Sex differences in schizophrenia, bipolar disorder, and post‐traumatic stress disorder: Are gonadal hormones the link?

British Journal of Pharmacology, Год журнала: 2019, Номер 176(21), С. 4119 - 4135

Опубликована: Янв. 18, 2019

In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident schizophrenia, bipolar disorder, post-traumatic stress disorder. Women with schizophrenia tend to exhibit less impairment than men. By contrast, women disorder more affected The most likely candidates explain these gonadal hormones. This review details clinical evidence oestradiol progesterone dysregulated psychiatric disorders. Notably, existing data on oestradiol, a lesser extent, progesterone, suggest low levels of hormones may increase risk development worsen severity. We argue future studies require inclusive, considered analysis steroid intricacies interactions between them, methodological rigour applied, enhance our understanding roles LINKED ARTICLES: article is part themed section Importance Sex Differences Pharmacology Research. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.

Язык: Английский

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X-linked diseases: susceptible females

Genetics in Medicine, Год журнала: 2020, Номер 22(7), С. 1156 - 1174

Опубликована: Апрель 13, 2020

The role of X-inactivation is often ignored as a prime cause sex differences in disease. Yet, the way males and females express their X-linked genes has major dissimilar phenotypes that underlie many rare common disorders, such intellectual deficiency, epilepsy, congenital abnormalities, diseases heart, blood, skin, muscle, bones. Summarized here are examples different presentations females. Other data include reasons why women protected from deleterious variants carried on X chromosome, factors render susceptible some instances.

Язык: Английский

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Sex differences in the human brain: a roadmap for more careful analysis and interpretation of a biological reality

Biology of Sex Differences, Год журнала: 2022, Номер 13(1)

Опубликована: Июль 26, 2022

Abstract The presence, magnitude, and significance of sex differences in the human brain are hotly debated topics scientific community popular media. This debate is largely fueled by studies containing strong, opposing conclusions: either little to no evidence exists for neuroanatomy, or there small-to-moderate size certain regions that highly reproducible across cohorts (even after controlling average size). Our Commentary uses specific comparison between two recent large-scale adopt these views—namely review Eliot colleagues (2021) direct analysis ~ 40k brains Williams (2021)—in an effort clarify this controversy provide a framework conducting research. First, we observations motivate research on including potential causes (evolutionary, genetic, environmental) effects (epidemiological clinical sex-biased disorders). We also summarize methodological empirical support using structural MRI investigate such patterns. Next, outline how researchers focused can better specify their study design (e.g., was defined, if adjusted for) results (by e.g., distinguishing sexual dimorphisms from differences). then compare different approaches available studying large number individuals: analysis, meta-analysis, review. stress reviews do not account studies, variation explains many apparent inconsistencies reported throughout (including work colleagues). For instance, show amygdala volume consistently as male-biased with sufficient sample sizes appropriate methods correction. In fact, comparing multiple analyses highlights small, (controlling Finally, describe best practices presentation interpretation findings. Care important all domains science, but especially so brain, given existence broad societal gender-biases history biological data being used justify sexist ideas. As such, urge discuss simultaneously anti-sexist viewpoints.

Язык: Английский

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The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

International Journal of Molecular Sciences, Год журнала: 2020, Номер 22(1), С. 373 - 373

Опубликована: Дек. 31, 2020

Increasing evidence suggests estrogen and signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation reproduction but also highly involved a wide range of brain functions, such as cognition, memory, neurodevelopment, neuroplasticity. To add more, the recent findings its neuroprotective anti-inflammatory effects have grown interested investigating potential therapeutic use to In this review, we analyze emerging literature on receptors disorders cellular, preclinical, clinical studies. Specifically, discuss contribution receptor cognition neuroprotection via mediating multiple neural systems, dopaminergic, serotonergic, glutamatergic systems. Then, assess their disruptions implications for pathophysiologies Further, current treatment strategies involving evaluated suggest future direction identifying novel

Язык: Английский

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Schizophrenia and Sex Hormones: What Is the Link?

Frontiers in Psychiatry, Год журнала: 2020, Номер 11

Опубликована: Июль 15, 2020

The involvement of gonadal hormones in the pathogenesis schizophrenia has long been suspected because psychosis differs women and men illness first makes its appearance shortly after puberty. Changes sex have linked with increased vulnerability to mood disorders women, while testosterone associated sexual drive aggressiveness as well women. Some studies found abnormal levels estrogens patients, but results inconsistent sometimes attributed hyperprolactinemia effect antipsychotics, which may interfere production. purpose this review is present current knowledge on link between blood sex-hormones during various stages female reproductive life (i.e. puberty, menstrual cycle, pregnancy, contraception, menopause) course schizophrenia. We also attempt optimize clinical approach at these different stages.

Язык: Английский

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Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable

British Journal of Pharmacology, Год журнала: 2019, Номер 176(21), С. 4081 - 4086

Опубликована: Авг. 23, 2019

Precision medicine is a buzz word mentioned frequently in the research world currently. Indeed, initiatives such as UK's 100,000 genomes project are based on premise that better understanding of an individual's biology and genomic profile enables clinicians to serve their patients. In some patients, this approach has led diagnosis rare disease effective treatment was not obvious without genetic information. light these technological advances, it seems unconscionable "sex," which probably most distinguishing characteristic humans, been largely ignored biomedical research. Hitherto, blame for frequent failure translate findings sciences into any human benefit focused issues subjective bias, flawed experimental design, inappropriate statistical analysis, causal factors. By contrast, little consideration given sex differences either efficacy existing therapeutics or implications refinement. Yet increasingly apparent long-established practice studying predominantly one (typically males) could contribute translate. To help rectify problem, editorial outlines rationale policy requires be considered categorical variable all studies submitted publication British Journal Pharmacology. We also offer advice how incorporate optimised design. clear, article, "sex" defined by status subject, whereas "gender" refers social cultural context. Conceptually, interventions animals, castration/ovariectomy, with hormone replacement/substitution, have already provided substantial information about importance hormones anatomical physiological development, well ensuing behavioural traits. The study gender animals possible at present remains clinical endeavour. Interest response harks back far Hippocrates, who noted fever outbreak women were less affected terms symptoms mortality (Hippocrates Kos, ca. 400 BCE). discovery systematic comparisons animals' responses challenge new. For instance, evidence learning behaviour female rats more than males reported 1930s (McNemar & Stone, 1932). Subsequent found higher variability (see, e.g., Broadhurst, 1957). A recent extended processes involved fear conditioning, clearly differ females, especially during extinction (Clark, Drummond, Hoyer, Jacobson, 2019). Likewise, 1947, Boynton Todd both systolic diastolic blood pressures, measured large cohort, young men women—a finding later replicated dogs (Van Liere, Stickney, Marsh, 1949). Despite accumulating leads biology, used rarely reported. Volume 1 Pharmacology (and Chemotherapy) (1946), there 27 papers, 21 did specify sex. majority cases, sexes used, numbers studied. Of remaining six only specified use three only, but two testis. papers included experiments uterine tissue. challenges females perceived justification male even groups had overall (e.g., Sinha, Singh, 1959). 1960, attempts reduce variance data driving investigators single sex, strategy endorsed prominent textbook (Lewis, 1960). section book, dealing amongst recommendation "[in experiments,] from same strain, similar age, weight should used." Meanwhile, world, emerging thalidomide causes congenital abnormalities humans. This preferential order avoid risk exposing novel drugs trials. late 1970s, clear wide range systems (circadian rhythms, feeding, effects localised lesion brain regions, sensory systems, Beatty, 1979). There further depends species animal stage development. reports, strong males, entrenched preclinical experiments, albeit different reasons. Exceptions using non-human primates, where pooled Yanagita Takahashi, 1970). However, motivated need unacceptable waste much drug group "typical" subjects sampled population. Sex now described major fields pathology, physiology, pharmacology humans animals. recognised ischaemic heart result disparities outcome increased morbidity post-myocardial infarction (Aggarwal et al., 2018). Another cohort study, European Prospective Investigation Cancer Nutrition (EPIC), prevalence certain diet-related cancers (Zamora-Ros 2018); attributed activity metabolic enzymes Dellinger, Garcia, Meyskens, 2014). numerous reports inflammatory stimuli confirmed healthy volunteers (Rathod 2017), report indicates genetically dependent incidence irritable bowel syndrome (Bonfiglio These few examples patients provide when investigating pathways disease, identifying targets teasing out therapeutics. tangible growing appreciation within community sex/gender important. PubMed search term "sex difference" 2018 identifies 41 reviews. particular, growth stimulated commissioning BJP Themed Issue topic 2019. themed issue alone, reviews original articles demonstrating important determinant phenotype, diverse body spanning across schizophrenia (Gogos, Ney, Seymour, Van Rheenen, Felmingham, 2019), sensation (Clark 2019) metabolism (Henstridge, Abildgaard, Lindegaard, Febbraio, obesity (Taylor, Ramirez, Musail, Sullivan, focus upon diversity evident literature: Recent include airway smooth muscle, isolated obese manifests greater agonist-induced excitation–contraction coupling those derived lean (Orfanos 2018) thermoregulatory CNS stimulant, cathinone (Alsufyani Docherty, identified. notable complication interest can depend interaction between genotype, case vulnerability strain altered mice (Pillidge, Heal, Stanford, 2016). Unlike 1946, today. consecutive (published Vol 176 3–7), 22 19 improvement. 19, 12 five females. tissues (tissue, blood, cell culture) source. Cell culture lines 16 studies, cultures being None compared sexes. contend whilst reporting encouraging, enough state so, improve our practices further, we encourage researchers Arguably, reason facilitate successful translation science goals well-being, regardless It encouraging new molecular entities, repurposing drugs, risks if supporting only. Furthermore, shows oestrous/menstrual cycle, just affect cardiac electrophysiology; see Salama Bett, Such underpin conventional view males. acknowledged concept challenged recently following meta-analysis (Prendergast, Onishi, Zucker, 2014) (Becker, Prendergast, Liang, 2016), conclusion "intrinsic … least great associated estrous cycle." Nevertheless, potential problems arise intention extrapolate whole population, obvious. Perhaps environment will stimulate much-needed, oestrous cycle actions. meantime, widely agreed problem no longer ignored, extent national funding agencies National Institutes Health (NIH) (USA) Swedish Research Council requiring and/or applications. Importantly, mandate includes cells maintained vitro, (https://orwh.od.nih.gov/sex-gender/nih-policy-sex-biological-variable). aspect critical since, electrophysiological muscle (Lu 2006) assess propensity cause ventricular arrhythmia Torsade de Pointes (Cubeddu, 2003), common level individual cardiomyocytes (Mason MacLeod, 2009; authors (human animal) primary (particularly purchased) mention lines, exceptions Chinese hamster ovary (CHO). address concerns regarding ethical burden surplus breeding. UK 1.81 million non-genetically (91% rats) bred scientific procedures 2017 killed, died, regulated procedure (Gov.uk, Some would collecting tissue post mortem, many stock comprise attrition taken account considering compliance 3Rs (Replacement, Reduction, Refinement), notably respect Reduction (Russell Burch, decided neglect variable, recommend future published journal acknowledge ideal scenario vivo researcher's relevant question, then statement providing required. Obvious reproduction, genitalia, actions hormones, sex-specific diseases immortalised lines. An example article details each Clark al. (2019). economics influence outcomes difficult until grant-funding insist adapt designs, accommodate necessary resources. manuscripts continue BJP. require justify decision gender. conclusions expressed cautiously; experiment, explicit effect work might Even once amended approach, fundamental pharmacological vitro (such receptors enzymes), still BJP, confirmation main sexes, unless doing so. shall review revise continually, ensure consistent funders they move towards mandatory support researchers, considerations, below, designing experiments. evidence, controversial, interest, comply homogeneity assumption must met valid parametric statistics. assumption, simple explained Curtis (2018). suitable transformation logarithm square root) applied responses, necessary, before carrying analysis. Overall and, importantly, interactions (i.e., intervention differs sexes) cannot inferred studied separate time frames. correct fully randomised study. If interventions, lead unequal replication versus groups. imbalance bias comparisons. technique "blocking" stratification so equally often is, randomise what looks like mini-study carried out, intervals, over long period time, subject tested once. appropriate treat "day" blocking factors, equal tested, parallel, day. distribution levels factor treatment) block, counterbalanced (as Williams Latin Square) series test days. conscious confounder close proximity opposite specific deal this, borne mind situation replicate "real world." ask merely consider whether physically separated, sight smell confound results, addressed Obviously, advisable house rooms because undermine exposed environmental factors properly controlled experiment. When vivo, experimenters blind animal. currently journal, blinding place whenever possible. example, samples coded processing them after taking analysis data, other resolve arising introduced earlier stages inevitable consequence used. adopting factorial "Sex" "Treatment" doses) relatively small number sufficient objectives experiment rest comparing pairs means, hoc vs. dose, vehicle sex) then, journal's rubric, sample sizes N ≥ 5 combination Treatment. follows doses (or drugs) plus vehicle, (with receiving treatment), total 40 (see Table 1). design two-way ANOVA analyse implies raw shared levels. As consequence, 40-animal wasting impact measure compromise Russell likely objective solely (across interest. arguing that, representative setting, incorporated interrogated, suggest sometimes adequate. Treatment yields Providing combine proceed illustrates prospective definition objective(s) careful planning size estimation documented manuscript. topic, see: Bate (2014); Percie du Sert (2017); NC3Rs Experimental Design Assistant (https://www.nc3rs.org.uk/experimental-designassistant-eda); Festing (2016). Unless specifically investigate drug-induced record journal. determine moderately stressful stress outcome. aware may particularly cocaine (Calipari 2017; Nicolas wish thank Simon T. his helpful comments early draft article. declare conflicts

Язык: Английский

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Sex differences in the blood–brain barrier: Implications for mental health

Frontiers in Neuroendocrinology, Год журнала: 2022, Номер 65, С. 100989 - 100989

Опубликована: Март 8, 2022

Prevalence of mental disorders, including major depressive disorder (MDD), bipolar (BD) and schizophrenia (SZ) are increasing at alarming rates in our societies. Growing evidence points toward sex differences these conditions, high treatment resistance support the need to consider novel biological mechanisms outside neuronal function gain mechanistic insights that could lead innovative therapies. Blood-brain barrier alterations have been reported MDD, BD SZ. Here, we provide an overview sex-specific immune, endocrine, vascular transcriptional-mediated changes affect neurovascular integrity possibly contribute pathogenesis disorders. We also identify pitfalls current literature highlight promising biomarkers. Better understanding how adaptations can health status is essential not only context SZ but cardiovascular diseases stroke which associated with higher prevalence conditions.

Язык: Английский

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Epigenetic mechanisms underlying sex differences in the brain and behavior

Trends in Neurosciences, Год журнала: 2023, Номер 47(1), С. 18 - 35

Опубликована: Ноя. 15, 2023

Sex differences are found across brain regions, behaviors, and diseases. Sexual differentiation of the is initiated prenatally but it continues throughout life, as a result interaction three major factors: gonadal hormones, sex chromosomes, environment. These factors thought to act, in part, via epigenetic mechanisms which control chromatin transcriptional states cells. In this review, we discuss evidence that underlie sex-specific neurobehavioral changes during critical organizational periods, estrous cycle, response diverse environments life. We further identify future directions for field will provide novel mechanistic insights into differences, inform disease treatments women's health particular, apply people genders.

Язык: Английский

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Sex/gender differences in cognitive abilities

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 152, С. 105333 - 105333

Опубликована: Июль 28, 2023

Язык: Английский

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Psychoneuroendocrinology

American Psychiatric Association Publishing eBooks, Год журнала: 2024, Номер unknown

Опубликована: Март 22, 2024

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