Impaired regulation of emotion: Neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD

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

Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder.

Bipolar disorder (BD) is characterized by emotional dysregulation and cognitive deficits associated with abnormal connectivity between subcortical-primarily emotional processing regions-and prefrontal regulatory areas. Given the significant contribution of genetic factors to BD, studies in unaffected first-degree relatives can identify neural mechanisms of genetic risk but also resilience, thus paving the way for preventive interventions. Dynamic causal modeling (DCM) and random-effects Bayesian model selection were used to define and assess connectomic phenotypes linked to facial affect processing and working memory in a demographically matched sample of first-degree relatives carefully selected for resilience (n=25), euthymic patients with BD (n=41) and unrelated healthy controls (n=46). During facial affect processing, patients and relatives showed similarly increased frontolimbic connectivity; resilient relatives, however, evidenced additional adaptive hyperconnectivity within the ventral visual stream. During working memory processing, patients displayed widespread hypoconnectivity within the corresponding network. In contrast, working memory network connectivity in resilient relatives was comparable to that of controls. Our results indicate that frontolimbic dysfunction during affect processing could represent a marker of genetic risk to BD, and diffuse hypoconnectivity within the working memory network a marker of disease expression. The association of hyperconnectivity within the affect-processing network with resilience to BD suggests adaptive plasticity that allows for compensatory changes and encourages further investigation of this phenotype in genetic and early intervention studies

Neurocognitive and Neuroimaging Predictors of Clinical Outcome in Bipolar Disorder

Historically, bipolar disorder has been conceptualized as a disease involving episodic rather than chronic dysfunction. However, increasing evidence indicates that bipolar disorder is associated with substantial inter-episode psychosocial and vocational impairment. Here we review the contributions of neurocognitive deficits and structural and functional neuroanatomic alterations to the observed functional impairments. In particular, compelling evidence now suggests that neurocognitive impairments, particularly in the areas of attention, processing speed, and memory, are associated with functional outcome. Although investigation of the neural correlates of functional disability in bipolar disorder is only in its nascent stages, preliminary evidence suggests that white matter abnormalities may be predictive of poor outcome. A better understanding of the relationship between neurocognitive and neuroimaging assays and functional outcome has the potential to improve current treatment options and provide targets for new treatment strategies in bipolar disorder

Social cognition in euthymic bipolar disorder: systematic review and meta-analytic approach.

Objective: Deficits in social cognition have been reported in euthymic subjects with bipolar disorder (BD). However, some studies have failed to find differences favoring controls. As most investigations have been conducted with small samples, they have not had sufficient power to detect statistically significant differences. Furthermore, studies communicating positive results have scarcely attempted to estimate effect sizes for patient-control differences. The aim of this study was to summarize the findings of reports on social cognition in patients with euthymic BD and to combine their data to identify possible deficits and quantify their magnitude. Method: Systematic literature review and meta-analysis. Results: Impairments of moderate magnitude (0.5 < d < 0.8) were noted across mentalizing skills, whereas small but significant effect sizes (d < 0.5) were observed for facial emotion recognition. No patient–control differences were found for decision-making. Conclusion: Meta-analytic findings provide evidence for emotion processing and theory of mind deficits in remitted bipolar patients. However, it is not yet clear whether these areas of impairment are related to neurocognitive dysfunctions or to medication effects. The results are discussed with regard to targets for future neuropsychological research on BDs.Fil: Samame, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Martino, Diego Javier. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Strejilevich, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentin

Neural basis of genetic vulnerability to bipolar disorder

Abnormalities of reward processing, decision-making and emotion processing are core features of bipolar I disorder (BD). These processes are closely linked with fronto-striatal and midbrain circuitry. I sought to test whether dysfunctions of these pathways were present in BD and whether they related to genetic vulnerability to illness or resilience. I recruited twenty-five BD I patients each with their unaffected sibling, and compared them to 24 healthy age- and gender-matched controls. In chapter 1, I provide a research background and literature review. Chapter 2 describes the neuropsychological assessments which demonstrated trait-related deficits in working memory with slower processing speed representing an endophenotype. Chapter 3 describes the implicit/ explicit facial emotion processing task performed during event-related functional MRI (erfMRI). Pairwise comparisons demonstrated implicit processing was associated with increases in lingual gyrus and insula activations and explicit processing elicited reduced fusiform activations in patients compared with controls. Increased posterior cingulate activations and reductions in putamen and cerebellar activity were found in siblings compared to controls, and reductions in parietal activations were noted in siblings compared to their ill relatives. These findings suggest over-activations in regions involved in facial expression recognition and attentional shifting (lingual and insula respectively) and deactivations in a region important for the perception and recognition of faces (fusiform) represent correlates of disease expression. Additionally regional deactivations associated with category learning and attentional processing (parietal, putamen and cerebellar) and increased activations in a region involved in emotional salience (posterior cingulate) may represent adaptive responses associated with resilience. Chapter 4 describes an instrumental reward-learning task performed during erfMRI. Data were analysed at whole brain level and using a priori region of interest analyses in ventral striatum/midbrain and prefrontal cortex (PFC). Results included increased ventral striatum activation in association with the difference between observed and expected rewarding outcomes (the prediction error (PE)) in patients compared to controls. Decreased prefrontal activations were seen in the patient and sibling groups compared to controls in association with the learning of the value of the conditioned stimulus. These findings suggest that i) PE associated circuitry (striatal) overactivation, and ii) prefrontal deactivations underlie the genetic vulnerability to BD

Activation and Habituation of the Cingulate Cortex during Emotion Processing in Healthy Controls, Borderline, and Schizotypal Personality Disorder

Disturbances in emotional functioning are central features of the clinical profiles of both borderline and schizotypal personality disorder (BPD and SPD, respectively). BPD is characterized by a high sensitivity to emotional stimuli and unusually strong and long-lasting reactions, indicative of impaired habituation to emotional stimuli (Linehan, 1993). Previous research suggests that SPD patients demonstrate limbic hyper-reactivity to unpleasant stimuli, at least initially, but intact habituation to repeated presentation of unpleasant stimuli (Hazlett et al., 2012). The cingulate cortex supports various aspects of emotion processing and regulation, and abnormalities of this region have been related to emotion dysfunction in SPD and BPD (Koenigsberg, Fan, et al., 2009; Modinos, Ormel, & Aleman, 2010). However, findings of functional cingulate abnormalities in the context of emotion processing have been inconsistent in BPD and limited in SPD. The current study utilized event-related functional magnetic resonance imaging (fMRI) in three groups, BPD patients, SPD patients, and healthy control individuals, during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures, each presented twice within their respective trial. This approach permitted the examination of reactivity to emotional stimuli and habituation of emotional responses within the cingulate. Blood-oxygen-level dependent response values were obtained within the manually delineated anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) and compared across groups. Compared to healthy controls and SPD patients, BPD patients exhibited significantly greater activity in the ACC during the presentation of neutral pictures. Heightened activity in the BPD group persisted across the initial and repeated presentations of neutral pictures. On the other hand, SPD patients exhibited greater activity in the ACC compared to healthy controls and BPD patients during the initial presentation of unpleasant pictures, but activity normalized when the pictures were repeated. The two patient groups demonstrated heightened ACC activation, but these abnormalities were differentiated by associated picture-type (neutral versus unpleasant) and attenuation of the response upon repeated presentation of the stimuli. Diagnostic differences in PCC activation did not reach significance. Overall results suggest unique involvement of the ACC in BPD and SPD symptomatology