الفهرس 
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Abstract
Schizophrenia is a polygenic psychiatric disorder defined by a complex of positive, negative and cognitive symptoms. Positive symptoms include delusions and hallucinations, whereas negative symptoms reflect the absence of an expected response such as blunted affect, anhedonia or loss of social drive. Individuals with schizophrenia also often suffer from cognitive difficulties that impact organized thought processes, concentration, task completion and memory (American Psychiatric Association, 2013). The cognitive impairments in schizophrenia often appear before the behavioral features—e.g., delusions and hallucinations—do. Further, the cognitive impairments associated with schizophrenia appear to be quite stable (Fervaha et al. 2014). These cognitive impairments also occur in a less severe form in relatives of individuals with schizophrenia who do not have schizophrenia (Dickinson et al. 2014). Various physiopathological mechanisms have been developed to explain that there are inflammatory mechanisms that underlie cognitive deterioration in schizophrenia and related disorders, including microglial activation, monoaminergic disequilibrium, cerebral abnormalities, and the kynurenine pathway (Ribeiro-Santos et al., 2014). An early literature has indicated that excessive inflammation is detrimental to BDNF expression (Meirelles et al., 2017). Animal experiments have shown that peripheral lipopolysaccharide (LPS) administration decreased the expression of BDNF in the hippocampus, which produces inflammatory cytokines in brain, and thereby induces neuroinflammation (Dantzer, 2004). Another study reported that tumor necrosis factor-α (TNF-α) is negatively correlated with BDNF in patients with schizophrenia (Zhang et al., 2017). The aim of the study was: 1. Assessment of the immunological profile, and Brain Derived Neurotrophic Factor (BDNF) in drug-free patients with schizophrenia compared to match for age, sex, and smoking non psychotic first degree relatives and healthy controls. 2. Assessment of the immunological profile and Brain Derived Neurotrophic Factor BDNF as biological markers in first degree relatives of patients with schizophrenia. 3. Assessment of cognitive functions in patients with schizophrenia and their first degree relatives in relation to these Cytokines and BDNF serum level. Study setting: The study was carried out at Neuropsychiatry Department, Tanta University Center for Psychiatry, Neurology and Neurosurgery and Neuropsychiatry Department in Damanhur Medical National Institute. Study subjects: 1. Thirty (30) drug free schizophrenia patients. 2. Thirty (30) Age, sex and smoking matched non psychotic first degree relatives. 3. Thirty (30) Individuals age, sex and smoking matched healthy control subject. Inclusion criteria: Patients (30 patients): 1. Patients diagnosed with schizophrenia according to DSM IV. 2. Age from 18 to 40 years. 3. Both males and females were included in the study. 4. Patients who can read and write. 5. All patients were drug free Exclusion criteria: 1. Present and past history of autoimmune disorders. 2. History of brain injury. 3. Neurological disorders. 4. Severe physical health impairments. 5. Co-morbid substance addiction (with exception of nicotine). 6. Current infections or allergies. 7. Pregnancy and lactation. First degree relatives: 1. Negative current or past history of psychiatric disorders. 2. Absence of current infections or allergies. 3. Absence of autoimmune diseases. 4. Subjects taking psychotropic medications. Control subjects: 1. Age and gender matched with the patient group. 2. Negative current or past history of psychiatric disorders. 3. Negative family history of psychotic spectrum disorder. 4. Absence of autoimmune disease. 5. Absence of current infections or allergies. Participants in this study were submitted to the following: 1. History taking. 2. Informed consent. 3. Mini International Neuro-psychiatric Interview(Shehan et al., 1998) (Arabic version by Ghanem et al., 2000) 4. Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS) (Kay et al., 1987 ( patients only). 5. Cognitive assessment: a) Wisconsin Card Sorting Test 128 computerized version (Heaton et al. 1993). b) Wechsler Memory Scale (Wechsler, 1987). 1. laboratory tests: b. Immunological tests: i. C reactive protein (CRP) ii. Interleukin- 2. iii. Interleukin-6. iv. Interleukin-8 v. Tumor necrosis factor alpha (TNF α). vi. Interferon gamma (INF-γ). b. Brain Derived Neurotrophic Factor (BDNF) Our study revealed that: The differences between the studied groups as regards the age, gender, educational level, smoking index and body mass index distribution did not reach statistical significance (p >0.05). A. As regard laboratory findings: We found that: 1. IL6, IL8 and TNF α levels were significantly higher in patients and their first degree relatives compared to controls. 2. CRP, IL6, IL8 and TNF α levels were significantly higher in patients compared to their first degree relatives. 3. No difference in serum levels of IL2 and INF-γ between the three groups. 4. BDNF levels were lower in patient and their first degree relatives compared with healthy control. 5. No significant difference in the serum level of BDNF between patients and their first-degree relative. B. As regard cognitive function: we found that 1. In WMS Different divisions and total scores were significantly lower in patient followed by first degree relative then healthy control groups (except in general information division between patients and relatives). 2. In WCST • Regarding the category completed, perseveration errors, correct responses and percent of conceptual level response mean were higher in control group followed by 1st degree relatives then patient group. • Regarding the trials to complete 1st category mean was significantly higher in in patient group than both 1st degree relative and control groups, however the difference between to the 1st degree relative group and the healthy control group was not significant. • Regarding number of trials and failure to maintain a set, there was no significant difference between patients and first degree relatives while the healthy controls showed significantly lower number of trials than both patients and 1st degree relatives. • Regarding perseveration response the levels were higher in the 1st degree relatives than both patients and healthy controls. C. As regard relationship between laboratory findings and cognitive functions we found that 1. BDNF showed a) Positive relationship with total memory percentage on WMS the three studied groups, with total digit percentage in first degree relatives and control subjects and with logical memory only in the healthy controls. b) Positive relationship with number of categories completed in the three studied groups. 2. CRP showed a) Negative relationship with total memory percentage of WMS in the three groups while positive relationship with associate learning the first degree relatives, and positive relationship with logical memory, total digit and visual reproduction in the control group only. b) Negative relationship with percent of conceptual level response in the three studied groups and with failure to maintain set only in the relatives. 3. IL2 showed a) Positive relationship with visual reproduction in the patient group only and positive relationship with total digit and total memory percentage in the healthy controls only. b) Positive relationship with perseveration errors and percent of conceptual level response only in the control group. 4. IL6 showed a) Negative relationship with total digit only in the healthy control group. b) Negative relationship with number of trials to complete first category in the three studied groups and positive relationship with failure to maintain set in both patient and relative groups. 5. IL8 showed a) Negative relationship with logical memory and associate learning in the first degree relatives and negative relationship with total memory percentage in the control group. b) Negative relationship with failure to maintain set in both patient and relative groups, positive relationship with non perseveration errors in the relative group. 6. TNF α showed a) Negative relationship with general information only in the first degree relative group. b) Positive relationship with number of trials to complete first category only in the relative group. 7. INF-γ showed a) Negative relationship with orientation and visual reproduction in the patient group and positive relationship with associate learning in the control group. b) Negative relationship with number of correct responses in the patient and control groups, negative relationship with percent of conceptual level response in the patient group only.