Review
Biochemistry & Molecular Biology
Lisa Mapelli, Teresa Soda, Egidio D'Angelo, Francesca Prestori
Summary: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with various forms. The identification of ASD hallmarks and key brain areas, such as the social brain and the cerebellum, has been made possible by recent advancements in brain assessment and the use of mouse models. This review provides a comprehensive perspective on the involvement of the cerebellum in ASD, from its connections to the social brain to the use of monogenic mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Psychology, Developmental
Mark H. Johnson, Tony Charman, Andrew Pickles, Emily J. H. Jones
Summary: The AMEND framework aims to redefine the field of future research on neurodevelopmental disorders by proposing methods to separate early-stage disturbance markers from later developmental modifiers. Understanding how different perturbations and modifiers interact to produce phenotypic outcomes can advance both theoretical understanding and clinical approaches to developmental psychopathology in early childhood.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Ya-Ting Chang, Max Kowalczyk, P. Michelle Fogerson, Yu-Ju Lee, Minza Haque, Eliza L. Adams, David C. Wang, Laura A. DeNardo, Marc Tessier-Lavigne, John R. Huguenard, Liqun Luo, Wei-Hsiang Huang
Summary: Hyperexcitability of brain circuits is a common feature of autism spectrum disorders. This study identifies Rai1 as a negative regulator of excitability, and its deletion results in increased seizure susceptibility and prolonged hippocampal seizure duration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Stefanie Grabrucker, Jessica Pagano, Johanna Schweizer, Carolina Urrutia-Ruiz, Michael Schoen, Kevin Thome, Guenter Ehret, Andreas M. Grabrucker, Rong Zhang, Bastian Hengerer, Juergen Bockmann, Chiara Verpelli, Carlo Sala, Tobias M. Boeckers
Summary: Shank2 deficiency in mice leads to a lack of social bonding behavior towards pups, but enhancing activity in the medial preoptic area of the hypothalamus can restore social bonding behavior.
Article
Endocrinology & Metabolism
Saijun Huang, Jiaying Zeng, Ruoyu Sun, Hong Yu, Haimou Zhang, Xi Su, Paul Yao
Summary: Prenatal exposure to progestin causes oxytocin suppression, leading to social deficits in mouse offspring.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pediatrics
Carolyn C. Foster, Anna Chorniy, Soyang Kwon, Kristin Kan, Nia Heard-Garris, Matthew M. Davis
Summary: Family income can impact child health, but the relationship can also work in the opposite direction. Research reveals that in families with children who have special health care needs, a significant percentage experience forgone family employment due to their child's health condition, with a strong association between the amount of medical care provided by family members and forgone employment.
Review
Pharmacology & Pharmacy
Chiara Villa, Romina Combi, Donatella Conconi, Marialuisa Lavitrano
Summary: Autism spectrum disorder is a group of neurodevelopmental diseases with complex etiology, limited by a lack of relevant human disease models. The development of iPSCs technology provides a promising cellular tool for disease modeling and development of novel drug treatments.
Review
Biochemistry & Molecular Biology
Lucia N. Peralta-Marzal, Naika Prince, Djordje Bajic, Lea Roussin, Laurent Naudon, Sylvie Rabot, Johan Garssen, Aletta D. Kraneveld, Paula Perez-Pardo
Summary: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by behavioral impairments and difficulties in social interaction and communication. Recent studies have shown that approximately 1 in 89 children in European countries have developed some form of ASD, presenting challenges in its diagnosis. Additionally, individuals with ASD often suffer from comorbid medical conditions, including gastrointestinal problems, which may indicate abnormal communication between the brain and gut.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Claudia Cristiano, Floriana Volpicelli, Marianna Crispino, Enza Lacivita, Roberto Russo, Marcello Leopoldo, Antonio Calignano, Carla Perrone-Capano
Summary: Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by social deficits, repetitive behaviors, and altered inflammatory responses. This study found that ASD children have decreased levels of lipoxin A4 (LXA4), a mediator involved in inflammation resolution. Activation of the receptor FPR2 by a compound called MR-39 had positive effects on inflammation markers, LXA4 expression, and social behavior in validated animal models of ASD. These findings suggest that FPR2 could be a potential target for therapeutic approaches in ASD.
Article
Genetics & Heredity
Mary C. Whitman, Brenda J. Barry, Caroline D. Robson, Flavia M. Facio, Carol Van Ryzin, Wai-Man Chan, Tanya J. Lehky, Audrey Thurm, Christopher Zalewski, Kelly A. King, Carmen Brewer, Konstantinia Almpani, Janice S. Lee, Angela Delaney, Edmond J. FitzGibbon, Paul R. Lee, Camilo Toro, Scott M. Paul, Omar A. Abdul-Rahman, Bryn D. Webb, Ethylin Wang Jabs, Hans Ulrik Moller, Dorte Ancher Larsen, Jayne H. Antony, Christopher Troedson, Alan Ma, Glad Ragnhild, Katrine Wirgenes, Emma Tham, Malin Kvarnung, Timothy James Maarup, Sarah MacKinnon, David G. Hunter, Francis S. Collins, Irini Manoli, Elizabeth C. Engle
Summary: Mutations in the TUBB3 gene can cause TUBB3 R262H syndrome, characterized by a range of eye, facial, and neurological symptoms, along with recognizable brain malformations. Patients with TUBB3 R262H syndrome can be distinguished from those with TUBB3 E410K syndrome by the presence of joint contractures, earlier onset neuropathy, impaired gait, and basal ganglia malformations.
Review
Genetics & Heredity
David Exposito-Alonso, Beatriz Rico
Summary: Recent advances in genomics have revealed the genetic variations associated with neurodevelopmental disorders, indicating the importance of synaptic formation and circuit balance in these disorders. This review summarizes the research progress on synaptic and circuit mechanisms implicated in neurodevelopmental disorders and discusses the disruptions in synaptic connections and imbalances in neuronal circuits that contribute to cognitive and behavioral changes in different disorders. Furthermore, new approaches that can restore or mitigate dysfunctional processes and the development of improved clinical biomarkers and strategies for early intervention are highlighted.
ANNUAL REVIEW OF GENETICS
(2022)
Article
Genetics & Heredity
Kevin Lee, Yewon Jung, Yukti Vyas, Imogen Skelton, Wickliffe C. Abraham, Yi-Ping Hsueh, Johanna M. Montgomery
Summary: This study demonstrates the efficacy and breadth of dietary zinc supplementation in preventing ASD-related behavioral deficits in Tbr1(+/-) mice and highlights its impact on synaptic mechanisms.
Article
Biochemistry & Molecular Biology
Fatemeh Hassani Nia, Daniel Woike, Isabel Bento, Stephan Niebling, Debora Tibbe, Kristina Schulz, Daniela Hirnet, Matilda Skiba, Hans-Hinrich Hoenck, Katharina Veith, Christian Guenther, Tasja Scholz, Tatjana Bierhals, Joenna Driemeyer, Renee Bend, Antonio Virgilio Failla, Christian Lohr, Maria Garcia Alai, Hans-Juergen Kreienkamp
Summary: This study investigates the impact of two mutations in the SHANK2 gene on neurodevelopment. The results show that these mutations disrupt the interactions of Shank2 with other proteins, leading to abnormal assembly of postsynaptic protein complexes into nanoclusters. This interference affects the positioning of neurons and synaptic transmission, ultimately impacting normal brain development in humans.
MOLECULAR PSYCHIATRY
(2022)
Article
Psychiatry
Liliana Dell'Osso, Giulia Amatori, Barbara Carpita, Gabriele Massimetti, Benedetta Nardi, Davide Gravina, Francesca Benedetti, Chiara Bonelli, Danila Casagrande, Mario Luciano, Isabella Berardelli, Natascia Brondino, Marianna De Gregorio, Giacomo Deste, Marta Nola, Antonino Reitano, Maria Rosaria Anna Muscatello, Maurizio Pompili, Pierluigi Politi, Antonio Vita, Mario Maj
Summary: Several studies have found a correlation between autism spectrum disorder (ASD) and catatonia, both of which are also associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum. The results showed strong positive correlations, with the strongest coefficient observed between AdAS Spectrum total score and CS total score. Mediation analysis revealed that the mood disorder spectrum had a significant indirect effect on the relationship between autistic traits and catatonic symptoms.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Salvatore Fioriniello, Federico Marracino, Luca Capocci, Vittorio Maglione, Maurizio D'Esposito, Alba Di Pardo, Floriana Della Ragione
Summary: Rett syndrome is a severe neurodevelopmental disorder caused by pathogenetic variants in the MECP2 gene. This study found that Rett syndrome patients have impaired brain vascular homeostasis and blood-brain barrier breakdown, which may contribute to the cognitive impairment. The study provides evidence of impaired blood-brain barrier integrity in Rett syndrome and offers new perspectives for novel therapeutic strategies.
Article
Biochemistry & Molecular Biology
Guangsen Shi, Chen Yin, Zenghua Fan, Lijuan Xing, Yulia Mostovoy, Pui-Yan Kwok, Liza H. Ashbrook, Andrew D. Krystal, Louis J. Ptacek, Ying-Hui Fu
Summary: Adequate and efficient sleep is crucial for our health, with natural short sleepers able to sleep significantly shorter without negative health consequences. A study identified two different mutations in the same gene from two independent natural short sleep families, which manifested as short sleep behavior in both in vitro and in vivo experiments. The mutations were found to change the electrical properties in brain slices, emphasizing the important role of the metabotropic glutamate receptor 1 in modulating sleep duration.
Article
Clinical Neurology
William V. McCall, Ruth M. Benca, Meredith E. Rumble, Andrew D. Krystal
Summary: Patients, coordinators, and physicians in the study had similar low accuracy rates in guessing the treatment assignment, indicating that the blind was maintained and assessment bias was minimized. The results may not be applicable to other hypnotics or RCT designs.
HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
(2021)
Article
Clinical Neurology
Andrew D. Krystal, Aurelia Mittoux, Annika Lindsten, Ross A. Baker
Summary: The study indicates that adjunctive brexpiprazole may help correct circadian dysfunction in patients with MDD. The phase angle between peak cortisol and DLMO could be a potential biomarker for depression and therapeutic response.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Article
Medicine, Research & Experimental
John H. Krystal, Bruce Chow, Jennifer Vessicchio, Adam M. Henrie, Thomas C. Neylan, Andrew D. Krystal, Brian P. Marx, Ke Xu, Ripu D. Jindal, Lori L. Davis, Paula P. Schnurr, Murray B. Stein, Michael E. Thase, Beverly Ventura, Grant D. Huang, Mei-Chiung Shih
Summary: This study aims to compare the effects of three widely prescribed insomnia medications for PTSD patients, utilizing an adaptive design to enhance statistical power and explore predictors of treatment response, ultimately seeking to identify effective pharmacotherapy for PTSD-related insomnia.
CONTEMPORARY CLINICAL TRIALS
(2021)
Article
Neurosciences
Katherine Wilson Scangos, Ankit N. Khambhati, Patrick M. Daly, Lucy W. Owen, Jeremy R. Manning, Josiah B. Ambrose, Everett Austin, Heather E. Dawes, Andrew D. Krystal, Edward F. Chang
Summary: Major depressive disorder is a common and disabling disease characterized by distributed network dysfunction. By analyzing large-scale direct neural recordings, a highly distributed pattern of neural activity and connectivity was discovered in depressed patients, with two subnetworks present across individuals, providing insights for personalized therapy.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Katherine W. Scangos, Ankit N. Khambhati, Patrick M. Daly, Ghassan S. Makhoul, Leo P. Sugrue, Hashem Zamanian, Tony X. Liu, Vikram R. Rao, Kristin K. Sellers, Heather E. Dawes, Philip A. Starr, Andrew D. Krystal, Edward F. Chang
Summary: Deep brain stimulation is a promising treatment for neuropsychiatric conditions, with the potential to be optimized by identifying neural biomarkers. A study showed that biomarker-driven closed-loop therapy resulted in rapid and sustained improvement in depression symptoms. Further research is needed to determine if these results and approach can be applied to a broader population.
Article
Clinical Neurology
Jennifer N. Felder, Elissa S. Epel, John Neuhaus, Andrew D. Krystal, Aric A. Prather
Summary: The study examines the effects of digital cognitive behavior therapy for insomnia (dCBT-I) during pregnancy on subjective sleep outcomes, depressive symptoms, and anxiety symptoms. The findings suggest that dCBT-I can improve postpartum insomnia remission rates and reduce the incidence of insomnia. Additionally, dCBT-I shows significant improvements in depressive and anxiety symptom severity, particularly among patients with minimal depressive symptoms at baseline.
Article
Medicine, Research & Experimental
J. Todd Arnedt, M. Elizabeth Cardoni, Deirdre A. Conroy, Mandilyn Graham, Sajni Amin, Kipling M. Bohnert, Andrew D. Krystal, Mark A. Ilgen
Summary: This trial aims to compare the effects of telemedicine-delivered CBT for insomnia (CBT-TM) and sleep hygiene education (SHE-TM) on improving insomnia/sleep, daytime symptoms, and drinking outcomes in treatment-seeking adults with AUD and insomnia. The study will also examine the impact of treatment on sleep mechanisms and their association with clinical outcomes.
Article
Clinical Neurology
Jessica R. Lunsford-Avery, Jack D. Edinger, Andrew D. Krystal
Summary: Sleep EEG factors, such as overnight delta decline and initial delta peak, contribute significantly to psychomotor functioning in adults with insomnia and healthy controls. These factors, along with sleep duration and continuity, support cognitive restoration during sleep and daytime functioning.
NATURE AND SCIENCE OF SLEEP
(2022)
Article
Medicine, General & Internal
Emerson M. Wickwire, Jennifer S. Albrecht, Vincent F. Capaldi, Sonia O. Jain, Raquel C. Gardner, J. Kent Werner, Pratik Mukherjee, Ashlee B. McKeon, Michael T. Smith, Joseph T. Giacino, Lindsay D. Nelson, Scott G. Williams, Jacob Collen, Xiaoying Sun, David M. Schnyer, Amy J. Markowitz, Geoffrey T. Manley, Andrew D. Krystal
Summary: This study identifies unique trajectories of insomnia in adults after traumatic brain injury (TBI) using latent class mixed models (LCMM). The results show that there is heterogeneity in the course of insomnia after TBI, with different trajectory classes including persistent mild insomnia, initially mild insomnia that resolves over time, persistent severe insomnia, initially severe insomnia that resolves by 12 months, and initially no insomnia symptoms but develop severe symptoms by 12 months. Factors such as female sex, Black race, history of psychiatric illness, and intracranial injury are significantly associated with insomnia trajectory class membership.
Correction
Biochemistry & Molecular Biology
Katherine W. Scangos, Ghassan S. Makhoul, Leo P. Sugrue, Edward F. Chang, Andrew D. Krystal
Article
Psychiatry
Andrew D. Krystal, Ruth M. Benca, Russell Rosenberg, Paula K. Schweitzer, Atul Malhotra, Kimberly Babson, Lawrence Lee, Shay Bujanover, Kingman P. Strohl
Summary: This study compares the effects of solriamfetol treatment on excessive daytime sleepiness (EDS) in individuals with and without a history of depression. The findings show that depression history does not affect the safety and efficacy of solriamfetol in treating EDS associated with narcolepsy or obstructive sleep apnea (OSA). Additionally, the study highlights the high prevalence of depression in individuals with sleep disorders and suggests the importance of recognizing this association in a clinical setting.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Letter
Clinical Neurology
Kristin K. Sellers, Noah Stapper, Daniela A. Astudillo Maya, Catherine Henderson, Ankit N. Khambhati, Joline M. Fan, Vikram R. Rao, Katherine W. Scangos, Edward F. Chang, Andrew D. Krystal
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
C. Neill Epperson, David R. Rubinow, Samantha Meltzer-Brody, Kristina M. Deligiannidis, Robert Riesenberg, Andrew D. Krystal, Kemi Bankole, Ming-Yi Huang, Haihong Li, Colville Brown, Stephen J. Kanes, Robert Lasser
Summary: The study demonstrates that Brexanolone is associated with rapid improvement in depressive symptoms and symptoms of anxiety and insomnia compared with placebo in women with postpartum depression.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Review
Medicine, General & Internal
Charles M. Morin, Suzanne M. Bertisch, Rafael Pelayo, Nathaniel F. Watson, John W. Winkelman, Phyllis C. Zee, Andrew D. Krystal
Summary: Insomnia is a significant public health problem that is often undiagnosed and untreated. Treatment practices are not always evidence-based, particularly when insomnia coexists with anxiety or depression. There is a gap between current clinical practices and evidence-based guidelines, highlighting the need for more awareness and distinct treatment of insomnia from comorbid psychiatric conditions.
JOURNAL OF CLINICAL MEDICINE
(2023)
