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JOURNAL ARTICLE
Soyolsaikhan Odkhuu, Woo-Sung Kim, Uyanga Tsogt, Jie Shen, Sahar Cheraghi, Ling Li, Fatima Zahra Rami, Thi-Hung Le, Keon-Hak Lee, Nam-In Kang, Sung-Wan Kim, Young-Chul Chung
There are no studies investigating topological properties of resting-state fMRI (rs-fMRI) in patients who have recovered from psychosis and discontinued medication (hereafter, recovered patients [RP]). This study aimed to explore topological organization of the functional brain connectome in the RP using graph theory approach. We recruited 30 RP and 50 age and sex-matched healthy controls (HC). The RP were further divided into the subjects who were relapsed after discontinuation of antipsychotics (RP-R) and who maintained recovered state without relapse (RP-M)...
September 29, 2023: Molecular Psychiatry
#2
JOURNAL ARTICLE
Candela González-Arias, Andrea Sánchez-Ruiz, Julio Esparza, Cristina Sánchez-Puelles, Lucia Arancibia, Jorge Ramírez-Franco, Davide Gobbo, Frank Kirchhoff, Gertrudis Perea
Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca2+ signaling in MDD are poorly understood. Here, we found that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic Ca2+ dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca2+ signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons...
September 29, 2023: Molecular Psychiatry
#3
JOURNAL ARTICLE
Huei-Ying Chen, BaDoi N Phan, Gina Shim, Gregory R Hamersky, Norah Sadowski, Thomas S O'Donnell, Srinidhi Rao Sripathy, Joseph F Bohlen, Andreas R Pfenning, Brady J Maher
Transcription factor 4 (TCF4) is a basic helix-loop-helix transcription factor that is implicated in a variety of psychiatric disorders including autism spectrum disorder (ASD), major depression, and schizophrenia. Autosomal dominant mutations in TCF4 are causal for a specific ASD called Pitt-Hopkins Syndrome (PTHS). However, our understanding of etiological and pathophysiological mechanisms downstream of TCF4 mutations is incomplete. Single cell sequencing indicates TCF4 is highly expressed in GABAergic interneurons (INs)...
September 28, 2023: Molecular Psychiatry
#4
JOURNAL ARTICLE
Lucia Marti-Prats, Chiara Giuliano, Ana Domi, Mickaël Puaud, Yolanda Peña-Oliver, Maxime Fouyssac, Colin McKenzie, Barry J Everitt, David Belin
Humans greatly differ in how they cope with stress, a natural behavior learnt through negative reinforcement. Some individuals engage in displacement activities, others in exercise or comfort eating, and others still in alcohol use. Across species, adjunctive behaviors, such as polydipsic drinking, are used as a form of displacement activity that reduces stress. Some individuals, in particular those that use alcohol to self-medicate, tend to lose control over such coping behaviors, which become excessive and compulsive...
September 28, 2023: Molecular Psychiatry
#5
JOURNAL ARTICLE
Romina Miranda-Olivos, Isabel Baenas, Trevor Steward, Roser Granero, Antoni Pastor, Isabel Sánchez, Asier Juaneda-Seguí, Amparo Del Pino-Gutiérrez, José A Fernández-Formoso, Nuria Vilarrasa, Fernando Guerrero-Pérez, Nuria Virgili, Rafael López-Urdiales, Susana Jiménez-Murcia, Rafael de la Torre, Carles Soriano-Mas, Fernando Fernández-Aranda
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI)...
September 28, 2023: Molecular Psychiatry
#6
JOURNAL ARTICLE
Kwan Young Lee, Haohan Wang, Yeeun Yook, Justin S Rhodes, Catherine A Christian-Hinman, Nien-Pei Tsai
Synaptic potentiation underlies various forms of behavior and depends on modulation by multiple activity-dependent transcription factors to coordinate the expression of genes necessary for sustaining synaptic transmission. Our current study identified the tumor suppressor p53 as a novel transcription factor involved in this process. We first revealed that p53 could be elevated upon chemically induced long-term potentiation (cLTP) in cultured primary neurons. By knocking down p53 in neurons, we further showed that p53 is required for cLTP-induced elevation of surface GluA1 and GluA2 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)...
September 28, 2023: Molecular Psychiatry
#7
REVIEW
Alaina M Jaster, Javier González-Maeso
Psychedelics, also known as classical hallucinogens, have been investigated for decades due to their potential therapeutic effects in the treatment of neuropsychiatric and substance use disorders. The results from clinical trials have shown promise for the use of psychedelics to alleviate symptoms of depression and anxiety, as well as to promote substantial decreases in the use of nicotine and alcohol. While these studies provide compelling evidence for the powerful subjective experience and prolonged therapeutic adaptations, the underlying molecular reasons for these robust and clinically meaningful improvements are still poorly understood...
September 27, 2023: Molecular Psychiatry
#8
JOURNAL ARTICLE
Nadine Parker, Weiqiu Cheng, Guy F L Hindley, Pravesh Parekh, Alexey A Shadrin, Ivan I Maximov, Olav B Smeland, Srdjan Djurovic, Anders M Dale, Lars T Westlye, Oleksandr Frei, Ole A Andreassen
Improved understanding of the shared genetic architecture between psychiatric disorders and brain white matter may provide mechanistic insights for observed phenotypic associations. Our objective is to characterize the shared genetic architecture of bipolar disorder (BD), major depression (MD), and schizophrenia (SZ) with white matter fractional anisotropy (FA) and identify shared genetic loci to uncover biological underpinnings. We used genome-wide association study (GWAS) summary statistics for BD (n = 413,466), MD (n = 420,359), SZ (n = 320,404), and white matter FA (n = 33,292) to uncover the genetic architecture (i...
September 27, 2023: Molecular Psychiatry
#9
REVIEW
Matthew B Wall, Rebecca Harding, Rayyan Zafar, Eugenii A Rabiner, David J Nutt, David Erritzoe
Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this movement, but substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The modern phase of development of these treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging...
September 27, 2023: Molecular Psychiatry
#10
JOURNAL ARTICLE
Camille Deforges, Vania Sandoz, Yvonnick Noël, Valérie Avignon, David Desseauve, Julie Bourdin, Yvan Vial, Susan Ayers, Emily A Holmes, Manuella Epiney, Antje Horsch
Preventive evidence-based interventions for childbirth-related posttraumatic stress disorder (CB-PTSD) are lacking. Yet, 18.5% of women develop CB-PTSD symptoms following an unplanned caesarean section (UCS). This two-arm, multicentre, double-blind superiority trial tested the efficacy of an early single-session intervention including a visuospatial task on the prevention of maternal CB-PTSD symptoms. The intervention was delivered by trained maternity clinicians. Shortly after UCS, women were included if they gave birth to a live baby, provided consent, and perceived their childbirth as traumatic...
September 27, 2023: Molecular Psychiatry
#11
REVIEW
Eva Lepinay, Francesca Cicchetti
Developing effective treatments for patients with Huntington's disease (HD)-a neurodegenerative disorder characterized by severe cognitive, motor and psychiatric impairments-is proving extremely challenging. While the monogenic nature of this condition enables to identify individuals at risk, robust biomarkers would still be extremely valuable to help diagnose disease onset and progression, and especially to confirm treatment efficacy. If measurements of cerebrospinal fluid neurofilament levels, for example, have demonstrated use in recent clinical trials, other proteins may prove equal, if not greater, relevance as biomarkers...
September 25, 2023: Molecular Psychiatry
#12
JOURNAL ARTICLE
Joseph O'Neill, Maylen Perez Diaz, Jeffry R Alger, Jean-Baptiste Pochon, Dara Ghahremani, Andrew C Dean, Rachel F Tyndale, Nicole Petersen, Shane Marohnic, Andrea Karaiskaki, Edythe D London
Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking...
September 25, 2023: Molecular Psychiatry
#13
JOURNAL ARTICLE
Kaizhong Xue, Bo Gao, Feng Chen, Meiyun Wang, Jingliang Cheng, Bing Zhang, Wenzhen Zhu, Shijun Qiu, Zuojun Geng, Xiaochu Zhang, Guangbin Cui, Yongqiang Yu, Quan Zhang, Weihua Liao, Hui Zhang, Xiaojun Xu, Tong Han, Wen Qin, Feng Liu, Meng Liang, Lining Guo, Qiang Xu, Jiayuan Xu, Jilian Fu, Peng Zhang, Wei Li, Dapeng Shi, Caihong Wang, Su Lui, Zhihan Yan, Jing Zhang, Jiance Li, Dawei Wang, Junfang Xian, Kai Xu, Xi-Nian Zuo, Longjiang Zhang, Zhaoxiang Ye, Tobias Banaschewski, Gareth J Barker, Arun L W Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Luise Poustka, Sarah Hohmann, Nathalie Holz, Juliane H Fröhner, Michael N Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Wen Shen, Yanwei Miao, Chunshui Yu
Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity...
September 22, 2023: Molecular Psychiatry
#14
REVIEW
Paul J Harrison, David M Bannerman
Involvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate GRIN2A, the gene encoding the NR2A (GluN2A) NMDA receptor subunit, in the aetiology of the disorder. Rare variants and common variants are both robustly associated with genetic risk for schizophrenia. Some of the rare variants are point mutations likely affecting channel function, but most are predicted to cause protein truncation and thence result, like the common variants, in reduced gene expression...
September 22, 2023: Molecular Psychiatry
#15
JOURNAL ARTICLE
David A Sbarra, Ferris A Ramadan, Karmel W Choi, Jorien L Treur, Daniel F Levey, Robyn E Wootton, Murray B Stein, Joel Gelernter, Yann C Klimentidis
Major depression (MD) is a serious psychiatric illness afflicting nearly 5% of the world's population. A large correlational literature suggests that loneliness is a prospective risk factor for MD; correlational assocations of this nature may be confounded for a variety of reasons. This report uses Mendelian Randomization (MR) to examine potentially causal associations between loneliness and MD. We report on analyses using summary statistics from three large genome wide association studies (GWAS). MR analyses were conducted using three independent sources of GWAS summary statistics...
September 21, 2023: Molecular Psychiatry
#16
JOURNAL ARTICLE
Salvatore P Mangiafico, Qing-Zhang Tuo, Xiao-Lan Li, Yu Liu, Christian Haralambous, Xu-Long Ding, Scott Ayton, Qing Wang, D Ross Laybutt, Jeng Yie Chan, Xiang Zhang, Cameron Kos, Helen E Thomas, Thomas Loudovaris, Chieh-Hsin Yang, Christos N Joannides, Benjamin J Lamont, Lunzhi Dai, Hai-Huai He, Biao Dong, Sofianos Andrikopoulos, Ashley I Bush, Peng Lei
Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet β-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis...
September 21, 2023: Molecular Psychiatry
#17
JOURNAL ARTICLE
Shinichiro Ochi, Bhaskar Roy, Kevin Prall, Richard C Shelton, Yogesh Dwivedi
Major depressive disorder (MDD) is highly prevalent in adolescents and is a major risk factor for suicidality. Recent evidence shows that accelerated cellular senescence/aging is associated with psychiatric illness, including depression, in adults. The present study examined if the relationships of telomere length (TL) and mitochondrial DNA copy number (mtDNAcn), two critical indicators of cellular senescence/aging, are altered in depressed adolescents and whether these alterations are associated with suicidality, early-life adversities, and other co-occuring factors...
September 21, 2023: Molecular Psychiatry
#18
JOURNAL ARTICLE
Reshma Bhagat, Miguel A Minaya, Arun Renganathan, Muneshwar Mehra, Jacob Marsh, Rita Martinez, Abdallah M Eteleeb, Alissa L Nana, Salvatore Spina, William W Seeley, Lea T Grinberg, Celeste M Karch
Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p...
September 21, 2023: Molecular Psychiatry
#19
REVIEW
Jacqueline Kaiser, Kevin Nay, Christopher R Horne, Luke M McAloon, Oliver K Fuller, Abbey G Muller, Douglas G Whyte, Anthony R Means, Ken Walder, Michael Berk, Anthony J Hannan, James M Murphy, Mark A Febbraio, Andrew L Gundlach, John W Scott
Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition...
September 20, 2023: Molecular Psychiatry
#20
N Runia, G J J Mol, T Hillenius, Z Hassanzadeh, D A J P Denys, I O Bergfeld
Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioning are unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRD with a systematic review and meta-analyses. After systematically searching PubMed we included 10 studies which compared standardized neuropsychological tests before and after DBS or between active and sham DBS in TRD. Different random-effects meta-analyses were done for different cognitive (sub-)domains and for different follow-up time windows (<6 months, 6-18 months, and >18 months)...
September 20, 2023: Molecular Psychiatry
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