The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00213-020-05597-7.Rationale: OCD is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. Objective: To investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD and healthy controls. Methods: A randomized double-blind crossover study assessed the effects of single dose escitalopram (20mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 hours after oral administration of the pharmacological challenge / placebo, and compared across and within groups using a mixed model ANOVA. Results: On the outcome measure of interest, i.e. the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59)=3.1; p=0.052), with patients (Least square [LS] mean: 1.43; Standard Error [SE]: 0.06; 95% confidence interval [CI], 1.31-1.55) and their relatives (LS mean: 1.46; SE: 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean: 1.26; SE: 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group x treatment interaction (F(2, 58)=2.8, p=0.069), with post hoc tests showing (i) patients (p=0.009; LS mean difference: 0.23; SE: 0.08) and relatives (p=0.03; LS mean difference: 0.22; SE: 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p=0.013; LS mean difference: 0.1; SE: 0.04), but not other groups (both p>0.1; controls: LS mean difference: -0.03; SE: 0.04; relatives: LS mean difference: 0.02; SE: 0.05). Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD, and that this constitutes a behavioral endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.Peer reviewe

Identification of response amplitude operators for ships based on full scale measurements

Heerema Marine Contractors (HMC) operates several crane vessels, barges and tug boats for the transportation, the installation and the removal of offshore facilities. To achieve safe and successful projects, the accurate prediction of vessel motions is of great importance. Vessel motions are calculated on the basis of wave energy spectra and motion Response Amplitude Operators (RAOs). The wave energy spectra are received from meteorological services or from wave rider buoys and the RAOs are typically calculated using diffraction software, based on potential theory. In order to validate the numerical models, HMC regularly monitors the motions of its vessels. In a number of cases, HMC has noticed that the calculated vessel motions do not fully match with the full scale measurements. This inaccuracy can occur due to several reasons such as forward speed of the vessel, awkward draught, viscous damping forces or the variations of mass distribution during the projects. The main objective of this graduation study is to develop a mathematical method which determines the motion RAOs using the full scale motion measurements and the available wave data. Basically, it is examined whether it is possible to calibrate the following model properties of the vessels: The potential added mass, the potential damping and the potential wave forces. The radii of gyration, the viscous damping matrix and the coordinates of the CoG. The procedure for the identification of the RAOs is applied on a specific vessel with a certain draft: the semi-submersible crane vessel Thialf at 22m draft in deep water. The first challenge of this graduation study is to find a method to express each element of the hydrodynamic database with a limited number of parameters for the entire frequency range. This is accomplished by applying the vector fitting method. According to this method, the hydrodynamic elements are fitted to approximation functions with a certain number of coefficients. In order to calibrate the motion RAOs, a sensitivity analysis is first be performed. The sensitivity analysis leads to the minimization of the number of parameters that is to be examined. The identification process is repeated several times until the best possible modifications are found. In order to choose the correct modification, the normalized root mean square error between the calculated and the measured vessel motions is determined. Apart from the normalised root mean square error, the selection of the possible modifications should be based on logical criteria as well. For this graduation study, the identification method is tested by several cases. These test cases are based on simulated data. The results of this study shows that we can identify several parameters that lead to more accurate response spectra. However, in most cases the solution is not unique and we have to choose between the calibration of two parameters or more. For instance, the same results can be achieved by either changing the radius of gyration or a diagonal element of the hydrodynamic added mass and damping. This can be solved by examining the causes of inaccuracies. If the draft of the vessel is such that the awkward draft does not occur, then the hydrodynamic data base should not be modified. Small changes of the viscous damping could not be identified for the SSCV ‘Thialf’. The viscous damping is much lower than the hydrodynamic damping and as a consequence, it doesn’t have noticeable impact on the vessel responses. However, this is not valid for rolling ships such as the deep-water construction vessel Aegir. Finally, it should be mentioned that the errors of the data processing influence the accuracy of the identification procedure.Offshore and Dredging EngineeringMaritime and Transportation TechnologyMechanical, Maritime and Materials Engineerin

Calibration of response amplitude operators based on measurements of vessel motions and directional wave spectra

A vessel's response to waves is dependent on a large number of parameters, some of which are both frequency and direction dependent. To predict vessel response, these parameters are used to construct response amplitude operators (RAOs) that act as transfer functions between the directional wave spectra and the motion spectra of the vessel. In particular situations, however, vessel motions predicted using RAOs calculated with general-purpose radiation-diffraction codes and measured wave spectra are found to deviate from measured vessel responses. To address this problem, a methodology for calibrating RAOs based on measurements of the directional wave spectra and vessel motions is proposed. Use is made of a vector fitting method through which the frequency dependent hydrodynamic properties of the vessel can be approximated by a ratio of two polynomials, thus greatly reducing the number of parameters that need to be calibrated. The reduced set of parameters is subsequently related to previously identified causes of RAO inaccuracy in order to arrive at optimization algorithms for identifying more accurate RAOs from the measurements. It is shown that the RAOs can be improved with accuracy in situations where the discrepancies are caused by imprecise estimates for the vessel's radii of gyration, center of gravity, or viscous damping. When the discrepancies in the RAOs are related to the potential mass, damping and wave forces, however, the problem becomes highly non-convex and it is not possible to find a unique RAO that satisfies the data.Accepted Author ManuscriptDynamics of StructuresOffshore Engineerin

The role of cholecystokinin in the induction of aggressive behavior: a focus on the available experimental data (review)

Cholecystokinin (CCK) is a neuropeptide that is (among others) reportedly involved in the pathophysiology of psychiatric disorders. The excitatory role of CCK in negative affective emotions as well as in aversive reactions, antisocial behaviors and memories, has been indicated by numerous electrophysiological, neurochemical and behavioral methodologies on both animal models for anxiety and human studies. The current review article summarizes the existing experimental evidence with regards to the role of CCK in the induction of aggressive behavior, and: (a) synopsizes the anatomical circuits through which it could potentially mediate all types of aggressive behavior, as well as (b) highlights the potential use of these experimental evidence in the current research quest for the clinical treatment of mood and anxiety disorders

The role of cholecystokinin in the induction of aggressive behavior: A focus on the available experimental data (review)

Cholecystokinin (CCK) is a neuropeptide that is (among others) reportedly involved in the pathophysiology of psychiatric disorders. The excitatory role of CCK in negative affective emotions as well as in aversive reactions, antisocial behaviors and memories, has been indicated by numerous electrophysiological, neurochemical and behavioral methodologies on both animal models for anxiety and human studies. The current review article summarizes the existing experimental evidence with regards to the role of CCK in the induction of aggressive behavior, and: (a) synopsizes the anatomical circuits through which it could potentially mediate all types of aggressive behavior, as well as (b) highlights the potential use of these experimental evidence in the current research quest for the clinical treatment of mood and anxiety disorders

Determination of Atomoxetine or Escitalopram in human plasma by HPLC. Applications in Neuroscience Research Studies

Background: Atomoxetine and escitalopram are potent and selective drugs approved for noradrenergic or serotonergic modulation of neuronal networks in attention-deficit hyperactivity disorder (ADHD) or depression, respectively. High-performance liquid chromatography (HPLC) methods still play an important role in the Therapeutic Drug Monitoring (TDM) of psychopharmacological drugs, and coupled with tandem mass spectrometry are the gold standard for the quantification of drugs in biological matrices, but not available everywhere. The aim of this work was to develop and validate a HPLC method for neuroscientific studies using atomoxetine or escitalopram as a test drug. Methods: A HPLC method from routine TDM determination of atomoxetine or citalopram in plasma was adapted and validated for use in neuroscientific research. Using photo diode array detection with UV absorption at 205 nm, the variation of internal standard within one chromatographic method enables separate drug monitoring for concentration-controlled explorative studies in healthy humans and patients with Parkinson’s disease. Results: The method described here was found to be linear in the range of 0.002 - 1.4 mg/L for atomoxetine and 0.0012 - 0.197 mg/L for escitalopram, with overall mean intra-day and inter-day imprecision and accuracy bias < 10% for both drugs. The method was successfully applied in concentration-controlled neuroimaging studies in populations of healthy humans and patients with Parkinson’s disease. Conclusion: A simple, sensitive, robust HPLC method capable of monitoring escitalopram and atomoxetine is presented and validated, as a useful tool for drug monitoring and the study of pharmacokinetics in neuroscientific study applications