Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action.

Purpose The aim of this study is to investigate the benefits of atorvastatin on the propionic acid-induced autism model via increasing sphingosine-1-phosphate and anti-inflammatory actions with imaging and brain tissue investigations. Materials and methods Twenty-five mg/kg/day/rat of propionic acid (PPA) was administered intraperitoneally to 20 male Wistar rats, and 10 male Wistar rats were fed orally. Study groups were designed as follows: Group 1: Control Group (orally fed control, n=10); Group 2 (PPA+saline, n=10); Group 3 (PPA+Atorvastatin, n=10). The brain biochemical and histopathology assessments and magnetic resonance (MR) imaging were conducted across groups in order to compare them. Results The PPA+Atorvastatin group was found to have significantly lower levels of brain malondialdehyde, IL-2 level, IL-17, tumor necrosis factor-alpha (TNF-α), and lactate compared to the PPA+saline group. The PPA+Atorvastatin group had higher levels of nerve growth factor and nuclear factor erythroid 2-related factor 2 (NRF-2) and sphingosine-1-phosphate. In histopathology assessments, the PPA+Atorvastatin group was found to have significantly higher neuronal counts of CA1 and CA2 in the hippocampus, and Purkinje cells in the cerebellum. Conclusions Current findings suggest that atorvastatin increases sphingosine-1-phosphate levels and decreases inflammatory actions which characterize the autism rodent model implemented in this study. These preliminary results have to be confirmed by further experimental and clinical studies.

Granulocyte colony-stimulating factor has a sex-dependent positive effect in the maternal immune activation-induced autism model.

OBJECTIVE: The medical intervention for autism spectrum disorder (ASD) is restricted to ameliorating comorbid situations. Granulocyte colony-stimulating factor (G-CSF) is a growth factor that enhances the proliferation, differentiation, and survival of hematopoietic progenitor cells. In the present study, we aimed to investigate the effects of G-CSF in a maternal immune activation-induced autism model. METHODS: Sixteen female and six male Wistar adult rats were included in the study. After 21 days, 48 littermates (eight male controls, eight female controls, 16 male lipopolysaccharide [LPS]-exposed rats, and 16 female LPS-exposed rats) were divided into groups. Sixteen male LPS-exposed and 16 female LPS-exposed rats were divided into saline and G-CSF treatment groups. RESULTS: In male rats, the LPS-exposed group was found to have significantly higher levels of TNF-α, IL-2, and IL-17 than the LPS-exposed G-CSF group. Levels of nerve growth factor, brain PSD-95, and brain GAD67 were higher in the LPS-exposed G-CSF group than in the LPS-exposed group in male rats. In female rats, brain NGF levels were similar between groups. There was no difference between groups in terms of brain GAD 67 levels. Brain PSD-95 levels were higher in the control group than in both the LPS-exposed and LPS-exposed G-CSF groups in female rats. Both neuronal CA1 and neuronal CA2 levels were lower, and the GFAP immunostaining index (CA1) and GFAP immunostaining index (CA3) were higher in the LPS-exposed group than in the LPS-exposed G-CSF group in male rats. However, neuronal count CA1 and neuronal count CA3 values were found to be similar between groups in female rats. CONCLUSIONS: The present research is the first to demonstrate the beneficial effects of G-CSF on core symptoms of ASD experimentally depending on male sex. G-CSF can be a good candidate for ameliorating the core symptoms of ASD without serious side effects in males.

Effects of the COVID-19 pandemic on anxiety and depressive symptoms in pregnant women: a preliminary study.

OBJECTIVE: The 2019 coronavirus disease (COVID-19) outbreak that began in China has turned into a pandemic that threatens global health, thereby prompting the concentration of studies and clinical routines on treating and preventing the disease. However, research on the psychological effects of the pandemic on the general population, particularly pregnant women, is lacking. Accordingly, the present study investigated the effects of the COVID-19 pandemic on depression and anxiety in pregnant women. STUDY DESIGN: An anonymous survey for assessing depression and anxiety in pregnant women was designed, after which a link to the online questionnaire was sent to the participants, who were being treated in a private medical center. One of the researchers followed up with the respondents, among whom 260 returned their questionnaires. RESULTS: Among the respondents, 35.4% (n = 92, case group) obtained scores higher than 13 on the Edinburgh Postpartum Depression Scale (EPDS). The comparison of the groups by years of education indicated statistically significant effects of COVID-19 on psychology, social isolation, and mean scores in the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). These effects were more severe in the case group than in the control group (psychology: 8.369 ± 2.003, social isolation: 8.000 ± 2.507, mean BDI and BAI scores: 20.565 ± 6.605 and 22.087 ± 8.689, respectively). A regression analysis revealed that the BDI scores and the disease's psychological effects, as well as the BAI scores and the illness's social isolation effects, exerted a statistically significant influence on the EPDS scores of the participants. CONCLUSION: This study illustrated the effects of the COVID-19 pandemic on the depression and anxiety levels of pregnant women. Our results point to an urgent need to provide psychosocial support to this population during the crisis. Otherwise, adverse events may occur during pregnancy and thus affect both mother and fetus.

Investigation of Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in Children with Wilson Disease.

BackgroundThe aim of the present study was to assess thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with Wilson Disease (WD) and to compare them to healthy controls. Methods: Based on the inclusion and exclusion criteria, fifteen children with WD and twenty-nine healthy children were enrolled, and serum thiol/disulfide and IMA levels were compared between groups. Results: The mean values of native and total thiols were significantly lower in the WD group than in the control group. The mean value of disulfide was significantly higher in the WD group than in the control group. The mean percentages of disulfide/total thiol and native thiol/total thiol were higher in the WD group than in the control group. The IMA value was also higher in the WD group than in the control group. Conclusion: The present study demonstrating altered thiol/disulfide parameters indicates increased oxidative stress in children with WD.

Effects of the Prenatal Administration of Tetanus Toxoid on the Sociability and Explorative Behaviors of Rat Offspring: A Preliminary Study.

OBJECTIVE: Autism spectrum disorder (ASD) is a severely disabling psychiatric disease characterized by impairments in communication and social skills. Although efforts have been made to explore the etiology of ASD, its pathophysiology remains unclear. This issue is rendered more challenging by confounding data about the effects of vaccination on disease etiology. In this study, therefore, we investigated the neurodevelopmental effects of maternal tetanus toxoid administration on rat offspring. We hypothesized that the vaccine affects the sociability and preference for social novelty of rat offspring as well as the production of immunological and neurotrophic factors, including tumor necrosis factor-alfa (TNF-α), neuregulin-1 (NRG-1), neuron growth factor (NGF), and oxytocin. METHODS: The study involved 12 female and 4 male adult Sprague-Dawley rats (238 ± 10 g), which were assigned to two groups. Group 1 (control group) was given 0.5 ml of normal saline (0.9% NaCl) on the 10th day of pregnancy, whereas Group 2 (experimental group) was administered 0.5 ml of tetanus vaccine (tetanus toxoid, 40 IU). RESULTS: Maternal tetanus toxoid administration exerted beneficial effects on the sociability and explorative behaviors of the rats. The brain tissue levels of TNF-α, NGF, NRG-1, and oxytocin were higher in the experimental group than those among the controls. All these significant differences were found in both the male and female rats. CONCLUSION: This study is the first to demonstrate the advantages of tetanus toxoid administration in relation to the sociability and explorative behaviors of rat offspring. The results showed that the vaccine also influences NRG-1, neuregulin, and oxytocin production.

Altered thiol/disulfide homeostasis and ischemia-modified albumin levels in children with irritable bowel syndrome.

BACKGROUND: In this study, we assessed thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with irritable bowel syndrome (IBS) compared with healthy children. METHODS: Fifty-six children with IBS and 53 healthy children were included in the study after assessment of inclusion and exclusion criteria. Plasma thiol/disulfide and IMA levels were compared between children with and without IBS. RESULTS: The mean values of native thiol, total thiol, and disulfide were 343.779 ± 138.654 µmol/L, 365.398 ± 140.148 µmol/L, and 23.190 ± 4.978 µmol/L, respectively, in the IBS group and 409.908 ± 69.288 µmol/L, 433.481 ± 76.891 µmol/L, and 20.090 ± 4.252 µmol/L, respectively, in the control group. Native thiol and total thiol values were significantly reduced in the IBS group compared with the control group. The mean IMA values were 0.835 ± 0.083 (g/L) and 0.778 ± 0.072 in the IBS and control groups, respectively. The IMA value was significantly increased in the IBS group. CONCLUSION: Impaired thiol/disulfide homeostasis and increased IMA levels can be considered etiological factors in children with IBS.

Comparison of sleep problems between term and preterm born preschool children.

OBJECTIVES: Sleep disorders are common problems among all age groups. If sleep problems detected in childhood are not resolved successfully, they become sleep disorders and a chronic state. In this study, we aimed to compare sleep problems between preterm-born and term-born preschool-age children. METHODS: In the cross-sectional study, children were grouped according to whether they were born preterm or at term. The preterm group included 137 children aged four to six years. The control group comprised 145 age-matched term-born preschool children. The prenatal, natal, demographical, and clinical characteristics of preterm- and term-born preschool-age children were compared. The Children's Sleep Habits Questionnaire (CSHQ) was used to identify sleep problems. The total score and subscores of the CSHQ were compared between the groups. RESULTS: The percentage of gastroesophageal reflux (GER) symptoms and obstructive sleep apnea (OSA) symptoms were significantly higher in the preterm group. According to the cutoff point of the CSHQ, 97 children in the preterm group (70.8%) and 88 children in the control group (60.7%) had a sleep disorder. The total score of the CSHQ was significantly higher in the preterm group compared with the control group; however, the scores of the subscales were similar between the groups. In the regression analysis, a significant association was found between being born preterm and having sleep disorder (ß = 0.308, OR = 1.36, p = 0.04). CONCLUSIONS: Our study reported a high percentage of sleep problems in preterm-born preschool children. We suggest that prematurity is associated with sleep problems even if the etiology of sleep problems is heterogeneous. Symptoms regarding GER and OAS should be investigated, and precautions, such as prohibiting maternal cigarette smoking, should be taken in preterm infants.

Increased serum BDNF and ProBDNF levels in children with irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders among the pediatric population. Recently, neurotrophins have been suggested to be etiological factors or causes of symptoms of IBS. In the present study, the aim was to research the serum brain-derived neurotrophic factor (BDNF) and proBDNF levels in children with IBS. METHODS: The study group was selected from pediatric gastroenterology outpatient clinic and control group was recruited from healthy children outpatient clinic. Based on the inclusion and exclusion criteria, 29 children with IBS and 55 healthy children were included in the study. The data were obtained from all participants, and if needed, from their parents. All participants were assessed in terms of anthropometric measurements. The serum (BDNF) and proBDNF levels were compared between the groups. RESULTS: The proBDNF levels in IBS patients were higher compared with the control group in covariance analysis (IBS patients group mean 492.4, SD 534.1; control group mean 332.8, SD 406.7) (p = 0.02; Cohen's d = 0.45). The serum BDNF levels of IBS patients were also higher compared with the control group (IBS patients group mean 3.1, SD 4.3; control group mean 1.7, SD 2.7) (p = 0.02; Cohen's d = 0.51). CONCLUSIONS: The present study is the first to demonstrate that there is a higher level of serum BDNF in children with IBS. Moreover, it is the first to demonstrate an increased level of proBDNF in IBS. Additional research is needed to confirm the preliminary results.

Beneficial Effects of Ibuprofen on Pentylenetetrazol-induced Convulsion.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used as an anti-inflammatory, anti-pyretic, and analgesic. Although some studies have focused on the anti-inflammatory and anti-pyretic properties of ibuprofen during febrile convulsions, only one has investigated its antiepileptic effects. In the present study, we aimed to investigate the effects of ibuprofen in rats exposed to pentylenetetrazol (PTZ)-induced seizures. In total, 48 rats were randomly divided in two groups: Group A for electroencephalography (EEG) recordings and Group B for behavioral assessment. All EEG recordings and behavioral assessment protocols were performed. In addition, groups were compared in terms of prostaglandin F2 alfa (PGF2α) levels in the brain. We demonstrated the beneficial effects of the administration of ibuprofen in PTZ-induced seizures in rats via the following findings: spike percentages and Racine convulsion scale values were significantly lower and first myoclonic jerk (FMJ) onset times were significantly higher in the ibuprofen-administered groups. Moreover, PGF2α levels in the brain were significantly higher in the saline and PTZ 70 mg/kg group than in the control and PTZ 70 mg/kg and 400 mg/kg ibuprofen groups. Our study is the first to demonstrate the beneficial effects of ibuprofen on seizures through behavioral, EEG, and PGF2α brain assessments. Ibuprofen can be used for epilepsy and febrile seizures safely and without inducing seizures. However, further experimental and clinical studies are needed to confirm our results.

Distinct temperament and character traits in patients with hyperemesis gravidarum.

Hyperemesis gravidarum (HG) is an extreme form of vomiting during pregnancy and is characterized with excessive vomiting and nausea and ketonuria, electrolyte imbalance, dehydration and severe nurtition deficiency. The etiology of HG is considered as multifactorial. Altough there is a great interest to HG in terms of psychiatric conditions, there have been limited numbers of studies that researched personality traits in patients with HG. In present study, we aimed to compare temperament and character traits between pregnant women with and without HG by Temperament and Character Inventory. 48 pregnant women with HG and 64 healthy pregnant women were included to study. The HG groups and control group were compared in terms of temperament and character traits and anxiety levels. The temperament scores of novelty seeking, harm avoidance and reward dependence were found to be similar between groups while the score of persistence was significantly lower in HG group compared with control group (p = .021). All character scores in HG group as cooperativeness, self-directedness, and self-transcendence were significantly lower compared with control groups (respectively; p = .002, p = .018 and p = .029). The scores of STAI-1 was higher in HG group compared with control group (p = .027) whereas the score of STAI-2 was found to be similar between groups. Present study is the first to demonstrate different temperament and character traits in patients with HG. We argue that our results support the psychiatric background of HG; however further studies are needed to confirm our results.

Decreased serum orexin A levels in drug-naive children with attention deficit and hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and characterized by inattention, hyperactivity, and impulsivity. ADHD is a neurodevelopmental disorder, and its etiology has not yet been determined precisely. Orexin A is thought to play an important role in different forms of learning, memory, and attention. Despite its importance in attention and learning, no study has investigated serum orexin levels in patients with ADHD. In the present study, we aimed to compare serum orexigenic neuropeptides such as orexin A and orexin B, neuropeptide Y, and ghrelin between drug naive children with ADHD and healthy children. Fifty-six drug-naive children with ADHD and 40 healthy controls were enrolled in the study. After comparison of serum orexin A and orexin B, neuropeptide Y, and ghrelin, we found that serum orexin A levels were significantly lower in the ADHD group (p = 0.001). Furthermore, serum orexin A levels were compared between ADHD subgroups. Orexin A levels were significantly lower in the inattentive subtype compared with the hyperactive subtype and combined subtype (p = 0.009). Our results indicate that orexin A might be a neurobiological etiological factor in ADHD, particularly associated with attention symptoms. The present study is the first to demonstrate decreased serum orexin A levels in drug-naive children with ADHD. Further studies are needed to confirm our results and to show the effects of treatments involving orexin A in patients with ADHD.

Altered methyltetrahydrofolate reductase gene polymorphism in mothers of children with attention deficit and hyperactivity disorder.

Attention Deficit and Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders in childhood and causes significant functional impairments in children. Behavioral genetic and molecular genetic studies have provided significant evidence in terms of highlighting the etiology of ADHD. Folate deficiency during pregnancy is an established risk factor for ADHD. Polymorphisms in the Methyltetrahydrofolate Reductase (MTHFR) encoding gene, such as A1298C and C667T, are associated with the decreased bioavailability of folate, and this condition can act like folate deficiency. In the literature, no study has investigated MTHFR polymorphisms in mothers of children with ADHD. Sixty-four children diagnosed with ADHD and their mothers as well as 40 healthy children and their mothers participated in this study. MTHFR polymorphisms were investigated in all participants. Comparison of the C677C and A1298C MTHFR polymorphisms in children with and without ADHD revealed no significant differences. We found that the maternal C677C_CT genotype counts, both observed and expected values, were significantly different from those based on Hardy-Weinberg Principle Analysis in the ADHD group. The most important result of this study was that maternal C677C MTHFR gene polymorphisms are significant risk factors in for ADHD, and we argue that children with ADHD are exposed to folate deficiency, even if their mothers received a sufficient amount of folate during pregnancy. This result also highlights one of the genetic factors of ADHD. Further studies should be performed to confirm this finding.

The effects of noise reduction by earmuffs on the physiologic and behavioral responses in very low birth weight preterm infants.

OBJECTIVE: Preterm infants are exposed to loud noises during their stay in the neonatal intensive care unit which can lead to physiologic and behavioral alterations and even hearing loss. The use of earmuffs can reduce sound level and these changes. The objective of the present study is to evaluate the effectiveness of the earmuffs in preterm infants solely cared for in closed incubators. METHODS: A comparative prospective study comprising 20 clinically stable preterm infants weighing less than 1500 g cared in closed incubator was conducted. Preterm infants acted as their own controls whereby they were observed without earmuffs (Group 1) for 2 days and with earmuffs (Group 2) on consecutive 2 days. The preterm infants' physiologic responses and Anderson Behavioral State Scoring System (ABSS) scores were assessed over 30s every 2h for 8h during daytime for 4 days. RESULTS: Out of 20 preterm infants, 6 were male and 14 female with a mean birth weight of 1220 ± 209 g, gestational age of 29.9 ± 2.1 weeks. The total number of measurements was 320. The mean ABSS scores of Group 1 and 2 were 3.07±1.1 and 1.34 ± 0.3, respectively. Statistically significant difference was noted between the means of ABSS scores (p<0.001). Preterm infants with earmuffs (87.5%) were more frequently observed in a quiet sleep state of ABSS compared with those without earmuffs (29.4%). CONCLUSIONS: Noise level reduction was associated with significant improvement in behavioral states of ABSS. We suggest that noise reduction in preterm infants with earmuffs is helpful by improving sleep efficiency and increasing time of quiet sleep.