Functional neuroimaging in patients with catatonia: A systematic review.

BACKGROUND: Catatonia is a challenging and heterogeneous neuropsychiatric syndrome of motor, affective and behavioral dysregulation which has been associated with multiple disorders such as structural brain lesions, systemic diseases, and psychiatric disorders. This systematic review summarized and compared functional neuroimaging abnormalities in catatonia associated with psychiatric and medical conditions. METHODS: Using PRISMA methods, we completed a systematic review of 6 databases from inception to February 7th, 2024 of patients with catatonia that had functional neuroimaging performed. RESULTS: A total of 309 studies were identified through the systematic search and 62 met the criteria for full-text review. A total of 15 studies reported patients with catatonia associated with a psychiatric disorder (n = 241) and one study reported catatonia associated with another medical condition, involving patients with N-methyl-d-aspartate receptor antibody encephalitis (n = 23). Findings varied across disorders, with hyperactivity observed in areas like the prefrontal cortex (PFC), the supplementary motor area (SMA) and the ventral pre-motor cortex in acute catatonia associated to a psychiatric disorder, hypoactivity in PFC, the parietal cortex, and the SMA in catatonia associated to a medical condition, and mixed metabolic activity in the study on catatonia linked to a medical condition. CONCLUSION: Findings support the theory of dysfunction in cortico-striatal-thalamic, cortico-cerebellar, anterior cingulate-medial orbitofrontal, and lateral orbitofrontal networks in catatonia. However, the majority of the literature focuses on schizophrenia spectrum disorders, leaving the pathophysiologic characteristics of catatonia in other disorders less understood. This review highlights the need for further research to elucidate the pathophysiology of catatonia across various disorders.

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.

Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity.

A key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model 'advanced brain aging' and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lacking Plp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventional Plp1 null mutants, subtle myelin defects were restricted to the cortex, hippocampus, and underlying callosal tracts. Moreover, forebrain-specific Plp1 mutants exhibited no defects of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventional Plp1 null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.

Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score ≥ 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior.

Cortical Contributions to Distinct Symptom Dimensions of Catatonia.

Catatonia is a central aspect of schizophrenia spectrum disorders (SSD) and most likely associated with abnormalities in affective, motor, and sensorimotor brain regions. However, contributions of different cortical features to the pathophysiology of catatonia in SSD are poorly understood. Here, T1-weighted structural magnetic resonance imaging data at 3 T were obtained from 56 right-handed patients with SSD. Using FreeSurfer version 6.0, we calculated cortical thickness, area, and local gyrification index (LGI). Catatonic symptoms were examined on the Northoff catatonia rating scale (NCRS). Patients with catatonia (NCRS total score ≥3; n = 25) showed reduced surface area in the parietal and medial orbitofrontal gyrus and LGI in the temporal gyrus (P < .05, corrected for cluster-wise probability [CWP]) as well as hypergyrification in rostral cingulate and medial orbitofrontal gyrus when compared with patients without catatonia (n = 22; P < .05, corrected for CWP). Following a dimensional approach, a negative association between NCRS motor and behavior scores and cortical thickness in superior frontal, insular, and precentral cortex was found (34 patients with at least 1 motor and at least 1 other affective or behavioral symptom; P < .05, corrected for CWP). Positive associations were found between NCRS motor and behavior scores and surface area and LGI in superior frontal, posterior cingulate, precentral, and pericalcarine gyrus (P < .05, corrected for CWP). The data support the notion that cortical features of distinct evolutionary and genetic origin differently contribute to catatonia in SSD. Catatonia in SSD may be essentially driven by cortex variations in frontoparietal regions including regions implicated in the coordination and goal-orientation of behavior.

Microglia ablation alleviates myelin-associated catatonic signs in mice.

The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology.

[Mechanisms of catatonia]. / Mechanismen van katatonie.

BACKGROUND: Catatonia is being increasingly viewed as a unique syndrome consisting of specific motor signs that respond characteristically and uniformly to benzodiazepines and electroconvulsive therapy. This interpretation is also reflected in changes in the classification of catatonia in DSM-5. An all-embracing pathogenesis of catatonia remains elusive. AIM: To review the mechanisms of catatonia. METHOD: We reviewed the literature. RESULTS: Certain aspects of catatonia can be explained by a number of different mechanisms. We present a new, more comprehensive model involving the vagal nerve. CONCLUSION: Further research into the underlying mechanisms of catatonia is needed in order to to find new therapies.

Catatonia after cerebral hypoxia: do the usual treatments apply?

BACKGROUND: Neurologic deterioration occurring days to weeks after a cerebral hypoxic event accompanied by diffuse white matter demyelination is called delayed posthypoxic leukoencephalopathy (DPHL). Manifestations of DPHL are diverse and include dementia, gait disturbance, incontinence, pyramidal tract signs, parkinsonism, chorea, mood and thought disorders, akinetic mutism, and rarely catatonia. METHODS: We report a case of malignant catatonia in a patient diagnosed with DPHL that was refractory to electroconvulsive therapy (ECT) and review the literature on catatonia in DPHL. RESULTS: The patient was a 56-year-old woman with schizoaffective disorder who was admitted with catatonia 2 weeks after hospitalization for drug overdose and respiratory failure. Her catatonic symptoms did not respond to treatment of lorazepam, amantadine, methylphenidate, or 10 sessions of bilateral ECT at maximum energy. Repeat magnetic resonance imaging revealed extensive periventricular white matter lesions not present on admission scans, and she was diagnosed with DPHL. DISCUSSION: No treatment for DPHL has been proven to be widely effective. Hyperbaric oxygen treatments may reduce the rate of development, and symptom improvement has been reported with stimulants and other psychotropic agents. Review of literature reveals rare success with GABAergic agents for catatonia after cerebral hypoxia and no cases successfully treated with ECT. There are 7 case reports of neurologic decompensation during ECT treatment after a cerebral hypoxic event. CONCLUSION: Caution is advised when considering ECT for catatonia when delayed sequelae of cerebral hypoxia are on the differential diagnosis, as there is a dearth of evidence to support this treatment approach.

Neuropathological evaluation of an 84-year-old man after 422 ECT treatments.

Concern remains among many that electroconvulsive therapy (ECT) causes "brain damage." This ambiguous term presumably refers to lesions that could, in principle, be observed either grossly or microscopically in postmortem studies, and the assertion that it occurs appears to be based largely on old reports with dubious relevance to modern practice. Fortunately, using modern technique, ECT is so safe that mortality around the time of treatment is extraordinarily rare and as a result there has been little opportunity for postmortem examination of individuals who had recently had ECT. We report a case in which postmortem brain examination was performed roughly a month after the patient's last treatment.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

BACKGROUND: Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. CASE: We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. CONCLUSION: In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.

[Selection for catatonic reaction in rats: a study of interstrain differences by magnetic resonance imaging].

Brain studies by magnetic resonance imaging, angiography, and spectroscopy have been performed with rat strains Wistar, GC (genetic and catatonia), and PM+ (pendulum movements). Both GC and PM+ rats show similar deviations from the ancestral Wistar population in having smaller areas of the right striatum (coronal slice). The anterior horns of lateral ventricles in GC rats are smaller than in the control strain. The maximum blood flow velocity in the common carotid arteries of PM+ rats is greater. The GC and PM+ strains differ in myo-inositol level in the hippocampus. The PM+ strain is characterized by a lower taurine level in the hippocampus, which may be one of the participants regulated the predisposition to audiogenic seizures.

Increased advanced glycation end-products (AGEs) assessed by skin autofluorescence in schizophrenia.

BACKGROUND: Oxidative stress has been intensively studied as a key biochemical system in the pathophysiology of schizophrenia. However, little is known about the implication of oxidative stress in the development of physical illnesses in schizophrenia patients, who are characterized by high cardiovascular risk and decreased life expectancy. Advanced glycation end-products (AGEs) are considered to be markers of oxidative stress and are linked to the development of atherosclerosis. METHODS: We investigated AGE levels determined by a noninvasive skin autofluorescence (skin AF) method (AGE-Reader™) in schizophrenia patients. Skin AF was assessed in 55 schizophrenia patients without diabetes or renal disease and 55 healthy controls matched for age, gender and smoking status. Nineteen of the 55 schizophrenia patients had a severe form of the disease (Kraepelinian schizophrenia). RESULTS: Skin AF was significantly higher in schizophrenia patients compared to controls (2.46 ± 0.52 and 1.90 ± 0.21, respectively, p < 0.0001). Kraepelinian schizophrenia patients had significantly higher skin AF than non-Kraepelinian schizophrenia patients (p = 0.05). CONCLUSIONS: This is the first study to demonstrate high AGE levels assessed by a noninvasive method in schizophrenia patients.

Etiopathogenesis of catatonia: generalizations and working hypotheses.

Catatonia has been rediscovered over the last 2 decades as a unique syndrome that consists of specific motor signs with a characteristic and uniform response to benzodiazepines and electroconvulsive therapy. Further inquiry into its developmental, environmental, psychological, and biological underpinnings is warranted. In this review, medical catatonia models of motor circuitry dysfunction, abnormal neurotransmitters, epilepsy, genetic risk factors, endocrine dysfunction, and immune abnormalities are discussed. Developmental, environmental, and psychological risk factors for catatonia are currently unknown. The following hypotheses need to be tested: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; Prader-Willi syndrome is a clinical GABAergic genetic-endocrine model of catatonia; Kleine-Levin syndrome represents a periodic form of adolescent catatonia; and anti-N-methyl-d-aspartate receptor encephalitis is an autoimmune type of catatonia.