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How can we characterize psychopathological symptoms and connect them to the brain? Current psychopathological symptoms only focus on either the symptoms themselves or predominantly on the brain. This leaves open their intimate connection. A novel approach, Spatiotemporal Psychopathology, proposes that the brain inner spatiotemporal organisation of its neural activity provides the spatiotemporal organization of the psychopathological symptoms. Specifically, the brains' neuronal topography and dynamic is manifest in a more or less analogous spatiotemporal organisation on the mental level, i.e., mental topography and dynamic. This is strongly supported by various examples including major depressive disorder, bipolar disorder, schizophrenia, and autism. We therefore conclude that Spatiotemporal Psychopathology provides a promising approach to intimately connect brain and symptoms. [ABSTRACT FROM AUTHOR]

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy. [ABSTRACT FROM AUTHOR]

The existential crisis of nihilism in schizophrenia has been reported since the early days of psychiatry. Taking first-person accounts concerning nihilistic experiences of both the self and the world as vantage point, we aim to develop a dynamic existential model of the pathological development of existential nihilism. Since the phenomenology of such a crisis is intrinsically subjective, we especially take the immediate and pre-reflective first-person perspective's (FPP) experience (instead of objectified symptoms and diagnoses) of schizophrenia into consideration. The hereby developed existential model consists of 3 conceptualized stages that are nested into each other, which defines what we mean by existential. At the same time, the model intrinsically converges with the phenomenological concept of the self-world structure notable inside our existential framework. Regarding the 3 individual stages, we suggest that the onset or first stage of nihilistic pathogenesis is reflected by phenomenological solipsism, that is, a general disruption of the FPP experience. Paradigmatically, this initial disruption contains the well-known crisis of common sense in schizophrenia. The following second stage of epistemological solipsism negatively affects all possible perspectives of experience, that is, the first-, second-, and third-person perspectives of subjectivity. Therefore, within the second stage, solipsism expands from a disruption of immediate and pre-reflective experience (first stage) to a disruption of reflective experience and principal knowledge (second stage), as mirrored in abnormal epistemological limitations of principal knowledge. Finally, the experience of the annihilation of healthy self-consciousness into the ultimate collapse of the individual's existence defines the third stage. The schizophrenic individual consequently loses her/his vital experience since the intentional structure of consciousness including any sense of reality breaks down. Such a descriptive-interpretative existential model of nihilism in schizophrenia may ultimately serve as input for future psychopathological investigations of nihilism in general, including, for instance, its manifestation in depression. [ABSTRACT FROM AUTHOR]

• Context-dependence of neuronal activity. • Divisive normalization can account for context-dependence. • Context-dependence is mediated by canonical microcircuits. • Canonical microcircuits include inhibition and excitation. • Inhibition and excitation are abnormal in psychiatric disorders like schizophrenia and depression. Neural activity on cellular, regional, and behavioral levels shows context-dependence. Here we suggest the processing of input-output relationships in terms divisive normalization (DN), including (i) summing/averaging inputs and (ii) normalizing output against input stages, as a computational mechanism to underlie context-dependence. Input summation and output normalization are mediated by input-output relationships in canonical microcircuits (CM). DN/CM are altered in psychiatric disorders like schizophrenia or depression whose various symptoms can be characterized by abnormal context-dependence. [ABSTRACT FROM AUTHOR]

Background: Accumulating neuroimaging evidence suggests that abnormal intrinsic neural activity could underlie auditory verbal hallucinations (AVH) in patients with schizophrenia. However, little is known about the functional interplay between distinct intrinsic neural networks and their association with AVH. Methods: We investigated functional network connectivity (FNC) of distinct resting-state networks as well as the relationship between FNC strength and AVH symptom severity. Resting-state functional MRI data at 3 T were obtained for 14 healthy controls and 10 patients with schizophrenia presenting with persistent AVH. The data were analyzed using a spatial group independent component analysis, followed by constrained maximal lag correlations to determine FNC within and between groups. Results: Four components of interest, comprising language, attention, executive control networks, as well as the default-mode network (DMN), were selected for subsequent FNC analyses. Patients with persistent AVH showed lower FNC between the language network and the DMN (p < 0.05, corrected for false discovery rate). FNC strength, however, was not significantly related to symptom severity, as measured by the Psychotic Symptom Rating Scale. Conclusion: These findings suggest that disrupted FNC between a speech-related system and a network subserving self-referential processing is associated with AVH. The data are consistent with a model of disrupted self-attribution of speech generation and perception. [ABSTRACT FROM AUTHOR]

Objective Manic and depressive phases of bipolar disorder (BD) show opposite symptoms in psychomotor, thought, and affective dimensions. Neuronally, these may depend on distinct patterns of alterations in the functional architecture of brain intrinsic activity. Therefore, the study aimed to characterize the spatial and temporal changes of resting-state activity in mania and depression, by investigating the regional homogeneity (ReHo) and degree of centrality (DC), in different frequency bands. Methods Using resting-state functional magnetic resonance imaging (fMRI), voxel-wise ReHo and DC were calculated—in the standard frequency band (SFB: 0.01–0.10 Hz), as well as in Slow5 (0.01–0.027 Hz) and Slow4 (0.027–0.073 Hz)—and compared between manic (n = 36), depressed (n = 43), euthymic (n = 29) patients, and healthy controls (n = 112). Finally, clinical correlations were investigated. Results Mania was mainly characterized by decreased ReHo and DC in Slow4 in the medial prefrontal cortex (as part of the default-mode network [DMN]), which in turn correlated with manic symptomatology. Conversely, depression was mainly characterized by decreased ReHo in SFB in the primary sensory-motor cortex (as part of the sensorimotor network [SMN]), which in turn correlated with depressive symptomatology. Conclusions Our data show a functional reconfiguration of the spatiotemporal structure of intrinsic brain activity to occur in BD. Mania might be characterized by a predominance of sensorimotor over associative networks, possibly driven by a deficit of the DMN (reflecting in internal thought deficit). Conversely, depression might be characterized by a predominance of associative over sensorimotor networks, possibly driven by a deficit of the SMN (reflecting in psychomotor inhibition). [ABSTRACT FROM AUTHOR]

Psychopathology as the investigation and classification of experience, behavior and symptoms in psychiatric patients is an old discipline that ranges back to the end of the 19th century. Since then different approaches to psychopathology have been suggested. Recent investigations showing abnormalities in the brain on different levels raise the question how the gap between brain and psyche, between neural abnormalities and alteration in experience and behavior can be bridged. Historical approaches like descriptive (Jaspers) and structural (Minkoswki) psychopathology as well as the more current phenomenological psychopathology (Paarnas, Fuchs, Sass, Stanghellini) remain on the side of the psyche giving detailed description of the phenomenal level of experience while leaving open the link to the brain. In contrast, the recently introduced Research Domain Classification (RDoC) aims at explicitly linking brain and psyche by starting from so-called 'neuro-behavioral constructs'. How does Spatiotemporal Psychopathology, as demonstrated in the first paper on depression, stand in relation to these approaches? In a nutshell, Spatiotemporal Psychopathology aims to bridge the gap between brain and psyche. Specifically, as demonstrated in depression in the first paper, the focus is on the spatiotemporal features of the brain's intrinsic activity and how they are transformed into corresponding spatiotemporal features in experience on the phenomenal level and behavioral changes, which can well account for the symptoms in these patients. This second paper focuses on some of the theoretical background assumptions in Spatiotemporal Psychopathology by directly comparing it to descriptive, structural, and phenomenological psychopathology as well as to RDoC. [ABSTRACT FROM AUTHOR]

Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. [ABSTRACT FROM AUTHOR]

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS. [ABSTRACT FROM AUTHOR]

A comprehensive assessment of catatonic symptoms is decisive for diagnosis, neuronal correlates, and evaluation of treatment response and prognosis of catatonia. Studies conducted so far used different cut-off criteria and clinical rating scales to assess catatonia. Therefore, the main aim of this study was to examine the frequency and distribution of diagnostic criteria and clinical rating scales for assessing catatonia that were used in scientific studies so far. We conducted a systematic review using PubMed searching for articles using catatonia rating scales/criteria published from January 1st 1952 (introduction of catatonic schizophrenia to first edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM]) up to December 5th, 2022. 1928 articles were considered for analysis. 1762 (91,39 %) studies used one and 166 (8,61 %) used ≥2 definitions of catatonia. However, 979 (50,7 %) articles did not report any systematic assessment of catatonia. As for clinical criteria, DSM criteria were used by the majority of studies (n = 290; 14.0 %), followed by International Classification of Diseases (ICD) criteria (n = 61; 2.9 %). The Bush-Francis Catatonia Rating Scale (BFCRS) was found to be by far the most frequently utilized scale (n = 464; 22.4 % in the respective years), followed by Northoff Catatonia Rating Scale (NCRS) (n = 31; 1.5 % in the respective years). DSM and ICD criteria as well as BFCRS and NCRS were most frequently utilized and can therefore be recommended as valid instruments for the assessment of catatonia symptomatology. [ABSTRACT FROM AUTHOR]

Background: Altered global signal (GS) topography features in the resting-state fMRI of major depressive disorder (MDD), showing abnormally strong global signal representation in the default-mode network (DMN). Whether the abnormal local to global change also shapes activity during task states, and how it relates to psychopathological symptoms, e.g., abnormally slow time speed of motor, cognitive, and affective symptoms, remains unknown.Methods: We investigated fMRI-based GS with its topographical representation during task states in unmedicated 51 MDD subjects and 28 healthy subjects. Task-related global signal correlation (GSCORR) was probed by a novel paradigm testing the processing of negative/neutral emotions during different time speeds, i.e., slow and fast.Results: We observed a significant interaction between time speed and emotion of GSCORR in various DMN regions in healthy subjects. Next, we showed that MDD exhibits reduced task-related GSCORR in various DMN regions during specifically the fast processing of negative emotions. Finally, we demonstrated that GSCORR in DMN and other brain regions (motor-related regions, inferior frontal cortex) correlated with the degree of psychomotor retardation especially during the fast emotional stimuli.Limitations: The measurement of interoceptive variables like respiration rate or heart rate were not included in our fMRI acquisition.Conclusion: Together, we demonstrated the functional relevance of GS topography by showing reduced GSCORR in DMN during specifically the fast processing of negative emotions in MDD, suggesting the abnormal slowness, i.e., reduced time speed, to be a key feature of both brain and symptoms in MDD. [ABSTRACT FROM AUTHOR]

Catatonia is a severe psychomotor syndrome that frequently occurs in patients with schizophrenia spectrum disorders (SSD). Accumulating neuroimaging evidence suggests orbitofrontal, frontoparietal and cerebellar network dysfunction in catatonia. Very little is known about contributions of brainstem regions (as part of the dopaminergic-based subcortical-cortical motor circuit) to catatonia in SSD patients. Here, we used structural magnetic resonance imaging (MRI) at 3 T to examine volumes of brainstem regions in catatonic SSD patients compared to non-catatonic SSD patients. Catatonia severity was measured with the Northoff Catatonia Rating Scale (NCRS). The segmentation of the brainstem in order to investigate the volumes of medulla oblongata, pons, superior cerebellar pedunculus, and midbrain was carried out using FreeSurfer vers. 6.0. Catatonic patients (NCRS total score ≥ 3; at least 1 point in the three different symptom categories; i.e., motor, behavioral, and affective; n = 30) had significantly smaller midbrain volumes (p = 0.004, Bonferroni corr.) when compared to non-catatonic patients (NCRS total score = 0; n = 29). In catatonic patients, significant correlations were detected between NCRS motor scores and whole brainstem (p = 0.015, Bonferroni corr.) volumes. These results support a neuromechanistically important role of brainstem structures in catatonia in SSD, particularly in motor symptom expression. [ABSTRACT FROM AUTHOR]

Previous neuroimaging studies have examined the association between changes in brain structure and gastrointestinal symptoms (GIS), seen in disorders such as Irritable Bowel Syndrome and Irritable Bowel Disease. Studies in adults have found changes in white and grey matter volume (GMV) in patients with various gastrointestinal disorders. However, it is unclear whether GIS‐related structural changes in the brain are limited to adults or could be present throughout the lifespan. Given that gastrointestinal disorders are typically diagnosed between 4 and 18 years old, we investigated GIS‐induced morphological changes in pre‐adolescents (8–10), adolescents (12–16 years) and young adults (17–21 years). Using a voxel‐based morphometry (VBM) analysis, we compared regional grey matter volume (GMV) between participants with GIS and controls, using structural brain images from the Philadelphia Neurodevelopmental Cohort (PNC) database. A total of 211 participants (107 participants with GISs and 104 control participants) who had undergone structural magnetic resonance imaging were analysed. VBM analysis was used to objectively analyse GMV across the whole brain and compare between participants with GIS and controls. Participants experiencing GIS showed smaller GMV in regions within the limbic system/basal ganglia (bilateral caudate, bilateral ventral hippocampus, bilateral amygdala and bilateral superior orbital frontal cortex), and larger GMV in regions within the pain‐matrix (thalamus, bilateral putamen, right mid‐frontal gyrus) compared to controls. These differences were most prominent in the adolescent and young adult groups compared to pre‐adolescents. In conclusion, the structural differences found in participants with GIS support the need for further research into the neurophysiological impact of these symptoms. [ABSTRACT FROM AUTHOR]