Response Inhibition and Emotional Modulation Effect on Response Inhibition in Biopolar I Disorder and Schizophrenia.

Response inhibition deficits and the influence of emotion on response inhibition were investigated in patients with schizophrenia (SZ), schizoaffective disorder (SAD) and bipolar I disorder (BD) with event-related brain potentials (ERPs). Further, it was tested whether the neural deficits in response inhibition can differentiate each group by applying discriminant functional analysis. In order to fulfill the study goal, two different versions of Go/NoGo tasks were used: non-affective stimulus (alphabet letters) and the other with affective stimulus (faces with emotions).Two event-related brain potentials (ERPs), N200 and P300 components were measured for non-affective Go/NoGo task, while face-specific ERPs, N170 and N250, in addition to P300, were further obtained for emotional Go/NoGo task . With lateralized non-affective Go/NoGo task, the first study revealed that SZ showed left-lateralized response inhibition deficit over the frontal region measured by P300. SAD showed prolonged stimulus evaluation time in the early stage of response inhibition manifested by N200 latency. The second study replicated SZ’s response inhibition deficit associated with left hemisphere dysfunction. BD disorder did not show deficits in response inhibition compared to that in SZ but delayed overall cognitive stimulus evaluation was observed. When the non-affective stimuli were replaced with faces with four categories of emotions (happy, angry, sad, and neutral), emotion modulation effect (larger ERP amplitudes for faces with emotions than for neutral faces) was observed only in response execution (Go trials) not in response inhibition (NoGo trials) process in both patients and controls. Both SZ and BD showed deficits in early facial structure encoding revealed by reduced amplitude in N170 component but relatively intact in early facial affect decoding compared to healthy controls (CT). In three studies, it was replicated that P300 amplitude and N200 latency successfully discriminated SZ, SAD (study 1), BD (study 2 & 3), and CT, which implicates that distinct ERP patterns in response inhibition task can become endophenotypes of each psychiatric disorder.Ph.D.PsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/78787/1/jschun_1.pd

Altered N170 and mood symptoms in bipolar disorder: An electrophysiological study of configural face processing

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145368/1/bdi12587.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145368/2/bdi12587_am.pd

Regulating the high: Cognitive and neural processes underlying positive emotion regulation in Bipolar I Disorder

Although it is well established that Bipolar Disorder (BD) is characterized by excessive positive emotionality, the cognitive and neural processes that underlie such responses are unclear. We addressed this issue by examining the role that an emotion regulatory process called self-distancing plays in two potentially different BD phenotypes—BD with vs. without a history of psychosis—and healthy individuals. Participants reflected on a positive autobiographical memory and then rated their level of spontaneous self-distancing. Neurophysiological activity was continuously monitored using electroencephalogram. As predicted, participants with BD who have a history of psychosis spontaneously self-distanced less and displayed greater neurophysiological signs of positive emotional reactivity compared to the other two groups. These findings shed light on the cognitive and neural mechanisms underlying excessive positive emotionality in BD. They also suggest that individuals with BD who have a history of psychosis may represent a distinct clinical phenotype characterized by dysfunctional emotion regulation

MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis

Background: Even though increasing evidences on miRNA involvement in human pathological responses, the distinct roles and related mechanisms of miRNAs in the pathology of osteoarthritis (OA) are not yet fully understood. Method: RNA levels or protein levels of Apoptotic genes, HDACs, MMP-13, and miRNAs in human chondrocytes isolated from normal biopsy sample and OA cartilages were analyzed by real-time PCR or western blotting. Exogenous modulation of miR-222 level was performed using delivery of its specific precursor or specific inhibitor and target validation assay was applied to identify its potent target. In vivo study using DMM mice model was performed and assessed the degree of cartilage degradation. Results: According to miRNA profiling, miR-222 was significantly down-regulated in OA chondrocytes. Over-expression of miR-222 significantly suppressed apoptotic death by down-regulating HDAC-4 and MMP-13 level. Moreover, 3′-UTR reporter assays showed that HDAC-4 is a direct target of miR-222. The treatment of chondrocytes with the HDAC inhibitor, trichostatin A (TSA), suppressed MMP-13 protein level and apoptosis, whereas the over-expression of HDAC-4 displayed opposite effects. The introduction of miR-222 into the cartilage of medial meniscus destabilized mice significantly reduced cartilage destruction and MMP-13 level. Conclusion: Taken together, our data suggest that miR-222 may be involved in cartilage destruction by targeting HDAC-4 and regulating MMP-13 level

Regulating the High

Although it is well established that Bipolar Disorder (BD) is characterized by excessive positive emotionality, the cognitive and neural processes that underlie such responses are unclear. We addressed this issue by examining the role that an emotion regulatory process called self-distancing plays in two potentially different BD phenotypes-BD with vs. without a history of psychosis-and healthy individuals. Participants reflected on a positive autobiographical memory and then rated their level of spontaneous self-distancing. Neurophysiological activity was continuously monitored using electroencephalogram. As predicted, participants with BD who have a history of psychosis spontaneously self-distanced less and displayed greater neurophysiological signs of positive emotional reactivity compared to the other two groups. These findings shed light on the cognitive and neural mechanisms underlying excessive positive emotionality in BD. They also suggest that individuals with BD who have a history of psychosis may represent a distinct clinical phenotype characterized by dysfunctional emotion regulation