scholarly journals The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review

2021 ◽  
Author(s):  
Anders Sørensen ◽  
Henricus G. Ruhé ◽  
Klaus Munkholm
Keyword(s):  
Serotonin Transporter ◽  
Antidepressant Treatment ◽  
Imaging Techniques ◽  
Small Sample ◽  
Short Treatment ◽  
Predicted Values ◽  
Small Sample Sizes ◽  
The Relationship ◽  
Short Treatment Duration

AbstractBrain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([11C]-DASB, [123I]-ADAM, and [11C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis–Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis–Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.

scholarly journals The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

2014 ◽  
Vol 34 (8) ◽  
pp. 1328-1339 ◽  
Author(s):  
Amy K Wagner ◽  
Joelle M Scanion ◽  
Carl R Becker ◽  
Anne C Ritter ◽  
Christian Niyonkuru ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Ventral Striatum ◽  
D2 Receptor ◽  
Variable Number ◽  
Small Sample ◽  
Post Injury ◽  
Positron Emission ◽  
Small Sample Sizes ◽  
Future Work

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [11C]βCFT and [11C]raclopride. We examined subjects with moderate/severe TBI ( N = 12) ~1 year post injury and similarly matched healthy controls ( N = 13). The variable number of tandem repeat polymorphism within the DAT gene and the Taql restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.

scholarly journals Resting heart rate and psychopathy: Findings from the Add Health Survey

2017 ◽  
Author(s):  
Nicholas Kavish ◽  
Q. John Fu ◽  
Michael G. Vaughn ◽  
Zhengmin Qian ◽  
Brian B. Boutwell
Keyword(s):  
Heart Rate ◽  
Small Body ◽  
Psychopathic Traits ◽  
Small Sample ◽  
Future Research ◽  
Alternative Measure ◽  
Resting Heart Rate ◽  
Nationally Representative ◽  
Small Sample Sizes ◽  
The Relationship

AbstractDespite the prior linkages of low resting heart rate to antisocial behavior broadly defined, less work has been done examining possible associations between heart rate to psychopathic traits. The small body of research on the topic that has been conducted so far seems to suggest an inverse relationship between the two constructs. A smaller number of studies have found the opposite result, however, and some of the previous studies have been limited by small sample sizes and unrepresentative samples. The current study attempts to help clarify the relationship between resting heart rate and psychopathic traits in a large, nationally representative sample (analytical N ranged from 14,173-14,220) using an alternative measure of psychopathic traits that is less focused on antisocial processes, and rooted in personality traits. No significant relationship between heart rate and psychopathic traits, or heart rate and a measure of cold heartedness, was found after controlling for age, sex, and race. Implications of the findings, study limitations, and directions for future research are discussed.

The Relationship Between Sample Sizes and Effect Sizes in Systematic Reviews in Education

2009 ◽  
Vol 31 (4) ◽  
pp. 500-506 ◽  
Author(s):  
Robert Slavin ◽  
Dewi Smith
Keyword(s):  
Sample Size ◽  
Effect Size ◽  
Secondary Mathematics ◽  
Significant Negative Correlation ◽  
Small Sample ◽  
Effect Sizes ◽  
Sample Sizes ◽  
Large Samples ◽  
Small Sample Sizes ◽  
The Relationship

Research in fields other than education has found that studies with small sample sizes tend to have larger effect sizes than those with large samples. This article examines the relationship between sample size and effect size in education. It analyzes data from 185 studies of elementary and secondary mathematics programs that met the standards of the Best Evidence Encyclopedia. As predicted, there was a significant negative correlation between sample size and effect size. The differences in effect sizes between small and large experiments were much greater than those between randomized and matched experiments. Explanations for the effects of sample size on effect size are discussed.

scholarly journals COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 817 ◽  
Author(s):  
Argirios E. Tsantes ◽  
Andreas G. Tsantes ◽  
Styliani I. Kokoris ◽  
Stefanos Bonovas ◽  
Frantzeska Frantzeskaki ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Small Sample ◽  
Close Monitoring ◽  
Rotational Thromboelastometry ◽  
Coagulation Tests ◽  
Attractive Option ◽  
Small Sample Sizes ◽  
Fibrinolysis Shutdown ◽  
Insight Into

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy.

scholarly journals MicroRNAs as Salivary Markers for Periodontal Diseases: A New Diagnostic Approach?

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gerhard Schmalz ◽  
Simin Li ◽  
Ralph Burkhardt ◽  
Sven Rinke ◽  
Felix Krause ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Small Sample ◽  
In Vivo Studies ◽  
Case Definitions ◽  
Tissue Samples ◽  
Cancer Types ◽  
Small Sample Sizes ◽  
Noninvasive Markers

The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies.

scholarly journals What’s in a Coefficient? The “Not so Simple” Interpretation of R2, for Relatively Small Sample Sizes

2019 ◽  
Vol 7 (12) ◽  
pp. 27
Author(s):  
Nizar Zaarour ◽  
Emanuel Melachrinoudis
Keyword(s):  
Standard Deviation ◽  
Linear Regression ◽  
Small Sample ◽  
Coefficient Of Determination ◽  
Simple Linear Regression ◽  
Sample Sizes ◽  
Simple Interpretation ◽  
Small Sample Sizes ◽  
Level Of Significance ◽  
The Relationship

There are several misconceptions when interpreting the values of the coefficient of determination, R2, in simple linear regression. R2 is heavily dependent on sample size n and the type of data being analyzed but becomes insignificant when working with very large sample sizes. In this paper, we comment on these observations and develop a relationship between R2, n, and the level of significance α, for relatively small sample sizes. In addition, this paper provides a simplified version of the relationship between R2 and n, by comparing the standard deviation of the dependent variable, Sy, to the standard error of the estimate, Se. This relationship will serve as a safe lower bound to the values of R2. Computational experiments are performed to confirm the results from both models. Even though the focus of the paper is on simple linear regression, we present the groundwork for expanding our two models to the multiple regression case.

scholarly journals Limits to Genomic Divergence Under Sexually Antagonistic Selection

2019 ◽  
Author(s):  
Katja R. Kasimatis ◽  
Peter L. Ralph ◽  
Patrick C. Phillips
Keyword(s):  
Genetic Model ◽  
Empirical Studies ◽  
Genetic Load ◽  
Small Sample ◽  
Sampling Variance ◽  
Antagonistic Selection ◽  
Genome Wide ◽  
Sexually Antagonistic Selection ◽  
Small Sample Sizes ◽  
The Relationship

AbstractSince the autosomal genome is shared between the sexes, sex-specific fitness optima present an evolutionary challenge. While sexually antagonistic selection might favor different alleles within females and males, segregation randomly reassorts alleles at autosomal loci between sexes each generation. This process of homogenization during transmission thus prevents between-sex allelic divergence generated by sexually antagonistic selection from accumulating across multiple generations. However, recent empirical studies have reported high male-female FST statistics. Here, we use a population genetic model to evaluate whether these observations could plausibly be produced by sexually antagonistic selection. To do this, we use both a single-locus model with nonrandom mate choice, and individual-based simulations to study the relationship between strength of selection, degree of between-sex divergence, and the associated genetic load. We show that selection must be exceptionally strong to create measurable divergence between the sexes and that the decrease in population fitness due to this process is correspondingly high. Individual-based simulations with selection genome-wide recapitulate these patterns and indicate that small sample sizes and sampling variance can easily generate substantial male-female divergence. We therefore conclude that caution should be taken when interpreting autosomal allelic differentiation between the sexes.

scholarly journals Resting Heart Rate and Psychopathy Revisited: Findings From the Add Health Survey

2018 ◽  
Vol 63 (4) ◽  
pp. 543-557 ◽  
Author(s):  
Nicholas Kavish ◽  
Q. John Fu ◽  
Michael G. Vaughn ◽  
Zhengmin Qian ◽  
Brian B. Boutwell
Keyword(s):  
Heart Rate ◽  
Antisocial Behavior ◽  
Small Body ◽  
Psychopathic Traits ◽  
Small Sample ◽  
Alternative Measure ◽  
Resting Heart Rate ◽  
Nationally Representative ◽  
Small Sample Sizes ◽  
The Relationship

Despite the prior linkages of low resting heart rate to antisocial behavior broadly defined, less work has been done examining possible associations between heart rate to psychopathic traits. The small body of research on the topic that has been conducted so far seems to suggest an inverse relationship between the two constructs. A smaller number of studies has found the opposite result, however, and some of the previous studies have been limited by small sample sizes and unrepresentative samples. The current study attempts to help clarify the relationship between resting heart rate and psychopathic traits in a large, nationally representative sample (analytical N ranged from 14,173-14,220) using an alternative measure of psychopathic traits that is less focused on antisocial processes, and rooted in personality traits. No significant relationship between heart rate and psychopathic traits, or heart rate and a measure of cold-heartedness, was found. It is possible that previous findings of a link between heart rate and psychopathy have been driven by the inclusion of overt antisocial behavior in many traditional psychopathy measures. Further work is needed to confirm the associations (or lack thereof) between heart rate and the behavioral, affective, and personality trait aspects of psychopathy.

Cluster headache is associated with an increased risk of depression: A nationwide population-based cohort study

Cephalalgia ◽  
2012 ◽  
Vol 33 (3) ◽  
pp. 182-189 ◽  
Author(s):  
Jen-Feng Liang ◽  
Yung-Tai Chen ◽  
Jong-Ling Fuh ◽  
Szu-Yuan Li ◽  
Chia-Jen Liu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cluster Headache ◽  
Population Based ◽  
Small Sample ◽  
Cross Sectional ◽  
Increased Risk ◽  
Taiwan National Health Insurance ◽  
Small Sample Sizes ◽  
The Relationship

Objective To investigate whether cluster headache (CH) was a risk factor for depression in a nationwide population-based follow-up study. Background There are few studies about the relationship between CH and depression, and prior research has been limited by cross-sectional studies or small sample sizes. Methods We identified 673 CH patients from the Taiwan National Health Insurance database between 2005 and 2009. The two comparison cohorts included age-, sex- and Charlson’s score-matched migraine patients ( n = 2692) and controls (patients free from migraine or CH, n = 2692). The cumulative incidence of depression was compared among these three cohorts until the end of 2009. We also calculated predictors of depression in the CH cohort. Results After the median 2.5-year follow-up duration, the CH cohort had a greater risk for developing depression compared to the control cohort (adjusted hazard ratio; aHR = 5.6, 95% CI 3.0–10.6, p < 0.001) but not the migraine cohort (aHR = 1.1, 95% CI 0.7–1.7, p = 0.77). Of the CH patients, the number of cluster bout periods per year was a risk factor for depression (aHR = 3.8, 95% CI 2.6–5.4, p < 0.001). Conclusion Our results showed that CH is associated with an increased risk for depression. The strength of this association is similar to that of migraine.

Examining the Relationship Between Weapon Type and Relationship Type in American Homicides: A Bayesian Approach

2020 ◽  
Author(s):  
Joshua J Reynolds ◽  
Paul - Christian Bürkner
Keyword(s):  
Bayesian Approach ◽  
Past Research ◽  
Small Sample ◽  
Limited Data ◽  
Relationship Type ◽  
Final Model ◽  
Categorical Regression ◽  
Small Sample Sizes ◽  
The Relationship ◽  
Data Analytic

Past research indicates that weapon type used in a homicide predicts the victim-perpetrator relationship. Limitations include small sample sizes, inconsistent findings, and limited data analytic techniques. To address these limitations, we examined 363,927 homicides and used Bayesian multilevel categorical regression. In addition to analyzing weapon type (final model consisted of 16 weapon categories), we examined the victims’ sex, age, and race as covariates and modeled the data across states and counties. Results indicate that weapon type is highly informative, however, the age of the victim and sex of the victim interact with weapon type in important ways.

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