{"title":"Front & Back Matter","authors":"A. Halaris, B. Leonard","doi":"10.1159/000504187","DOIUrl":"https://doi.org/10.1159/000504187","url":null,"abstract":"","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"2017 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86769058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research Domain Criteria: Strengths, Weaknesses, and Potential Alternatives for Future Psychiatric Research","authors":"C. Ross, R. Margolis","doi":"10.1159/000501797","DOIUrl":"https://doi.org/10.1159/000501797","url":null,"abstract":"The Research Domain Criteria (RDoC) paradigm was launched 10 years ago as a superior approach for investigation of mental illness. RDoC conceptualizes normal human behavior, emotion, and cognition as dimensional, with mental illnesses as dimensional extremes. We suggest that RDoC may have value for understanding normal human psychology and some conditions plausibly construed as extremes of normal variation. By contrast, for the most serious of mental illnesses, including dementia, autism, schizophrenia, and bipolar disorder, we argue that RDoC is conceptually flawed. RDoC conflates variation along dimensional axes of normal function with quantitative measurements of disease phenotypes and with the occurrence of diseases in overlapping clusters or spectra. This moves away from the disease model of major mental illness. Further, RDoC imposes a top-down approach to research. We argue that progress in major mental illness research will be more rapid with a bottom-up approach, starting with the discovery of etiological factors, proceeding to investigation of pathogenic pathways, including use of cell and animal models, and leading to a refined nosology and novel, targeted treatments.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"31 1","pages":"218 - 236"},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83322721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Wiersinga, G. Kahaly, V. Blanchette, L. Brandão, V. Breakey, S. Revel-Vilk, W. Byerley, J. Gelernter, T. Petryshen
{"title":"Front & Back Matter","authors":"W. Wiersinga, G. Kahaly, V. Blanchette, L. Brandão, V. Breakey, S. Revel-Vilk, W. Byerley, J. Gelernter, T. Petryshen","doi":"10.1159/000501491","DOIUrl":"https://doi.org/10.1159/000501491","url":null,"abstract":"","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84506051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity","authors":"N. Clifton, Simon Trent, K. Thomas, J. Hall","doi":"10.1159/000500267","DOIUrl":"https://doi.org/10.1159/000500267","url":null,"abstract":"Alterations in synaptic signaling and plasticity occur during the refinement of neural circuits over the course of development and the adult processes of learning and memory. Synaptic plasticity requires the rearrangement of protein complexes in the postsynaptic density (PSD), trafficking of receptors and ion channels and the synthesis of new proteins. Activity-induced short Homer proteins, Homer1a and Ania-3, are recruited to active excitatory synapses, where they act as dominant negative regulators of constitutively expressed, longer Homer isoforms. The expression of Homer1a and Ania-3 initiates critical processes of PSD remodeling, the modulation of glutamate receptor-mediated functions, and the regulation of calcium signaling. Together, available data support the view that Homer1a and Ania-3 are responsible for the selective, transient destabilization of postsynaptic signaling complexes to facilitate plasticity of the excitatory synapse. The interruption of activity-dependent Homer proteins disrupts disease-relevant processes and leads to memory impairments, reflecting their likely contribution to neurological disorders.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"29 1","pages":"147 - 161"},"PeriodicalIF":0.0,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73173818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"κ-Opioid Receptor Modulation of GABAergic Inputs onto Ventrolateral Periaqueductal Gray Dopamine Neurons","authors":"Chia Li, T. Kash","doi":"10.1159/000496974","DOIUrl":"https://doi.org/10.1159/000496974","url":null,"abstract":"The κ-opioid receptor (KOR) system has been implicated in the regulation of many behaviors including pain. While there are numerous studies suggesting KOR regulation of pain being mediated spinally, there have been reports of pain-like behaviors regulated by central KOR signaling. In particular, oxytocin-induced analgesia appears to be mediated by KOR receptors within the ventrolateral periaqueductal gray (vlPAG). We recently found that activation of dopamine (DA) neurons within the vlPAG is antinociceptive. In this study, we sought to determine the impact of KOR signaling on GABAergic inputs onto vlPAG DA neurons, and the mechanism through which KOR impacts these inputs. We found that activation of KOR reduced GABAergic transmission onto vlPAG DA neurons. In addition, our data suggest this effect is mediated presynaptically via the G protein βγ-subunit. They raise the possibility that KOR activation disinhibits vlPAG DA neurons, which could lead to altered regulation of pain-related behaviors.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"43 1","pages":"190 - 199"},"PeriodicalIF":0.0,"publicationDate":"2019-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87007169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Barko, W. Paden, Kelly M. Cahill, M. Seney, R. Logan
{"title":"Sex-Specific Effects of Stress on Mood-Related Gene Expression","authors":"K. Barko, W. Paden, Kelly M. Cahill, M. Seney, R. Logan","doi":"10.1159/000499105","DOIUrl":"https://doi.org/10.1159/000499105","url":null,"abstract":"Women are twice as likely as men to be diagnosed with major depressive disorder (MDD). Recent studies report distinct molecular changes in depressed men and women across mesocorticolimbic brain regions. However, it is unclear which sex-related factors drive distinct MDD-associated pathology. The goal of this study was to use mouse experimental systems to investigate sex-specific mechanisms underlying the distinct molecular profiles of MDD in men and women. We used unpredictable chronic mild stress to induce an elevated anxiety-/depressive-like state and “four core genotypes” (FCG) mice to probe for sex-specific mechanisms. As predicted, based on previous implications in mood, stress impacted the expression of several dopamine-, GABA-, and glutamate-related genes. Some of these effects, specifically in the prefrontal cortex, were genetic sex-specific, with effects in XX mice but not in XY mice. Stress also impacted gene expression differently across the mesocorticolimbic circuit, with increased expression of mood-related genes in the prefrontal cortex and nucleus accumbens, but decreased expression in basolateral amygdala. Our results suggest that females are sensitive to the effects of chronic stress, partly due to their genetic sex, independent of gonadal hormones. Furthermore, these results point to the prefrontal cortex as the node in the mesocorticolimbic circuitry with the strongest female-specific effects.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"45 1","pages":"162 - 176"},"PeriodicalIF":0.0,"publicationDate":"2019-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86501837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew F Pescosolido, Brian C Kavanaugh, Nathalie Pochet, Michael Schmidt, Beth A Jerskey, Jeffrey M Rogg, Philip L De Jager, Tracy L Young-Pearse, Judy S Liu, Eric M Morrow
{"title":"Complex Neurological Phenotype in Female Carriers of <i>NHE6</i> Mutations.","authors":"Matthew F Pescosolido, Brian C Kavanaugh, Nathalie Pochet, Michael Schmidt, Beth A Jerskey, Jeffrey M Rogg, Philip L De Jager, Tracy L Young-Pearse, Judy S Liu, Eric M Morrow","doi":"10.1159/000496341","DOIUrl":"https://doi.org/10.1159/000496341","url":null,"abstract":"<p><p>Mutations in <i>NHE6</i> (also termed <i>SLC9A6</i>) cause the X-linked neurological disorder Christianson syndrome (CS) in males. The purpose of this study was to examine the phenotypic spectrum of female carriers of <i>NHE6</i> mutations. Twenty female carriers from 9 pedigrees were enrolled, ranging from approximately age 2 to 65. A subset of female carriers was assessed using standardized neuropsychological measures. Also, the association of <i>NHE6</i> expression with markers of brain age was evaluated using 740 participants in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). A majority, but not all, female carriers demonstrated a deficit in at least one neurocognitive domain (85%). A recognizable neuropsychological profile emerged, revealing impairments in visuospatial function, attention, and executive function. Common neuropsychiatric diagnoses included: intellectual disability/developmental delay (20%), learning difficulties (31%), speech/language delays (30%), and attention-deficit/hyperactivity disorder (20%). Notable neurological diagnoses in aging CS female carriers include corticobasal degeneration and atypical parkinsonism. In postmortem brains from the ROS/MAP dataset of normal and pathological aging, decreased <i>NHE6</i> expression was correlated with greater tau deposition. Our study provides an examination of the phenotypic range in female carriers of <i>NHE6</i> mutations. The findings indicate that NHE6-related disease in females represents a new neurogenetic condition.</p>","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"98-108"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000496341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37329507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sana A Ali, Nandita Mathur, Anil K Malhotra, Raphael J Braga
{"title":"Electroconvulsive Therapy and Schizophrenia: A Systematic Review.","authors":"Sana A Ali, Nandita Mathur, Anil K Malhotra, Raphael J Braga","doi":"10.1159/000497376","DOIUrl":"https://doi.org/10.1159/000497376","url":null,"abstract":"<p><p>Electroconvulsive therapy (ECT) is a remarkably effective treatment for major depressive disorder, but is less commonly utilized for treatment of psychotic disorders. Recent literature indicates that ECT can be a useful strategy for a wide range of psychotic disorders, including treatment-resistant schizophrenia. The purpose of this review is to examine the extant literature on ECT in schizophrenia with a primary focus on its efficacy, its impact on cognitive function, the role of maintenance ECT, and the potential role of neuroimaging biomarkers to provide more precise ECT treatment strategies. We evaluated the available literature, with a particular focus on prospective, randomized trials. Our review suggests that ECT can be an effective treatment strategy in this severely ill patient population. Studies suggest that while ECT in schizophrenia is a safe treatment modality, the potential for cognitive impairment must always be carefully weighed. The use and investigation of new biomarker strategies for the pharmacological treatment of schizophrenia, and the extension of these approaches to ECT are also discussed.</p>","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"75-83"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000497376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37329506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Wiersinga, G. Kahaly, V. Blanchette, L. Brandão, V. Breakey, S. Revel-Vilk, W. Byerley, J. Gelernter, T. Petryshen
{"title":"Front & Back Matter","authors":"W. Wiersinga, G. Kahaly, V. Blanchette, L. Brandão, V. Breakey, S. Revel-Vilk, W. Byerley, J. Gelernter, T. Petryshen","doi":"10.1159/000500647","DOIUrl":"https://doi.org/10.1159/000500647","url":null,"abstract":"","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91381834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria Nudell, Heather Wei, Caroline Nievergelt, Adam X Maihofer, Paul Shilling, Martin Alda, Wade H Berrettini, Kristen J Brennand, Joseph R Calabrese, William H Coryell, Jonathan M Covault, Mark A Frye, Fred Gage, Elliot Gershon, Melvin G McInnis, John I Nurnberger, Ketil J Oedegaard, Tatyana Shekhtman, Peter P Zandi, John R Kelsoe, Michael J McCarthy
{"title":"Entrainment of Circadian Rhythms to Temperature Reveals Amplitude Deficits in Fibroblasts from Patients with Bipolar Disorder and Possible Links to Calcium Channels.","authors":"Victoria Nudell, Heather Wei, Caroline Nievergelt, Adam X Maihofer, Paul Shilling, Martin Alda, Wade H Berrettini, Kristen J Brennand, Joseph R Calabrese, William H Coryell, Jonathan M Covault, Mark A Frye, Fred Gage, Elliot Gershon, Melvin G McInnis, John I Nurnberger, Ketil J Oedegaard, Tatyana Shekhtman, Peter P Zandi, John R Kelsoe, Michael J McCarthy","doi":"10.1159/000497354","DOIUrl":"https://doi.org/10.1159/000497354","url":null,"abstract":"<p><p>Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD. <i>CACNA1C</i> encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is involved in -circadian phase delays. It is unknown whether variants in <i>CACNA1C</i> or other calcium channels contribute to the circadian phenotype in BD. We hypothesized that, by using temperature cycles, we could model circadian entrainment in fibroblasts from BD patients and controls to interrogate the circadian functions of LTCCs. Using Per2-luc, a bioluminescent reporter, we verified that cells entrain to temperature rhythms in vitro. Under constant temperature conditions, the LTCC antagonist verapamil shortened the circadian period, and the RYR antagonist dantrolene lengthened the period. However, neither drug affected temperature entrainment. Fibroblasts from BD patients and controls also entrained to temperature. In cells from BD patients, the rhythm amplitude was lower under entrained, but not constant, conditions. Temperature entrainment was otherwise similar between BD and control cells. However, the <i>CACNA1C</i> genotype among BD cells predicted the degree to which cells entrained. We conclude that assessment of rhythms under entrained conditions reveals additional rhythm abnormalities in BD that are not observable under constant temperature conditions.</p>","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"115-124"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000497354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37329509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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