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- 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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- 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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- Vrettou, Maria, et al.
(författare)
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VGLUT2 genotype interacts with environmental experiences to predict alcohol misuse in young adults
- 2016
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Ingår i: ISBRA ESBRA World Congress on Alcohol an Alcoholism, Berlin, Germany.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The heritability of alcohol use disorder (AUD) ranges between 40 to 60%, as demonstrated by twin studies. Environmental factors are hence of importance for the developmental trajectory of the disorder. Gene-by-environment interactions indeed influence neuroplasticity and determine the individual’s susceptibility or resilience to AUD. Lately, a role of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been indicated in studies of addiction- and alcohol-related phenotypes. We previously demonstrated an association between the single nucleotide polymorphism (SNP) rs2290045 in the VGLUT2 gene and alcohol dependence as well as showed an interaction effect between voluntary ethanol drinking and early life stress on Vglut2 expression in the ventral tegmental area of outbred rats. In the present study, using a population-based, cross-sectional and retrospective design, we aimed to investigate the association between two candidate VGLUT2 SNPs, rs1900586 and rs2290045, and aversive as well as supportive environmental factors on alcohol misuse in young adults. A total of 2,500 (52.6% females) individuals (mean age: 22.15 years) were included in the study. Aversive life events (i.e., physical violence, verbal aggression, witnessing violence) and parent-child relationship (i.e., early: until 18 years of age; lifetime: until present) were self-reported. Alcohol misuse was assessed using the AUD Identification Test (AUDIT). Preliminary results showed no main genotype effects on drinking profile. Multivariable analyses revealed that SNP rs1900586 interacted with exposure to verbal aggression and early parent-child relationship in respect to AUDIT scores. Male carriers of the major (T) allele reported higher AUDIT scores when exposed to verbal aggression and poor early parent-child relationship than the C carriers exposed to the same environment, while the opposite pattern was noted in the presence of supportive parent-child relationship. In individuals with symptoms of dependence or harmful alcohol use, SNP rs1900586 interacted with exposure to physical violence and parent-child relationship (early and lifetime) in both sexes. The same interaction effect was detected for SNP rs2290045 in females. These preliminary findings provide the first evidence that VGLUT2 genotype moderates the environmental sensitivity to alcohol misuse among young adults and call for further investigation in independent cohorts, including clinical samples.
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