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T13. CORNEAL CONFOCAL MICROSCOPY DETECTS NEURAL CHANGES IN SCHIZOPHRENIA

Abstract Background A combination of neurodevelopmental and degenerative neural changes are likely to underpin positive and negative symptoms in schizophrenia. However, there are currently no validated biomarkers to accurately quantify the extent of neural changes in schizophrenia. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has been used to demonstrate in vivo corneal nerve fiber abnormalities in a range of peripheral neuropathies and central neurodegenerative disorders including Parkinson’s disease, multiple sclerosis and dementia. We wished to test the hypothesis that corneal nerve abnormalities occur in patients with schizophrenia, particularly those with negative symptoms and cognitive impairment. Methods Patients with DSM-V schizophrenia without other causes of peripheral neuropathy other than metabolic syndrome underwent assessment of clinical ratings (Positive and Negative Symptoms Scale (PANSS), cognitive function (Montreal Cognitive Assessment (MOCA) and Corneal confocal microscopy (CCM), vibration perception threshold (VPT) and sudomotor function testing. Healthy controls underwent the same assessments apart from PANSS. Results 55 subjects without (n=38) and with schizophrenia (n=17) with comparable mean age (35.7±8.5 vs 35.6±12.2, P=0.96) were studied. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02) and lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02) compared with healthy controls. The proportion of gender, systolic and diastolic blood pressure, HbA1c, cholesterol, triglyceride and High Density Lipoproteins were comparable between the two groups. Patients with schizophrenia had significantly lower corneal nerve fibre density (CNFD, fibers/mm2) (35.6±6.5 vs 23.5±7.8, p<0.0001), branch density (CNBD, branches/mm2) (98.1±30.6 vs 34.4±26.9, p<0.0001), and fibre length (CNFL, mm/mm2) (24.2±3.9 vs 14.3±4.7, p<0.0001) compared with healthy controls but no difference in peripheral neuropathy assessed by VPT and sudomotor function testing. The area under the Receiver Operating Characteristic Curve (95% CI) of CNFD, CNBD, CNFL to distinguish patients with schizophrenia from healthy controls were 87.0% (76.8–98.2%), 93.2% (84.2–102.3%), 93.2% (84.4–102.1%), respectively. Discussion These preliminary results: support the hypothesis that corneal nerve abnormalities occur in schizophrenia; corneal confocal microscopy has high diagnostic capability to distinguish subjects with schizophrenia from healthy controls; provide evidence to support the potential application of corneal confocal microscopy as a non-invasive technique to detect neural change in schizophrenia.


T12. THE RELATIONSHIP OF INTESTINAL PERMEABILITY FACTORS WITH SOCIODEMOGRAPHIC AND PHYSICAL HEALTH FACTORS AND PANSS SCORES IN SCHIZOPHRENIA PATIENTS AND HEALTHY CONTROLS
Jenny Borkent* 1 , Iris E. C. Sommer 1 , Bartholomeus C. M. Haarman 1 1 University Medical Center Groningen Background: Recent studies have pointed to the gut-brain axis as a new venue for treatment of psychiatric disorders, with increased inflammation stemming from increased intestinal permeability to further affect brain functioning in a significant subset of patients. Yet, this line of research is still in its infancy, with multiple studies showing increased intestinal permeability in schizophrenia and bipolar disorders, demonstrated as translocation of food and bacterial antigens, as well as intestinal microbiome disturbances. Methods: Therefore, we measured intestinal permeability markers soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in schizophrenia patients and healthy controls. Intestinal permeability markers were compared to several sociodemographic, including age, gender and BMI, and physical health variables, including CRP, glucose, cholesterol, triglycerides, HDL, LDL and non-HDL, and Positive and Negative Syndrome Scale (PANSS) scores. Of the control group (n = 43), 76.7% was male, with a mean age of 25.1 years. Of the schizophrenia group (n = 105) 75.2 % was male, with a mean age of 27.4 years and an average PANSS score of 57.2. Results: Levels of LBP and sCD14 were not significantly different between schizophrenia patients and controls. LBP and sCD14 levels were neither correlated in the control group, nor in the schizophrenia group. In the control group Females had elevated LBP levels compared to males (p < 0.01), but not in the schizophrenia group. Quantitative levels of LBP, but not sCD14, correlated with triglycerides in the schizophrenia group (R2 = 0.049, p < 0.05). Furthermore, quantitative levels of sCD14, but not LBP, correlated with CRP in the schizophrenia group (R2 = 0.078, p < 0.05). Finally, LBP levels in patients correlated with PANSS negative scores (R2 = 0.055, p < 0.05). Neither a correlation of LBP and sCD14 with age, nor with BMI was observed in both the control and the schizophrenia group. Discussion: In conclusion, these intestinal permeability markers showed few differences between the schizophrenia and the control group. We found weak, yet significant correlations with triglycerides, CRP and severity of negative symptoms, which may be caused by poor eating habits or metabolic syndrome leading to leaky gut in the more severely affected patients. These results are not in line with results of Severance et al. (2013), who performed a similar analysis and found differences in intestinal permeability markers between a control group and a schizophrenia group. Furthermore, they did observe a positive correlation between sCD14 and LBP in both the control and the schizophrenia group. The difference between that study and our current findings may stem from the different patients samples, as we assessed patients in their first five years after diagnosis, when metabolic syndrome was less abundant.

Academic Health System-Mental Health, Hamad Medical Corporation; 2 Weil Cornell Medical College-Qatar; 3 Neuroscience Institute, Hamad Medical Corporation; 4 Hamad Medical Corporation
Background: A combination of neurodevelopmental and degenerative neural changes are likely to underpin positive and negative symptoms in schizophrenia. However, there are currently no validated biomarkers to accurately quantify the extent of neural changes in schizophrenia. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has been used to demonstrate in vivo corneal nerve fiber abnormalities in a range of peripheral neuropathies and central neurodegenerative disorders including Parkinson's disease, multiple sclerosis and dementia. We wished to test the hypothesis that corneal nerve abnormalities occur in patients with schizophrenia, particularly those with negative symptoms and cognitive impairment. Methods: Patients with DSM-V schizophrenia without other causes of peripheral neuropathy other than metabolic syndrome underwent assessment of clinical ratings (Positive and Negative Symptoms Scale (PANSS), cognitive function (Montreal Cognitive Assessment (MOCA) and Corneal confocal microscopy (CCM), vibration perception threshold (VPT) and sudomotor function testing. Healthy controls underwent the same assessments apart from PANSS. Results: 55 subjects without (n=38) and with schizophrenia (n=17)  1. support the hypothesis that corneal nerve abnormalities occur in schizophrenia; 2. corneal confocal microscopy has high diagnostic capability to distinguish subjects with schizophrenia from healthy controls; 3. provide evidence to support the potential application of corneal confocal microscopy as a non-invasive technique to detect neural change in schizophrenia. Background: Kraepelin (1909) wrote about the association between female sex hormones and psychotic symptoms. He observed that women diagnosed with schizophrenia showed signs of gonadal dysfunction and hypoestrogenism. Antipsychotic drugs had not yet been introduced, so it cannot be interpreted as side effects. At the beginning of the 20th-century rhythmicity of psychotic symptoms through menstrual cycle was observed. The symptoms ameliorated when higher levels of estrogens were found. It was also noted during pregnancy. Reported cases and some studies confirmed these observations. Epidemiology shows a later peak of onset of psychosis in women. This protective role, also observed in clinical and animal studies, remains for the reproductive years and decreases by the time of menopause, when there's a second important peak of onset in women.

T14. HYPOTHALAMIC-PITUITARY-GONADAL AXIS HORMONES IN ANTIPSYCHOTIC NAÏVE FIRST-EPISODE OF PSYCHOSIS AND HEALTHY CONTROLS
In spite of all these observations, few systematic investigations have been published about the effects of estrogens in women with schizophrenia. This study aims to investigate differences in the levels of sexual hormones between antipsychotic-naïve women with and without psychosis.

Methods:
We performed a retrospective case-control study to compare the levels of sex hormones in blood of first-episode psychosis (FEP) and healthy control women (HC) of reproductive age, as a part of a NIH-NIDDK project on the study of hormonal factors and metabolism in psychosis. All participants were antipsychotic-naïve, in order to avoid bias from antipsychotic medication use. Four cases and four controls were recruited: cases were women newly diagnosed with primary non-affective psychosis at the emergency department of our hospital, and controls were mental health workers of similar age with no history of psychosis. Blood samples were obtained at the luteal phase of the menstrual cycle. We registered the following variables: age, psychosis status, last menstrual day and hormone blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone. We used descriptive statistics for age and hormone blood levels (mean and standard deviation -SD-) and we performed the Kruskal-Wallis test to determine any statistical differences of these variables regarding psychosis status. All participants provided informed consent. Ethical approval was obtained from the institutional ethics review board.

Results:
The mean age of FEP was 31.4 years (SD 1.9) and 26.1 years (SD 3.5) for HC, with no statistically significant differences. Both FSH and LH were higher in FEP (FSH: mean 7 U/L, SD 1.7; LH: mean 8.4 U/L, SD 2.6) compared to HC (FSH: mean 3.5 U/L, SD 1.2; LH: mean 5.7 U/L, SD 3.3), reaching statistical significance in the case of FSH (p=0.015). 17-b-estradiol was lower in FEP (mean 75.3 pg/mL, SD 54.6) than in HC (mean 151 ng/ mL, SD 102.1), although differences were not statistically significant Discussion: We observed higher levels of FSH in women with psychosis compared to controls in the luteal phase. These women were antipsychotic-naïve; thus, these results are not a consequence of medication use. Our observations add evidence to the known relationship between altered hormonal levels and schizophrenia in women. The increase in FSH stimulates the production of estrogens, which are known to be low in psychosis compared to healthy controls. This finding supports the hypoestrogenism hypothesis of schizophrenia. Future studies with larger samples evaluating hormonal levels, psychotic symptoms and differences with hormonal treatments could lead to research of new adjunctive therapies or approaches.