Association of low 25-OH-vitamin D levels and peripheral inflammatory markers in patients with autism spectrum disorder: Vitamin D and inflammation in Autism.

Inflammatory mechanisms and Vitamin D are reported to play important roles in the pathophysiology of Autism Spectrum Disorders (ASD). There are ample evidences that vitamin D has an anti-inflammatory effect. In this study, we aimed, for the first time, to investigate the 25-OH-vitamin D with inflammation markers in ASD patients. The study included 154 patients with ASD and 98 healthy subjects. 25-OH-Vitamin D levels and simple peripheral inflammatory markers such as Neutrophil-Lymphocyte ratio (NLR), C-reactive protein (CRP) and, sedimentation were measured in all subjects. K-SADS-PL-DSM 5 were administered to all subjects to evaluate the psychiatric diagnosis. Childhood Autism Rating Scale was used to asses severity of autism. In the patient group, high CRP rate, leukocyte, neutrophil and NLR were significantly high compared to the healthy control group. 25-OH-Vitamin D levels were found to be statistically significantly lower in the ASD group. While a significant negative correlation was found between 25-OH-Vitamin D and CRP, NLR, neutrophil counts in ASD patients, a positive correlation was found between lymphocyte counts. Especially in male ASD patients, the relationship between 25-OH-Vitamin D and inflammation markers was more pronounced. Our findings support the association of vitamin D and inflammation in ASD.

The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents.

BACKGROUND: Depression is a heterogeneous disorder and is thought to develop as a result of complex interactions between genetic and environmental factors. One-carbon metabolism that includes vitamin B12, folic acid, and homocysteine has been investigated in psychiatric disorders like depression. In recent years, vitamin D has also been considered to contribute to psychiatric disorders. In this study, serum levels of folate, vitamin B12, and homocysteine related to one-carbon metabolism and vitamin D were investigated in children and adolescents with depression and to assess possible roles in depression pathogenesis. METHODS: The study included 89 children and adolescents with depression (69 female, 20 male; mean age ± SD = 15.08 ± 1.46) and 43 control subjects (31 female, 12 male; mean age ± SD = 14.41 ± 2.32) without any DSM-5 diagnosis. Each subject completed a sociodemographic form, Childhood Depression Inventory, State-Trait Anxiety Inventory 1-2 and measured serum folate, vitamin B12, homocysteine, and 25-OH vitamin D levels. RESULTS: There was no significant difference between the groups in terms of folate levels (p = .052). In the patient group, the vitamin B12 and vitamin D levels were clearly low (p values for both levels were <.001), while homocysteine levels were found to be remarkably high (p < .001). In addition, there was a negative correlation between depression severity and vitamin B12 and vitamin D, while a positive correlation was found with homocysteine. CONCLUSIONS: The results of the study show that vitamin B12 deficiency or insufficiency and elevated homocysteine may contribute to the etiopathogenesis of depression. Additionally, it was shown that lower vitamin D levels may be associated with depression. KEY PRACTITIONER MESSAGE: Depression of children and adolescents is associated with the interaction of environmental and genetic factors. Homocysteine, vitamin B12, and folate related to one-carbon metabolism are associated with psychiatric disorders such as depression in adulthood. Vitamin D also contributes to psychiatric disorders pathogenesis. There are not enough studies in the literature about these parameters in children with depression. Low vitamin B12 and vitamin D levels and increased homocysteine levels may play a role in the pathogenesis of depression in children and adolescents. Investigation of vitamin B12, folate, homocysteine, and vitamin D levels are recommended in children and adolescents with depression.

Levels of peripheral Neuregulin 1 are increased in non-medicated autism spectrum disorder patients.

Though schizophrenia and autism spectrum disorders (ASD) are separate diseases, they have some common clinical manifestations and common pathogenic mechanisms. Numerous genes are associated with these conditions. Among these genes, Neuregulin-1 forms a risk for schizophrenia and some studies have shown polymorphism of this gene accompanies schizophrenia. NRG1 has a wide variety of functions, including neuronal migration, axon guidance, synaptic transmission, oligodendroglial maturation, and neurite outgrowth. To date, NRG1 levels have not been researched in ASD patients and considering the neurodevelopmental effects of NRG1, this study aimed to research the peripheral NRG1 levels in ASD patients. The study compared 32 ASD patients and 32 healthy controls. Serum NRG-1 levels were measured with ELISA. In ASD patients (mean ±â€¯SD, 10.80 ±â€¯4.78 ng/ml), the NRG1 levels were found to be statistically significantly high compared to the health control group (mean ±â€¯SD, 6.92 ±â€¯4.91 ng/ml) (p = 0.004). According to the results we obtained, NRG1 was shown to play a possible role in ASD pathogenesis. There is a need for advanced studies on the possible role of NRG1 in ASD patients. This study is significant as it is the first study to measure peripheral NRG1 in ASD patients.

Decreased plasma agmatine levels in autistic subjects.

Agmatine is a polyamine endogenously synthesized from arginine and is considered to be a new neurotransmitter. Agmatine has been implicated in the pathophysiology of several diseases such as anxiety disorder, depression, and schizophrenia. Agmatine also possesses anticonvulsant, neuroprotective, antiapoptotic, antioxidant, anxiolytic, and antidepressant effects. Furthermore, agmatine inhibits the nitric oxide synthase enzyme and exerts antagonist effects on NMDA, alpha-2, and imidazoline receptors. Considering these characteristics, the present study investigated whether agmatine plays a role in the pathogenesis of autistic spectrum disorders (ASDs). Therefore, plasma agmatine levels were evaluated in 34 patients with ASD and 28 non-ASD controls. Plasma agmatine levels were measured using the HPLC method. The study found remarkably lower agmatine levels in patients with ASD compared with the non-ASD control group (p < 0.001). These findings support the notion that agmatine might contribute to the pathogenesis of ASD and may serve as a new target for treatment.

Increased serum midkine levels in autism spectrum disorder patients.

BACKGROUND: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis. METHODS: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale. RESULTS: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007). CONCLUSIONS: According to these results, MK may play a role in ASD pathogenesis.

Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder.

The neurodevelopment and functioning of the central nervous system, and especially the cerebral cortex, have basic importance to understand neuropsychiatric disorders like autism. Fibroblast growth factor-2 (FGF-2) plays a very important role in the development and functioning of the cortex. FGF-2 is related to developmental processes in the central nervous system such as neurogenesis, migration, differentiation and survival. This study researched the serum FGF-2 levels in children with autism spectrum disorder (ASD). With this aim, 60 ASD children and 40 healthy controls were compared. We applied a sociodemographic form and the Childhood Autism Rating Scale (CARS) to each subject with their family to assess the severity of autism. Additionally, all subjects had routine laboratory tests performed. Serum samples were studied with ELISA. The results found that serum FGF-2 levels were statistically significantly low in the patient group compared to the healthy control group (p value 0.003). Additionally there was a statistically significant negative correlation identified between serum FGF-2 levels and CARS score for all subjects (r = -0.300; p = 0.02). In conclusion, FGF-2 may contribute to the etiopathogenesis of ASD.

Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder.

OBJECTIVE: Brain specific-proteins are not found in other tissues and measurement non-invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain-specific protein values as brain damage markers in children with autism spectrum disorder (ASD). METHOD: 35 children with ASD and 31 healthy subjects were included in the study. Sociodemographic form and Childhood Autism Rating Scale (CARS) were applied to each subject. Serum neuron specific enolase (NSE), S100B, Myelin basic protein (MBP) and Glial fibrillary acidic protein (GFAP) values ​​were measured with ELISA. RESULTS: There was no significant difference between the two groups for NSE, MBP and S100B values (p=0.242; p=0.768; p=0.672, respectively). However, GFAP values ​​in the patient group were statistically significantly higher (mean±SD: 0.463±0.392ng/ml) than in the healthy control group (mean±SD: 0.256±0.111ng/ml) (p<0.001). In addition, there was a significant positive correlation between serum GFAP values ​​and CARS score in all subjects and in the patient group (r=0.599; p<0.001 and r=0.380; p=0.024, respectively). CONCLUSIONS: While serum NSE, MBP, and S100B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity.

Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects.

OBJECTIVE: To evaluate the serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). STUDY DESIGN: Serum zonulin levels were determined in 32 patients with ASD and 33 healthy controls using an enzyme-linked immunosorbent assay. The severity of ASD symptoms was assessed with the Childhood Autism Rating Scale. RESULTS: Serum zonulin levels were significantly higher in the patients with ASD (122.3 ± 98.46 ng/mL) compared with the healthy controls (41.89 ± 45.83 ng/mL). There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed (r = 0.523; P < .001). CONCLUSIONS: This study suggests that zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD.

Vitamin B12, folic acid, homocysteine and vitamin D levels in children and adolescents with obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a complex disorder with a poorly understood aetiopathogenesis. One carbon metabolism that includes vitamin B12, folic acid and homocysteine has been investigated in many psychiatric disorders like OCD. In recent years, vitamin D has also been considered to contribute to many of these psychiatric disorders. In this study we investigated whether vitamin B12, homocysteine and vitamin D play a role in the aetiology of paediatric OCD. With this aim we compared 52 children and adolescent OCD patients with 30 healthy controls. The participants were tested for vitamin B12, folic acid, homocysteine and vitamin D levels and were evaluated with a sociodemographic form, state-trait anxiety inventory 1 and 2, Kovacs Depression Inventory and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). As a result we found significantly lower levels of vitamin B12 and vitamin D and higher levels of homocysteine in the patient group compared to control group (p values for all three scores were <0.001), whereas there was no significant difference between groups in terms of folate levels (p=0.083). This demonstrates that one carbon metabolism and vitamin D deficiency can play a role in the aetiology of OCD.