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.
Psychomotor slowing is frequently distressing patients with depression and schizophrenia. Increased neural activity within premotor cortices is linked to psychomotor slowing. This transdiagnostic study tested whether add-on inhibitory repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) may alleviate psychomotor slowing. Forty-five patients with severe psychomotor slowing (26 psychosis, 19 major depression) were randomized in this transdiagnostic, double-blind, parallel-group, sham-controlled trial of 15 daily sessions of add-on rTMS over 3 weeks. Treatment arms included inhibitory 1 Hz stimulation of the SMA, facilitatory intermittent theta burst stimulation (iTBS) of the SMA, facilitatory 15 Hz stimulation of the left dorsolateral prefrontal cortex (DLPFC), and sham stimulation of the occipital cortex. The primary outcome was response (>30% reduction from baseline) according to the Salpêtrière Retardation Rating Scale (SRRS). Secondary outcomes were course of SRRS and further symptom rating scales. Last-observation carried forward method was applied to all subjects with baseline data. Response rates differed between protocols: 82% with inhibitory 1 Hz rTMS of the SMA, 0% with facilitatory iTBS of the SMA, 30% with sham, and 33% with 15 Hz DLPFC rTMS (χ 2 = 16.6, P < .001). Dropouts were similarly distributed across protocols. Response rates were similar in the completer analysis. This transdiagnostic trial of rTMS demonstrates that inhibitory SMA stimulation may ameliorate psychomotor slowing in severely ill patients. It further provides proof-of-concept that motor inhibition is linked to increased neural activity in the SMA because the inhibitory protocol performed best in reducing symptoms. Trial registration: NCT03275766 (www.clinicaltrials.gov).
IntroductionAberrant motor function is an integral part of schizophrenia. In fact, abnormalities are frequently found in patients, in populations at risk, and in unaffected relatives. Motor abnormalities are suspected to be relevant for the clinical outcome and could probably predict the conversion from at-risk individuals to schizophrenia. Furthermore, motor function has been argued as endophenotype of the disorder. Yet, which particular motor domain may classify as a potential endophenotype is unknown. We aimed to compare schizophrenia patients, unaffected first-degree relatives and healthy controls for different motor domains. We expected impairments in all domains in patients and in some domains in relatives.MethodWe included 43 schizophrenia patients, 34 unaffected first-degree relatives of schizophrenia patients, and 29 healthy control subjects, matched for age, gender, and education level. We compared motor function of four motor domains between the groups. The domains comprise neurological soft signs (NSS), abnormal involuntary movements (dyskinesia), Parkinsonism, and fine motor function including simple [finger tapping (FT)] and complex fine motor function, (i.e., dexterity as measured with the coin rotation test). Furthermore, we tested the association of motor function of the four domains with working memory, frontal lobe function, and nonverbal intelligence for each group separately using within-group bivariate correlations.ResultsSchizophrenia patients showed poorer motor function in all tested domains compared to healthy controls. First-degree relatives had intermediate ratings with aberrant function in two motor domains. In detail, relatives had significantly more NSS and performed poorer in the FT task than controls. In contrast, complex fine motor function was intact in relatives. Relatives did not differ from controls in dyskinesia or Parkinsonism severity.DiscussionTaken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first-degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and FT. Thus, NSS and FT may be potential markers of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia.
Background Personal space is the safe area around us causing discomfort when violated by others. Previous research has shown that our need for personal space can be shaped by previous and current experiences. For instance, childhood maltreatment is associated with altered personal space in healthy controls. Additionally, space regulation is altered in schizophrenia (with personal space being increased in patients with paranoia). Whether childhood maltreatment and dimensions of delusions are associated with increased safety behaviour in patients with schizophrenia is unknown. We therefore aim to test the association of childhood trauma and delusions with interpersonal distance in schizophrenia patients and healthy controls. Methods We assessed childhood trauma (CT) in both, healthy subjects and schizophrenia patients (matched for age, gender and education) with the childhood trauma scale. This scale is a self-report screening tool for experiences of abuse & neglect during childhood. Additionally, we assessed delusions in schizophrenia patients, using the dimensions of delusional experience scale (DDE), which includes ‘conviction’, ‘extension’, ‘bizarreness’, ‘disorganization’, and ‘pressure’ dimensions. We compared the interpersonal distance (stop-distance test) and comfort ratings at predetermined distances (fixed-distance test) between subjects with low/medium and high CT ratings. Likewise, interpersonal distance and comfort ratings of patients with and without delusions were compared. Results In our preliminary data (n = 27), subjects with high CT ratings showed an increased need for interpersonal space compared to subjects with low/medium CT. Additionally, the high CT group showed reduced comfort ratings at varying fixed distances. Likewise, patients with delusions had an increased interpersonal space and reduced comfort at fixed distances. Moreover, interpersonal space was associated with the severity of childhood trauma, and in particular with emotional neglect. Finally, interpersonal distance was associated with the degree to which the delusional belief involves various areas of patients’ lives (‘extension’ dimension of the DDE). Discussion Our preliminary data suggests that childhood maltreatment and dimensions of delusions are associated with increased safety behaviour in patients with schizophrenia. These findings are in line with previous studies, which found associations of interpersonal distance and childhood maltreatment in healthy controls as well as paranoia in patients with schizophrenia. Our findings are of particular interest, as increased safety behaviour may impact social functioning (i.e. lead to more social withdrawal) in patients with schizophrenia.
Background Schizophrenia is a disabling disorder with tremendous individual burden, reduced quality of life, leading to intense costs for society. Paranoia is a central feature of schizophrenia. In particular, paranoid experience is thought to be associated with aggressive behaviour, and poor social and functional outcome. Since paranoid threat is sometimes hard to detect in the clinical interview, a simple bedside test to identify patients suffering from paranoid experience was recently proposed: the interpersonal distance test. Methods For measuring interpersonal distance in patients with schizophrenia and age-, gender- and education-matched healthy controls, we performed a stop-distance paradigm. To accomplish the paradigm, we positioned experimenter and participant at opposite ends of the room with a distance of seven meters facing each other. The stop-distance paradigm contained four different conditions; two active conditions (i.e. participant is approaching experimenter) and two passive conditions (i.e. experimenter is approaching participant) both, with and without eye contact. Participants were instructed to stop or tell the experimenter to stop at a distance, at which they would start to feel less comfortable. Moreover, we assessed paranoid threat with the Bern Psychopathology Scale. We compared the interpersonal distance between patients with current experiences of paranoid threat, schizophrenic patients without paranoia and healthy controls. Results Patients with higher ratings in paranoid experience presented with higher interpersonal distance than patients without paranoid threat and matched healthy controls. This effect was most prominent in the passive conditions. Patients without paranoia did not differ from healthy controls in the interpersonal distance test. Discussion Interpersonal distance is a reliable indicator of current paranoid threat in patients with schizophrenia. In fact, interpersonal distance is not generally altered in schizophrenia. However, paranoid threat leads to impairments in interpersonal space regulation. This is of particular relevance as interpersonal distance might be predictive of social and functional outcome and aggressive behaviour in schizophrenia.
BackgroundAberrant motor function is an integral part of Schizophrenia. In fact, abnormalities are frequently found in patients, in populations at risk, and in unaffected relatives. Motor abnormalities are suspected to be relevant for the clinical outcome and could probably predict the conversion from at-risk individuals to schizophrenia. Furthermore, motor function and has been argued as endophenotype of the disorder. Yet, which particular motor domain may classify as a potential endophenotype is unknown. We aimed to compare schizophrenia patients, unaffected first degree relatives and healthy controls for different motor domains. We expected impairments in all domains in patients and in some domains in relatives.MethodsWe included 43 schizophrenia patients, 34 unaffected first degree relatives of schizophrenia patients and 29 healthy control subjects, matched for age, gender and education level. We compared motor function of five domains between the groups. The domains comprise neurological soft sings (NSS), abnormal involuntary movements (dyskinesia), Parkinsonism, complex fine motor function applying the coin rotation task as well as finger tapping. Furthermore, we tested the association of motor function of the five domains with working memory, frontal lobe function and nonverbal intelligence for each group separately using within-group bivariate correlations.ResultsSchizophrenia patients showed poorer motor function in all tested domains compared to healthy controls. First-degree relatives had intermediate ratings with aberrant function in two motor domains. In detail, relatives had significantly more NSS and performed poorer in the finger tapping task than controls. In contrast, in relatives complex fine motor function was intact. Relatives did not differ from controls in dyskinesia or Parkinsonism severity.DiscussionTaken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and finger tapping. Thus, NSS and finger tapping may be a potential marker of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia.
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