Behavioral effects of toll-like receptor-4 antagonist 'eritoran' in an experimental model of depression: role of prefrontal and hippocampal neurogenesis and γ-aminobutyric acid/glutamate balance.

Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS). Long-term administration of ERI ameliorated CRS-induced depressive-like symptoms and hypothalamic-pituitary-adrenal axis hyperactivity alongside reducing levels of hippocampal and PFC inflammatory cytokines, restoring GABA and glutamate balance, and enhancing PFC and hippocampal neurogenesis, by increasing BDNF gene and protein expression in a dose-dependent manner. The results demonstrate an antidepressant-like activity of ERI in Wistar rats exposed to CRS, which may be largely mediated by its ability to reduce neuroinflammation, increase BDNF, and restore GABA/glutamate balance in prefrontal cortex and hippocampus. Nonetheless, further studies are needed to characterize the mechanism of the antidepressant effect of ERI.

Polysomnographic characteristics of bipolar hypomanic patients: Comparison with unipolar depressed patients.

BACKGROUND: Sleep profile in bipolar disorder has received little attention in comparison to sleep studies in major depressive disorders. Specific sleep abnormalities especially in REM sleep parameters have been detected in depression. The current study aimed at investigating whether bipolar disorder shares the same polysomnographic (PSG) changes or not. METHODS: All night polysomnographic assessments were made for 20 patients diagnosed to have hypomania, in addition to 20 patients with major depression and 20 healthy matched controls. All participants were examined using Standardized Sleep Questionnaire, SCID-I for psychiatric diagnosis, based on DSM-IV criteria, YMRS (for hypomanic patients), HAMD (for major depression patients), and all-night polysomnography (for all subjects). RESULTS: The two patient groups differed significantly from controls in their sleep profile, especially regarding sleep continuity measures, Short REML (Rapid Eye Movement Latency), with increased REMD (Rapid Eye Movement sleep density). High similarity was found in EEG sleep profile of the two patient groups, though the changes were more robust in patients with depression LIMITATIONS: A relatively small sample size, the absence of follow up assessment, lack of consideration of other variables like body mass index, nicotine and caffeine intake. CONCLUSION: Similarity in EEG sleep profile between Bipolar disorder patients and patients with major depression suggests a common biological origin for both conditions, with the difference being "quantitative" rather than "qualitative". This quantitative difference in sleep efficiency and SWS (Slow wave sleep), being higher in hypomania, might explain the rather "refreshing" nature of sleep in hypomanic patients, compared to depression.

Correlates of psychiatric co-morbidity in a sample of Egyptian patients with bipolar disorder.

BACKGROUND AND OBJECTIVES: Bipolar disorder (BD) is a complex, chronic mood disorder involving repeated episodes of depression and mania/hypomania. Two thirds of patients with bipolar disorder have a comorbid psychiatric condition. This study aims to assess the prevalence of Axis I diagnosis with its socio-demographic and clinical correlates among a sample of Egyptian patients with bipolar disorder. METHODS: Out of the 400 patients who were enrolled in the study from number of governmental and private psychiatric hospitals in Cairo, Egypt, 350 patients diagnosed with bipolar affective disorders (157 females and 193 males) with age ranging from 18 to 55years were selected. Patients were assessed using the Structured Clinical Interview for DSM-IV Axis I disorder (Research Version) (SCID-I). RESULTS: Prevalence of psychiatric comorbidity among BD patients was 20.3% (71 patients) among which 63 patients (18%) had comorbid substance abuse and 8 patients (2.3%) had comorbid anxiety disorders. LIMITATIONS: The study was limited by its cross sectional design with some patients having florid symptoms during assessment, not having a well representative community sample. This might have decreased the reliability and prevalence of lifetime psychiatric comorbidity due to uncooperativeness or memory bias. The study group was composed of bipolar patients attending tertiary care service which limits the possibility of generalizing these results on different treatment settings. CONCLUSIONS: Substance abuse followed by anxiety disorders was found to be the most common psychiatric comorbidity. Family history of psychiatric disorders and substance abuse as well as current psychotic features were highly correlated with comorbidity.

Melatonin and sleep-related problems in children with intractable epilepsy.

Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures.

Prevalence and risk factors of violence among elementary school children in Cairo.

UNLABELLED: School violence is a growing problem that has received widespread attention. Violent behavior for elementary school children is primarily expressed as physical or verbal aggression. Various factors contribute to violent and aggression by children at homes, schools or individual risk factors. The aim of the present study is to measure the prevalence of violence, risk factors, and different forms among elementary school children, to identify consequence of violent exposure and children with abnormal behavior score. A cross-sectional study was done enrolling a total of 500 elementary students from two mixed schools (private and public) 250 from each in North Cairo Educational Zone. Data collected from students, parents and teachers were: violence behavior, home and family atmosphere, peer relation, exposure to violence at school; being victimized, witness, or initiator, and other risk factors. Standardized questionnaires were used as Achenback Child Behavior checklist, parent and teacher forms of Strength and Difficulty questionnaires (SDQ), and developmental history of child. Monthly grades of students, IQ assessment, physical examination of students were recorded. RESULTS: Prevalence of different forms of violence was higher in public school than private; physical violence 76%, 62% respectively. All forms of violence were higher among boys. Living with a single parent (OR = 2.3), absence of an attachment figure (OR = 13.6), instrumental delivery or cesarean section (OR = 1.9), corporal punishment (OR = 3), violent video games preference (OR = 2.5), exposure to verbal aggression (OR = 3), relations with aggressive peers (OR = 3) were risk factors for violence. Teacher's report of SDQ revealed abnormal score of student's behavior in (32.4%) and (22%) students of public and private schools respectively. The most frequent problems revealed by SDQ among victimized students of both schools was conduct problems (64.7%) in teacher's report and peer relation problems 93.6% in parent's report. CONCLUSION AND RECOMMENDATIONS: Abnormal and borderline scores of SDQ are high among studied students, Follow up and supervision is needed to prevent violence among them. An effective role model to direct student's behavior should receive more concern at the school and home level.

Sleep EEG findings in ICD-10 borderline personality disorder in Egypt.

BACKGROUND: Previous work has demonstrated that patients with borderline personality disorder show some similarities to patients with major depression, especially regarding their sleep profile. This study aimed at investigating such a hypothesis in an Egyptian sample, considering the possible influence of cultural differences. METHODS: All night polysomnographic assessments were made for 20 ICD-10 diagnosed borderline patients (without co-morbid depression), in addition to 20 patients with major depression and 20 healthy matched controls. RESULTS: The two patient groups differed significantly from controls in their sleep profile, especially regarding sleep continuity measures, decreased SWS and REM sleep abnormalities. High similarity was found in EEG sleep profile of the two patient groups, though the changes were more robust in patients with depression. LIMITATION: The small number of subjects precluded finer analyses of sleep microstructure by depressive symptoms. CONCLUSIONS: The great similarity in EEG sleep profile between borderline personality disorder patients and patients with major depression suggests a common biological origin for both conditions, with the difference being 'quantitative' rather than 'qualitative'. Our data are all the more compelling in that the presumed personality disturbance in the Egyptian culture manifests neurophysiologically as in the Western world.