16 results on '"Ho Namkung"'
Search Results
2. Causal impact of local inflammation in the nasal cavity on higher brain function and cognition
- Author
-
Atsushi Kamiya, Akira Sawa, Andrew P. Lane, Xiaolei Zhu, Ho Namkung, Shinji Sakamoto, Amy Smith, Koko Ishizuka, and Yuto Hasegawa
- Subjects
0301 basic medicine ,Nasal cavity ,Inflammation ,Disease ,Mice ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,medicine ,Animals ,Pathological ,SARS-CoV-2 ,business.industry ,General Neuroscience ,Brain ,COVID-19 ,General Medicine ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Mood disorders ,Schizophrenia ,Immunology ,Nasal Cavity ,medicine.symptom ,business ,Olfactory epithelium ,030217 neurology & neurosurgery - Abstract
Epidemiological evidence suggests that adverse environmental factors in the nasal cavity may increase the risk for neuropsychiatric diseases. For instance, air pollution and nasal viral infection have been underscored as risk factors for Parkinson's disease, schizophrenia, and mood disorders. These adverse factors can elicit local inflammation in the nasal cavity, which may in turn influence higher brain function. Nevertheless, evidence that directly supports their causal link is missing. To fill this knowledge gap, we used an inducible mouse model for olfactory inflammation and showed the evidence that this local pathological factor can elicit behavioral abnormalities.
- Published
- 2021
3. Anterior Insula-Associated Social Novelty Recognition: Pivotal Roles of a Local Retinoic Acid Cascade and Oxytocin Signaling
- Author
-
Sun-Hong Kim, Kyongman An, Ho Namkung, Atsushi Saito, Matthew D. Rannals, James R. Moore, Marina Mihaljevic, Sneha Saha, Seyun Oh, Mari A. Kondo, Koko Ishizuka, Kun Yang, Brady J. Maher, Minae Niwa, and Akira Sawa
- Subjects
Psychiatry and Mental health - Abstract
Deficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a "common core" brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive. This study aims to fill this knowledge gap.To determine the role of the anterior insula in social cognition, the authors manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and is involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. Multimodal analyses were conducted at the molecular, cellular, circuitry, and behavioral levels.At the molecular and cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. The authors also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, although not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts with the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus, where serotonergic neurons are projected to the anterior insula. Furthermore, the authors show that serotonin 5-HTThe anterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade but also remotely regulated by oxytocin via a long-range circuit mechanism.
- Published
- 2022
4. Nuclear GAPDH in cortical microglia mediates stress-induced cognitive inflexibility
- Author
-
Adriana Ramos, Koko Ishizuka, Ho Namkung, Lindsay N. Hayes, Atsushi Saito, Arisa Hayashida, Rupali Srivastava, Noah Elkins, Trexy Palen, Elisa Carloni, Tsuyoshi Tsujimura, Coleman Calva, Satoshi Ikemoto, Rana Rais, Barbara S. Slusher, Minae Niwa, Toshiaki Saitoh, Eiki Takimoto, and Akira Sawa
- Abstract
We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. Furthermore, hyperactivation of the prelimbic layer 5 excitatory neurons, which are known to be a neuronal substrate of cognitive inflexibility, was also normalized by the pharmacological and microglia-specific genetic interventions. The RR compound may offer a mechanism-driven, translational opportunity against stress-induced cognitive inflexibility. Taken together, we show a pivotal role of cortical microglia and microglia-neuron interaction in stress-induced cognitive inflexibility. We underscore the N-GAPDH cascade in microglia, which causally mediates stress-induced cognitive alteration.
- Published
- 2022
5. The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder
- Author
-
Ho Namkung, Hiroshi Yukitake, Daisuke Fukudome, Brian J. Lee, Mengnan Tian, Gianluca Ursini, Atsushi Saito, Shravika Lam, Suvarnambiga Kannan, Rupali Srivastava, Minae Niwa, Kamal Sharma, Peter Zandi, Hanna Jaaro-Peled, Koko Ishizuka, Nilanjan Chatterjee, Richard L. Huganir, and Akira Sawa
- Subjects
General Neuroscience - Abstract
Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124-3p in the medial prefrontal cortex. We demonstrated that the upregulation of miR-124-3p increases GRIA2-lacking calcium-permeable AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.
- Published
- 2023
6. Tagging active neurons by soma-targeted Cal-Light
- Author
-
Jung Ho Hyun, Kenichiro Nagahama, Ho Namkung, Neymi Mignocchi, Seung-Eon Roh, Patrick Hannan, Sarah Krüssel, Chuljung Kwak, Abigail McElroy, Bian Liu, Mingguang Cui, Seunghwan Lee, Dongmin Lee, Richard L. Huganir, Paul F. Worley, Akira Sawa, and Hyung-Bae Kwon
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Verifying causal effects of neural circuits is essential for proving a direct circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we develop the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, lever-pressing choice behavior, and social interaction behaviors. We also target kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppress seizure symptoms, suggesting ST-Cal-Light’s applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.
- Published
- 2021
7. The anterior insular cortex associates temporally discontiguous stimuli during threat learning
- Author
-
Ho Namkung, J. de Chabot, Akira Sawa, L. Guttman, Hyung Bae Kwon, Sedona Lockhart, and I. Isehak
- Subjects
Filling-in ,Biology ,Insular cortex ,medicine.disease ,Posttraumatic stress ,medicine.anatomical_structure ,Dopamine receptor D1 ,Dopamine ,medicine ,Association (psychology) ,Neuroscience ,Anxiety disorder ,Basolateral amygdala ,medicine.drug - Abstract
Learning about potential threats in the environment is indispensable for survival. Deficits in threat learning constitute a key dimension of multiple brain disorders, which include posttraumatic stress disorder and anxiety disorder. While human brain imaging studies have highlighted a reliable engagement of the anterior insular cortex (AIC) in threat learning, its precise role remains elusive partly due to the lack of animal studies that can address causality and mechanistic questions. Filling in this gap, the present mouse study proposes a novel AIC-mediated mechanism underlying the association of temporally discontiguous stimuli during threat learning. We identified that activity of AIC layer 5 (L5) pyramidal neurons is required for associating temporally discontiguous stimuli, specifically during a time interval between them. Notably, the AIC is not required for associating temporally contiguous stimuli during threat learning. The AIC not only sends the essential information, via its L5 pyramidal neurons, to the basolateral amygdala (BLA) during the time interval, but also receives from the BLA. We also identified a modulatory role of AIC dopamine D1 receptor (D1R)-mediated dopamine signaling in associating temporally discontiguous stimuli during the time interval.
- Published
- 2021
8. The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder
- Author
-
Nilanjan Chatterjee, Atsushi Saito, Richard L. Huganir, Minae Niwa, Hanna Jaaro-Peled, Kamal Sharma, Hiroshi Yukitake, Brian J. Lee, Peter P. Zandi, Ho Namkung, Akira Sawa, Suvarnambiga Kannan, Gianluca Ursini, Shravika Lam, Koko Ishizuka, and Daisuke Fukudome
- Subjects
biology ,business.industry ,AMPA receptor ,medicine.disease ,Mediator ,Downregulation and upregulation ,Schizophrenia ,medicine ,biology.protein ,Biomarker (medicine) ,Bipolar disorder ,GRIA2 ,business ,Prefrontal cortex ,Neuroscience - Abstract
SUMMARYSchizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. The present study shows the miR-124-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered upregulation of miR-124 in biopsied neuronal cells and postmortem prefrontal cortex from both SZ and BP patients, implying its role not only as a biomarker, but also as a pathophysiological mediator. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124 in the medial prefrontal cortex, which includes brain regions homologous to sub-regions of the human prefrontal cortex. We demonstrated that upregulation of miR-124 increases GRIA2-lacking calcium permeable-AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.
- Published
- 2021
9. Tagging active neurons by soma-targeted Cal-Light
- Author
-
Sarah Kruessel, Dongmin Lee, Patrick Hannan, Neymi Layne Mignocchi, Chuljung Kwak, Bian Liu, Hyung Bae Kwon, Ho Namkung, Abigail McElroy, Seung Hwan Lee, Mingguang Cui, Jung Ho Hyun, Richard L. Huganir, Akira Sawa, and Kenichiro Nagahama
- Subjects
Reporter gene ,medicine.anatomical_structure ,Somatic cell ,Gene expression ,Cell ,medicine ,Biological neural network ,Hippocampus ,Soma ,Fear conditioning ,Biology ,Neuroscience - Abstract
Verifying causal effects of neural circuits is essential for proving direct a circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we developed the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio (SNR) of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, leverpressing choice behavior, and social interaction behaviors. We also targeted kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppressed seizure symptoms, suggesting ST-Cal-Light’s applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in (KI) mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.
- Published
- 2021
10. Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex
- Author
-
Marina Mihaljevic, Semra Etyemez, F. C. Nucifora, Andreia V. Faria, Hironori Kuga, Ho Namkung, Jeffrey L. Crawford, Peeraya Piancharoen, Jennifer M. Coughlin, Koko Ishizuka, Kun Yang, Rebecca Schaub, Jun Miyata, Thomas W. Sedlak, Zui Narita, Luisa Longo, Akira Sawa, David J. Schretlen, and Gerald Nestadt
- Subjects
Social Cognition ,Psychosis ,medicine.medical_specialty ,Functional connectivity ,Audiology ,medicine.disease ,Gyrus Cinguli ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,medicine.anatomical_structure ,Psychotic Disorders ,Social cognition ,First episode psychosis ,Brain size ,medicine ,Humans ,In patient ,Association (psychology) ,Psychology ,Facial Recognition ,Biological Psychiatry ,Anterior cingulate cortex - Abstract
The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 79 FEP patients and 80 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.
- Published
- 2021
11. Anterior insula-associated social novelty recognition: orchestrated regulation by a local retinoic acid cascade and oxytocin signaling
- Author
-
Sneha Saha, Mari Kondo, Ho Namkung, Minae Niwa, Akira Sawa, Marina Mihaljevic, Brady J. Maher, Lina S. Oh, Matthew D. Rannals, Sun Hong Kim, Kyongman An, Tyler Cash-Padgett, James R. Moore, and Kun Yang
- Subjects
Novelty ,Retinoic acid ,Biology ,Serotonergic ,Social relation ,chemistry.chemical_compound ,Dorsal raphe nucleus ,chemistry ,Oxytocin ,Social cognition ,medicine ,Insula ,Neuroscience ,medicine.drug - Abstract
BackgroundDeficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a ‘common core’ brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive.MethodsTo determine the role of anterior insula in social cognition, we manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. We conducted multimodal analyses at the molecular, cellular, circuitry, and behavioral levels.ResultsAt the molecular/cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. We also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus where serotonergic neurons are projected to the anterior insula. Furthermore, we show that serotonin 5HT2C receptor expressed in the anterior insula influences social novelty recognition.ConclusionsAnterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade, but also remotely regulated by oxytocin via a non-classic mechanism.
- Published
- 2021
12. Parsing neural circuits of fear learning and extinction across basic and clinical neuroscience: Towards better translation
- Author
-
Ho Namkung, Kerrie L. Thomas, Jeremy Hall, and Akira Sawa
- Subjects
Behavioral Neuroscience ,Neuropsychology and Physiological Psychology ,Cognitive Neuroscience ,Conditioning, Classical ,Animals ,Brain ,Humans ,Learning ,Fear ,Extinction, Psychological - Abstract
Over the past decades, studies of fear learning and extinction have advanced our understanding of the neurobiology of threat and safety learning. Animal studies can provide mechanistic/causal insights into human brain regions and their functional connectivity involved in fear learning and extinction. Findings in humans, conversely, may further enrich our understanding of neural circuits in animals by providing macroscopic insights at the level of brain-wide networks. Nevertheless, there is still much room for improvement in translation between basic and clinical research on fear learning and extinction. Through the lens of neural circuits, in this article, we aim to review the current knowledge of fear learning and extinction in both animals and humans, and to propose strategies to fill in the current knowledge gap for the purpose of enhancing clinical benefits.
- Published
- 2022
13. Causal Inference on Pathophysiological Mediators in Psychiatry
- Author
-
Ho Namkung, Akira Sawa, and Brian J. Lee
- Subjects
0301 basic medicine ,Nosology ,medicine.medical_specialty ,Schizophrenia (object-oriented programming) ,medicine.disease ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,Causal inference ,Genetics ,medicine ,Major depressive disorder ,Relevance (information retrieval) ,Construct (philosophy) ,Psychology ,Psychiatry ,Molecular Biology ,Psychiatric genetics ,Genetic association - Abstract
Supported by technological advances and collaborative efforts, psychiatric genetics has provided robust genetic findings in the past decade, particularly through genome-wide association studies (GWASs). However, translating these genetic findings into biological mechanisms and new therapies has been enormously challenging because of the complexity of their interpretation. Furthermore, the heterogeneity among patients with the same diagnosis, such as schizophrenia or major depressive disorder, challenges the biological validity of existing categorical approaches in clinical nosology, which is further complicated by the pleiotropic nature of many genetic variants across multiple disorders. Therefore, in the post-GWAS era, the greatest challenge lies in integrating such enriched genetic information with functional dimensions of neurobiological measures and observable behaviors. In this integration, the causal inference from genotypes to phenotypes through intermediate biological processes is of particular importance. In this review, we aim to construct an intellectual framework in which we may obtain causal, mechanistic insights into how multifactorial etiologies-in particular, many genetic variants-affect downstream biological pathways that lead to dimensions of psychiatric relevance.
- Published
- 2019
14. The Insula: An Underestimated Brain Area in Clinical Neuroscience, Psychiatry, and Neurology
- Author
-
Ho Namkung, Sun Hong Kim, and Akira Sawa
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Neurology ,media_common.quotation_subject ,MEDLINE ,behavioral disciplines and activities ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neuroimaging ,mental disorders ,medicine ,Animals ,Humans ,Psychiatry ,Pathological ,media_common ,Cerebral Cortex ,Brain Diseases ,Clinical neuroscience ,General Neuroscience ,Mental Disorders ,Cognition ,030104 developmental biology ,Feeling ,nervous system ,behavior and behavior mechanisms ,Psychology ,Neuroscience ,Insula ,030217 neurology & neurosurgery ,psychological phenomena and processes ,Clinical psychology - Abstract
Supported by recent human neuroimaging studies, the insula is re-emerging as an important brain area not only in the physiological understanding of the brain, but also in pathological contexts in clinical research. In this opinion article, we briefly introduce the anatomical and histological features of the human insula. We then summarize the physiological functions of the insula and underscore its pathological roles in psychiatric and neurological disorders that have long been underestimated. We finally propose possible strategies through which the role of the insula may be further understood for both basic and clinical neuroscience.
- Published
- 2016
15. Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels
- Author
-
Daniel N. Yue, John B. Issa, Jacqueline Niu, Jennifer Babich, Shin Rong Lee, Wanjun Yang, Po Wei Kang, Philemon S. Yang, Hojjat Bazzazi, Jiangyu Li, Lingjie Sang, Worawan B. Limpitikul, Manu Ben-Johny, Rosy Joshi-Mukherjee, Ho Namkung, Manning Zhang, David T. Yue, Rahul Banerjee, Ivy E. Dick, and Paul J. Adams
- Subjects
Physics ,Feedback, Physiological ,Voltage-dependent calcium channel ,Voltage-gated ion channel ,Calmodulin ,biology ,Extramural ,Sodium channel ,Chemical signaling ,General Medicine ,Voltage-Gated Sodium Channels ,Models, Biological ,Article ,biology.protein ,Animals ,Humans ,Calcium ,Calcium Channels ,Unified field theory ,Neuroscience ,Ion Channel Gating ,Ion channel - Abstract
Voltage-gated Na and Ca(2+) channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca(2+) and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.
- Published
- 2015
16. Causal Inference on Pathophysiological Mediators in Psychiatry.
- Author
-
HO NAMKUNG, LEE, BRIAN J., and SAWA, AKIRA
- Subjects
- *
PSYCHIATRY , *MENTAL depression , *SCHIZOPHRENIA , *GENOTYPES , *PHENOTYPES - Abstract
Supported by technological advances and collaborative efforts, psychiatric genetics has provided robust genetic findings in the past decade, particularly through genome-wide association studies (GWASs). However, translating these genetic findings into biological mechanisms and new therapies has been enormously challenging because of the complexity of their interpretation. Furthermore, the heterogeneity among patients with the same diagnosis, such as schizophrenia or major depressive disorder, challenges the biological validity of existing categorical approaches in clinical nosology, which is further complicated by the pleiotropic nature of many genetic variants across multiple disorders. Therefore, in the post-GWAS era, the greatest challenge lies in integrating such enriched genetic information with functional dimensions of neurobiological measures and observable behaviors. In this integration, the causal inference from genotypes to phenotypes through intermediate biological processes is of particular importance. In this review, we aim to construct an intellectual framework in which we may obtain causal, mechanistic insights into how multifactorial etiologies--in particular, many genetic variants--affect downstream biological pathways that lead to dimensions of psychiatric relevance. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.