models (GEE) to determine the relevance of NMDAR1-abs seropositivity on cognitive function after stroke. 10.2% (58/569) DEMDAS patients were NMDAR1-abs seropositive (IgM:n = 44/IgA:n = 21/IgG:n = 2). Seropositivity was not associated with global cognitive impairment after stroke. However, NMDAR1-abs seropositive patients performed lower in the memory domain (β_adjusted = −0.11; 95%CI = −0.57 to −0.03) and were at increased risk for memory impairment (OR_adjusted= 3.8; 95%CI = 1.33–10.82) compared to seronegative patients, 12 months after stroke. Further, NMDAR1-abs were linked to memory impairment over time in GEE from 6- to 12-months follow-up (OR_adjusted= 2.41; 95%CI = 1.05–5.49). Our data suggests that NMDAR1-abs contribute to memory dysfunction 1 year after stroke while not affecting other cognitive subdomains. Hence, antineuronal autoimmunity may be involved in distinct mechanisms of post-stroke memory impairment. <i>Clinical trial name and registration number</i>: The Determinants of Dementia After Stroke (DEMDAS; study identifier on clinical trials.gov: NCT01334749)</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"195 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival","authors":"Alexandra Strauss, Peter Swann, Stacey L. Kigar, Rafailia Christou, Natalia Savinykh Yarkoni, Lorinda Turner, Alexander G. Murley, Leonidas Chouliaras, Noah Shapiro, Nicholas J. Ashton, George Savulich, W. Richard Bevan-Jones, Ajenthan Surendranthan, Kaj Blennow, Henrik Zetterberg, John T. O’Brien, James B. Rowe, Maura Malpetti","doi":"10.1038/s41380-024-02809-w","DOIUrl":"https://doi.org/10.1038/s41380-024-02809-w","url":null,"abstract":"<p>The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells in n = 148 people with Alzheimer’s disease (AD), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), Lewy body dementia (LBD) as compared to n = 37 healthy controls. To compare groups, we used multivariate dissimilarity analysis and principal component analysis across 19 innate immune cell types. We identified pro-inflammatory profiles that significantly differ between patients with all-cause dementia and healthy controls, with some significant differences between patient groups. Regression analysis confirmed that time to death following the blood test correlated with the individuals’ immune profile weighting, positively to TREM2+ and non-classical monocytes and negatively to classical monocytes. Taken together, these results describe transdiagnostic peripheral immune profiles and highlight the link between prognosis and the monocyte cellular subdivision and function (as measured by surface protein expression). The results suggest that blood-derived innate immune profiles can inform sub-populations of cells relevant for specific neurodegenerative diseases that are significantly linked to accelerated disease progression and worse survival outcomes across diagnoses. Blood-based innate immune profiles may contribute to enhanced precision medicine approaches in dementia, helping to identify and monitor therapeutic targets and stratify patients for candidate immunotherapies.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"15 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole exome sequencing identified six novel genes for depressive symptoms","authors":"Ze-Yu Li, Chen-Jie Fei, Rui-Ying Yin, Ju-Jiao Kang, Qing Ma, Xiao-Yu He, Xin-Rui Wu, Yu-Jie Zhao, Wei Zhang, Wei-Shi Liu, Bang-Sheng Wu, Liu Yang, Ying Zhu, Jian-Feng Feng, Jin-Tai Yu, Wei Cheng","doi":"10.1038/s41380-024-02804-1","DOIUrl":"https://doi.org/10.1038/s41380-024-02804-1","url":null,"abstract":"<p>Previous genome-wide association studies of depression have primarily focused on common variants, limiting our comprehensive understanding of the genetic architecture. In contrast, whole–exome sequencing can capture rare coding variants, helping to explore the phenotypic consequences of altering protein-coding genes. Here, we conducted a large-scale exome-wide association study on 296,199 participants from the UK Biobank, assessing their depressive symptom scores through the Patient Health Questionnaire-4. We identified 22 genes associated with depressive symptoms, including 6 newly discovered genes (<i>TRIM27</i>, <i>UBD</i>, <i>SVOP</i>, <i>ADGRB2</i>, <i>IRF2BPL</i>, and <i>ANKRD12</i>). Both ontology enrichment analysis and plasma proteomics association analysis consistently revealed that the identified genes were associated with immune responses. Furthermore, we identified associations between these genes and brain regions related to depression, such as anterior cingulate cortex and orbitofrontal cortex. Additionally, phenome-wide association analysis demonstrated that <i>TRIM27</i> and <i>UBD</i> were associated with neuropsychiatric, cognitive, biochemistry, and inflammatory traits. Our findings offer new insights into the potential mechanisms and genetic architecture of depressive symptoms.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"31 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrity of the circadian clock determines regularity of high-frequency and diurnal LFP rhythms within and between brain areas","authors":"Paul Volkmann, Annika E. I. Geiger, Anisja Hühne-Landgraf, Nina Miljanovic, Jessica Bly, Tobias Engl, Heidrun Potschka, Moritz J. Rossner, Dominic Landgraf","doi":"10.1038/s41380-024-02795-z","DOIUrl":"https://doi.org/10.1038/s41380-024-02795-z","url":null,"abstract":"<p>Circadian clocks control most physiological processes of many species. We specifically wanted to investigate the influence of environmental and endogenous rhythms and their interplay on electrophysiological dynamics of neuronal populations. Therefore, we measured local field potential (LFP) time series in wild-type and <i>Cryptochrome 1</i> and <i>2</i> deficient (<i>Cry1/2</i>^{<i>−/−</i>}) mice in the suprachiasmatic nucleus and the nucleus accumbens under regular light conditions and constant darkness. Using refined descriptive and statistical analyses, we systematically profiled LFP time series activity. We show that both environmental and endogenous rhythms strongly influence the rhythmicity of LFP signals and their frequency components, but also shape neuronal patterns on much smaller time scales, as neuronal activity in <i>Cry1/2</i>^{<i>−/−</i>} mice is significantly less regular but at each time more synchronous within and between brain areas than in wild-type mice. These results show that functional circadian rhythms are integral for both circadian and non-circadian coordination of neuronal ensemble dynamics.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"103 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}