BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.
- MeSH
- bipolární porucha * patofyziologie diagnostické zobrazování MeSH
- depresivní porucha unipolární * patofyziologie diagnostické zobrazování MeSH
- dospělí MeSH
- konektom metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mapování mozku metody MeSH
- mozek patofyziologie diagnostické zobrazování MeSH
- multivariační analýza MeSH
- nervová síť diagnostické zobrazování patofyziologie MeSH
- nervové dráhy patofyziologie diagnostické zobrazování MeSH
- průřezové studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. METHODS: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. RESULTS: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm2, respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 μm2/μm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm2, respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 μm2/μm, respectively (p = 0.0002). CONCLUSIONS: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Despite the clinical importance of bipolar depression (BDE), effective treatment options are still limited. Transcranial magnetic stimulation (rTMS) has proven of moderate efficacy in major depression, but the evidence remains inconclusive for BDE. METHODS: A 4-week, double-blind, randomised, parallel-group, sham-controlled study (trial ID ISRCTN77188420) explored the benefits of 10 Hz MRI-guided right ventrolateral (RVL) rTMS and left dorsolateral (LDL) rTMS as add-on treatments for BDE. Outcome measures included changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) score, self-assessment, response and remission rates, and side effects. RESULTS: Sixty patients were randomly assigned to study groups, and forty-six completed the double-blind phase. The mean change from baseline to Week 4 in MADRS was greater in both active groups compared to the sham, yet differences did not achieve significance (RVL vs sham: -4.50, 95%CI -10.63 to 1.64, p = 0.3; LDL vs sham: -4.07, 95%CI -10.24 to 2.10, p = 0.4). None of the other outcome measures yielded significant results. CONCLUSIONS: While not demonstrating the superiority of either 10 Hz rTMS over sham, with the limited sample size, we can not rule out a moderate yet clinically meaningful effect. Further well-powered studies are essential to elucidate the role of rTMS in managing BDE.
- MeSH
- bipolární porucha * terapie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- psychiatrické posuzovací škály MeSH
- transkraniální magnetická stimulace * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
- MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- fokální adheze MeSH
- fosfatidylinositol-3-kinasy genetika MeSH
- lidé MeSH
- lithium * farmakologie terapeutické užití MeSH
- multiomika MeSH
- protoonkogenní proteiny c-akt genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The study aimed to assess the efficacy of transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric (NP) symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC), known as the long COVID. A double-blind, randomized, sham-controlled study compared the efficacy and safety of prefrontal cortex active tDCS to sham-tDCS in treating NP-PASC. Patients diagnosed with NP-PASC, with a Fatigue Impact Scale (FIS) score ≥ 40, were eligible for the study. Twenty tDCS sessions were administered within four weeks, with continuous, end-of-treatment, and follow-up measurements. The primary outcome was a change in the FIS at the end-of-treatment, analyzed in the intention-to-treat population. Data from 33 patients assigned to active (n = 16) or sham-tDCS (n = 17) were analyzed. After the treatment, a decrease in the FIS score was more pronounced in the sham than in the active group, yet the intergroup difference was insignificant (11.7 [95% CI -11.1 to 34.5], p = 0.6). Furthermore, no significant intergroup differences were observed regarding anxiety, depression, quality of life, and cognitive performance. The small cohort sample, differences in baseline FIS scores between groups (non-stratified randomization), or chosen stimulation parameters may have influenced our findings. However, it might also be possible that the expected mechanism of action of tDCS is insufficient to treat these conditions.
- MeSH
- COVID-19 * terapie MeSH
- dvojitá slepá metoda MeSH
- kvalita života MeSH
- lidé MeSH
- postakutní syndrom COVID-19 MeSH
- prefrontální mozková kůra fyziologie MeSH
- přímá transkraniální stimulace mozku * MeSH
- SARS-CoV-2 MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). METHODS: Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. RESULTS: AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LIMITATIONS: Limitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. CONCLUSIONS: LF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.
