scholarly journals Decreased Medial Prefrontal Cortex Glutamate Levels in Perimenopausal Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Sidney Yap ◽  
Jessica Luki ◽  
Christopher C. Hanstock ◽  
Peter Seres ◽  
Tami Shandro ◽  
...  

Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women.Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal (n = 15) and healthy RD women (n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC).Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = −3.84, df = 23.97, p = 0.001).Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD.

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1679-1686 ◽  
Author(s):  
C M Yelnik ◽  
M Lambert ◽  
E Drumez ◽  
V Le Guern ◽  
J-L Bacri ◽  
...  

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41–17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.


2020 ◽  
Author(s):  
Jessica A. Cooper ◽  
Makiah R. Nuutinen ◽  
Victoria M. Lawlor ◽  
Brittany A. M. DeVries ◽  
Elyssa M. Barrick ◽  
...  

ABSTRACTStress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Stéphane Potvin ◽  
Andràs Tikàsz ◽  
Stéphane Richard-Devantoy ◽  
Ovidiu Lungu ◽  
Alexandre Dumais

Despite the high prevalence of suicidal ideas/attempts in schizophrenia, only a handful of neuroimaging studies have examined the neurobiological differences associated with suicide risk in this population. The main objective of the current exploratory study is to examine the neurofunctional correlates associated with a history of suicide attempt in schizophrenia, using a risky decision-making task, in order to show alterations in brain reward regions in this population. Thirty-two male outpatients with schizophrenia were recruited: 13 patients with (SCZ + S) and 19 without a history of suicidal attempt (SCZ − S). Twenty-one healthy men with no history of mental disorders or suicidal attempt/idea were also recruited. Participants were scanned using fMRI while performing the Balloon Analogue Risk Task. A rapid event-related fMRI paradigm was used, separating decision and outcome events, and the explosion probabilities were included as parametric modulators. The most important finding of this study is that SCZ + S patients had reduced activations of the medial prefrontal cortex during the success outcome event (with parametric modulation), relative to both SCZ − S patients and controls, as illustrated by a spatial conjunction analysis. These exploratory results suggest that a history of suicidal attempt in schizophrenia is associated with blunted brain reward activity during emotional decision-making.


2020 ◽  
Author(s):  
Paul Faulkner ◽  
Susanna Lucini Paioni ◽  
Petya Kozhuharova ◽  
Natasza Orlov ◽  
David J. Lythgoe ◽  
...  

AbstractCigarette smoking is still the largest contributor to disease and death worldwide. Successful cessation is hindered by decreases in prefrontal glutamate concentrations and gray matter volume due to daily smoking. Because non-daily, intermittent smoking also contributes greatly to disease and death, understanding whether infrequent tobacco use is associated with reductions in prefrontal glutamate concentrations and gray matter volume may aid public health. Eighty-five young participants (41 non-smokers, 24 intermittent smokers, 20 daily smokers, mean age ~23 years old), underwent 1H-magnetic resonance spectroscopy of the medial prefrontal cortex, as well as structural MRI to determine whole-brain gray matter volume. Compared to non-smokers, both daily and intermittent smokers exhibited lower concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol in the medial prefrontal cortex, and lower gray matter volume in the right inferior frontal gyrus; these measures of prefrontal metabolites and structure did not differ between daily and intermittent smokers. Finally, medial prefrontal metabolite concentrations and right inferior frontal gray matter volume were positively correlated, but these relationships were not influenced by smoking status. This study provides the first evidence that both daily and intermittent smoking are associated with low concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol, and low gray matter volume in the prefrontal cortex. Future tobacco cessation efforts should not ignore potential deleterious effects of intermittent smoking by considering only daily smokers. Finally, because low glutamate concentrations hinder cessation, treatments that can normalize tonic levels of prefrontal glutamate, such as N-acetylcysteine, may help intermittent and daily smokers to quit.


Cephalalgia ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 702-709 ◽  
Author(s):  
Jiing-Feng Lirng ◽  
Hung-Chieh Chen ◽  
Jong-Ling Fuh ◽  
Chia-Fen Tsai ◽  
Jen-Feng Liang ◽  
...  

Background Although the comorbidity between migraine and major depressive disorder (MDD) has been recognized, the pathophysiology remains unclear. The dorsolateral prefrontal cortex (DLPFC) is a well-known neural substrate for MDD. We investigated the relationship between brain metabolites in DLPFC and comorbid MDD in migraine patients. Methods We recruited migraine patients from a tertiary headache clinic. A board-certified psychiatrist conducted a structured interview for MDD diagnosis. The severity of depression was evaluated by the Beck Depression Inventory (BDI). Thirty migraine patients (five men, 25 women; mean age: 40.4 ± 12.4 years) completed the study, and 16 of them were diagnosed with MDD. All patients underwent a magnetic resonance spectroscopy (MRS) examination focusing on bilateral DLPFC. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to total creatine (tCr) were compared between migraine patients with and without MDD, and were correlated with BDI scores. Results Relative to patients without MDD, migraine patients with MDD had higher mI/tCr ratios in the bilateral DLPFC ( p = 0.02, left; p = 0.02, right, Mann-Whitney U test). The mI/tCr ratios in the right DLPFC were positively correlated with BDI scores ( r = 0.52, p = 0.003). The NAA/tCr and Cho/tCr ratios did not differ between migraine patients with and without MDD. Conclusion Increased mI/tCr within the DLPFC might be associated with the presence of MDD in migraine patients.


2012 ◽  
Vol 13 (3) ◽  
pp. 286-296 ◽  
Author(s):  
J D Tapocik ◽  
M Solomon ◽  
M Flanigan ◽  
M Meinhardt ◽  
E Barbier ◽  
...  

2011 ◽  
Vol 26 (S2) ◽  
pp. 1874-1874
Author(s):  
M. Flores-Ramos ◽  
I. Méndez Ramírez

ObjectiveTo determine if serum levels of Follicle Stimulating Hormone, Luteinizing Hormone, estradiol, progesterone, Free Testosterone and Total Testosterone differ between perimenopausal women with first depressive episode, recurrent depression and without depression.MethodsDemographic and clinical characteristics were evaluated in 63 perimenopausal women with first depressive episode (N = 20), recurrent depression (N = 23) or non-depressed (N = 20). Hormonal measurements were evaluated at follicular and luteal menstrual phases and mid-cycle, around one menstrual cycle.ResultsWhen compared depressed and non-depressed women we observed lower levels of luteal progesterone, higher levels of total testosterone and an increasing level of FSH in depressed patients. Differences between the three groups were observed in luteal progesterone levels, luteal FT, and luteal TT. Independently of current diagnosis, women with and without pmdd antecedent, differed in progesterone and testosterone levels. We did not find association of perimenopausal depression and history of post partum depression.ConclusionsHormonal profiles differed between groups. Patients with antecedent of pmdd had a similar progesterone and testosterone profile to perimenopausal depressed women.


2021 ◽  
Author(s):  
Cong-Cong Fu ◽  
Xin-Yi Zhang ◽  
Liu Xu ◽  
Hui-Xian Huang ◽  
Shuang Xu ◽  
...  

Abstract ObjectiveEpidemiological studies suggest a bidirectional association between depression and obesity; however, the biological mechanisms that link the development of depression to a metabolic disorder remain unclear. Even though nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) agonists show anti-depressive effect, and high-fat diet-(HFD)-induced PPARγ dysfunction is involved in the pathogenesis of metabolic disorders, the neuronal PPARg has never been studied in HFD-induced depression. Thus, we aimed to investigate the effect of neuronal PPARγ on depressive-like behaviors in HFD-induced obese mice. MethodsWe fed male C57BL/6J mice with HFD to generate obese mice and conducted a series of behavioral tests to assess the effects of HFD feeding on depression. We generated neuron-specific PPARγ knockout mice (NKO) to determine whether neuronal PPARg deficiency was correlated with depressive-like behaviors. To further prove whether PPARγ in the medial prefrontal cortex (mPFC) neurons is involved in depressive-like behaviors, we applied AAV- CaMKIIa-Cre approach to specifically knockout PPARγ in the mPFC neurons of LoxP mice and used AAV-syn-PPARγ vectors to overexpress PPARγ in the mPFC neurons of NKO mice. ResultsWe observed a low mPFC PPARγ level and an increase in depressive-like behaviors in the HFD-fed mice. Moreover, neuronal-specific PPARγ deficiency in mice induced depressive-like behaviors, which could be abolished by imipramine. Furthermore, overexpressing PPARg in the mPFC reversed the depressive-like behaviors in HFD-fed mice as well as in neuronal-specific PPARγ knockout mice. ConclusionsThese results implicate that dysregulation of neuronal PPARγ in the mPFC may contribute to an increased risk for depression in obese populations.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Federica Lucantonio ◽  
Eunyoung Kim ◽  
Zhixiao Su ◽  
Anna J Chang ◽  
Bilal A Bari ◽  
...  

Making predictions about future rewards or punishments is fundamental to adaptive behavior. These processes are influenced by prior experience. For example, prior exposure to aversive stimuli or stressors changes behavioral responses to negative- and positive-value predictive cues. Here, we demonstrate a role for medial prefrontal cortex (mPFC) neurons projecting to the paraventricular nucleus of the thalamus (PVT; mPFC→PVT) in this process. We found that a history of aversive stimuli negatively biased behavioral responses to motivationally relevant cues in mice and that this negative bias was associated with hyperactivity in mPFC→PVT neurons during exposure to those cues. Furthermore, artificially mimicking this hyperactive response with selective optogenetic excitation of the same pathway recapitulated the negative behavioral bias induced by aversive stimuli, whereas optogenetic inactivation of mPFC→PVT neurons prevented the development of the negative bias. Together, our results highlight how information flow within the mPFC→PVT circuit is critical for making predictions about motivationally-relevant outcomes as a function of prior experience.


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