الفهرس 
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Abstract
Schizophrenia is a chronic, debilitating mental health illness affecting 0.5 to 2% of the worldwide population (Goldner et al., 2002).
A first-degree relative is one’s offspring, sibling or parent, but without spouses (Nicholas, 2007).
Statistics derived from pooling data across family studies suggest the prevalence for first degree relatives is between 10 and 15 percent (Kendler and Gardner 1997). Yung et al., 2004 have been noted a significant predisposition to develop schizophrenia in the first degree relatives up to 40%.
BDNF has been attracting attention as a potential biomarker capable of advancing the elusive field of personalized medicine in psychiatry (Frey et al., 2013). Since its levels in peripheral blood can be assessed easily and relatively non-invasively through venipuncture, and BDNF levels in serum and plasma are highly correlated with BDNF levels in the central nervous system, as BDNF freely crosses the blood–brain barrier (Karege et al., 2002).
The neurotrophin hypothesis of schizophrenia has postulated that the changes in the brain of schizophrenic patients are the result of disturbances of developing processes involving these molecules (Koeva et al., 2014) and the majority of studies showed a reduction of BDNF protein expression as detected through ELISA in drug naïve patients with schizophrenia (Chen et al., 2009).
The aim of this work: was to assess serum level of BDNF in drug naive patients with schizophrenia and their first degree relatives, measure cognitive functions in patients with schizophrenia and their first degree relatives in relation to BDNF serum level and assess BDNF serum level as a biological marker as biological marker in first degree relatives of patients with schizophrenia.
This work included two parts: the theoretical part and the practical part
the theoretical part consisted of four chapters:
A-Theoretical part: -
In this part we reviewed the following:
1-Chapter 1: we discussed schizophrenia and its biomarker: including prevalence, sign and symptoms, etiology, Vulnerability and Resilience in Mental Disorders, in addition to Biomarkers in schizophrenia (Inflammation Biomarkers-Neuroendocrine Related Biomarkers- Neurotrophins as Candidate Biomarkers- Neurotransmitter Biomarkers- Neuro imaging biomarkers- Electrophysiological Biomarkers- Neuromotor markers and minor physical anomalies)
2- Chapter 2: we reviewed Brain-derived Neurotrophic factor and its relation to psychiatry including: BDNF structure, transport and release, role as a neurotrophin. Moreover, we highlighted BDNF &schizophrenia. In addition, to its relation to major depressive disorder, bipolar disorder, anxiety disorder and eating disorder.
3-Chapter 3: we reviewed cognitive functions in patient with Schizophrenia and it is relation to BDNF: we started with what does the word COGNITION mean? Then, Profile of Cognitive Impairment in Schizophrenia (1-General intellectual ability 2-Vigilance 3-working memory, episodic memory 4- Social cognition 5-Executive functions 6- processing speed) finally, we highlighted BDNF &cognitive functions: emphasized the role of BDNF in cognitive functioning, especially memory.
4- chapter 4: we reviewed characters of the First degree relatives in patients with schizophrenia, we begin with the definition of first-degree, prevalence of schizophrenia in first degree relatives of schizophrenia, then we emphasis on Biomarkers in relatives: A-Cognitive functions profile in First degree relatives in patients with schizophrenia. B-Imaging studies in First degree relatives in patients with schizophrenia. C-Low Olfactory Bulb Volume in First-Degree Relatives of Patients with Schizophrenia. D-Psychiatric disorder in First degree relatives in patients with schizophrenia. E- medical disorder in in First degree relatives in patients with schizophrenia.
B-Practical part: -
The sample of this study was selected from psychiatric outpatient clinic of Beni-Suef University Hospital 1- Group: This group was consisting of 30 patients that include all subtypes of schizophrenia as diagnosed according to DSM-IV 2-Group:30 first degree relatives to the selected patients, (A person’s first degree relative is a parent, sibling, or child. A first degree relative shares about half of their genes with the person). 3-Group: 28 persons with no apparent psychiatric illness was selected from paramedical staff of Beni-Suef University Hospital and matched with the patients group in age, sex, education, socio demographic and economic status.
All the subjects of the study will be subjected to
I-semi structural psychiatric interview of Kasr El Aini psychiatric sheet
II-Psychological assessment will include the following: -
1-Structured Clinical Interview for DSM-IV (SCID I) :( psychotic disorder section).
2-Positive and negative syndrome scale (PANSS)
3- PRIME-Screening test: (for group B&C)
4-wechler memory scale revised
5-Wisconsin card sorting test
III-The serum BDNF level was measured by enzyme –linked Immunoassay(ELISA)
The main results of this study includes: -
I) As regards descriptive demographic data: - all confounders were non statistically significant
II) As regards Comparative data: -
1-Cognitive subtests of WMS, impairment in cognitive functions were significant lower in patients with schizophrenia group, than first degree relatives, whereas the control group showed higher scores in all subtests.
2- There was no significant difference between male and female regarding WMS tests in schizophrenic group
3- Gender differences in first degree group regarding WMS test showing that female group (5.37±1.50) has significant cognitive impairment than male group (6.85± 1.09) regarding Verbal paired associates I(hard).
4- Gender differences regarding WMS test in control group, the male group (37.14±2.90) has significant cognitive impairment than female group (33.71±4.30) regarding Visual Reproduction I. while female group (18.28±3.42) has significant cognitive impairment than male group (21.78±1.71) regarding Visual memory span.
5-WCST test: the control group has significantly higher Categories Completed\Experienced and less Perseverative Errors (percent) than first degree relatives group and lowest Categories Completed\Experienced and high Perseverative Errors (percent) were in schizophrenic group.
6- There were no significant differences between first degree relatives and control group regarding Prim test.
III) As regards Chemical data: -
1- Regarding BDNF, the schizophrenic group has significant lower PDNF than First degree relatives and control groups
2- Regarding BDNF, the First degree relatives group has significant lower BDNF than control group
III) As regards Correlation data: -
1- Correlation between age and WMS in the three group, there was significant negative correlation in the schizophrenic group in the following (Visual paired associates I, Visual reproduction I and Digit span) and there was no significant relation in the first degree and control groups.
2- There was no significant correlation between age and WCST in schizophrenia group, First degree relatives group and control group
3- No significant correlation between WMS subtests and BDNF in schizophrenic and control group.
4-A significant positive correlation between WMS subtests (Figural memory, Visual reproduction I and Digit span) and BDNF in the first degree relatives
5- WCST: there was significant negative relationship in Schizophrenic group between BDNF and Perseverative Errors (percent) also, in First degree relatives group there were negative relationship between BDNF and Perseverative Errors (percent) in addition to positive relationship between BDNF and Categories completed. On the hand there was no significant relation in control group
6- A statistically positive correlation in General Psychopathology scale (Unusual thought content) PANSS test and BDNF concentration in schizophrenic group.
7- ROC curve analysis was used to assess the clinical diagnostic accuracy of BDNF patients with Schizophrenia; the results showed p-value <0.05 so; the serum BDNF level diagnosed the disease state at a statistically significant level with a 98% Sensitivity (true positive cases) and 90% Specificity (true negative cases) at a cutoff point level ≤ 29.0.
8- ROC curve analysis was used to assess the risk for schizophrenia by measuring BDNF in first degree relatives for patients with Schizophrenia and the normal individuals; the results of BDNF (ROC) curve analysis showed p-value <0.05 so; the serum BDNF level diagnosed the disease state at a statistically significant level with a 90% Sensitivity (true positive cases) and 37% Specificity (true negative cases) at a cutoff point level ≤ 42.07.