Shared Neural Circuitry in Comorbid Schizophrenia and Nicotine Addiction

共病精神分裂症和尼古丁成瘾的共享神经回路

• 批准号: 8489266
• 负责人: L Elliot Elliot Hong
• 金额: $ 45.94万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489266
• 关键词: Accounting; Adverse effects; Alleles; Amygdaloid structure; Anatomy; Anterior; Antipsychotic Agents; Area; Behavioral; Biological Markers; Brain; Carbon Monoxide; Chronic; Cigarette Smoker; Clinical; Comorbidity; Corpus striatum structure; Data; Diagnosis; Dorsal; Etiology; Event; Exposure to; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Genes; Genetic; Genotype; Globus Pallidus; Goals; Health; Heritability; High Prevalence; Image; Impairment; Incentives; Lead; Link; Measures; Minnesota; Modeling; Molecular; Moods; Neurocognition; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Nucleus Accumbens; Outcome; Pathology; Pathway interactions; Patients; Personality; Pharmaceutical Preparations; Population; Public Health; Questionnaires; RTN4 gene; Recruitment Activity; Resistance; Rest; Rewards; Risk; Schizophrenia; Secondary to; Selection for Treatments; Self Medication; Severities; Siblings; Signal Transduction; Smoke; Smoker; Smoking; Smoking Behavior; Smoking Status; Stress; Structure; Subgroup; Substantia Innominata; Symptoms; Syndrome; System; Target Populations; Testing; Thalamic structure; Tobacco use; Ventral Striatum; Withdrawal; Withdrawal Symptom; addiction; base; behavior change; caudate nucleus; cingulate cortex; craving; design; follow-up; heuristics; high risk; neural circuit; non-smoker; novel; novel therapeutics; prospective; public health relevance; putamen; response; severe mental illness; smoking cessation; social; success; therapeutic development; trait; treatment strategy

DESCRIPTION (provided by applicant): The health risk associated with tobacco use in people with severe mental illness is much higher than the general population. Among them, patients with schizophrenia are the population with perhaps the highest risk for nicotine addition. Current conceptualizations of the possible etiologies of the severe schizophrenia-smoking comorbidity include self-medication for neurocognition deficits, overcoming antipsychotic medication side effects, and shared nicotinic molecular pathways. However, the underlying brain circuitry for the comorbidity is unknown. Identifying brain comorbidity circuitry is critical for developing valid biomarkers for clinical therapeutic development, individualizing treatment selection and outcome prediction. Recent data suggest that the cingulate-ventral striatum circuit appears to be one of the key pathways associated with nicotine addiction. These same areas are also among the regions most commonly implicated in schizophrenia, and additional preliminary studies suggest that the same circuit is impaired in schizophrenia. Therefore, we hypothesize that abnormal cingulate-ventral striatum circuit is a key path for schizophrenia/nicotine addiction comorbidity. We propose to test the hypotheses that the cingulate-ventral striatum circuit is abnormal in nicotine addiction and in schizophrenia, and that schizophrenia pathology disrupts this circuit and predisposes patients to more severe nicotine addiction, leading to the severe nicotine addiction/schizophrenia comorbidity. We will also examine the clinical validities of the circuit in prediction of long-term smoking behavioral change, in genetics, and in its relationships to putative addiction mechanisms. Identifying the key brain circuits associated with smoking in this high risk population will provide concrete biomarkers for new therapeutic development, and ultimately reducing the smoking related health burden in schizophrenia patients. In addition, as public health efforts have reduced smoking, those who still smoke in the population may be more dependent and more treatment-resistant. An effort targeting the population most addicted to smoking may also yield novel perspectives to treat nicotine addiction in the general population.

描述（由申请人提供）：严重精神疾病患者与烟草使用相关的健康风险远高于一般人群。其中，精神分裂症患者可能是尼古丁添加风险最高的人群。目前对严重精神分裂症吸烟合并症可能病因的概念化包括神经认知缺陷的自我药物治疗，克服抗精神病药物副作用，以及共享的烟碱分子途径。然而，合并症的潜在脑回路尚不清楚。识别脑共病电路对于开发用于临床治疗开发、个体化治疗选择和结果预测的有效生物标志物至关重要。最近的数据表明，扣带-腹侧纹状体回路似乎是与尼古丁成瘾相关的关键通路之一。这些相同的区域也是精神分裂症最常见的区域之一，另外的初步研究表明，精神分裂症患者的相同回路受损。因此，我们推测扣带回-腹侧纹状体回路异常是精神分裂症/尼古丁成瘾共病的关键通路。我们建议测试的假设，扣带回腹侧纹状体电路是异常的尼古丁成瘾和精神分裂症，精神分裂症的病理破坏这一电路，使患者更严重的尼古丁成瘾，导致严重的尼古丁成瘾/精神分裂症合并症。我们还将研究该回路在预测长期吸烟行为变化、遗传学及其与假定成瘾机制的关系方面的临床有效性。在这一高风险人群中识别与吸烟相关的关键脑回路将为新的治疗开发提供具体的生物标志物，并最终减少精神分裂症患者与吸烟相关的健康负担。此外，由于公共卫生工作减少了吸烟，人口中仍然吸烟的人可能更依赖和更耐治疗。针对吸烟成瘾最严重的人群的努力也可能产生治疗普通人群尼古丁成瘾的新观点。