Sex and gender in neurodevelopmental conditions

Nature Reviews Neurology, Год журнала: 2023, Номер 19(3), С. 136 - 159

Опубликована: Фев. 6, 2023

Язык: Английский

---

Biological hypotheses, risk factors, and biomarkers of schizophrenia

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2022, Номер 120, С. 110626 - 110626

Опубликована: Авг. 31, 2022

Язык: Английский

---

Exploring sex differences: insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 21, 2024

Increased knowledge about sex differences is important for development of individualized treatments against many diseases as well understanding behavioral and pathological differences. This review summarizes chromosome effects on gene expression, epigenetics, hormones in relation to the brain. We explore neuroanatomy, neurochemistry, cognition, brain pathology aiming explain current state art. While some domains exhibit strong differences, others reveal subtle whose overall significance warrants clarification. hope that increases awareness serves a basis planning future studies consider both sexes equally regarding similarities

Язык: Английский

---

Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Molecular Psychiatry, Год журнала: 2023, Номер 28(5), С. 2008 - 2017

Опубликована: Май 1, 2023

Abstract Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups—a ‘lower brain volume’ subgroup (SG1) and an ‘higher striatal (SG2) with otherwise normal structure. In this study, investigated whether MRI signatures these subgroups were also already present at time first-episode psychosis (FEP) they related clinical presentation remission over 1-, 3-, 5-years. We included 572 FEP 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) PHENOM consortium. Our prior subgrouping models (671 participants; USA, Germany, China) applied both HC. Participants assigned into 1 categories: (SG1), 2 (SG2), no membership (‘None’), mixed SG1 + SG2 (‘Mixed’). Voxel-wise analyses characterized subgroups. Supervised learning baseline membership. The dominant patterns in (with neuromorphology) identified first episode psychosis. had a significantly higher proportion (32%) vs. HC (19%) than (FEP, 21%; HC, 23%). Clinical multivariate separated (balanced accuracy = 64%; p < 0.0001), showing education but greater positive symptoms presentation, association symptom 1-year, 5-year, when timepoints combined. Neuromorphological subtypes are evident illness onset, by distinct presentations, differentially associated subsequent remission. These results suggest that may be underlying risk phenotypes could targeted future treatment trials critical consider interpreting neuroimaging literature.

Язык: Английский

---

A case for seeking sex-specific treatments in Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Фев. 13, 2024

There is no satisfactory explanation for the sex-related differences in incidence of many diseases and this also true Alzheimer’s disease (AD), where females have a higher lifetime risk developing make up about two thirds AD patient population. The importance understanding cause(s) that account disproportionate distribution cannot be overestimated, likely to significant factor search therapeutic strategies will combat and, furthermore, potentially point sex-targeted approach treatment. This review considers literature context what known impact sex on processes targeted by drugs are clinical trial AD, existing knowledge differing responses males these drugs. Current strongly supports view trials should assessing difference priority with focus exploring sex-stratified treatments.

Язык: Английский

---

A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions

Biomolecules, Год журнала: 2022, Номер 12(7), С. 881 - 881

Опубликована: Июнь 24, 2022

Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young senescent brains, including motricity, sleep, attention, emotion, learning memory, social reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine amphetamines) were historically used to shape mood cognition, but substances typically lead severe negative side effects (tolerance, abuse, addiction, dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric progressive disorders, Parkinson’s Alzheimer diseases, drug addiction dementia, resulting devastating personal familial concerns high socioeconomic costs worldwide. development of low-side-effect, new/selective medicaments reduced abuse-liability which ameliorate DA/DAT-related is therefore crucial fields medicine healthcare. Using rat as experimental animal model, present work describes synthesis pharmacological profile (S)-MK-26, a new modafinil analogue markedly improved potency selectivity for over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered (S)-MK-26 treatment, whereas experiments hole-board test showed only lesser on reference memory performance aged rats. However, effort-related FR5/chow PROG/chow feeding choice experiments, treatment reversed depression-like behavior induced by dopamine-depleting tetrabenazine (TBZ) increased selection high-effort alternatives. Moreover, microdialysis extracellular levels prefrontal cortex nucleus accumbens core shell. These studies highlight potent enhancer promoter plasticity, predominant beneficial behaviors, thus proposing therapeutic potentials low-effort exertion motivational characteristic depression aging-related disorders.

Язык: Английский

---

A sex difference in mouse dopaminergic projections from the midbrain to basolateral amygdala

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

Опубликована: Дек. 30, 2022

Abstract Background Dopaminergic circuits play important roles in the motivational control of behavior and dysfunction dopaminergic have been implicated several psychiatric disorders, such as schizophrenia depression. While these disorders exhibit different incidence rates men women, potential sex differences underlying neural are not well-understood. Previous anatomical tracing studies mammalian species revealed a prominent circuit projection connecting midbrain ventral tegmental area (VTA) to basolateral amygdala (BLA), which is involved emotional processing associative learning. However, whether there any difference this remains unknown. Methods To study VTA-to-BLA circuit, we injected two viral vectors encoding fluorescent reporters axons synaptic boutons (AAV–FLEX–tdTomato AAV–FLEX–SynaptophysinGFP, respectively) into VTA mouse transgenic driver line (tyrosine hydroxylase promoter-driven Cre, or TH-Cre), restricts reporter expression neurons. We then used confocal microscopy image distribution density serial sections both male female brain. Results found that overall labeling intensity projections intermediate among forebrain pathways, significantly higher than prefrontal cortex, but lower nucleus accumbens. Within areas, concentrated BLA. Although size BLA within similar between mice, brain Conclusions Our results demonstrate an innervations from This finding may provide structural foundation mechanisms behaviors related dysfunctions.

Язык: Английский

---

D_2/3Agonist during Learning Potentiates Cued Risky Choice

Journal of Neuroscience, Год журнала: 2023, Номер 43(6), С. 979 - 992

Опубликована: Янв. 9, 2023

Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological mechanisms underlying these adverse effects are unknown. Recent data show that adding win-paired sound light cues rat task (rGT) potentiates risky decision-making impulsivity via system, changing dopaminergic tone has a greater influence on behavior while subjects learning contingencies. Dopamine therapy may therefore potentiating risk-taking amplifying behavioral impact of gambling-related novel behavior. Here, we ropinirole treatment in male rats transiently increased motor robustly progressively choice high-risk/high-reward options when administered during acquisition cued not uncued rGT. Early training, win-stay after large unlikely wins rGT, indicative enhanced model-free learning, which mediated drug's effect later risk preference. Ex vivo cFos imaging showed both chronic addition suppressed activity midbrain neurons. The ratio midbrain:prefrontal + neurons was lower animals with suboptimal patterns tended predict preference across all rats. Network analyses further suggested induced decoupling cells VTA nucleus accumbens only were present. Frontostriatal uninformed endogenous teaching signal appeared perpetuate choice, exaggerated this disconnect synergy reward-paired cues. SIGNIFICANCE STATEMENT D 2/3 receptor agonists, cause disorder through an unknown mechanism. Ropinirole rats, paired casino-inspired sounds lights. This early indicating learning. neurons, mimicked degree exhibited uniquely predicted dopamine:PFC activity. Depriving PFC drive on-task, acts synergistically amplify this.

Язык: Английский

---

Sex‐specific susceptibility to psychotic‐like states provoked by prenatal THC exposure: Reversal by pregnenolone

Journal of Neuroendocrinology, Год журнала: 2023, Номер 35(2)

Опубликована: Фев. 1, 2023

Abstract Sociocultural attitudes towards cannabis legalization contribute to the common misconception that it is a relatively safe drug and its use during pregnancy poses no risk fetus. However, longitudinal studies demonstrate maternal exposure results in adverse outcomes offspring, with heightened for developing psychopathology. One of most reported psychiatric proneness psychotic‐like experiences childhood. How gestation increases psychosis susceptibility children adolescents remains elusive. Preclinical research has indicated utero major psychoactive component cannabis, delta‐9‐tetrahydrocannabinol (THC), deranges brain developmental trajectories vulnerable endophenotypes later life. Here, we present how prenatal THC (PCE) deregulates mesolimbic dopamine development predisposing offspring schizophrenia‐relevant phenotypes, exclusively when exposed environmental challenges, such as stress or THC. Detrimental effects PCE are sex‐specific because female do not display upon these challenges. Moreover, pregnenolone, neurosteroid showed beneficial properties on elicited by intoxication, normalizes function rescues phenotypes. We, therefore, suggest this “disease‐modifying” aid prevent onset psychoses individuals. Our findings corroborate clinical evidence highlight relevance early diagnostic screening preventative strategies young individuals at mental diseases, male offspring.

Язык: Английский

---

Sex‐based disparities in dopamine agonist response in patients with restless legs syndrome

Journal of Sleep Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

This study aimed to investigate sex-related differences in the response ropinirole and pramipexole patients with restless legs syndrome (RLS). By analysing clinical parameters polysomnographic (PSG) findings, we sought elucidate potential factors related sex disparities modulating treatment responses sleep quality RLS. A total of 41 drug-free RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before second night, 26 received an oral dose 0.25 mg whereas 15 0.5 ropinirole. After each recording, self-evaluated severity their previous night symptoms by means ad hoc visual analogue scale (VAS). At baseline, efficiency percentage Stage N2 tended be higher females while wakefulness after onset was significantly males. treatment, leg movements during (LMS), periodic LMS (PLMS), periodicity indexes were lower than The VAS score all patients, between sexes. demonstrates a acute responsiveness PLMS dopamine agonists (pramipexole ropinirole) males These findings might explained differential expression receptors, especially D

Язык: Английский

---