Abstracts for the Sixth Biennial SIRS Conference

Poster Session I S117 Mental Health Centre Copenhagen, Copenhagen University Hospital; 2Copenhagen University Hospital; 3Mental Health Centre Copenhagen 1

Background: Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet synthesized all the available data on cerebrospinal fluid (CSF) immune-alterations. We conducted the first systematic review of the immunological findings from CSF studies among patients with schizophrenia or affective disorders. Methods: All studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 were identified searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. The literature search, data extraction and assessment of risk of bias were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on studies including healthy controls. Results: We identified 112 CSF studies published between 1942–2016, of which 32 were included in meta-analyses; however, only few studies investigated identical biomarkers. The CSF/serum albumin ratio was increased in both schizophrenia (54 patients; SMD=0.62; 95%CI=0.24–1.00) and affective disorders (302 patients; SMD=0.43; 95%CI=0.25–0.61, I2=0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (97 patients; SMD=0.38; 95%CI=0.12–0.65, I2=0%) and affective disorders (53 patients; SMD=0.77; 95%CI=0.36–1.18, I2=0%). The IgG ratio was increased in schizophrenia (54 patients; SMD=0.60; 95%CI=0.23–0.98), whereas the IgG Albumin ratio was decreased (32 patients; SMD= -0.62; 95%CI= -1.13 to -0.12). Interleukin-8 (IL-8) (95 patients; SMD=0.46; 95%CI=0.17– 0.75, I2=0%) and IL-6 levels (230 patients; SMD=0.38; 95%CI=0.02–0.74; I2=64%) were increased among individuals with schizophrenia but not significantly increased in affective disorders. None of the remaining inflammatory markers were significantly different compared to healthy controls in the metaanalyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and CSF dependent re-diagnosis occurred in 3.2–6% in the two studies investigating this. Discussion: Our findings suggests that schizophrenia spectrum and affective disorders are associated with CSF abnormalities including signs of blood-brain barrier impairment and inflammation, supporting a role of the immune system in mental disorders. However, only few studies investigated the same parameters with healthy controls and high quality longitudinal CSF studies are lacking, including impact of psychotropic medications and potential benefits of anti-inflammatory treatment in subgroups with abnormal CSF inflammatory markers

T12. VITAMIN D STATUS AND PSYCHOTIC DISORDER: ASSOCIATIONS WITH CLINICAL VARIABLES AND RISK FACTORS Christine van der Leeuw*,1, Lot de Witte2, Claude van der Ley3, Richard Bruggeman3, Jim van Os4, Machteld Marcelis5 1 Maastricht University Medical Center; 2Icahn School of Medicine, University Medical Center Utrecht, Utrecht University; 3University of Groningen, University Medical Center Groningen; 4University Medical Center Utrecht, Utrecht University, Maastricht University Medical Center, Institute of Psychiatry, King’s College London; 5 Maastricht University Medical Center, Institute for Mental Health Care Eindhoven (GGzE) Background: The association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Vitamin D deficiency in patients diagnosed with schizophrenia is presumably (also) the result of diseaserelated factors.

Furthermore, certain demographic risk factors such as urbanicity may be associated with vitamin D. Methods: In a large study population of 347 patients with psychotic disorder and 282 controls, associations between vitamin D levels in blood and clinical variables and risk factors were investigated. Regression analyses were conducted correcting for gender, age, ethnicity, body mass index (BMI), smoking and sampling season. Group × symptomatology and group × urbanicity interactions were investigated. Both current urbanicity and urbanicity at birth were assessed. Results: Vitamin D concentrations were significantly lower in patients (B= -8.05; 95% confidence interval (CI) -13.68 to -2.42; p=0.005). There were (trend) significant interactions between group and vitamin D for symptomatology (positive symptoms: χ2=2.81 and p=0.094; negative symptoms: χ2=5.63 and p=0.018). A small but significant effect was detected: higher vitamin D concentration was associated with lower positive (B= -0.02; 95% CI -0.04 to 0.00; p=0.049) and negative symptom levels (B= -0.03; 95% CI -0.05 to -0.01; p=0.008) in patients. The group × current urbanicity interaction was not significant. However, the group × urbanicity at birth was significant when corrected for current urbanicity (χ2=11.26 and p=0.001). Discussion: Vitamin D levels in patients with psychotic disorder were lower than in controls, with an interaction between group and urbanicity at birth. In the patient group, symptom levels were lower when vitamin D concentration was higher.

T13. PROGRESSIVE SPONTANEOUS AND SYNCHRONY GAMMA-BAND OSCILLATION DEFICITS IN FIRST EPISODE SCHIZOPHRENIA Yoji Hirano*,1, Naoya Oribe1, Toshiaki Onitsuka1, Shigenobu Kanba1, Martha Shenton2, Margaret A. Niznikiewicz3, Larry J. Seidman4, Robert W. McCarley3, Kevin M. Spencer3 1 Kyushu University; 2Brigham & Women’s Hospital, Harvard Medical School; 3Harvard Medical School, Veterans Affairs Boston Healthcare System; 4Harvard Medical School, Beth Israel Deaconess Medical Center Background: Deficits in the gamma-band (30–100 Hz) auditory steady-state response (ASSR) and progressive volumetric decreases in the primary auditory cortex have been detected shortly after the onset of schizophrenia (SZ), and may be associated with symptoms such as auditory hallucinations. Disruption of gamma-band oscillation has received considerable interest, as the basic mechanisms underlying these oscillations are understood and are conserved across species. Despite the importance of abnormal gammaband oscillations in SZ, it remains unclear whether the gamma-band ASSR deficit shows progressive change over time during the early stages of the disease. Moreover, animal models based on NMDA receptor hypofunction demonstrate an increase in spontaneous gamma power, which has been reported in chronic SZ (Hirano et al., JAMA Psychiatry 2015), yet it still remains unclear in first-episode schizophrenia (FESZ). Hence, a longitudinal electroencephalogram study of the spontaneous and synchrony gamma-band oscillation in FESZ is important to better understand the pathophysiology and trajectory of early-stage schizophrenia. Methods: Subjects were 23 FESZ (14 treated and 9 untreated with antipsychotics), and 39 matched healthy controls (HC). Dipole source localization of dense electrode EEG data was used to examine oscillatory activities in auditory cortices during auditory steady-state stimulation (20/30/40-Hz rates). ICA was used to remove artifacts. Phase locking factor (PLF) and induced power (not phase-locked) were calculated from artifact-free single trial source estimates. Clinical symptoms were assessed by SAPS and SANS. Subjects were recruited as part of the Boston CIDAR Center (www. bostoncidar.org). Test sessions (Time-1/Time-2) were 11.9 months apart. Results: Compared to HC, FESZ showed reduced 40-Hz ASSR PLF (synchrony gamma) and increased induced gamma power (spontaneous gamma) during continuous auditory stimuli at time-1. Longitudinally,

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