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）：患有严重精神疾病的人与吸烟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添加尼古丁风险最高的人群。目前对严重精神分裂症吸烟合并症的可能病因的概念包括针对神经认知缺陷的自我治疗、克服抗精神病药物的副作用以及共同的烟碱分子途径。然而，合并症的潜在大脑回路尚不清楚。识别大脑共病回路对于开发临床治疗开发、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，扣带回腹侧纹状体回路似乎是与尼古丁成瘾相关的关键途径之一。这些相同的区域也是最常与精神分裂症有关的区域之一，另外的初步研究表明，同一回路在精神分裂症中受到损害。因此，我们假设异常的扣带回腹侧纹状体回路是精神分裂症/尼古丁成瘾共病的关键途径。我们建议检验这样的假设：在尼古丁成瘾和精神分裂症中扣带回腹侧纹状体回路异常，并且精神分裂症病理学破坏了该回路并使患者容易出现更严重的尼古丁成瘾，从而导致严重的尼古丁成瘾/精神分裂症合并症。我们还将检查该电路在预测长期吸烟行为变化、遗传学及其与假定的成瘾机制的关系方面的临床有效性。确定这一高危人群中与吸烟相关的关键大脑回路将为新疗法的开发提供具体的生物标志物，并最终减轻精神分裂症患者与吸烟相关的健康负担。此外，随着公共卫生努力减少了吸烟，人群中那些仍然吸烟的人可能会更加依赖和更加抵抗治疗。针对吸烟最成瘾人群的努力也可能会产生治疗普通人群尼古丁成瘾的新观点。

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