@article{13168,
  abstract     = {Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1, explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group (r = 0.10, Pperm < 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3, explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group (r = 0.03, Pperm < 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.},
  author       = {Xu, Jiayuan and Liu, Nana and Polemiti, Elli and Garcia-Mondragon, Liliana and Tang, Jie and Liu, Xiaoxuan and Lett, Tristram and Yu, Le and Nöthen, Markus M. and Feng, Jianfeng and Yu, Chunshui and Marquand, Andre and Schumann, Gunter and Walter, Henrik and Heinz, Andreas and Ralser, Markus and Twardziok, Sven and Vaidya, Nilakshi and Serin, Emin and Jentsch, Marcel and Hitchen, Esther and Eils, Roland and Taron, Ulrike Helene and Schütz, Tatjana and Schepanski, Kerstin and Banks, Jamie and Banaschewski, Tobias and Jansone, Karina and Christmann, Nina and Meyer-Lindenberg, Andreas and Tost, Heike and Holz, Nathalie and Schwarz, Emanuel and Stringaris, Argyris and Neidhart, Maja and Nees, Frauke and Siehl, Sebastian and A. Andreassen, Ole and T. Westlye, Lars and Van Der Meer, Dennis and Fernandez, Sara and Kjelkenes, Rikka and Ask, Helga and Rapp, Michael and Tschorn, Mira and Böttger, Sarah Jane and Novarino, Gaia and Marr, Lena and Slater, Mel and Viapiana, Guillem Feixas and Orosa, Francisco Eiroa and Gallego, Jaime and Pastor, Alvaro and Forstner, Andreas and Hoffmann, Per and M. Nöthen, Markus and J. Forstner, Andreas and Claus, Isabelle and Miller, Abbi and Heilmann-Heimbach, Stefanie and Sommer, Peter and Boye, Mona and Wilbertz, Johannes and Schmitt, Karen and Jirsa, Viktor and Petkoski, Spase and Pitel, Séverine and Otten, Lisa and Athanasiadis, Anastasios Polykarpos and Pearmund, Charlie and Spanlang, Bernhard and Alvarez, Elena and Sanchez, Mavi and Giner, Arantxa and Hese, Sören and Renner, Paul and Jia, Tianye and Gong, Yanting and Xia, Yunman and Chang, Xiao and Calhoun, Vince and Liu, Jingyu and Thompson, Paul and Clinton, Nicholas and Desrivieres, Sylvane and H. Young, Allan and Stahl, Bernd and Ogoh, George},
  issn         = {1546-170X},
  journal      = {Nature Medicine},
  pages        = {1456--1467},
  publisher    = {Springer Nature},
  title        = {{Effects of urban living environments on mental health in adults}},
  doi          = {10.1038/s41591-023-02365-w},
  volume       = {29},
  year         = {2023},
}

@article{6198,
  abstract     = {Stroke is a major public health problem leading to high rates of death and disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are crucial for neuronal injury after stroke insult. However, directly inhibiting NMDARs or nNOS can cause severe side effects because they have key physiological functions in the CNS. Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95 interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction, ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively, had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke, perhaps without major side effects. },
  author       = {Zhou, L and Li, F and Xu, Haibing and Luo, CX and Wu, HY and Zhu, MM and Lu, W and Ji, X and Zhou, QG and Zhu, DY},
  issn         = {1078-8956},
  journal      = {Nature Medicine},
  number       = {12},
  pages        = {1439--1443},
  publisher    = {Nature Publishing Group},
  title        = {{Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95}},
  doi          = {10.1038/nm.2245},
  volume       = {16},
  year         = {2010},
}