Cognitive Behavior Therapy (CBT) and Positive Psychotherapy (PPT) for the treatment of anxiety disorders in an online group setting: A randomized controlled trial.

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized not only by motor symptoms but also by a wide range of non-motor manifestations. Among these, depression is one of the most prevalent and clinically impactful complications, significantly impairing the quality of life of patients with PD [,,]. Previous studies have reported that depression affects up to 50% of patients with PD, encompassing both major and minor depressive episodes [,]. Despite its high prevalence and clinical impact, the neural mechanisms underlying depression in PD remain incompletely understood, particularly at the level of distributed brain networks. Alterations in the serotonergic system have long been implicated in the pathophysiology of depression. The dorsal raphe (DR) and median raphe (MR) nuclei are the principal sources of ascending serotonergic projections. While the DR provides the major serotonergic innervation to widespread cortical and subcortical regions, including the amygdala involved in mood regulation, the MR preferentially projects to limbic and hippocampal structures and also contributes to emotional and cognitive processing [,]. In PD, neuropathological and molecular imaging studies have demonstrated degeneration of serotonergic neurons within the raphe nuclei and abnormalities of serotonin transporter availability, suggesting that disruption of serotonergic pathways may contribute to depressive symptoms [,]. However, in vivo imaging studies examining regional serotonin transporter availability have yielded inconsistent results, and the relationship between regional serotonergic alterations and depression in PD remains incompletely understood [,]. Notably, a recent PET study using the highly selective SERT tracers [C]DASB and [C]MADAM demonstrated preserved regional SERT availability in patients with early nondepressed PD []. Together, these findings underscore the complexity of serotonergic alterations in PD. Although N-3-[F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane ([F]FP-CIT) was originally developed as a dopamine transporter tracer, its extrastriatal uptake has been used as a surrogate marker of serotonin transporter–related signal because dopamine transporter expression is relatively sparse outside the striatum []. Nevertheless, extrastriatal [F]FP-CIT does not selectively quantify serotonergic terminals and likely reflects mixed monoamine transporter binding. Considering that depression in PD is widely recognized as a multifaceted condition involving alterations across various monoaminergic systems rather than isolated serotonergic deficits [], extrastriatal [F]FP-CIT uptake may nevertheless provide information relevant to broader monoamine transporter-related alterations. Accordingly, throughout the present study, extrastriatal [F]FP-CIT is interpreted as a putative marker of raphe-centered monoamine transporter–related organization rather than a selective measure of serotonergic integrity. This interpretation is consistent with previous molecular imaging studies investigating non-motor manifestations of PD using extrastriatal FP-CIT imaging []. However, conventional molecular imaging studies have focused on regional tracer uptake, which may overlook coordinated alterations across distributed brain networks. Group-level covariance analysis provides a complementary framework for characterizing coordinated interregional variations in tracer uptake across individuals, thereby enabling the investigation of network-level organization beyond conventional regional analyses.