Cognitive and neural basis of emotion regulation in bipolar disorder

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Cognitive and neural basis of emotion regulation in bipolar disorder Psychiatry Associate Professor Melissa Green, PhD. NHMRC Biomedical Career Development Fellow School of Psychiatry, Faculty of Medicine University of New South Wales, Australia.

Emotion Regulation Includes all the conscious and nonconscious strategies we use to increase, maintain, or decrease the components of an emotional response, in accord with our goals

A process model of emotion regulation Gross, 1998 Emotional Cues Emotional Response Tendencies Experiential Behavioural Physiological Emotional Responses Evaluation Modulation

S1 S2 Emotion regulation Gross, 2001, Current Directions in Psychological Science S1x S1y S1z a1 a2 a3 a4 a5 c1 c2 c3 Emotion Response Tendencies + Experiential - + Behavioural - + Physiological - Situation Situation Attentional Cognitive Response Selection Modification Deployment Appraisal Modulation Cognitive emotion regulation

Gross process model Situation Situation Attentional Cognitive Emotion Response Selection Modification Deployment Appraisal Response Modulation Tendencies Antecedent-focused (PROBLEM FOCUSED) Response-focused (EMOTION-FOCUSED) Antecedent-focused strategies are implemented before an emotional response has been fully activated Eg., cognitive reappraisal: PROBLEM-FOCUSED STRATEGY Response-focused strategies refer to things we do once an emotional reaction is underway Eg., suppression: EMOTION-FOCUSED STRATEGY

PROBLEM- Vs. EMOTION-Focused tendencies Cognitive Reappraisal (Problem-focused) Most flexible and effective means of regulating negative emotion Involves active re-construal of an emotion-eliciting event Requires mental flexibility to generate alternative explanations, set-shifting (executive) capacities to view events from alternative perspectives decreases experiential & behavioural responses, little effect on physiological responses Suppression (Emotion-focused) Involves active inhibition of outward signs of emotion Requires cognitive effort to inhibit pre-potent responses decreases emotionally expressive behaviour but has no impact upon (sometimes increases) the emotional experience Increases physiological response (e.g., heart rate, SCR, blood pressure, pulse, temperature) Impairs memory for the emotional event (increased cognitive load of continual self-monitoring) Decreases emotional support (less sharing of emotions with others)

Questionnaire Measurement Emotion Regulation Questionnaire (ERQ) Gross & John, 2001 Measures tendency to use cognitive reappraisal and suppression 1-----------------2------------------3------------------4------------------5------------------6------------------7 strongly neutral strongly disagree agree 1. I keep my emotions to myself. 2. When I want to feel less negative emotion (such as sadness or anger), I change what I m thinking about. 3. When I am feeling positive emotions, I am careful not to express them. 4. When I m faced with a stressful situation, I make myself think about it in a way that helps me stay calm. 5. I control my emotions by not expressing them.

Gruber, Harvey, & Gross, 2012.

Early studies in BD: Coping Style origins Thomas and Bentall (2002) & Knowles et al (2005) Modified version of Nolen-Hoeksema s Response Style Questionnaire (RSQ) assesses responses to depressed mood Rumination, distraction, and engagement in dangerous activities predicted hypomanic personality traits Rumination (only) predicted depression Van Der Gucht (2009) Clinical BD sample: RSQ rumination associated w/ depressive symptoms but not mania

Questionnaire Measurement Difficulties in Emotion Regulation Scale (DERS) Graetz & Roemer, 2004 This scale was developed to assess emotion dysregulation 40 items, chosen to reflect difficulties with Emotional Awareness: I am attentive to my feelings Emotional Clarity: I have difficulty making sense out of my feelings Goal-directed Behaviour: When I m upset, I have difficulty concentrating Impulse control: I experience emotions as overwhelming and out of my control Access to strategies: When I m upset, I believe I will end up feeling very depressed

Van Rheenan et al., 2015, Psychiatry Research

Questionnaire Measurement Cognitive Emotion Regulation Questionnaire (CERQ) Garnefski, Kraaij, Spinhoven, 2002 36 items: 9 conceptually distinct subscales Self-blame: I think that basically the cause must lie with myself Other-blame: I feel that others are responsible for this matter Rumination: I dwell upon the feelings the situation has evoked in me Catastrophizing: I keep thinking how terrible it is, this experience Putting into Perspective: I think it all could have been much worse Positive Refocusing: I think of something nice instead Positive Reappraisal: I think I can learn something from the situation Accepting: I think that I must learn to live with it Refocus on Planning: I think about how to change the situation: Depression symptoms consistently associated with increased selfblame, rumination, catastrophizing, decreased positive reappraisal (Garnefski et al., 2001, 2002, 2006)

CERQ strategies in BD (Green et al, 2012) 15 14 13 * * * * 12 11 10 9 8 7 6 Bipolar Disorder Unaffected Relatives Healthy controls

Rumination had the strongest associations with mood symptoms in BD 0,6 0,5 0,4 0,3 0,2 0,1 0-0,1-0,2-0,3-0,4-0,5 depression anxiety stress hypomania

TASIT: The Awareness of Social Inference Test Part 1 - Emotion Perception 28 vignettes assesses emotion perception through facial expression, body language and vocal inflection. Part 2 - Social Inference (Minimal) 15 vignettes assess the ability to comprehend sincere and sarcastic social exchanges. In simple sarcastic exchanges, the speaker means the opposite of what he/she is actually saying. In paradoxical exchanges the dialogue doesn t make sense unless sarcasm is perceived. Part 3 - Social Inference (Enriched) 15 vignettes assess the ability to detect lies and sarcasm, with additional contextual information given before or after the scene; requires integration of context information and inferences from different sources.

(Rowland, et al. 2013) Association between CERQ strategies and social cognitive skills 0,5 0,4 0,3 0,2 0,1 0-0,1-0,2 HC BD -0,3-0,4-0,5-0,6 Rumination Other blame Catastrophising

Pathways between neurocognition, social cognition, and emotion regulation in bipolar disorder (Van Rheenan et al, 2014) Healthy controls Bipolar Disorder

Potential neuropsychological contributions Green, Cahill & Mahli, 2007, Journal of Affective Disorders Rumination Self Blame Inhibitory deficits: intrusive emotional stimuli, lack of inhibition of self perspective Positive Reappraisal Putting into Perspective Positive Refocusing Refocus on Planning Generation of alternative appraisals; Reappraisal of meaning & significance; Generation of new goals; Reallocation of attention. Consistent with known neuropsychological deficits in BD (e.g., Robinson et al., 2006) Sustained & selective attention Set shifting & mental flexibility Inhibition Working memory Theory of Mind / other perspective taking

Common cognitive deficits in Sz & BD

Structural Neuropathology in BD Reduced volume of PFC & ACC (Subgenual prefrontal cortex) Enlarged striatum and amygdala (Strakowski, 2005; Savitz, 2005; Goodwin & Jamison, 2007; Konarski, 2008)

Phillips et al, 2008, Molecular Psychiatry.

Neural mechanisms Phillips et al., 2003 Keener & Phillips, 2007, Current Psychiatry Reports

fmri studies: cognitive reappraisal task OBSERVE, OR DECREASE EMOTION NEGATIVE OR NEUTRAL PHOTO Strength of Affect Rating 0 1 2 3 4 5 6 7 RELAX 2 secs 10 secs 4 secs 4 secs Instructional Cue Online regulation Affect Rating Relax before next trial Oschner et al., 2002, Journal of Cognitive Neuroscience Participants view emotional scenes designed to elicit negative affect 2 conditions: cognitive reappraisal Vs passive viewing

Neural mechanisms of cognitive reappraisal Ochsner et al, 2002, JCN Inhibitory role of Left Left Prefrontal Cortex Mediated by Medial Orbital Frontal Cortex With attenuated Amygdala

Previous study in depression Johnstone et al, JoN, 2007.

Participants Healthy Adults (n =15) Bipolar I (n =13) Schizophrenia (n = 12) Mean Age (SD) 35 (2) 41 (3) 44 (3)* Females 9 5 4 Years of Education (SD) 16 (1) 16 (1) 13 (1)* Handedness (SD) 90 (4) 92 (5) 85 (5) NART Premorbid IQ (SD) 114 (2) 118 (2) 109 (3) Antipsychotic CPZ Equiv (mg) -- 168 (106) 352 (58) Antidepressant IMI Equiv (mg) -- -- 132 (32) DASS: Anxiety 2 (1) 12 (3)* 8 (2)* DASS: Stress 6 (2) 18 (3)* 11 (3) DASS: Depression 2 (1) 10 (3)* 8 (4) PANSS: Positive -- 10 (1) 19 (2)^ PANSS: Negative -- 11 (1) 22 (2)^ PANSS: General -- 25 (2) 32 (2)^ * p < 0.05

** = p <.01 * = p <.05 Subjective AFFECT Image RATINGS Ratings ** ** ** ** ** ** *

IFG % change How do healthy brains downregulate emotion? Amygdala % change Downregulation of negative affect elicited bilateral prefrontal activity in the VLPFC, OFC, DLPFC and rostral ACC;The left IFG was inversely correlated with amygdala activation during downregulation of affect Morris et al., 2012, Translational Psychiatry

Down-regulation of negative affect in BD Morris, Sparks, Shannon-Weickert, Mitchell, Green, Trans Psy, 2012.

Lack of IFG-amygdala coupling in BD + Heightened amygdala activity in BD only

Lack of PFC and subjective ratings coupling in BD (Morris, Sparks, Shannon- Weickert, Mitchell, Green, Trans Psychiatry, 2012.)

Biological Psychiatry, 2013

Emotion dysregulation BD Functional impairment absence or disruption of capacity disturbances in integrity of regulatory processes Potential mechanisms structural and functional brain abnormalities neuropsychological impairments in attention, inhibition, WM Process impairment Inappropriate implementation of otherwise adaptive regulatory processes Potential Mechanisms Misuse of otherwise adaptive strategies Eg, out of context, in extreme form, due to misperception of other s emotions/intentions, and the meaning of events Kring and Werner, 2002

SUMMARY Similar cognitive regulatory styles among BD and families Increased tendency for rumination Increased tendency toward catastrophising Increased tendency toward self-blame Less likely to put things into perspective All associated with mood symptoms Links between social cognition and emotion regulation are broken in BD: Suggests that strengthening understanding of social context and emotions may be worthwhile in treatment Fronto-limbic connectivity in BD may impede efficient regulation: One avenue may be to undertake cognitive remediation of brain circuitry required for effortful control

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