Arthur Schopenhauer: An underappreciated philosopher in psychiatry and his applied epistemology of body and self- experience.

BACKGROUND: Arthur Schopenhauer (1788-1860) was one of the most important thinkers of the 19th century. Although his writings have exerted great influence in many different disciplines, his epistemological concepts and analysis of the body and self-experience were rarely considered in the context of psychiatric research of schizophrenia spectrum disorders (SSD) and depression (MDD). METHODS: The method applied for the study of anomalous self and body-experience first consists in the close reading and analysis of Schopenhauer's most influential writings, namely his opus magnus "The World as Will and Representation" and his dissertation "On the Fourfold Root of the Principle of Sufficient Reason". Second, psychopathological and phenomenological aspects of the anomalous body and self, as well as altered space and time experience, are discussed by means of Schopenhauer's philosophy and four patient cases. RESULTS: Schopenhauer's insights contribute to contemporary psychiatry by (1) unifying materialistic (neurobiological) and idealistic (subjective) conceptions of psychiatric disorders and improving the awareness of methods in psychiatric research; (2) emphasizing the integral significance of the body as a gateway to the surrounding world and basal self-experience; (3) delineating subjective space and time-experience as crucial dimensions of the conditio humana in SSD and MDD; and (4) demonstrating the feasibility of transferring his theories directly to clinical case vignettes stemming from the daily clinical routine. CONCLUSION: Close reading of Schopenhauer's texts might help bridge the gap between different scientific methods in psychiatry and overcome the translational crisis of contemporary psychiatry by unifying neurobiological and subjective approaches to SSD and MDD.

The risk of cannabis use disorder is mediated by altered brain connectivity: A chronnectome study.

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.

Scale for time and space experience in anxiety (STEA): Phenomenology and its clinical relevance.

Anxiety is a pervasive emotional state where, phenomenologically, subjects often report changes in their experience of time and space. However, a systematic and quantified examination of time and space experience in terms of a self-report scale is still missing which eventually could also be used for clinical differential diagnosis. Based on historical phenomenological literature and patients' subjective reports, we here introduce, in a first step, the Scale for Time and Space Experience of Anxiety (STEA) in a smaller sample of 19 subjects with anxiety disorders and, in a second step, validate its shorter clinical version (cSTEA) in a larger sample of 48 anxiety subjects. The main findings are (i) high convergent and divergent validity of STEA with both Beck Anxiety Inventory (BAI) (r = 0.7325; p < 0.001) and Beck Depression Inventory (BDI) (r = 0.7749; p < 0.0001), as well as with spontaneous mind wandering (MWS) (r = 0.7343; p < 0.001) and deliberate mind wandering (MWD) (r = 0.1152; p > 0.05), (ii) statistical feature selection shows 8 key items for future clinical usage (cSTEA) focusing on the experience of temporal and spatial constriction, (iii) the effects of time and space experience (i.e., for both STEA and cSTEA scores) on the level of anxiety (BAI) are mediated by the degree of spontaneous mind wandering (MWS), (iv) cSTEA allows for differentiating high levels of anxiety from the severity of comorbid depressive symptoms, and (v) significant reduction in the cSTEA scores after a therapeutic intervention (breathing therapy). Together, our study introduces a novel fully quantified and highly valid self-report instrument, the STEA, for measuring time-space experiences in anxiety. Further we develop a shorter clinical version (cSTEA) which allows assessing time space experience in a valid, quick, and simple way for diagnosis, differential diagnosis, and therapeutic monitoring of anxiety.

Parkinsonism, Psychomotor Slowing, Negative and Depressive Symptoms in Schizophrenia Spectrum and Mood Disorders: Exploring Their Intricate Nexus Using a Network Analytic Approach.

BACKGROUND AND HYPOTHESIS: Parkinsonism, psychomotor slowing, negative and depressive symptoms show evident phenomenological similarities across different mental disorders. However, the extent to which they interact with each other is currently unclear. Here, we hypothesized that parkinsonism is an independent motor abnormality showing limited associations with psychomotor slowing, negative and depressive symptoms in schizophrenia spectrum (SSD), and mood disorders (MOD). STUDY DESIGN: We applied network analysis and community detection methods to examine the interplay and centrality (expected influence [EI] and strength) between parkinsonism, psychomotor slowing, negative and depressive symptoms in 245 SSD and 99 MOD patients. Parkinsonism was assessed with the Simpson-Angus Scale (SAS). We used the Positive and Negative Syndrome Scale (PANSS) to examine psychomotor slowing (item #G7), negative symptoms (PANSS-N), and depressive symptoms (item #G6). STUDY RESULTS: In SSD and MOD, PANSS item #G7 and PANSS-N showed the largest EI and strength as measures of centrality. Parkinsonism had small or no influence on psychomotor slowing, negative and depressive symptoms in SSD and MOD. In SSD and MOD, exploratory graph analysis identified one community, but parkinsonism showed a small influence on its occurrence. Network Comparison Test yielded no significant differences between the SSD and MOD networks (global strength p value: .396 and omnibus tests p value: .574). CONCLUSIONS: The relationships between the individual domains followed a similar pattern in both SSD and MOD highlighting their transdiagnostic relevance. Despite evident phenomenological similarities, our results suggested that parkinsonism is more independent of negative and depressive symptoms than psychomotor slowing in both SSD and MOD.

Predictors of adherence to exercise interventions in people with schizophrenia.

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants' characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Deciphering the interplay between psychopathological symptoms, sensorimotor, cognitive and global functioning: a transdiagnostic network analysis.

BACKGROUND: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample. METHODS: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST). RESULTS: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength. CONCLUSIONS: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups.

Intensive Longitudinal Social Sensing in Patients With Psychosis Spectrum Disorders: An Exploratory Pilot Study.

BACKGROUND: Psychosis spectrum disorders are characterized by significant alterations in social functioning, which is a major factor for patient recovery. Despite its importance, objectively quantifying the complex day-to-day social behavior in real-life settings has rarely been attempted. Here, we conducted a pilot study with wearable sensors that passively and continuously register interactions with other participants. We hypothesized that the amount and pattern of social interaction was associated with the severity of psychotic symptoms. STUDY DESIGN: We recruited 7 patients with psychosis spectrum disorders and 18 team members from a Soteria-style ward. Each participant wore a radio frequency identification badge, sending and receiving signals from nearby badges, allowing passive quantification of social interactions. In addition, symptom severity was assessed weekly by the Positive and Negative Syndrome Scale (PANSS). STUDY RESULTS: During an 11-week period, we identified 17 970 interactions among patients and staff. On average, patients spent 2.6 h per day interacting, capturing relevant aspects of daily social life. Relative daily interaction time, average interaction duration, and clustering coefficient, a measure of local network integration, were significantly associated with lower PANSS scores. Self-reported interaction time did not correlate with measured interaction time or with PANSS, indicating the importance of objective markers. CONCLUSIONS: This pilot study demonstrates the feasibility of passively recording social interaction of patients and staff at high resolution and for a long observation period in a real-life setting in a psychiatric department. We show links between quantified social interaction and psychopathology that may facilitate development and personalization of targeted treatments.

[Diagnosis and admission center : Establishment and evaluation of an integrated translational infrastructure for clinical psychiatric research]. / Diagnose- und Aufnahmezentrum : Etablierung und Evaluation einer integrierten translationalen Infrastruktur für die klinisch-psychiatrische Forschung.

The routine in-depth characterization of patients with methods of clinical and scale-based examination, neuropsychology, based on biomaterials, and sensor-based information opens up transformative possibilities on the way to personalized diagnostics, treatment and prevention in psychiatry, psychotherapy, and psychosomatics. Effective integration of the additional temporal and logistical effort into everyday care as well as the acceptance by patients are critical to the success of such an approach but there is little evidence on this to date. We report here on the establishment of the Diagnosis and Admission Center (DAZ) at the Central Institute of Mental Health (ZI) in Mannheim. The DAZ is an outpatient unit upstream of other care structures for clinical and scientific phenotyping across diagnoses as a starting point for data-driven, individualized pathways to further treatment, diagnostics or research. We describe the functions, goals, and implementation of the newly created clinical scientific translational structure, provide an overview of the patient populations it has reached, and provide data on its acceptance. In this context, the close integration with downstream clinical processes enables a better coordinated and demand-oriented allocation. In addition, DAZ enables a faster start of disorder-specific diagnostics and treatment. Since its launch in April 2021 up to the end of 2022, 1021 patients underwent psychiatric evaluation at DAZ during a pilot phase. The patient sample corresponded to a representative sample from standard care and the newly established processes were regarded as helpful by patients. In summary, the DAZ uniquely combines the interests and needs of patient with the collection of scientifically relevant data.

Radiomic tractometry reveals tract-specific imaging biomarkers in white matter.

Tract-specific microstructural analysis of the brain's white matter (WM) using diffusion MRI has been a driver for neuroscientific discovery with a wide range of applications. Tractometry enables localized tissue analysis along tracts but relies on bare summary statistics and reduces complex image information along a tract to few scalar values, and so may miss valuable information. This hampers the applicability of tractometry for predictive modelling. Radiomics is a promising method based on the analysis of numerous quantitative image features beyond what can be visually perceived, but has not yet been used for tract-specific analysis of white matter. Here we introduce radiomic tractometry (RadTract) and show that introducing rich radiomics-based feature sets into the world of tractometry enables improved predictive modelling while retaining the localization capability of tractometry. We demonstrate its value in a series of clinical populations, showcasing its performance in diagnosing disease subgroups in different datasets, as well as estimation of demographic and clinical parameters. We propose that RadTract could spark the establishment of a new generation of tract-specific imaging biomarkers with benefits for a range of applications from basic neuroscience to medical research.

Distribution and frequency of clinical criteria and rating scales for diagnosis and assessment of catatonia in different study types.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report.

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA.

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

[German version of the Northoff scale for subjective experience in catatonia (NSSC-dv) : A validated instrument for examination of the subjective experience in catatonia]. / Deutsche Version der Northoff Skala für subjektives Erleben bei Katatonie (NSSC-dv) : Ein validiertes Messinstrument zur Erfassung des subjektiven Erlebens bei Katatonie.

Patients with catatonia often show serious motor, affective and behavioral symptoms, behind which the subjective experience often remains hidden. Therefore, this study disseminates our own systematic empirical investigation of the subjective experience of catatonia patients to a German-speaking audience of clinicians and researchers. Based on current evidence and the clinical experience of the authors, the self-report questionnaire Northoff Scale for Subjective Experience in Catatonia (NSSC) was modified, extended and validated and now consists of 26 items capturing the subjective experience of catatonia in its clinical diversity. A total of 46 patients with catatonia according to the International Classification of Diseases (11th revision, ICD-11) were asked about their subjective experience during the acute phase of the disease using the NSSC. The NSSC showed high internal consistency (Cronbach's alpha = 0.91). The NSSC total score was significantly associated with the Northoff Catatonia Rating Scale (NCRS; r = 0.46; p < 0.05), the total score of the Positive and Negative Syndrome Scale (PANSS; r = 0.30; p < 0.05), the Brief Psychiatric Rating Scale (BPRS; r = 0.33; p < 0.05), and Trait Anxiety (STAI; r = 0.64; p < 0.01), supporting its validity. Preliminary validation of the NSSC revealed good psychometric properties. The NSSC is a useful instrument for routine clinical use to assess the subjective experience of patients with catatonia in order to provide tailored psychotherapeutic interventions.

Microstructural white matter biomarkers of symptom severity and therapy outcome in catatonia: Rationale, study design and preliminary clinical data of the whiteCAT study.

The number of magnetic resonance imaging (MRI) studies on neuronal correlates of catatonia has dramatically increased in the last 10 years, but conclusive findings on white matter (WM) tracts alterations underlying catatonic symptoms are still lacking. Therefore, we conduct an interdisciplinary longitudinal MRI study (whiteCAT) with two main objectives: First, we aim to enroll 100 psychiatric patients with and 50 psychiatric patients without catatonia according to ICD-11 who will undergo a deep phenotyping approach with an extensive battery of demographic, psychopathological, psychometric, neuropsychological, instrumental and diffusion MRI assessments at baseline and 12 weeks follow-up. So far, 28 catatonia patients and 40 patients with schizophrenia or other primary psychotic disorders or mood disorders without catatonia have been studied cross-sectionally. 49 out of 68 patients have completed longitudinal assessment, so far. Second, we seek to develop and implement a new method for semi-automatic fiber tract delineation using active learning. By training supportive machine learning algorithms on the fly that are custom tailored to the respective analysis pipeline used to obtain the tractogram as well as the WM tract of interest, we plan to streamline and speed up this tedious and error-prone task while at the same time increasing reproducibility and robustness of the extraction process. The goal is to develop robust neuroimaging biomarkers of symptom severity and therapy outcome based on WM tracts underlying catatonia. If our MRI study is successful, it will be the largest longitudinal study to date that has investigated WM tracts in catatonia patients.

Extension, translation and preliminary validation of the Northoff Scale for Subjective Experience in Catatonia (NSSC).

BACKGROUND: In the last two decades, much neuroscientific research has been done on the pathomechanisms of catatonia. However, catatonic symptoms have mainly been assessed with clinical rating scales based on observer ratings. Although catatonia is often associated with strong affective reactions, the subjective domain of catatonia has simply been neglected in scientific research. METHODS: The main objective of this study was to modify, extend and translate the original German version of the Northoff Scale for Subjective Experience in Catatonia (NSSC) and to examine its preliminary validity and reliability. Data were collected from 28 patients diagnosed with catatonia associated with another mental disorder (6A40) according to ICD-11. Descriptive statistics, correlation coefficients, internal consistency and principal component analysis were employed to address preliminary validity and reliability of the NSSC. RESULTS: NSSC showed high internal consistency (Cronbach's alpha = 0.92). NSSC total scores were significantly associated with Northoff Catatonia Rating Scale (r = 0.50, p < .01) and Bush Francis Catatonia Rating Scale (r = 0.41, p < .05) thus supporting its concurrent validity. There was no significant association between NSSC total score and Positive and Negative Symptoms Scale total (r = 0.26, p = .09), Brief Psychiatric Rating Scale (r = 0.29, p = .07) and GAF (r = 0.03, p = .43) scores. CONCLUSION: The extended version of the NSSC consists of 26 items and was developed to assess the subjective experience of catatonia patients. Preliminary validation of the NSSC revealed good psychometric properties. NSSC is a useful tool for everyday clinical work to assess the subjective experience of catatonia patients.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

Historical postmortem studies on catatonia: Close reading and analysis of Kahlbaum's cases and scientific texts between 1800 and 1900.

In the 19th century, postmortem brain examination played a central role in the search for the neurobiological origin of psychiatric and neurological disorders. During that time, psychiatrists, neurologists, and neuropathologists examined autopsied brains from catatonic patients and postulated that catatonia is an organic brain disease. In line with this development, human postmortem studies of the 19th century became increasingly important in the conception of catatonia and might be seen as precursors of modern neuroscience. In this report, we closely examined autopsy reports of eleven catatonia patients of Karl Ludwig Kahlbaum. Further, we performed a close reading and analysis of previously (systematically) identified historical German and English texts between 1800 and 1900 for autopsy reports of catatonia patients. Two main findings emerged: (i) Kahlbaum's most important finding in catatonia patients was the opacity of the arachnoid; (ii) historical human postmortem studies of catatonia patients postulated a number of neuroanatomical abnormalities such as cerebral enlargement or atrophy, anemia, inflammation, suppuration, serous effusion, or dropsy as well as alterations of brain blood vessels such as rupture, distension or ossification in the pathogenesis of catatonia. However, the exact localization has often been missing or inaccurate, probably due to the lack of standardized subdivision/nomenclature of the respective brain areas. Nevertheless, Kahlbaum's 11 autopsy reports and the identified neuropathological studies between 1800 and 1900 made important discoveries, which still have the potential to inform and bolster modern neuroscientific research in catatonia.

A systematic scoping review of rodent models of catatonia: Clinical correlations, translation and future approaches.

Catatonia is a psychiatric disorder, which subsumes a plethora of affective, motor and behavioral symptoms. In the last two decades, the number of behavioral and neuroimaging studies on catatonia has steadily increased. The majority of behavioral and neuroimaging studies in psychiatric patients suggested aberrant higher-order frontoparietal networks which, on the biochemical level, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. However, the pathomechanisms of catatonic symptoms have rarely been studied using rodent models. Here, we performed a scoping review of literature available on PubMed for studies on rodent models of catatonia. We sought to identify what we could learn from pre-clinical animal models of catatonia-like symptoms, their underlying neuronal correlates, and the complex molecular (i.e. genes and neurotransmitter) mechanisms by which its modulation exerts its effects. What becomes evident is that although many transgenic models present catatonia-like symptoms, they have not been used to better understand the pathophysiological mechanisms underlying catatonia so far. However, the identified neuronal correlates of catatonia-like symptoms correlate to a great extent with findings from neuroscience research in psychiatric patients. This points us towards fundamental cortical-striatal-thalamocortical and associated networks modulated by white matter inflammation as well as aberrant dopaminergic, GABAergic, and glutamatergic neurotransmission that is involved in catatonia. Therefore, this scoping review opens up the possibility of finally using transgenic models to help with identifying novel target mechanisms for the development of new drugs for the treatment of catatonia.