Preprint Depression in Parkinson’s disease associated w. dopamine unresponsive reduced reward sensitivity during effort-based decision making, 2024, Costello +

Abstract

Willingness to exert effort for a given goal is dependent on the magnitude of the potential rewards and effort costs of an action. Such effort-based decision making is an essential component of motivation, in which the dopaminergic system plays a key role. Depression in Parkinson’s disease (PD) is common, disabling and has poor outcomes. Motivational symptoms such as apathy and anhedonia, are prominent in PD depression and related to dopaminergic loss. We hypothesised that dopamine-dependent disruption in effort-based decision-making contributes to depression in PD.

In the present study, an effort-based decision-making task was administered to 62 patients with PD, with and without depression, ON and OFF their dopaminergic medication across two sessions, as well as to 34 patients with depression and 29 matched controls on a single occasion. During the task, on each trial, participants decided whether to accept or reject offers of different levels of monetary reward in return for exerting varying levels of physical effort via grip force, measured using individually calibrated dynamometers. The primary outcome variable was choice (accept/decline offer), analysed using both logistic mixed-effects modelling and a computational model which dissected the individual contributions of reward and effort on depression and dopamine state in PD.

We found PD depression was characterised by lower acceptance of offers, driven by markedly lower incentivisation by reward (reward sensitivity), compared to all other groups. Within-subjects analysis of the effect of dopamine medication revealed that, although dopamine treatment improves reward sensitivity in non-depressed PD patients, this therapeutic effect is not present in PD patients with depression.

These findings suggest that disrupted effort-based decision-making, unresponsive to dopamine, contributes to PD depression. This highlights reward sensitivity as a key mechanism and treatment target for PD depression that potentially requires non-dopaminergic therapies.



Citation: Costello, H et al. 2024, Depression in Parkinson’s disease is associated with dopamine unresponsive reduced reward sensitivity during effort-based decision making, bioRxiv 2024.05.09.592897; doi: https://doi.org/10.1101/2024.05.09.592897 2024

Full text PDF only --https://www.biorxiv.org/content/10.1101/2024.05.09.592897v1.full.pdf

All authors: Harry Costello, Yumeya Yamamori, Karel Kieslich, Mackenzie Murphy, Kamilla Bobyreva, Anette-Eleonore Schrag, Robert Howard, Jonathan P Roiser

 

Research on 'effort-based decision making' maybe a bit trendy currently?

(Sorry not up to reading / commenting on the paper, just stumbled across it when searching for something else)

 

(Presumably these researchers recognised that EEfRT, with its repetitive finger tapping paradigm, was entirely inappropriate in PD.)

 

Besides being an inappropriate use of this test, which is frankly a ridiculous test, given the physical difficulties involved that are not supposed to influence outcomes, does it mean that PD is a problem of effort preference, as the NIH study has decided? Obviously not. And yet the same could be said because generic nonsense is just that, generic nonsense.

The idea that this reveals a key mechanism and therapeutic target is completely ridiculous and doesn't even make sense. All they are showing is that they have zero understanding of the reality of illness, and are willing to apply useless nonsense for their own self-interest.

And on what basis can they decide that this is because of "the depression" and not the illness? It's completely arbitrary, they're not even trying to make sense.