1,721,598 research outputs found
From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD
No full textStimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response
Association between single dose and longer-term clinical response to stimulants in ADHD: a systematic review of randomized controlled trials.: Single dose and long-term ADHD treatment response
No full textObjectives: stimulants, such as methylphenidate (MPH) and amphetamines, represent the first-line pharmacological option for Attention-deficit/hyperactivity disorder (ADHD). Randomized controlled trials (RCTs) have demonstrated beneficial effects at a group level but could not identify characteristics consistently associated with varying individual response. Thus, more individualized approaches are needed. Experimental studies have suggested that the neurobiological response to a single dose is indicative of longer-term response. It is unclear whether this also applies to clinical measures. Methods: we carried out a systematic review of RCTs testing the association between the clinical response to a single dose of stimulants and longer-term improvement. Potentially suitable single-dose RCTs were identified from the MED-ADHD dataset, the European ADHD Guidelines Group (EAGG) RCT Dataset (https://med-adhd.org/), as updated on the 01/02/2024. Quality assessment was carried out using the Cochrane Risk of Bias (RoB) 2.0 tool.Results: 63 single-dose RCTs (94% testing MPH, 85% in children) were identified. Among these, only one RCT tested the association between acute and longer-term clinical response. This showed that the clinical improvement after a single dose of MPH was significantly associated with symptom improvement after four-week MPH treatment in 46 children (89% males) with ADHD. The risk of bias was rated as moderate. A further RCT used near-infrared spectroscopy (NIRS), thus did not meet inclusion criteria, and reported an association between brain changes under a single dose and longer-term clinical response in 22 children (82% males) with ADHD. The remaining RCTs only reported single dose effects on neuropsychological, neuroimaging or neurophysiological measures. Conclusion: this systematic review highlighted an important gap in the current knowledge. Investigating how acute and long-term response may be related can foster our understanding of stimulant mechanism of action and help develop stratification approaches for more tailored treatment strategies. Future studies need to investigate potential age and sex-related differences. <br/
Single–dose methylphenidate induces shift in functional connectivity associated with positive longer term clinical response in adult attention–deficit/hyperactivity disorder
Full text linkStimulants, such as methylphenidate (MPH), are beneficial for attention-deficit/hyperactivity disorder (ADHD), but individual response varies. A deeper understanding of the mechanisms underpinning response is needed. Previous studies suggest that a single MPH dose modulates resting-state functional connectivity (rs-fc). We investigated whether single-dose induced rs-fc changes were associated with post-dose optimization clinical response. Fifty-six adults with ADHD underwent rs-functional magnetic resonance imaging (rs-fMRI) under placebo and a single MPH dose, before starting MPH treatment. Clinical response was measured at two months. We tested if a single MPH dose (vs. placebo) shifted rs-fc; how these shifts were associated with treatment response (categorical approach); and whether these associations were driven by improvement on either ADHD symptom domain. A single MPH dose (vs. placebo) increased rs-fc in three subcortical-cortical and cerebellar-cortical clusters. Enhanced rs-fc between the cerebellar vermis (lobule 6) and the left precentral gyrus was associated with a greater probability of responding to treatment (χ2(7) = 22.740, p = .002) and with an improvement on both inattentive and hyperactive/impulsive symptoms (both p ≤ .001). We provide proof-of-concept that the brain functional response to a single MPH dose, administered before starting routine treatment, is indicative of two-month clinical response in adult ADHD. This may encourage future replication using clinically applicable measures.<br/
Robot-Assisted Adrenalectomy Workup and Management
No full textRobot-assisted approach for adrenalectomy is feasible and safe. Although adrenalectomy is a purely extirpative procedure requiring no further reconstruction, wristed instruments, increased precision, and magnified three-dimensional vision may aid in dissection of large and small vessels and more precise delineation of the tumor lesion during both radical and partial adrenalectomies. These advantages may allow more surgeons, including those with limited laparoscopic experience, to offer their patients an effective and minimally invasive approach to adrenalectomy
More Accurate Imaging Is Not Stage Migration: Time To Move from "Hubble" to "Webb" in Hormone-sensitive Prostate Cancer
No full textProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) produces strikingly superior images compared to conventional imaging, raising the important question of whether conventional imaging is sufficiently accurate to guide patient management. Reducing false positive results with consequent improvement in accuracy is not stage migration and PSMA PET/CT can be a successor to conventional imaging in the staging of metastatic hormone-sensitive prostate cancer
A comparison of patient reported outcome measures in patients who received both DIEP flap and PAP flap breast reconstructions
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Asymmetry of attentive networks contributes to adult Attention-deficit/hyperactivity disorder (ADHD) pathophysiology
Full text linkDiffusion imaging studies in Attention-deficit/hyperactivity disorder (ADHD) have revealed alterations in anatomical brain connections, such as the fronto-parietal connection known as superior longitudinal fasciculus (SLF). Studies in neurotypical adults have shown that the three SLF branches (SLF I, II, III) support distinct brain functions, such as attention and inhibition; and that their pattern of lateralization is associated with attention performance. However, most studies in ADHD have investigated the SLF as a single bundle and in children; thus, the potential contribution of the lateralization of the SLF branches to adult ADHD pathophysiology remains to be elucidated. We used diffusion-weighted spherical deconvolution tractography to dissect the SLF branches in 60 adults with ADHD (including 26 responders and 34 non-responders to methylphenidate, MPH) and 20 controls. Volume and hindrance modulated orientational anisotropy (HMOA), which respectively reflect white matter macro- and microstructure, were extracted to calculate the corresponding lateralization indices. We tested whether neurotypical controls differed from adults with ADHD, and from treatment response groups in sensitivity analyses; and investigated associations with clinico-neuropsychological profiles. All the three SLF branches were lateralized in adults with ADHD, but not in controls. The lateralization of the SLF I HMOA was associated with performance at the line bisection, not that of the SLF II volume as previously reported in controls. Further, an increased left-lateralization of the SLF I HMOA was associated with higher hyperactivity levels in the ADHD group. Thus, an altered asymmetry of the SLF, perhaps especially of the dorsal branch, may contribute to adult ADHD pathophysiology
Genetic relationship between the immune system and autism
Full text linkAutism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined; however, it includes a strong genetic component and there is increasing evidence to support a role of immune dysregulation. Nonetheless, it is unclear which immune phenotypes link to ASD through genetics. Hence, we investigated the genetic correlation between ASD and diverse classes of immune conditions and markers; and if these immune-related genetic factors link to specific autistic-like traits in the population. We estimated global and local genetic correlations between ASD (n = 55,420) and 11 immune phenotypes (n = 14,256–755,406) using genome-wide association study summary statistics. Subsequently, polygenic scores (PGS) for these immune phenotypes were calculated in a population-based sample (n = 2487) and associated to five autistic-like traits (i.e., attention to detail, childhood behaviour, imagination, rigidity, social skills), and a total autistic-like traits score. Sex-stratified PGS analyses were also performed. At the genome-wide level, ASD was positively correlated with allergic diseases (ALG), and negatively correlated with lymphocyte count, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) (FDR-p = 0.01–0.02). At the local genetic level, ASD was correlated with RA, C-reactive protein, and granulocytes and lymphocyte counts (p = 5.8 × 10−6–0.002). In the general population sample, increased genetic liability for SLE, RA, ALG, and lymphocyte levels, captured by PGS, was associated with the total autistic score and with rigidity and childhood behaviour (FDR-p = 0.03). In conclusion, we demonstrated a genetic relationship between ASD and immunity that depends on the type of immune phenotype considered; some increase likelihood whereas others may potentially help build resilience. Also, this relationship may be restricted to specific genetic loci and link to specific autistic dimensions (e.g., rigidity).</p
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