PS198. Pathological analysis of refractory depression using fetal alcohol and adolescent corticosterone double stress model

Objectives: The purpose of this study is to investigate the alterations of the hypothalamic-pituitary-adrenal axis hormones, especially salivary cortisol and dehydroepiandrosterone (DHEA) in perinatal depression. Methods: 44 patients with depression and 217 normal subjects in perinatal period were included in this study. Edinburgh Postnatal Depression Scale(EPDS) and Beck Depression Inventory II(BDI-II) were performed. The subjects below 10 points of EPDS score or below 13 points of BDI-II score were classified to normal subjects. Among the subjects more than 11 points of EPDS score or more than 14 points of BDI-II score were diagnosed depression by DSM-IV TR by psychiatrists. All subjects were to collect their saliva in each 4 collecting tubes, immediately upon awakening(IA), 30 minutes after awakening(30A), 60 minutes after awakening(60A) and before bedtime(BB). Results: The number of subjects in antenatal period were 103, and antenatal depression(AD) patients were 21, antenatal normal(AN) subjects were 82. The number of subjects in postnatal period were 114, and postnatal depression(PD) patients were 23, postnatal normal(PN) subjects were 91. Salivary cortisol levels in subjects with AD collected IA, 30A and 60A were lower than with AN subjects significantly except BB. Salivary cortisol levels in subjects with PD collected 60A only were lower than with PN subjects significantly. Salivary DHEA levels in subjects with both AD and PD were lower than with normal subjects significantly. Also cortisol/DHEA ratio(F/D ratio) in subjects with both AD and PD were much higher than with normal subjects significantly. Conclusions: These results suggest that the blunted response was shown in AD, and the characteristics between AD and PD are different. Also the differences of salivary DHEA levels and F/D ratio between subjects with PD and normal subjects are suggested the one of the key points of difference among both groups. PS197 Low level of perineuronal nets in the medial prefrontal cortex predicts vulnerability to stress Na Chen,1 Die Hu,1 Lin Lu,1,2,3 Jie Shi 1 1National Institute on Drug Dependence, Peking University, Beijing, China; 2Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Ministry of Health, Beijing, China; 3Peking-Tsinghua Center for Life Sciences and PKU-IDG/ McGovern Institute for Brain Research; Abstract Perineuronal nets (PNNs) are extracellular matrix structures enwrapping parvalbumin-positive γ-aminobutyric acid (GABA)ergic interneurons which are crucial for modulating anxiety and depressive-like behaviors. Perineuronal nets have recently been implicated in experience-dependent neuroplastic changes in central nervous system, but it is poorly understood that whether PNNs modulates the neural maladaptation after repeated exposure to stress. We found that adolescent rats with vulnerability to chronic unpredictable mild stress (CUMS) showed decreased level of PNNs, tenascin-R and aggrecan in the medial prefrontal cortex (mPFC). Degradation of PNNs in mPFC produced vulnerability to stress in adult rats. Elevating PNNs in the mPFC through environment enrichment prevented CUMS-induced depressive and anxiety-like behavior. Fluoxetine reversed the stress vulnerability in adolescent rats and increased PNNs levels. Lower level of PNNs rendered GABAergic neurons susceptible to CUMS, manifesting as decreases in expression of glutamic acid decarboxylase 67 (GAD 67) and frequency and amplitude of inhibitory postsynaptic current (IPSC) after CUMS. The organization of PNNs coincided with the developmental switch in stress vulnerability to resilience. These findings indicate a role of PNNs in mPFC in predicting and modulating vulnerability to stressinduced depressive-like behavior, and the effect may be produced though regulating GABAergic functions.