Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment

2018

Preprint

Given the heterogeneity of depression the Research Domain Criteria Framework suggests a dimensional approach to understanding the nature of mental health and illness. Neural reward function has been suggested as underpinning the symptom of anhedonia in depression but less is known about how anhedonia is related to aversion processing. We examined how anhedonia relates to neural activity during reward and aversion processing in adolescents and emerging adults (N=84) in the age range 13-21yrs. Using a dimensional approach we examined how anhedonia and depression severity correlated with an fMRI task measuring anticipation, effort and consummation of reward and aversion. We show for the first time that the dimensional experience of anhedonia correlated with neural responses during effort to avoid aversion in the precuneus with a trend in the insula and during aversive consummation in the caudate. Using a categorical approach we also examined how the neural responses during each phase of the task differed in those with depression symptoms compared to healthy controls. We found participants with depression symptoms invested less physical effort to gain reward than controls and had blunted neural anticipation of reward and aversion in the precuneus, insula, and prefrontal cortex and blunted neural effort for reward in the putamen. This work highlights blunted neural responses to reward and aversion in depression and how anticipatory and consummatory anhedonia may be enhanced via dysfunctional neural processing of aversion. Future work will assess if these neural mechanisms can be used to predict blunted behavioural approach to reward and avoidance of negative experiences in adolescents at risk of depression.

“…Volunteers also rated ‘wanting’, ‘pleasantness’ (+2 to –2) and ‘intensity’ (0 to +4) on a VAS on each trial. For design (Figure S1 and previously published here 25 ).…”

Section: Methodsmentioning

confidence: 99%

“…The tasteless solution (25 x 10 - ³mol/L KCL and 2.5×10 - ³mol/L NaHCO 3 in distilled H 2 O) was also used as a rinse between trials. Solutions were delivered through three Teflon tubes allowing 0.5 mL to be manually delivered, similar to our previous studies 25 .…”

Section: Methodsmentioning

confidence: 99%

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

2018

Preprint

“…Solutions were delivered manually through three Teflon tubes allowing 0.5 mL to be delivered, similar to our previous studies. 27 Functional MRI scan An event-related interleaved design and Siemens Magnetom Trio 3T whole-body MRI scanner and a 32-channel head coil were used. Multiband accelerated pulse sequencing (version no.…”

Section: Stimulimentioning

confidence: 99%

Dimensional anhedonia and the adolescent brain: reward and aversion anticipation, effort and consummation

2019

BJPsych open

Background Given the heterogeneity of depression the Research Domain Criteria Framework suggests a dimensional approach to understanding the nature of mental illness. Neural reward function has been suggested as underpinning the symptom of anhedonia in depression but how anhedonia is related to aversion processing is unclear. Aims To assess how the dimensional experience of anhedonia and depression severity relate to reward and aversion processing in the human brain. Method We examined adolescents and emerging adults (n = 84) in the age range 13–21 years. Using a dimensional approach we examined how anhedonia and depression related to physical effort to gain reward or avoid aversion and neural activity during the anticipation, motivation/effort and consummation of reward and aversion. Results As anhedonia increased physical effort to gain reward decreased. As anhedonia increased neural activity decreased during effort to avoid in the precuneus and insula (trend) and increased in the caudate during aversive consummation. We found participants with depression symptoms invested less physical effort than controls and had blunted neural anticipation of reward and aversion in the precuneus, insula and prefrontal cortex and blunted neural activity during effort for reward in the putamen. Conclusions We show for the first time that both physical effort and neural activity during effort correlate with anhedonia in adolescents and that amotivation might be a specific deficit of anhedonia irrespective of valence. Future work will assess if these neural mechanisms can be used to predict blunted approach and avoidance in adolescents at risk of depression.

“…Moreover, reports suggest that SSRIs can contribute to emotional blunting in patients, where experiences both positive and negative are flattened ( Price et al, 2009 ), whereas catecholamine antidepressants like bupropion (dopamine and noradrenaline reuptake inhibitor) ( Stahl et al, 2004 ; Dwoskin et al, 2006 ) might be more efficacious at improving anhedonia in depression ( Dunlop and Nemeroff, 2007 ; Nutt et al, 2007 ; McCabe et al, 2009 ). In light of this, we recently examined the effects of 7 days treatment with bupropion and found, unlike with citalopram (SSRI), enhanced neural activity in healthy controls during the anticipation, effort, and consummation of rewarding and aversive stimuli ( Dean et al, 2016 ). However, how bupropion affects RSFC remains as-yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex

Dean

International Journal of Neuropsychopharmacology

2017

Background:Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown.Methods:Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity.Results:Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network.Conclusions:These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients.