Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also ...highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.
Abstract Background There is substantial evidence regarding a social cognitive deficit in schizophrenia, and it has been suggested to be a trait-marker of this disorder. However, a domain-by-domain ...analysis of social cognitive deficits in individuals at clinical high risk (CHR) for psychosis has not been performed. Method Electronic databases were searched for studies regarding social cognitive performance in individuals at CHR. The included social cognitive domains, which were classified based on the Social Cognition Psychometric Evaluation (SCOPE) initiative of the National Institute of Mental Health (NIMH), were as follows: theory of mind (ToM), social perception (SP), attributional bias (AB), and emotion processing (EP). Results Twenty studies that included 1229 individuals at CHR and 825 healthy controls met the inclusion criteria. The overall effect size for social cognition was medium ( g = − 0.477). The largest effect size was identified for AB ( g = − 0.708). A medium effect size was identified for EP ( g = − 0.446) and ToM ( g = − 0.425), and small effects were identified for SP ( g = − 0.383). Conclusion This is the first quantitative domain-by-domain social cognitive meta-analysis regarding CHR individuals. The present study indicated that individuals at CHR exhibited significant impairments in all domains of social cognition compared with healthy controls, with the largest effect size identified for AB. The identification of social cognitive domains that reflect an increased risk for impending psychosis and of predictors of the conversion to psychosis via a longitudinal follow-up study is required.
▶ The default mode network and brain areas associated with meditation have similarities. ▶ Meditators showed greater functional connectivity in the medial prefrontal cortex. ▶ Long-term practice of ...meditation may be associated with functional changes in brains.
Areas associated with the default mode network (DMN) are substantially similar to those associated with meditation practice. However, no studies on DMN connectivity during resting states have been conducted on meditation practitioners. It was hypothesized that meditators would show heightened functional connectivity in areas of cortical midline activity. Thirty-five meditation practitioners and 33 healthy controls without meditation experience were included in this study. All subjects received 4.68-min resting state functional scanning runs. The posterior cingulate cortex and medial prefrontal cortex were chosen as seed regions for the DMN map. Meditation practitioners demonstrated greater functional connectivity within the DMN in the medial prefrontal cortex area (xyz=339−21) than did controls. These results suggest that the long-term practice of meditation may be associated with functional changes in regions related to internalized attention even when meditation is not being practiced.
Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine ...use and the risk of major congenital malformations.
Using Korea's nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean SD age, 32.4 4.1 years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13, p < 0.001) for overall malformations and 1.15 (1.10 to 1.21, p < 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12, p = 0.077) and 1.12 (1.04 to 1.21, p = 0.004) for <1 mg/day and 1.26 (1.17 to 1.36, p < 0.001) and 1.31 (1.19 to 1.45, p < 0.001) for >2.5 mg/day doses, respectively, suggesting a dose-response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births.
In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk.
ClinicalTrials.gov NCT04856436.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the ...structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Disturbances of the minimal self, characterized by abnormal sense of the body, body ownership and agency have been proposed as the phenomenological phenotype of schizophrenia. However, ...self-disturbances have not been extensively investigated, in part, due to the subjective nature of such processes, and the associated difficulty of studying these phenomena using empirical methodology. Of 115 potential studies on self-awareness in schizophrenia, a total of 25 studies met the inclusion criteria for the meta-analysis comprising 690 patients with schizophrenia and 979 healthy controls. We calculated Hedge's g to obtain a better estimate for the standardized mean difference in small samples. We identified significant basic self-disturbance in schizophrenia, as compared with healthy controls (25 studies, effect size = 0.51). Additional comparison of three sub-categories of the sense of body ownership (4 studies, effect size = 0.91), the sense of agency (15 studies, effect size = 0.49), and self-reported subjective experiences (6 studies, effect size = 0.57) also confirmed group differences. The complete set of 25 studies, and the studies in the sub-categories showed the statistical homogeneity of the characteristics. After a correction for potential publication bias using the trim-and-fill method, the main findings for all studies combined remained significant. Overall, patients with schizophrenia showed deficits in the sense of the minimal self, driven by abnormal sense of body ownership and sense of agency. Interestingly, the disturbed sense of agency in schizophrenia suggests an exaggerated self-consciousness rather than a diminished sense of self. Further research that utilizes sophisticated study designs is needed to examine the nature of self-disturbances in schizophrenia.
Background Previous neuroimaging studies of obsessive-compulsive disorder (OCD) have reported both baseline functional alterations and pharmacological changes in localized brain regions and ...connections; however, the effects of selective serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional network have not yet been elucidated. Methods Twenty-five drug-free OCD patients underwent resting-state functional magnetic resonance imaging. After 16-weeks, seventeen patients who received SSRI treatment were rescanned. Twenty-three matched healthy control subjects were examined at baseline for comparison, and 21 of them were rescanned after 16 weeks. Topological properties of brain networks (including small-world, efficiency, modularity, and connectivity degree) were analyzed cross-sectionally and longitudinally with graph-theory approach. Results At baseline, OCD patients relative to healthy control subjects showed decreased small-world efficiency (including local clustering coefficient, local efficiency, and small-worldness) and functional association between default-mode and frontoparietal modules as well as widespread altered connectivity degrees in many brain areas. We observed clinical improvement in OCD patients after 16 weeks of SSRI treatment, which was accompanied by significantly elevated small-world efficiency, modular organization, and connectivity degree. Improvement of obsessive-compulsive symptoms was significantly correlated with changes in connectivity degree in right ventral frontal cortex in OCD patients after treatment. Conclusions This is first study to use graph-theory approach for investigating valuable biomarkers for the effects of SSRI on neuronal circuitries of OCD patients. Our findings suggest that OCD phenomenology might be the outcome of disrupted optimal balance in the brain networks and that reinstating this balance after SSRI treatment accompanies significant symptom improvement.
Abstract
The dopamine blockade by antipsychotics trigger subjective dysphoria. Compared with D2 antagonists, aripiprazole, a D2 partial agonist, was expected to produce a different experience. ...Indeed, a previous study reported no relationship between the D2 receptor occupancy by aripiprazole and subjective dysphoria, while the D2 receptor occupancy by antagonists was associated with negative subjective experiences. This study revisited the relationship in patients treated with aripiprazole by using an inhibitory E
max
model, which enables the individual drug-free binding potential and D2 receptor occupancy to be properly estimated. Eight patients with schizophrenia who have been clinically stable on aripiprazole were enrolled. Assessments including Positive and Negative Syndrome Scale (PANSS) and Subjective Well-being under Neuroleptics Scale (Kv-SWN) were administered.
11
Craclopride PET scan were conducted 2, 26, and 74 h after aripiprazole administration. Regression analysis showed a significant negative association between the D2 receptor occupancy by aripiprazole in the striatum and the Kv-SWN (R
2
= 0.55, p = 0.036), but the PANSS total score was not associated with the Kv-SWN (R
2
= 0.42, p = 0.080). The negative association between D2 receptor occupancy by aripiprazole and subjective well-being implies that clinicians should find the lowest effective doses of aripiprazole for clinically stable patients to improve their subjective experiences and clinical outcomes.
Abstract
BACKGROUND
It remains controversial whether carotid artery stenting (CAS) is needed in cases of tandem cervical internal carotid artery occlusion (cICAO) and intracranial large vessel ...occlusion (LVO).
OBJECTIVE
To investigate the efficacy and safety of CAS in combination with endovascular thrombectomy (CAS-EVT) in cICAO-LVO patients and to compare its outcomes with those of EVT without CAS (EVT-alone).
METHODS
We identified all patients who underwent EVT for tandem cICAO-LVO from the prospectively maintained registries of 17 stroke centers. Patients were classified into 2 groups: CAS-EVT and EVT-alone. Clinical characteristics and procedural and clinical outcomes were compared between 2 groups. We tested whether CAS-EVT strategy was independently associated with recanalization success.
RESULTS
Of the 955 patients who underwent EVT, 75 patients (7.9%) had cICAO-LVO. Fifty-six patients underwent CAS-EVT (74.6%), and the remaining 19 patients underwent EVT-alone (25.4%). The recanalization (94.6% vs 63.2%, P = .002) and good outcome rates (64.3% vs 26.3%, P = .007) were significantly higher in the CAS-EVT than in the EVT-alone. Mortality was significantly lower in the CAS-EVT (7.1% vs 21.6%, P = .014). There was no significant difference in the rate of symptomatic intracranial hemorrhage between 2 groups (10.7 vs 15.8%; P = .684) and according to the use of glycoprotein IIb/IIIa inhibitor (10.0% vs 12.3%; P = .999) or antiplatelet medications (10.2% vs 18.8%; P = .392). CAS-EVT strategy remained independently associated with recanalization success (odds ratio: 24.844; 95% confidence interval: 1.445-427.187).
CONCLUSION
CAS-EVT strategy seemed to be effective and safe in cases of tandem cICAO-LVO. CAS-EVT strategy was associated with recanalization success, resulting in better clinical outcome.
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