Antidepressant and anti-suicidal effects of ketamine in treatment-resistant depression associated with psychiatric and personality comorbidities: A double-blind randomized trial.

OBJECTIVE: To evaluate the effects of ketamine treatment on depression and suicidal ideation in treatment resistant depression (TRD) and to determine whether they are influenced by other psychiatric and personality comorbidities. METHODS: A randomized double-blind parallel-arm controlled study on 36 patients with TRD. Patients were divided into two treatment groups: ketamine (K group) and placebo (P group). Patients in the K and P groups received one infusion of medicine per week for two weeks. All participants were assessed using the Structured Interview for the Five-Factor Personality Model (SIFFM), Hamilton Depression Rating Scale (HDRS), Suicide Probability Scale (SPS), and Symptom Checklist 90 (SCL 90). RESULTS: After treatment, there was a significant decrease in the total HDRS and SPS scores in the K group compared to the P group, but the magnitude of response was not influenced by the presence of other psychiatric symptoms. Regression model, only receive ketamine treatment was significant factor for improve suicide and depression scores. LIMITATIONS: lack of data on other outcomes that are important to patients (e.g., quality of life, cognition) and need for a larger sample size. CONCLUSIONS: Ketamine infusions in TRD reduce suicidal ideation and depression despite the presence other psychiatric and personality disorders.

Polymorphism of interleukin-1ß and interleukin-1 receptor antagonist genes in children with autism spectrum disorders.

In this study, we first investigated interleukin-1 beta (IL-1ß) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions -31 and - 511 of the IL-1ß gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1ß promoter polymorphism at -511 (IL-1ß-511) and - 31 (IL-1ß-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1ß and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1ß-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1ß-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1ß-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1ß system, with abnormally increased serum levels of IL-1ß and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1ß-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1ß-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1ß and IL-1RA systems may have a role in the pathophysiology of ASD.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. METHODS: This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

Repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorders: Double blind randomized clinical trial.

Repetitive transcranial magnetic stimulation (rTMS) has become widely used as a therapeutic tool in psychiatric research. The aim of this study was to evaluate the impact of different frequencies of rTMS over right dorsolateral prefrontal cortex (DLPFC) in OCD. Forty five patients with OCD participated in the study. Patients were evaluated using: Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity scale (CGI-S). They were randomly classified into three groups: 1st group received 1Hz rTMS; 2nd group received 10Hz rTMS; and 3rd group received sham stimulation all at 100% of the resting motor threshold for 10 sessions. They were followed up after the last treatment session and 3 months later. There was a significant "time"×"group" interaction for 1Hz versus Sham but not for 10Hz versus Sham. 1Hz versus 10Hz groups showed a significant interaction for Y-BOCS and HAM-A (P=0.001 and 0.0001 respectively). 1Hz rTMS has a greater clinical benefit than 10Hz or Sham. There was also a significantly larger percentage change in GCI-S in the 1Hz group versus either 10Hz or sham. We conclude that 1Hz-rTMS, targeting right DLPFC is a promising tool for treatment of OCD.

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

OBJECTIVES: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. METHODS: We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. RESULTS: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. CONCLUSION: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial Number: R000016846.

Psychopathological and peripheral levels of neurobiological correlates of obsessive-compulsive symptoms in patients with epilepsy: a hospital-based study.

OBJECTIVES: Obsessive-compulsive symptoms (OCSs) and disorder (OCD) are often underdiagnosed in the out-patient epilepsy clinic. This work aimed at determining the risks and comorbidities (psychopathological and neurobiological correlates) of OCSs in treated adults with idiopathic epilepsy recruited from a university hospital. METHODS: Psychiatric evaluation was done using DSM-IV (The Diagnostic and Statistical Manual of Mental Health Disorders). Obsessive-compulsive disorder was identified using the Mini International Neuropsychiatric Interview (MINI). The Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were used to determine the severity of the related psychiatric symptoms. RESULTS: Out of 474 patients screened, included in this study were 107 with no psychiatric symptoms and 188 with OCSs [classified as those with at least OCSs=93; mild OCSs=36; moderate, severe, and extreme OCSs=59]. A hundred healthy subjects were included as controls. Blood concentrations of serotonin, adrenaline, noradrenaline, and dopamine were measured. Compared with controls, patients with OCSs had higher frequencies of depression and anxiety. Low concentrations of serotonin, adrenaline, noradrenaline, and dopamine were reported regardless of the presence or the absence of psychiatric symptoms, OCS severities, and antiepileptic drug (AED)-related variables (dose and serum drug level). Significant correlations were identified between Y-BOCS, BDI-II, and HAM-A scores, age, age at onset, and concentrations of noradrenaline. CONCLUSION: This study indicates that a) OCSs are common in patients with epilepsy. Male sex, age, duration of illness, seizure focus, lateralization, and intractability to AEDs are its main risks; b) depression and anxiety are comorbid psychopathologies; and c) serotonin, catecholamines, and dopamine are linked to epilepsy-related variables and its comorbid psychopathies but not to its medications.

Assessment of biocorrelates for brain involvement in female patients with rheumatoid arthritis.

Central nervous system (CNS) abnormalities are rare in patients with rheumatoid arthritis (RA). Direct studies done to investigate brain involvement in RA are few or even absent. We hypothesized that CNS is not excluded from the inflammatory disease process in RA. Thus we systematically investigated markers of brain involvement in 55 females with RA. We examined patients' cognition using battery of sensitive psychometric testing [Mini-Mental State Examination, Stanford-Binet test (fourth edition) and Wechsler Memory Scale-Revised] and by recording P300 component of event-related potentials, a neurophysiological analogue. We also measured the serum levels of S100B and neuron-specific enolase (NSE), markers of glial and neuronal cells. Compared to control subjects, lower scores in cognitive testing were reported in 71% of the patients (n=39) and abnormal P300 latency and amplitude (P<0.001, 0.050). Patients had higher levels of S100B (P<0.029) and higher levels of S100B were correlated with lower total scores of cognitive functions (P<0.01), P300 latency (P<0.05), and NSE concentrations (P<0.01). However, cognitive scores did not correlate with disease activity or severity. Although depression scores were significant in patients with RA (P<0.001), but they did not correlate with cognitive scores. Seven patients had white matter hyperintensities in MRI brain suggesting vasculitis, ischemic brain lesions and dots of demyelination, and all had higher levels of S100B. Results of this study directly indicate that the disease process (inflammation and demyelination) is associated with cognitive deficits observed with RA.