Neural Correlates of Formal Thought Disorder Dimensions in Psychosis.

BACKGROUND AND HYPOTHESIS: Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure. STUDY DESIGN: This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales. STUDY RESULTS: Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings. CONCLUSION: These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels.

Measuring catatonia motor behavior with objective instrumentation.

Objective: Catatonia is a neuropsychiatric syndrome, with important psychomotor features, associated with schizophrenia and other psychiatric disorders. The syndrome comprises multiple symptoms including abnormal motor control, behaviors, volition, and autonomic regulation. Catatonia assessment relies on clinical rating scales and clinicians familiar with the catatonia exam. However, objective instrumentation may aid the detection of catatonia. We aimed to investigate the relationship between movement parameters derived from actigraphy and expert ratings of catatonia symptoms measured by the Bush Francis Catatonia Rating Scale (BFCRS) and the Northoff Catatonia scale (NCS). Methods: Eighty-six acutely ill inpatients with schizophrenia spectrum disorders were assessed with the BFCRS, the NCS, and 24 h continuous actigraphy. Non-wear and sleep periods were removed from the actigraphy data prior to analysis. Associations between total catatonia scores, derived from both BFCRS and NCS, and actigraphy parameters as well as between single BFCRS items and actigraphy parameters were calculated using Spearman's rank correlation and non-parametric ANCOVAs (Quade's ANCOVAs), respectively. Results: Both higher BFCRS total scores (r = 0.369, p = 0.006) and NCS total scores (r = 0.384, p = 0.004) were associated with lower activity levels (AL). Higher scores on single BFCRS items such as immobility/stupor or staring were linked to lower AL (immobility/stupor: F = 17.388, p < 0.001, η2 = 0.175; staring: F = 7.849, p = 0.001, η2 = 0.162) and lower metabolic equivalents of task (MET). Conclusion: Specific catatonia symptoms such as immobility/stupor and staring can be measured with actigraphy. This may aid the detection, staging, and monitoring of catatonia in clinical settings.

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia.

BACKGROUND: Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10-20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. METHODS: We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). RESULTS: Our analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least -0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least -0.203, p-value<0.001) and between NES and SOFAS (tau = -0.137, p-value = 0.033). CONCLUSION: Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.

The Impact of Poor Nonverbal Social Perception on Functional Capacity in Schizophrenia.

Background: Nonverbal social perception is the ability to interpret the intentions and dispositions of others by evaluating cues such as facial expressions, body movements, and emotional prosody. Nonverbal social perception plays a key role in social cognition and is fundamental for successful social interactions. Patients with schizophrenia have severe impairments in nonverbal social perception leading to social isolation and withdrawal. Collectively, these aforementioned deficits affect patients' quality of life. Here, we compare nonverbal social perception in patients with schizophrenia and controls and examine how nonverbal social perception relates to daily functioning. Methods: We compared nonverbal social perception in 41 stable outpatients with schizophrenia and 30 healthy controls using the Mini Profile of Nonverbal Sensitivity (Mini-PONS). The participants evaluated 64 video clips showing a female actor demonstrating various nonverbal social cues. Participants were asked to choose one of two options that best described the observed scenario. We correlated clinical ratings (Positive and Negative Syndrome Scale, Brief Negative Syndrome Scale), Self-report of Negative Symptoms, and functional assessments (functional capacity and functional outcome) with Mini-PONS scores. Results: Patients performed significantly poorer in the Mini-PONS compared to controls, suggesting deficits in nonverbal social perception. These deficits were not associated with either positive symptoms or negative symptoms (including self-report). However, impaired nonverbal social perception correlated with distinctive domains of BNSS (mainly avolition and blunted affect), as well as functional capacity and functional outcome in patients. Conclusion: We demonstrate that nonverbal social perception is impaired in stable outpatients with schizophrenia. Nonverbal social perception is directly related to specific negative symptom domains, functional capacity and functional outcome. These findings underline the importance of nonverbal social perception for patients' everyday life and call for novel therapeutic approaches to alleviate nonverbal social perception deficits.

Using dynamic point light display stimuli to assess gesture deficits in schizophrenia.

BACKGROUND: Gesture deficits are ubiquitous in schizophrenia patients contributing to poor social communication and functional outcome. Given the dynamic nature of social communications, the current study aimed to explore the underlying socio-cognitive processes associated with point-light-displays (PLDs) of communicative gestures in the absence of any other confounding visual characteristics, and compare them to other well-established stimuli of gestures such as pictures by examining their association with symptom severity and motor-cognitive modalities. METHODS: We included 39-stable schizophrenia outpatients and 27-age-gender matched controls and assessed gesture processing using two tasks. The first task used static stimuli of pictures of a person performing a gesture. The limbs executing the gesture were missing and participants' task was to choose the correct gesture from three-options provided. The second task included videos of dynamic PLDs interacting with each other. One PLD performed communicative gestures, while the other PLD imitated/followed these performed gestures. Participants had to indicate, which of the two PLDs was imitating/following the other. Additionally, we evaluated symptom severity, as well as, motor and cognitive parameters. RESULTS: Patients underperformed in both gesture tasks compared to controls. Task performance for static stimuli was associated with blunted affect, motor coordination and sequencing domains, while PLD performance was associated with expressive gestures and sensory integration processes. DISCUSSION: Gesture representations of static and dynamic stimuli are associated with distinct processes contributing to poor social communication in schizophrenia, requiring novel therapeutic interventions. Such stimuli can easily be applied remotely for screening socio-cognitive deficits in schizophrenia.

Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior.

HIV infection and drug use intersect epidemiologically, and their combination can result in complex effects on brain and behavior. The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics, use patterns, stage of HIV disease and its treatment, comorbid factors, and age. To consider the range of drug effects, we have selected two that are in common use by PWH: methamphetamine and cannabis. We compare the effects of methamphetamine with those of cannabis, to illustrate how substances may potentiate, worsen, or even buffer the effects of HIV on the CNS. Data from human, animal, and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection, including effects on viral replication, immune activation, mitochondrial function, gut permeability, blood brain barrier integrity, glia and neuronal signaling. Moving forward, we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH. This review summarizes literature from clinical and preclinical studies demonstrating the adverse effects of METH, as well as the potentially beneficial effects of cannabis, on the interacting systemic (e.g., gut barrier leakage/microbial translocation, immune activation, inflammation) and CNS-specific (e.g., glial activation/neuroinflammation, neural injury, mitochondrial toxicity/oxidative stress) mechanisms underlying HIV-associated neurocognitive disorders.