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Dialogues in Clinical Neuroscience

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https://www.readbyqxmd.com/read/28179817/the-placenta-and-neurodevelopment-sex-differences-in-prenatal-vulnerability
#1
Tracy L Bale
Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including increased rates of autism, mental retardation, stuttering, dyslexia, and attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin with sex chromosomes, are likely to produce sex-specific transplacental signals to the developing brain. Our studies and others have identified X-linked genes that are expressed at higher levels in the female placenta...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179816/sex-differences-in-the-psychopharmacological-treatment-of-depression
#2
John J Sramek, Michael F Murphy, Neal R Cutler
Although a number of studies have observed that females respond better to serotonergic antidepressants than males and that postmenopausal females have a diminished response to antidepressants compared with younger females, there are also studies that conflict with both of these findings, making any generalizations regarding sex differences difficult to make. Sex variance in antidepressant efficacy and pharmacokinetics profiles have been attributed to sex-based physiological differences, behavioral differences, related disorders, and sex-specific conditions, including pregnancy and menopause...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179815/considering-sex-and-gender-in-alzheimer-disease-and-other-dementias
#3
Jessica L Podcasy, C Neill Epperson
Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179814/prenatal-stress-immune-programming-of-sex-differences-in-comorbidity-of-depression-and-obesity-metabolic-syndrome
#4
Jill M Goldstein, Laura Holsen, Grace Huang, Bradley D Hammond, Tamarra James-Todd, Sara Cherkerzian, Taben M Hale, Robert J Handa
Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179813/sex-differences-in-the-effects-of-androgens-acting-in-the-central-nervous-system-on-metabolism
#5
Jamie Morford, Franck Mauvais-Jarvis
One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179812/stress-related-disorders-pituitary-adenylate-cyclase-activating-peptide-pacap-ergic-system-and-sex-differences
#6
Teniel S Ramikie, Kerry J Ressler
Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other stress-related disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179811/sex-differences-in-addiction
#7
Jill B Becker
Women exhibit more rapid escalation from casual drug taking to addiction, exhibit a greater withdrawal response with abstinence, and tend to exhibit greater vulnerability than men in terms of treatment outcome. In rodents, short-term estradiol intake in female rats enhances acquisition and escalation of drug taking, motivation for drugs of abuse, and relapse-like behaviors. There is also a sex difference in the dopamine response in the nucleus accumbens. Ovariectomized female rats exhibit a smaller initial dopamine increase after cocaine treatment than castrated males...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179810/sex-biased-cellular-signaling-molecular-basis-for-sex-differences-in-neuropsychiatric-diseases
#8
Rita J Valentino, Debra A Bangasser
The recognition that there are fundamental biological sex differences that extend beyond those that define sexual behavior and reproductive function has inspired the drive toward inclusion of both sexes in research design. This is supported by an underlying clinical rationale that studying both sexes is necessary to elucidate pathophysiology and develop treatments for the entire population. However, at a more basic level, sex differences, like genetic differences, can be exploited to better understand biology...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179809/sex-in-the-brain-hormones-and-sex-differences
#9
Jordan Marrocco, Bruce S McEwen
Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179808/sex-differences-in-the-developing-brain-as-a-source-of-inherent-risk
#10
Margaret M McCarthy
Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179807/sex-influences-in-neurological-disorders-case-studies-and-perspectives
#11
Janine Austin Clayton
Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28179806/the-role-of-sex-and-gender-in-neuropsychiatric-disorders
#12
Florence Thibaut
The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757067/transforming-big-data-into-computational-models-for-personalized-medicine-and-health-care
#13
S M Reza Soroushmehr, Kayvan Najarian
Health care systems generate a huge volume of different types of data. Due to the complexity and challenges inherent in studying medical information, it is not yet possible to create a comprehensive model capable of considering all the aspects of health care systems. There are different points of view regarding what the most efficient approaches toward utilization of this data would be. In this paper, we describe the potential role of big data approaches in improving health care systems and review the most common challenges facing the utilization of health care big data...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757066/pharmacogenetic-tests-for-antipsychotic-medications-clinical-implications-and-considerations
#14
Seenae Eum, Adam M Lee, Jeffrey R Bishop
Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757065/personalized-prescribing-a-new-medical-model-for-clinical-implementation-of-psychotropic-drugs
#15
Chin B Eap
The use of pharmacogenetic tests was already being proposed in psychiatry in the early 2000s because genetic factors were known to influence drug pharmacokinetics and pharmacodynamics. However, sufficient levels of evidence to justify routine use have been achieved for only a few tests (eg, major histocompatibility complex, class I, B, allele 1502 [HLA-B*1502] for carbamazepine in epilepsy and bipolar disorders); many findings are too preliminary or, when replicated, of low clinical relevance because of a small effect size...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757064/genomic-sequencing-in-clinical-practice-applications-challenges-and-opportunities
#16
Joel B Krier, Sarah S Kalia, Robert C Green
The development of massively parallel sequencing (or next-generation sequencing) has facilitated a rapid implementation of genomic sequencing in clinical medicine. Genomic sequencing (GS) is now an essential tool for evaluating rare disorders, identifying therapeutic targets in neoplasms, and screening for prenatal aneuploidy. Emerging applications, such as GS for preconception carrier screening and predisposition screening in healthy individuals, are being explored in research settings and utilized by members of the public eager to incorporate genomic information into their health management...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757063/an-epigenomics-approach-to-individual-differences-and-its-translation-to-neuropsychiatric-conditions
#17
J David Sweatt, Carol A Tamminga
This review concerns epigenetic mechanisms and their roles in conferring interindividual differences, especially as related to experientially acquired and genetically driven changes in central nervous system (CNS) function. In addition, the review contains commentary regarding the possible ways in which epigenomic changes may contribute to neuropsychiatric conditions and disorders and ways in which epigenotyping might be cross-correlated with clinical phenotyping in the context of precision medicine. The review begins with a basic description of epigenetic marking in the CNS and how these changes are powerful regulators of gene readout...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757062/individual-variation-in-functional-brain-connectivity-implications-for-personalized-approaches-to-psychiatric-disease
#18
Emily S Finn, R Todd Constable
Functional brain connectivity measured with functional magnetic resonance imaging (fMRI) is a popular technique for investigating neural organization in both healthy subjects and patients with mental illness. Despite a rapidly growing body of literature, however, functional connectivity research has yet to deliver biomarkers that can aid psychiatric diagnosis or prognosis at the single-subject level. One impediment to developing such practical tools has been uncertainty regarding the ratio of intra- to interindividual variability in functional connectivity; in other words, how much variance is state- versus trait-related...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757061/human-ipsc-derived-neurons-and-lymphoblastoid-cells-for-personalized-medicine-research-in-neuropsychiatric-disorders
#19
David Gurwitz
The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27757060/omics-approaches-to-individual-variation-modeling-networks-and-the-virtual-patient
#20
Hans Lehrach
Every human is unique. We differ in our genomes, environment, behavior, disease history, and past and current medical treatment-a complex catalog of differences that often leads to variations in the way each of us responds to a particular therapy. We argue here that true personalization of drug therapies will rely on "virtual patient" models based on a detailed characterization of the individual patient by molecular, imaging, and sensor techniques. The models will be based, wherever possible, on the molecular mechanisms of disease processes and drug action but can also expand to hybrid models including statistics/machine learning/artificial intelligence-based elements trained on available data to address therapeutic areas or therapies for which insufficient information on mechanisms is available...
September 2016: Dialogues in Clinical Neuroscience
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