Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults

奖励、冲动感觉寻求和情绪失调：年轻人双相情感障碍潜在风险的神经机制

• 批准号: 10542658
• 负责人: Mary Louise Phillips
• 金额: $ 69.92万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542658
• 关键词: Accounting; Adult; Affect; Age; American; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Behavior; Behavioral; Biological Markers; Bipolar Disorder; Brain; Brain imaging; Clinical; Cues; Data; Dimensions; Disease; Disease remission; Dorsal; Emotions; Esthesia; Feeling suicidal; Future; Gender; Impulsivity; Intervention; Left; Manic; Measures; Mediating; Mediator; Mental Depression; Mental disorders; Mood Disorders; Onset of illness; Outcome; Parietal Lobe; Personality Disorders; Pharmaceutical Preparations; Prefrontal Cortex; Psychopathology; Quality of life; Regulation; Rest; Rewards; Risk; Risk Marker; Sampling; Scanning; Severities; Symptoms; Thick; Ventral Striatum; age group; anxiety symptoms; bipolar spectrum; cingulate cortex; cohort; common symptom; depressive symptoms; disability; disorder risk; emerging adult; emotion dysregulation; emotion regulation; follow-up; gray matter; hypomania; imaging biomarker; interest; neural; neural circuit; neuroimaging; neuromechanism; neuroregulation; novel; predictive marker; prevent; recruit; reward circuitry; reward expectancy; trait; trait impulsivity; white matter; young adult

ABSTRACT. Bipolar Spectrum Disorders (BPSD) affect up to 4.5% of Americans, are the 4th leading cause of disability worldwide, with onset peaking in early adulthood. Yet, it is very difficult to identify young adults at risk for BPSD, as there are no objective biomarkers of BPSD risk. Identifying these biomarkers can be facilitated by elucidating neural biomarkers of behaviors that predispose to key symptoms of BPSD: hypomania and mania. While emotional dysregulation characterizes BPSD, it also characterizes, and predisposes to, anxiety, depression, and anxiety, affective and personality disorders. Impulsive sensation seeking (ISS) comprises the component traits impulsivity and sensation seeking. High trait ISS characterizes BPSD, and predisposes to hypomania and mania in young adults. Thus, high trait ISS predisposes to hypo/mania, and emotional dysregulation, to anxiety and depression. The combination of both may ultimately confer risk for BPSD. In the first 4 years of R01MH100041, examining neural biomarkers of dimensions of psychopathology and 1-year outcome neural predictors in transdiagnostically-recruited young adults, we show (in n=100) a positive association between trait ISS and activity in reward circuitry: left ventrolateral prefrontal cortex (vlPFC) and ventral striatum (VS) during uncertain reward expectancy (RE). Greater left vlPFC and VS activity to uncertain RE is also shown by BPSD vs healthy adults. In MH100041, greater left vlPFC-parietal cortical functional connectivity (FC) to uncertain RE is associated with greater mania severity 6 months post scan; and greater left VS-left vlPFC resting state FC, with higher trait ISS. By contrast, greater amygdala activity, and lower amygdala-dorsal/rostral anterior cingulate cortical (dACC/rACC) FC, during emotion processing and regulation are associated with greater emotional dysregulation, anxiety and depression, and risk for anxiety, affective and personality disorders. Elevated reward circuitry activity and FC to uncertain RE and rest are thus promising neural biomarkers of hypo/mania risk, and, with the above amygdala-ACC abnormalities, may predispose to BPSD. We propose a renewal of MH100041 to: 1. Replicate and extend our neural biomarker findings in a new cohort of 180 young adults (18-30 years; recruited transdiagnostically; no BPSD); 2. Determine if these neural biomarkers are present in a new group of 60 age- and gender-ratio-matched adults with BPSD (30 bipolar disorder I, 30 bipolar disorder II, prototypical types of BPSD; remitted to avoid confounds of high severity symptoms; unmedicated/ specific medications); 3. Identify across original and new non-BPSD cohorts neural biomarkers of trait ISS and emotional dysregulation that predict worsening hypo/mania vs. worsening anxiety and depression over extended (2 years’) follow up, and explore which neural biomarkers predispose to BPSD vs. other disorders. Identifying neural biomarkers of BPSD risk will help to better identify BPSD at-risk young adults, and provide neural targets for novel (e.g., neuromodulation) interventions to delay, or prevent, BPSD.

摘要。双相情感障碍（BPSD）影响高达4.5%的美国人，是第四大原因

项目成果

A pathway linking reward circuitry, impulsive sensation-seeking and risky decision-making in young adults: identifying neural markers for new interventions.

• DOI: 10.1038/tp.2017.60
• 发表时间: 2017-04-18
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Chase HW;Fournier JC;Bertocci MA;Greenberg T;Aslam H;Stiffler R;Lockovich J;Graur S;Bebko G;Forbes EE;Phillips ML
• 通讯作者: Phillips ML

Brain morphometric biomarkers distinguishing unipolar and bipolar depression. A voxel-based morphometry-pattern classification approach.

• DOI: 10.1001/jamapsychiatry.2014.1100
• 发表时间: 2014-11
• 期刊: JAMA psychiatry
• 影响因子: 25.8
• 作者: Redlich R;Almeida JJ;Grotegerd D;Opel N;Kugel H;Heindel W;Arolt V;Phillips ML;Dannlowski U
• 通讯作者: Dannlowski U

Bipolar disorder diagnosis: challenges and future directions.

• DOI: 10.1016/s0140-6736(13)60989-7
• 发表时间: 2013-05-11
• 期刊: Lancet (London, England)
• 作者: Phillips ML;Kupfer DJ
• 通讯作者: Kupfer DJ

Working memory updating in individuals with bipolar and unipolar depression: fMRI study.

• DOI: 10.1038/s41398-022-02211-6
• 发表时间: 2022-10-11
• 期刊: TRANSLATIONAL PSYCHIATRY
• 影响因子: 6.8
• 作者: Manelis, Anna;Halchenko, Yaroslav O.;Bonar, Lisa;Stiffler, Richelle S.;Satz, Skye;Miceli, Rachel;Ladouceur, Cecile D.;Bebko, Genna;Iyengar, Satish;Swartz, Holly A.;Phillips, Mary L.
• 通讯作者: Phillips, Mary L.

Elucidating neural network functional connectivity abnormalities in bipolar disorder: toward a harmonized methodological approach.

• DOI: 10.1016/j.bpsc.2015.12.006
• 发表时间: 2016-05
• 期刊: Biological psychiatry. Cognitive neuroscience and neuroimaging
• 作者: Chase HW;Phillips ML
• 通讯作者: Phillips ML