Unmedicated Group Research Articles

Chronic Use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

To determine if individuals chronically (>1 yr) prescribed antihypertensive medications have a normal BP response to peak exercise compared with unmedicated individuals. Participants included 2555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 yr were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the American Heart Association. The unmedicated group had a greater prevalence ( P < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence ( P < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher ( P < 0.01) in medicated compared with unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP ( P = 0.613), risk factors ( P = 0.104), or cardiorespiratory fitness ( P = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP ( P = 0.039), but not for men ( P = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors, and cardiorespiratory fitness ( P = 0.022). Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

Prefrontal Glutathione Levels in Major Depressive Disorder Are Linked to a Lack of Positive Affect.

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders, with symptoms including persistent sadness and loss of interest. MDD is associated with neurochemical alterations in GABA, glutamate, and glutamine levels but, to date, few studies have examined changes in glutathione (GSH) in MDD. This study investigated changes in GSH in an unmedicated group of young adults, including 46 participants with current (n = 12) or past MDD (n = 34) and 20 healthy controls. Glutathione levels were assessed from GSH-edited magnetic resonance (MR) spectra, acquired from a voxel in the left prefrontal cortex, and depressive symptoms were evaluated with validated questionnaires and clinical assessments. Cortisol levels were also assessed as a marker for acute stress. Participants with current MDD demonstrated elevated GSH in comparison to participants with past MDD and controls, although the results could be influenced by differences in tissue composition within the MRS voxel. In addition, participants with both current and past MDD showed elevated cortisol levels in comparison to controls. No significant association was observed between GSH and cortisol levels, but elevated GSH levels were associated with a decrease in positive affect. These results demonstrate for the first time that elevated GSH in current but not past depression may reflect a state rather than a trait neurobiological change, related to a loss of positive affect.

Dose-dependent QTc interval prolongation under haloperidol and pipamperone in the management of delirium in a naturalistic setting.

Delirium is an acute, life-threatening neuropsychiatric disorder frequently occurring among hospitalized patients. Antipsychotic medications are often recommended for delirium management but are associated with cardiovascular risks. This study aimed to investigate the frequency and magnitude of QTc interval prolongation and clinically relevant side effects occurring in delirium patients managed with haloperidol and/or pipamperone. This descriptive retrospective cohort study evaluated 102 elderly (mean age: 73.2 years) inpatients with delirium treated with either haloperidol, pipamperone, a combination of both, or neither in a naturalistic setting over the course of up to 20 days or until the end of delirium. A total of 86.3% of patients were treated with haloperidol and/or pipamperone at a mean daily haloperidol-equipotent dose of 1.2 ± 1 mg. Non-cardiovascular side effects were registered in 2.9% of all patients and correlated with higher scores on the Delirium Observation Screening Scale. They did not occur more frequently under antipsychotic treatment. The frequency of QTc interval prolongation was comparably common among all groups, but prolongation magnitude was higher under antipsychotic treatment. It was positively correlated with antipsychotic dosage and the total number of QTc interval-prolonging substances administered. Critical QTc interval prolongation was registered in 21.6% (n = 19) of patients in the group treated with antipsychotics compared to 14.3% (n = 2) of patients in the unmedicated group; however, the difference was not statistically significant. Polypharmacy was associated with a higher risk of critical QTc interval prolongation and increased mortality during delirium. Delirium treatment with haloperidol and/or pipamperone was not associated with a higher risk of QTc-interval prolongation in this naturalistic patient sample but was greater in magnitude and correlated with equipotent dosage and the number of QT interval-prolonging substances used. Polypharmacy was associated with higher mortality and increased risk of critical QTc prolongation.

Longitudinal Examination of Sexual Risk Behavior in College Students With and Without Attention-Deficit/Hyperactivity Disorder

The present study sought to identify differences in the rates and predictors of risky sexual behavior among college students with and without attention-deficit hyperactivity disorder (ADHD). Current ADHD diagnosis, medication status among those with ADHD, executive functioning, substance use, comorbid anxiety, comorbid depression, and gender were identified as potential predictors of increased risky sexual behavior. Multiple group latent growth curve modeling was used to estimate trajectories of risky sexual behavior across four years of college among college students with ADHD (nmedicated = 99, nunmedicated = 105) and a comparison group (n = 217) recruited from colleges throughout the eastern United States (M age = 18.23 years, 53% female, 70% White). First-year college students with ADHD reported significantly higher rates of sexual risk behavior than their peers without ADHD, with no significant differences found based on medication status. Students with ADHD who were taking medication for ADHD reported significant decreases in risky sexual behavior over time. Among college students with ADHD, anxiety was related to increased current risky sexual behavior in the medicated group, while depression was predictive of decreased future risky sexual behavior in the unmedicated group. Alcohol and cannabis use were significantly associated with increased mean levels of risky sexual behavior across all three groups, and cannabis use was associated with decreased future risky sexual behavior within the comparison group. Executive functioning deficits and male gender were predictive of risky sexual behavior within the comparison group. The results demonstrate that college students with ADHD, regardless of medication status, are at an increased likelihood of engaging in risky sexual behavior.

The Effect of Methylphenidate Treatment on Olfactory Function in Children and Adolescents With ADHD

Objective: This study aimed to research whether there is an olfactory disorder in ADHD, and if so, what is the effect of methylphenidate on this condition. Method: This is a cross-sectional study aiming to evaluate olfactory threshold, identification, discrimination and threshold, discrimination, and identification (TDI) scores in 109 children and adolescents, 33 of whom have ADHD without medication, 29 with ADHD with medication and 47 control groups. Result: In the post hoc tests, the mean odor discrimination test, the mean odor identification test, and the mean TDI scores of the unmedicated ADHD group were significantly lower than those of the other two groups, and that the mean odor threshold test scores of the medicated ADHD group were significantly lower than those of the control and unmedicated groups. Conclusion: Olfactory function could be a useful tool to monitor treatment effects and may be a promising candidate as a biomarker in ADHD.

The Burden of Attention-Deficit/Hyperactivity Disorder in Adults: A Real-World Linked Data Study.

Objective: To assess the humanistic and economic burden of attention-deficit/hyperactivity disorder (ADHD) among adult patients treated with immediate-release (IR) only or extended-release (ER) only stimulants and those unmedicated versus treated with ER + IR stimulants. Methods: This study analyzed linked data from National Health and Wellness Survey and claims to assess the differences in patient characteristics and outcomes, including health-related quality of life (HRQoL), work productivity and activity impairment, and health care resource utilization (HRU) and associated costs by comparing ADHD patients treated with either IR or ER and those unmedicated for ADHD versus ER + IR. Results: The burden of ADHD was compared among adults on stimulant medications with different duration of effect (DoE) (ER + IR: n = 34, ER: n = 184, IR: n = 149) and the unmedicated group (n = 114). Bivariate analysis showed the IR (P = .047) and unmedicated groups (P = .01) had significantly lower Medical Outcomes Study 36-item Short Form physical component summary scores versus ER + IR. The unmedicated group had higher HRU and associated costs versus other groups. Multivariable analysis revealed that the unmedicated group had twice as many outpatient visits (P = .001) and higher total annual direct costs than those on ER + IR (risk ratio = 2.20, P = .016). Patients with mental health comorbidities had significantly poorer HRQoL mental component summary scores and higher activity impairment versus those without mental health comorbidities (P = .001 and P < .001, respectively). Conclusions: Patients with ADHD treated with longer DoE formulations had substantially better economic outcomes versus shorter DoE formulation or unmedicated groups, offering potential cost savings to the health care system and the patient. Furthermore, it is important to consider the effect of mental health comorbidities in the overall management of ADHD.

Subchronic toxicity of oral deltamethrin in laying chickens.

Pyrethroid pesticides, with low toxicity to birds and mammals and short persistence in the environment, are widely used now. With the development of intensive poultry farming, pesticide application leads to residues in poultry products and pollution in ecological environment. The aim of the present study was to examine deltamethrin subchronic toxicity in laying chickens. One hundred and twelve laying chickens were randomly assigned to 14 groups including 13 groups medicated with deltamethrin (n = 8) and one unmedicated group used as control (n = 8). Tissue samples were collected during and after administration for weighing and histopathological analysis. A single dose of deltamethrin (20 mg·kg-1·BW·d) was administered orally to laying chickens for 14 days. The results showed that deltamethrin has no significant effect on the relative organ weight of laying chickens (p > 0.05). The activities of aspartate aminotransferase and cholinesterase in the plasma gradually decreased over time in the medicated group (p < 0.05). Plasma concentrations of urea nitrogen, uric acid, cholesterol, triglycerides, and creatinine significantly increased during treatment (p < 0.05), and significant liver damage and loss of intestinal villous epithelium were observed. The intestinal wall thickness, villus height, and crypt depth of laying chickens were altered by deltamethrin treatment. During treatment was withdrawn, the intestinal repair was more extensive than the liver repair.

Spatial and chronic differences in neural activity in medicated and unmedicated schizophrenia patients

A major caveat with investigations on schizophrenic patients is the difficulty to control for medication usage across samples as disease-related neural differences may be confounded by medication usage. Following a thorough literature search (632 records identified), we included 37 studies with a total of 740 medicated schizophrenia patients and 367 unmedicated schizophrenia patients. Here, we perform several meta-analyses to assess the neurofunctional differences between medicated and unmedicated schizophrenic patients across fMRI studies to determine systematic regions associated with medication usage. Several clusters identified by the meta-analysis on the medicated group include three right lateralized frontal clusters and a left lateralized parietal cluster, whereas the unmedicated group yielded concordant activity among right lateralized frontal-parietal regions. We further explored the prevalence of activity within these regions across illness duration and task type. These findings suggest a neural compensatory mechanism across these regions both spatially and chronically, offering new insight into the spatial and temporal dynamic neural differences among medicated and unmedicated schizophrenia patients.

Investigating the effects of antihypertensive medication use in AD patients using multi‐modal neuroimaging

AbstractBackgroundHypertension is a known risk factor for Alzheimer’s disease (AD). Both conditions cause significant irreversible damage to cerebral constituents that can result in a more severe AD phenotype. Although there are no effective treatments available for AD, hypertension is a modifiable risk factor and its detrimental effects can be alleviated with antihypertensive drug treatments and through primary prevention.MethodPatients with mild to moderate AD (N = 133) were divided into two groups to examine differences in cerebral constituents and cognitive function in patients who were medicated (n = 71) and unmedicated (n = 62) for hypertension. Within the medicated patient group, a post hoc analysis was conducted to examine differences in patients based on the class of antihypertensive treatment. We used multi‐modal neuroimaging to explore these differences in cerebral blood flow (CBF), white matter integrity, grey matter volume (GMV) and vascular burden.ResultNo differences were detected between the medicated and unmedicated AD patients in the multi‐modal comparisons, although the medicated group showed a slightly better cognitive profile than the unmedicated group, despite having a higher burden of cardiovascular comorbidities and similar blood pressure readings to the unmedicated group. In the post hoc analysis, AD patients who were on beta‐blockers only, presented with higher GMV, CBF and neuropsychological scores and also a lower vascular burden compared to AD patients on other classes of antihypertensive treatment or a combination of the two. In the post hoc analysis of the unmedicated AD patient subgroup, variability in pulse pressure (the difference between systolic and diastolic blood pressure) was linked with lower CBF in subcortical structures.ConclusionThe use of antihypertensive treatment in AD could mitigate progression of damage to cerebral constituents related to chronically elevated blood pressure. The class of antihypertensive treatment used has varied effects on cerebral constituents in AD patients, pointing towards the need for future longitudinal studies exploring these effects. Evidence from this study also suggests that implementation of antihypertensive treatment could be beneficial in AD patients with uncontrolled hypertension. Measures to promote early identification of comorbidities and targeted interventions could thus help reduce AD severity in patients.

Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (www.psymri.com). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

A Retrospective Examination of the Impact of Pharmacotherapy on Parent-Child Interaction Therapy.

Objective: Parent-child interaction therapy (PCIT) is an evidence-based approach for children aged 2-7 years with disruptive behavior problems. This study examined the effectiveness of PCIT with and without concurrent pharmacotherapy. Methods: A convenience sample was collected from a retrospective chart review of preschool-aged children treated with PCIT at the Mayo Clinic Young Child Clinic between 2016 and 2020. Quantitative and qualitative data were abstracted from all patients. The sample was divided into two groups based on psychotropic medications status (medicated and unmedicated) at the initiation of PCIT. Effectiveness of treatment was assessed with the change in Eyberg Child Behavior Inventory (ECBI) score. The change over time in ECBI score was compared between the two PCIT groups with and without concurrent pharmacotherapy using a linear mixed model. Results: Of the 62 youth, 38.71% were females. Mean age was 4.71 ± 1.17 years. The mean baseline ECBI score was 148.74 ± 30.86, indicating clinically significant disruptive behaviors. The mean number of PCIT sessions was 6.59 ± 3.82. There was no statistically significant difference in ECBI scores between the two groups at pre-PCIT (medication group: 149.68, standard error [SE] = 11.61 vs. unmedicated group: 147.92, SE = 10.93, p = 0.8904) and at post-PCIT (medication group: 116.27 [SE = 11.89] vs. unmedicated group: 128.86 [SE = 11.57], p = 0.3464). There was a statistically significant improvement in ECBI scores for both groups after completing therapy (medication group = -33.41 [-22.32%], SE = 6.27, p < 0.0001; d = 1.144; unmedicated group = -19.06 [-12.88%], SE = 5.78, p = 0.0022; d = 1.078). Conclusions: PCIT reduced disruptive behaviors in this sample of young children regardless of concurrent pharmacotherapy. Future prospective studies should consider one particular pharmacological agent and long-term outcomes of treatment. PCIT and certain pharmacological treatments could have complex and important bidirectional priming effects for both treatments.

Effect of Rumex nervosus Leaf Powder on the Breast Meat Quality, Carcass Traits, and Performance Indices of Eimeria tenella Oocyst-Infected Broiler Chickens.

Simple SummaryRecent research has demonstrated the beneficial effects associated with the addition of Rumex nervosus leaves (RNL) to the diet of broiler chickens. Coccidiosis, a disease caused by Eimeria, causes great economic losses in the poultry industry worldwide due to its prevalence and associated management issues. There has been some evidence that RNL can be fed to broiler chicks to prevent infections of the protozoa Eimeria tenella; however, there is no or insufficient evidence on the effects of RNL on growth performance and meat quality of broilers infected with Eimeria tenella. This research aimed to evaluate the effects of RNL on performance indices, carcass traits, and meat quality of broilers infected with Eimeria tenella-fed diets supplemented with RNL as a natural anticoccidial drug replacement. RNL had a positive effect on performance indices, meat quality, and some carcass traits in broilers infected with Eimeria tenella, according to the findings. Furthermore, 1 g of RNL led to a better quality of meat than other RNL doses concerning enhanced holding capacity of water, drip loss, myofibrillar fragmentation index (MFI), springiness, and tenderness. At higher doses (3 g of RNL), there was a noticeable decrease in the meat’s final pH, MFI, and springiness.This work aimed to assess the effect of using the RNL on performance indices, carcass trait, and meat quality of broiler chicken infected with Eimeria tenella compared with commercially used anticoccidials salinomycin. Moreover, we compare these selected variables between infected medicated groups and a non-infected unmedicated group (UUT) and an infected unmedicated group (IUT). A total of 150 1-day-old Ross 308 mixed-sex broilers were divided into 6 groups. Birds in groups 1, 2, and 3 were fed basic diets supplemented with 1, 3, and 5 g of RNL/kg diet, respectively. Group 4 received a basic diet with 66 mg of salinomycin. The control groups (5 and 6) were given a basic diet with no RNL or salinomycin added. All groups except the negative controls were challenged with Eimeria tenella at 21 days old. Birds in RNL groups outperformed those in the IUT group in performance indices, and they have a similar effect to the salinomycin group. Enhancement-infected birds with RNL affected some chickens’ carcass traits. Drip loss, water-holding capacity, and meat tenderness were improved by RNL inclusion (1 g) in the diet. In conclusion, the meat of infected birds receiving 1 g RNL had increased quality attributes, with preferable tenderness and springiness when compared to the IUT group. RNL could therefore also be considered a promising non-conventional feed source in the future. Further research is needed to optimize the use of RNL to improve broilers production and meat quality in both infected and non-infected conditions.

Current diagnosis and treatment of acute pancreatitis in China: a real-world, multicenter study

BackgroundEfficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China.AimsWe aimed to present the current status of AP and evaluate the efficacy of pancreatic enzyme inhibitors in a larger population in China.MethodA retrospective, cross-sectional, real-world, multicenter analysis of a large dataset of patients presenting with AP from four hospitals of China over a two-year period was performed. Data were collected from the existing clinical records and the patients were grouped into medication group (somatostatin or octreotide or somatostatin and octreotide) and no medication group. Pair wise propensity score matching was performed for comparing somatostatin, octreotide and somatostatin/octreotide. The end points were incidence of disease complications, organ failure, hospitalization duration, and recovery time taken (hours) for serum amylase/serum lipase to normalcy.ResultsA total of 3900 patients were recruited and 2775 patients were included for analysis. A total of 1100, 661, 676 and 338 patients received either somatostatin or octreotide or somatostatin and octreotide or no medication, respectively. The incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) were higher in unmedicated group. Complications at discharge (2.91 times), organ failure (2.53 times), and hospitalization stay were higher in octreotide-treated patients compared with somatostatin-treated patients. In comparison to the octreotide group, the serum amylase/lipase recovery time was shorter in the somatostatin group.ConclusionThis real-world study suggested that the use of pancreatic enzyme inhibitors was positively associated with greater clinical efficacy in AP patients and somatostatin might be more effective than octreotide in real-world settings in China.

Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) Imaging in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is characterised by structural and functional deficits in the cortico-striato-thalamic-cortical (CSTC) circuitry and abnormal neurochemical changes are thought to modulate these deficits. The hypothesis that an imbalanced concentration of the brain neurotransmitters, in particular glutamate (Glu) and gamma-amino-butyric acid (GABA), could impair the normal functioning of the CSTC, thus leading to OCD symptoms, has been tested in humans using magnetic resonance spectroscopy (MRS) and positron emission tomography (PET). This chapter summarises these neurochemical findings and represents an attempt to condense such scattered literature. We also discuss potential challenges in the field that may explain the inconsistent findings and suggest ways to overcome them. There is some convergent research from MRS pointing towards abnormalities in the brain concentration of neurometabolite markers of neuronal integrity, such as N-acetylaspartate (NAA) and choline (Cho). Lower NAA levels have been found in dorsal and rostral ACC of OCD patients (as compared to healthy volunteers), which increase after CBT and SSRI treatment, and higher Cho concentration has been reported in the thalamus of the OCD brain. However, findings for other neurometabolites are very inconsistent. Studies have reported abnormalities in the concentrations of creatine (Cr), GABA, glutamate (Glu), glutamine (Gln), Ins (myo-inositol), and serotonin (5-HT), but most of the results were not replicated. The question remains whether the NAA and Cho findings are genuinely the only neurochemical abnormalities in OCD or whether the lack of consistent findings for the other neurometabolites is caused by the lower magnetic field (1-3 Tesla (T)) used by the studies conducted so far, their small sample sizes or a lack of proper control for medication effects. To answer these questions and to further inform the biological underpinning of the symptoms and the cognitive problems at the basis of OCD we need better controlled studies using clear medicated vs unmedicated groups, larger sample sizes, stronger magnetic fields (e.g. at 7T), and more consistency in the definition of the regions of interest.

Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders.

Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics.Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration.Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group.Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function.

No robust differences in fear conditioning between patients with fear-related disorders and healthy controls

Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences.We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (n = 73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, n = 21) to a group of carefully screened healthy controls (n = 35).Bayesian statistics showed no convincing evidence for a difference in physiological and subjective responses between the groups during fear acquisition, extinction learning or recall. Only the PTSD subgroup had altered startle reactions during extinction learning.Our data do not provide evidence for general differences in associative fear or extinction learning in fear-related pathologies and thereby question the diagnostic validity of the associative fear learning model of these disorders.

Influence of Gonadotropin Hormone Releasing Hormone Agonists on Interhemispheric Functional Connectivity in Girls With Idiopathic Central Precocious Puberty.

Purpose: The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa treatment influences the brain function of treated children. The present study investigated the differences in the homotopic resting-state functional connectivity patterns in girls with idiopathic central precocious puberty (ICPP) with and without GnRHa treatment using voxel-mirrored homotopic connectivity (VMHC).Methods: Eighteen girls with ICPP who underwent 12 months of GnRHa treatment, 40 treatment-naïve girls with ICPP, and 19 age-matched girls with premature thelarche underwent resting-state functional magnetic resonance imaging using a 3T MRI. VMHC method was performed to explore the differences in the resting-state interhemispheric functional connectivity. The levels of serum pubertal hormones, including luteinizing hormone (LH), follicular-stimulating hormone, and estradiol, were assessed. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales, and VMHC values of different brain regions were performed with the data of the GnRHa treated group.Results: Significant decreases in VMHC of the lingual, calcarine, superior temporal, and middle frontal gyri were identified in the untreated group, compared with the control group. Medicated patients showed decreased VMHC in the superior temporal gyrus, when compared with the controls. Compared to the unmedicated group, the medicated group showed a significant increase in VMHC in the calcarine and middle occipital gyrus. Moreover, a positive correlation was observed between basal LH levels and VMHC of the middle occipital gyrus in medicated patients.Conclusions: These findings indicate that long-term treatment with GnRHa was associated with increased interhemispheric functional connectivity within several areas responsible for memory and visual process in patients with ICPP. Higher interhemispheric functional connectivity in the middle occipital gyrus was related to higher basal LH production in the girls who underwent treatment. The present study adds to the growing body of research associated with the effects of GnRHa on brain function.

Functional connectivity of the right inferior frontal gyrus and orbitofrontal cortex in depression.

The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 were unmedicated) and 254 controls, using FDR correction P < 0.05 for pairs of voxels. In the unmedicated group, higher functional connectivity was found of the right inferior frontal gyrus with voxels in the lateral and medial orbitofrontal cortex, cingulate cortex, temporal lobe, angular gyrus, precuneus, hippocampus and frontal gyri. In medicated patients, these functional connectivities were lower and toward those in controls. Functional connectivities between the lateral orbitofrontal cortex and the precuneus, posterior cingulate cortex, inferior frontal gyrus, ventromedial prefrontal cortex and the angular and middle frontal gyri were higher in unmedicated patients, and closer to controls in medicated patients. Medial orbitofrontal cortex voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus and fusiform gyrus, and medication did not result in these being closer to controls. These findings are consistent with the hypothesis that the orbitofrontal cortex is involved in depression, and can influence mood and behavior via the right inferior frontal gyrus, which projects to premotor cortical areas.

Does empiric superovulation improve fecundity in healthy women undergoing therapeutic donor insemination without a male partner?

To evaluate whether superovulation improves fecundity in women undergoing therapeutic donor insemination (TDI). Retrospective cohort study. University-affiliated fertility clinic. Healthy women aged 23-45years with no history of or risk factors for infertility who underwent 152 medicated and 104 unmedicated TDI cycles from 2013 to2018. Unmedicated TDI versus use of medication in a TDI cycle (clomiphene citrate or letrozole). Cumulative probability of pregnancy in six TDI cycles. In adjusted all-cycle analysis, medicated TDI cycles were less likely to result in pregnancy compared with unmedicated cycles. The incidence of twins was 23% in the medicated group and 0% in the unmedicated group. Medicated cycles were less likely to result in pregnancy in women younger than 40years or with an antimüllerian hormone (AMH) level >1.2. After three cycles not resulting in pregnancy, the only women who conceived were those who crossed over from an unmedicated to a medicated cycle (12% vs. 0%). Patients undergoing unmedicated TDI cycles had higher fecundity and no incidence of twin gestations. Older women, those with low AMH, and those who fail to conceive after three unmedicated cycles may benefit from medication.

Creativity in children with ADHD: Effects of medication and comparisons with normal peers

This study is to identify the performance of children with and without ADHD in open-ended and closed-ended creativity assessments, and investigate the moderating effect of medicated and unmedicated Children. The study subjects included third to sixth graders: 43 children with ADHD and 43 typically developing children. The participants with ADHD were those who were identified by local Committees of Identification, Placement and Consultation for Children with Special Needs or those who were diagnosed by medical institutions. Children with ADHD were further divided into medicated (22 participants) and unmedicated groups (21 participants) based on their current medication treatment. This study employed the New Tests of Creative Thinking to gauge the participants’ open-ended creativity, while Remote Associates Test and the Insight Test were used to assess the participants’ closed-ended creativity. Although previous evidence for creativity in children with ADHD have been mixed, this study includes medication as moderation variable and suggests that the performance of unmedicated children with ADHD in the open-ended creativity assessments was better than medicated children with ADHD and typically developing children. The study results can further explore the creativity characteristics of children with ADHD.