SyNoPsis: Response to the Commentators

Abstract

In their commentary, Manuel Cuesta and Víctor Peralta [1] acknowledge several of the basic contributions and challenges of our SyNoPsis project. They appreciate the attempt to link clinical manifestations with the neurobiology of schizophrenia by means of a revised semiology, and the proposal to understand its essence as a disorder of interpersonal communication. The authors also recognize the aspects contributed by the important work of Carl Wernicke and Karl Leonhard [2,3]. Also, they carve out some relevant limitations of SyNoPsis. Although a relationship of specific symptom dimensions to the respective sensorimotor and corticostriatal brain systems has been shown in several studies [4], the functional specificity of these systems has yet to be defined [5]. Further, different within-systems dynamics may result in different symptom patterns, and the anatomical connections and functional interactions between the systems have not yet been sufficiently understood.In their commentary, Cuesta and Peralta raise two critical clinical aspects: the course of the illness, and the representation of negative symptoms. We agree that the course of psychotic disorders is of eminent importance for clinical management, but also for understanding the long-term dynamics of the brain systems involved. In fact, our clinical instrument, the Bern Psychopathology Scale (BPS) [6], was designed as an instrument for crosssectional assessment. However, it allows recurrent assessments at deliberate intervals for follow-up observations. First retrospective studies have recently been published [7], and the issue of the course of psychosis dimensions will be addressed in detail in future projects.Regarding negative symptoms, we pursued a novel approach, mapping "negative" behavior onto inhibitory states of the respective brain functions. Following our objective to revise the semiology of psychosis based on the best of our knowledge about the related brain functions, this group of symptoms was disentangled respecting the boundaries of higher brain functions. For instance, we conceptualize alogia as "inhibition of verbal expression," and avolition as "lack of spontaneous actions." Thus, negative symptoms are redefined according to the tripartite symptom structure of SyNoPsis to match dysfunctions of the three brain circuits in question. In fact, most overlap was found between the motor dimension and negative symptoms [8].

Converging Resting State Networks Unravels Potential Remote Effects of Transcranial Magnetic Stimulation for Major Depression

“…The idea of the current study is inspired by the findings reported by previous researchers who attempted to link psychiatric illness with brain functions and circuits ( 33 , 34 ). For instance, the activity of the NAC, highly associated with reward processing, was found to decrease in MDD subjects ( 17 , 58 , 75 ).…”

“…The ROIs for the AMY, NAC, and VMPFC were the same as those used in the FC analysis while the ROIs for the DLPFC, DMPFC, and insula were specified by the 8-mm radius of a spherical ROI centered at the peak coordinate adopted from the conjunction analysis (right DLPFC [x, y, z] = [40,36,34]; left DLPFC [−36, 44, 28]; DMPFC [4,18,46]; right insula [46,18,2]; left insula [−40, 16, 4]).…”

“…Several studies proposed that the resting-state functional magnetic resonance imaging (fMRI) data of the healthy control (HC) can be used to determine the optimal stimulation site of rTMS treatment for MDD (31,32). Furthermore, linking the psychopathological characteristics to certain brain regions, which are identified by their known functions or associated neural circuits, have been considered as an important approach to redefine the diagnostic system of psychiatry disorders (33)(34)(35)(36). Therefore, we have investigated the functional interactions of HC subjects between rTMS stimulation sites and regions associated with MDD symptoms, aiming to capture clues of the potential mechanisms of rTMS treatment for MDD.…”