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: 8689997
• 负责人: L Elliot Elliot Hong
• 金额: $ 47.84万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8689997
• 关键词: Accounting; Adverse effects; 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; psychotic symptoms; putamen; response; risk variant; 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）：严重精神疾病患者中与烟草使用相关的健康风险远高于一般人群。其中，精神分裂症患者是增加尼古丁风险最高的人群。严重精神分裂症的合并症的可能病因的当前概念包括神经认知缺陷的自我药物，克服抗精神病药物副作用和共享烟碱分子途径。但是，合并症的基础脑电路尚不清楚。识别脑合并症电路对于开发有效的生物标志物至关重要，以用于临床治疗性发育，个性化治疗选择和结果预测。最近的数据表明，扣带回的腹纹状体电路似乎是与尼古丁成瘾相关的关键途径之一。这些相同的领域也是精神分裂症最常见的地区之一，其他初步研究表明，在精神分裂症中相同的电路受损。因此，我们假设异常的扣带回 - 腹纹状体回路是精神分裂症/尼古丁成瘾合并症的关键途径。我们建议测试以下假设：戒指 - 腹纹状体回路在尼古丁成瘾和精神分裂症中是异常的，而精神分裂症病理学会破坏这一回路，使患者倾向于更严重的尼古丁成瘾，导致严重的尼古丁成瘾/精神分裂症的合并症。我们还将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中的临床有效性。确定与吸烟相关的关键大脑回路将为新的治疗性发育提供具体的生物标志物，并最终减轻精神分裂症患者的吸烟相关的健康负担。此外，随着公共卫生的努力减少了吸烟，那些仍在人口中吸烟的人可能更依赖和更耐药。针对最沉迷于吸烟的人群的努力也可能会产生新的观点，以治疗普通人群中的尼古丁成瘾。

项目成果

Down-regulation of amygdala and insula functional circuits by varenicline and nicotine in abstinent cigarette smokers.

• DOI: 10.1016/j.biopsych.2013.01.035
• 发表时间: 2013-10-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Sutherland, Matthew T.;Carroll, Allison J.;Salmeron, Betty Jo;Ross, Thomas J.;Hong, L. Elliot;Stein, Elliot A.
• 通讯作者: Stein, Elliot A.

Dipyridamole monotherapy in schizophrenia: pilot of a novel treatment approach by modulation of purinergic signaling.

双嘧达莫单药治疗精神分裂症：通过调节嘌呤能信号传导的新型治疗方法的试点。

• DOI: 10.1007/s00213-011-2315-3
• 发表时间: 2011
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Wonodi,Ikwunga;Gopinath,HirekaturV;Liu,Judy;Adami,Helene;Hong,LElliot;Allen-Emerson,Robert;McMahon,RobertP;Thaker,GunvantK
• 通讯作者: Thaker,GunvantK

Individual differences in amygdala reactivity following nicotinic receptor stimulation in abstinent smokers.

戒烟者烟碱受体刺激后杏仁核反应性的个体差异。

• DOI: 10.1016/j.neuroimage.2012.10.043
• 发表时间: 2013
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Sutherland,MatthewT;Carroll,AllisonJ;Salmeron,BettyJo;Ross,ThomasJ;Hong,LElliot;Stein,ElliotA
• 通讯作者: Stein,ElliotA

Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism.

物质使用者的前额白质损伤取决于儿茶酚邻甲基转移酶 (COMT) val158met 多态性。

• DOI: 10.1016/j.neuroimage.2012.11.056
• 发表时间: 2013
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Zhang,Xiaochu;Lee,MaryR;Salmeron,BettyJo;Stein,DanJ;Hong,LElliot;Geng,Xiujuan;Ross,ThomasJ;Li,Nan;Hodgkinson,Colin;Shen,Pei-Hong;Yang,Yihong;Goldman,David;Stein,ElliotA
• 通讯作者: Stein,ElliotA