| 1. |
- Dubol, Manon, et al.
(författare)
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Acute nicotine exposure blocks aromatase in the limbic brain of healthy women : A [11C]cetrozole PET study
- 2023
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Ingår i: Comprehensive Psychiatry. - : Elsevier. - 0010-440X .- 1532-8384. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.
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| 2. |
- Dubol, Manon, et al.
(författare)
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Brain volumes and surface relate to clinical correlates of PMDD
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Premenstrual dysphoric disorder (PMDD) is characterized by severe negative mood symptoms occurring during the luteal phase of the menstrual cycle. Accumulative evidence indicates that sex hormones in adult women can influence not only behavior and brain reactivity, but also brain morphology. Moreover, structural imaging studies suggest an association between brain anatomy and negative mood symptoms including depression, anxiety and irritability. In line with these observations, a dysregulation of brain structural changes in response to hormonal fluctuations during the menstrual cycle could be involved in the etiology of PMDD. In the present study we investigated the brain structural correlates of common PMDD symptoms during the late luteal phase of the menstrual cycle.Methods: We sought to explore the brain signature of PMDD using Magnetic Resonance (MR) imaging in patients diagnosed with PMDD. Self-evaluations on the Daily Record of Severity of Problems (DRSP) were used to assess the symptoms related to PMDD and gonadal hormone levels were measured in blood. We performed Voxel Based Morphometry (VBM) and Surface Based Morphometry (SBM) analyses on T1-weighted images to assess regional brain volumes and surface parameters such as cortical thickness and gyrification. The relationships between structural, clinical, and hormonal measures were investigated. Image preprocessing and hypothesis-free analysis was carried out in SPM12.Results: Our preliminary findings (n = 27) indicate a relationship between symptoms severity and both grey matter volume and surface measures of the anterior cingulate cortex (ACC). Thus, higher DRSP scores, irritability, depression and physical symptoms levels were associated with lower ACC gyrification, cortical thickness, cortical complexity and grey matter volume. Additionally, on the whole brain level, grey matter volume of the caudate nucleus was negatively correlated to DRSP, depression, and irritability scores.Discussion: We report an association between brain structure and symptoms severity in PMDD patients, which particularly involves the ACC. Interestingly this region has an important role in emotion regulation and has been previously reported to be functionally impaired in PMDD patients (Comasco et al., 2014). These preliminary findings indicate that structural changes over the ACC may be involved of the pathogenesis of PMDD.
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| 3. |
- Dubol, Manon, PhD, 1991-, et al.
(författare)
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Cortical morphology variations during the menstrual cycle in individuals with and without premenstrual dysphoric disorder
- 2024
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 355, s. 470-477
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPremenstrual dysphoric disorder (PMDD) is hypothesized to stem from maladaptive neural sensitivity to ovarian steroid hormone fluctuations. Recently, we found thinner cortices in individuals with PMDD, compared to healthy controls, during the symptomatic phase. Here, we aimed at investigating whether such differences illustrate state-like characteristics specific to the symptomatic phase, or trait-like features defining PMDD.MethodsPatients and controls were scanned using structural magnetic resonance imaging during the mid-follicular and late-luteal phase of the menstrual cycle. Group-by-phase interaction effects on cortical architecture metrics (cortical thickness, gyrification index, cortical complexity, and sulcal depth) were assessed using surface-based morphometry.ResultsIndependently of menstrual cycle phase, a main effect of diagnostic group on surface metrics was found, primarily illustrating thinner cortices (0.3 < Cohen's d > 1.1) and lower gyrification indices (0.4 < Cohen's d > 1.0) in patients compared to controls. Furthermore, menstrual cycle-specific effects were detected across all participants, depicting a decrease in cortical thickness (0.4 < Cohen's d > 1.7) and region-dependent changes in cortical folding metrics (0.4 < Cohen's d > 2.2) from the mid-follicular to the late luteal phase.LimitationsSmall effects (d = 0.3) require a larger sample size to be accurately characterized.ConclusionsThese findings provide initial evidence of trait-like cortical characteristics of the brain of individuals with premenstrual dysphoric disorder, together with indications of menstrual cycle-related variations in cortical architecture in patients and controls. Further investigations exploring whether these differences constitute stable vulnerability markers or develop over the years may help understand PMDD etiology.
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| 4. |
- Dubol, Manon, et al.
(författare)
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Differential grey matter structure in women with premenstrual dysphoric disorder : evidence from brain morphometry and data-driven classification
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual—5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen’s d = 0.45–0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen’s d = 0.34–0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen’s d = 0.20–0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology.
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| 5. |
- Dubol, Manon, et al.
(författare)
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Grey matter correlates of affective and somatic symptoms of premenstrual dysphoric disorder
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology.
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| 6. |
- Dubol, Manon, et al.
(författare)
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Grey matter morphometry and MRI data-driven classification of premenstrual dysphoric disorder
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. Premenstrual dysphoric disorder (PMDD) is recognized in the DSM-5 as a hormone-related depressive disorder, specific to women’s mental health 1. Women who suffer from PMDD experience affective, cognitive, and physical symptoms that peak during the late luteal phase of the menstrual cycle, and remit shortly in the beginning of the next cycle 2. The key affective symptoms of PMDD point to anatomical and functional brain impairment, suggesting an impaired top-down inhibitory process involving limbic brain structures 3. However, very little is known about brain morphological alterations in PMDD. The present study aimed at investigating the grey matter structures that distinguish women with PMDD from healthy controls, by use of multiscale structural MRI analyses. Differences in grey matter morphology between women with PMDD and healthy controls were expected within regions of cortico-limbic networks. Methods. Women meeting DSM-5 criteria for PMDD (N=89) and healthy controls (N=42) underwent structural 3T-MRI during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of Voxel- and Surface Based Morphometry in SPM12, using whole-brain and region-of-interest approaches. Voxel- and vertex-wise analyses were conducted using the non-parametric permutation-based threshold-free cluster enhancement method 4. In order to account for the nuisance variance of regressors of non-interest, total intracranial volume and age were included as confounding covariates. Furthermore, machine learning and multivariate pattern analysis was performed using a leave-one-fold-out cross-validation procedure with the MVPANI toolbox 5, to test whether MRI measures (volume, thickness, gyrification, sulcal depth and cortical complexity) could distinguish women with PMDD from healthy controls.Results. Compared to controls over the whole brain, women with PMDD had smaller grey matter volumes in ventral posterior cortices (fusiform, lingual, inferior occipital and parahippocampal cortices) and the cerebellum (Cohen’s d = 0.45 ― 0.76). Region-of-interest analyses further indicated smaller volumes in the right amygdala and putamen of women with PMDD (Cohen’s d = 0.34 ― 0.55). Likewise, women with PMDD displayed thinner cortices compared to controls, in widespread clusters covering frontal, temporal, insular, paracentral, parietal, and occipital areas (Cohen’s d = 0.20 ― 0.74). No differences in gyrification, sulcal depth and cortical complexity were found between women with PMDD and controls. Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, above chance level. Notably, grey matter volume was the best measure for distinguishing the groups, with a mean accuracy of about 73%.Conclusions. The present findings point to PMDD-specific grey matter structure in regions of corticolimbic networks, in line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD. Furthermore, the results include widespread cortical regions and cerebellar areas, suggesting the involvement of distinct networks in PMDD pathophysiology. These effects prominently involved volumetric and cortical thickness measures, as further highlighted by multivariate pattern classification analyses. Such differences in brain structure may help explaining the variations in brain function previously reported in women with PMDD during the symptomatic phase.
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| 7. |
- Dubol, Manon, et al.
(författare)
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Neuroimaging premenstrual dysphoric disorder : A systematic and critical review
- 2020
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Ingår i: Frontiers in neuroendocrinology (Print). - : Elsevier BV. - 0091-3022 .- 1095-6808. ; 57
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Forskningsöversikt (refereegranskat)abstract
- Endocrine organizational and activational influences on cognitive and affective circuits are likely critical to the development of premenstrual dysphoric disorder (PMDD), a sex-specific hormone-dependent mood disorder. An overview of the anatomical and functional neural characterization of this disorder is presented here by means of neuroimaging correlates, identified from eighteen publications (n = 361 subjects). While white matter integrity remains uninvestigated, greater cerebellar grey matter volume and metabolism were observed in patients with PMDD, along with altered serotonergic and GABAergic neurotransmission. Differential corticolimbic activation in response to emotional stimuli distinguishes the PMDD brain, namely enhanced amygdalar and diminished fronto-cortical function. Thus far, the emotional distress and dysregulation linked to PMDD seem to be defined by structural, chemical and functional brain signatures; however, their characterization remains sparsely studied and somewhat inconsistent. Clear and well-replicated neurobiological features of PMDD are needed to promote timely diagnoses and inform development of prevention and treatment strategies.
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| 8. |
- Dubol, Manon, et al.
(författare)
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Neuroimaging the menstrual cycle : A multimodal systematic review
- 2021
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Ingår i: Frontiers in neuroendocrinology (Print). - : Frontiers Media S.A.. - 0091-3022 .- 1095-6808. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior and mental health. Throughout the reproductive years, estrogens and progesterone levels fluctuate across the menstrual cycle and can modulate neural circuits involved in affective and cognitive processes. Here, we review seventy-seven neuroimaging studies and provide a comprehensive and data-driven evaluation of the accumulating evidence on brain plasticity associated with endogenous ovarian hormone fluctuations in naturally cycling women (n = 1304). The results particularly suggest modulatory effects of ovarian hormones fluctuations on the reactivity and structure of cortico-limbic brain regions. These findings highlight the importance of performing multimodal neuroimaging studies on neural correlates of systematic ovarian hormone fluctuations in naturally cycling women based on careful menstrual cycle staging.
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| 9. |
- Dubol, Manon, 1991-
(författare)
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Trait- versus state- grey matter volume alterations in premenstrual dysphoric disorder
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. Premenstrual dysphoric disorder (PMDD) is a hormone-related mood disorder characterized by cyclic affective symptoms that peak in the luteal phase and are absent during the follicular phase of the menstrual cycle (DSM-5) (A.P.A. 2013). The prevalence (up to 8%) and morbidity of PMDD (Epperson, Steiner et al. 2012, Wikman, Sacher et al. 2022), along with the lack of universally efficient treatment, highlight the need for a better understanding of the etiology of this disorder. Recently, we highlighted differences in grey matter volume between women with PMDD and healthy controls during the luteal phase, depicting smaller volumes in women diagnosed with the condition. However, it is unknown whether such alterations represent state-like changes specific to the symptomatic phase, or trait-like characteristics. The present study aimed at answering this question, by investigating grey matter volumes in women with PMDD and controls across the menstrual cycle. We expected to find differential volumes in areas previously reported to differ between groups in the luteal phase (Dubol, Stiernman et al. 2022). Methods. Women meeting DSM-5 criteria for PMDD (N=28) and healthy controls (N=26) underwent structural 3T-MRI during the mid-follicular phase and the late-luteal phase of the menstrual cycle. For each time point, grey matter volumes were assessed using voxel-based morphometry in SPM12. Group-by-Phase interaction analyses were conducted using whole-brain and region-of-interest approaches. Voxel-wise whole-brain analyses were conducted using the non-parametric permutation-based threshold-free cluster enhancement method (Smith and Nichols 2009). The ROI analyses focused on the left and right amygdala.Results. No Group-by-Phase interaction effect on grey matter volumes was found, suggesting trait rather that state structural markers of PMDD. Smaller grey matter volumes were found in women with PMDD compared to controls across menstrual cycle phases, mostly in cerebellar, occipital, ventral occipito-temporal, parietal, paracentral and orbitofrontal areas, as well as in the putamen (pFWE < 0.1, threshold-free cluster enhancement). Regions-of-interest analyses additionally point to a smaller volume of the right amygdala in women with PMDD compared to controls, across the menstrual cycle.Conclusions. This study provided the first evidence for an altered grey matter structure in the brain of women with PMDD across the symptomatic and asymptomatic phases of the menstrual cycle, which might represent trait-like characteristics of the PMDD brain. Further investigations are needed to elucidate whether the observed smaller volumes in women with PMDD constitute stable vulnerability markers or whether they gradually develop over the course of the disorder. Such differences in brain structure may help explain the variations in brain function previously reported in women with this condition.
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| 10. |
- Gu, Xuan, et al.
(författare)
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White matter microstructure and volume correlates of premenstrual dysphoric disorder
- 2022
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Ingår i: Journal of Psychiatry & Neuroscience. - : Canadian Medical Association. - 1180-4882 .- 1488-2434. ; 47:1, s. E67-E76
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by psychological and physical symptoms. Differences in white matter have been associated with affective and anxiety disorders, which share some symptoms with PMDD. However, whether white matter structure differs between the brains of individuals with PMDD and healthy controls is not known, nor is its relation to symptom severity.METHODS: We performed tract-based spatial statistics and voxel-based morphometry analyses of diffusion tensor imaging metrics and white matter volume, using 2 neuroimaging data sets (n = 67 and n = 131) and a combined whole-brain and region-of-interest approach. We performed correlation analyses to investigate the relationship between regions with different white matter microstructure and volume and PMDD symptom severity.RESULTS: We found greater fractional anisotropy in the left uncinate fasciculus (d = 0.69) in individuals with PMDD compared to controls. Moreover, the volume of the right uncinate fasciculus was higher in individuals with PMDD compared to controls (d = 0.40). As well, the severity of premenstrual depression was positively correlated with fractional anisotropy in the right superior longitudinal fasciculus (r = 0.35).LIMITATIONS: It is challenging to interpret group differences in diffusion tensor imaging metrics in terms of their underlying biophysical properties. The small size of the control group in the diffusion tensor imaging study may have prevented effects of interest from being detected.CONCLUSION: The findings of the present study provide evidence of differential cerebral white matter structure associated with PMDD and its symptoms.
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