The Positive Valence Systems (PVS) are a major domain of the Research
Domain Criteria framework (RDoC), which aims at promoting precision medicine
for psychiatry, based on a profound understanding of the psychological and
biological basis of shared behavioral symptoms. The PVS domain describes
basic processes of reward processing, which can be disrupted in several mental
disorders, such as schizophrenia, substance use disorders, and major
depressive disorder. Investigating basic mechanisms of PVS constructs is
important to understand central aspects which contribute to these transdiagnostic
motivational syndromes.
In my doctoral thesis, I investigated pharmacological, sex-specific, and
hormonal modulators of PVS constructs. I focused on the constructs reward
responsiveness and reward valuation in the context of motivational behavior in
healthy humans. In study 1, I examined the neurotransmitter serotonin, and in
particular a selective serotonin reuptake inhibitor (SSRI) as modulator of reward
responsiveness on a neural level, using functional magnetic resonance imaging
(fMRI). In studies 2 and 3, I inquired into sex-specific and hormonal modulators
of reward valuation to elucidate sex-specific integration of benefits and costs on
a behavioral level.
In study 1, I found that an acute SSRI dose modulated the processing of
punishment cues in caudate and thalamus brain regions, which have been
identified as transdiagnostic neural markers of disrupted reward responsiveness.
In study 2, I identified sex differences in reward valuation, which depended on
different encoding of benefits, not costs. Study 3 did not yield substantial
differences in reward valuation depending on different hormonal states in women.
The RDoC initiative aims at understanding core features and modulators of
shared behavioral symptoms, ranging from normal to abnormal behavior.
Understanding basic mechanisms is an important first step towards
transdiagnostic clinical translation. Within this scope, my work has implications
for testing clinical translation of pharmacological and behavioral treatments specifically targeted to PVS constructs, which take sex-specific behavioral
variability into account
