Abstract
Background and hypothesis
Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. ...Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP). We hypothesized that patients with higher central antioxidant tone at first presentation will have better functional outcomes in early stages of illness.
Study design
We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimized the confounding effects of illness chronicity, long-term treatment exposure, and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes.
Study results
Patients who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in EET did not differ from healthy subjects in their GSH levels.
Conclusion
Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.
Abstract
Background and Hypothesis
The integration of information that typifies working memory (WM) operation requires a flexible, dynamic functional relationship among brain regions. In ...schizophrenia, though WM capacity is prominently impaired at higher loads, the mechanistic underpinnings are unclear. As a result, we lack convincing cognitive remediation of load-dependent deficits. We hypothesize that reduced WM capacity arises from a disruption in dynamic functional connectivity when patients face cognitive demands.
Study Design
We calculate the dynamic voxel-wise degree centrality (dDC) across the functional connectome in 142 patients with schizophrenia and 88 healthy controls (HCs) facing different WM loads during an n-back task. We tested associations of the altered variability in dDC and clinical symptoms and identified intermediate connectivity configurations (clustered states) across time during WM operation. These analyses were repeated in another independent dataset of 169 subjects (102 with schizophrenia).
Study Results
Compared with HCs, patients showed an increased dDC variability of supplementary motor area (SMA) for the “2back vs. 0back” contrast. This instability at the SMA seen in patients correlated with increased positive symptoms and followed a limited “U-shape” pattern at rest-condition and 2 loads. In the clustering analysis, patients showed reduced centrality in the SMA, superior temporal gyrus, and putamen. These results were replicated in a constrained search in the second independent dataset.
Conclusions
Schizophrenia is characterized by a load-dependent reduction of stable centrality in SMA; this relates to the severity of positive symptoms, especially disorganized behaviour. Restoring SMA stability in the presence of cognitive demands may have a therapeutic effect in schizophrenia.
With our rapidly expanding population of older adults, identifying effective intervention strategies to improve cognitive functioning is an increasing priority. This study sought to examine whether ...4 weeks of thrice-weekly meditation training can improve attention in older adults, as well as whether such benefits may extend to other domains of cognition as well as mobility.
Forty-three participants (mean age 68 years) were randomized into either the focused attention meditation group or the music listening control group (Clinicaltrials.gov ID NCT03417635). Participants completed three 20-minute guided group sessions per week for four consecutive weeks. Our primary outcome measure was behavioural performance on the Sustained Attention to Response Task (SART). Secondary and tertiary outcome measures included event-related potentials (ERPs) during the SART task, measures of executive functioning, and measures of mobility.
We found that meditation training significantly improved attention, as demonstrated by improved SART accuracy and changes in N2 ERP amplitude and latency.
These findings suggest that meditation may lead to changes in attention and underlying cognitive processing in older adults, although a full-scale definitive trial is needed. Future research on the long-term benefits with real world applications is warranted.
Introduction
Symptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to ...relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structure, is suspected in schizophrenia, we aimed to first seek patient subgroups with different neurobiological signatures and then quantify linguistic indices that capture the symptoms of “negative formal thought disorder” (i.e., fluency, cohesion, and complexity of language production).
Methods
Atlas-based cortical thickness values (obtained with a 7T MRI scanner) of 66 patients with first-episode psychosis and 36 healthy controls were analyzed with hierarchical clustering algorithms to produce neuroanatomical subtypes. We then examined the generated subtypes and investigated the quantitative differences in MRS-based glutamate levels in the dorsal anterior cingulate cortex (dACC) as well as in three aspects of language production features: fluency, syntactic complexity, and lexical cohesion.
Results
Two neuroanatomical subtypes among patients were observed, one with near-normal cortical thickness patterns while the other with widespread cortical thinning. Compared to the subgroup of patients with relatively normal cortical thickness patterns, the subgroup with widespread cortical thinning was older, with higher glutamate concentration in dACC and produced speech with reduced mean length of T-units (complexity) and lower repeats of content words (lexical cohesion), despite being equally fluent (number of words).
Conclusion
We characterized a patient subgroup with thinner cortex in first-episode psychosis. This subgroup, identifiable through macroscopic changes, is also distinguishable in terms of neurochemistry (frontal glutamate) and language behavior (complexity and cohesion of speech). This study supports the hypothesis that glutamate-mediated cortical thinning may contribute to a phenotype that is detectable using the tools of computational linguistics in schizophrenia.
Abstract
Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool ...to study schizophrenia. At present, we do not know if these word-level choices in speech are sensitive to the illness stage (i.e., acute untreated vs. stable established state), track cognitive deficits in major domains (e.g., cognitive control, processing speed) or relate to established dimensions of formal thought disorder. In this study, we collected samples of descriptive discourse in patients experiencing an untreated first episode of schizophrenia and healthy control subjects (246 samples of 1-minute speech;
n
= 82, FES = 46, HC = 36) and used a co-occurrence based vector embedding of words to quantify semantic similarity in speech. We obtained six-month follow-up data in a subsample (99 speech samples,
n
= 33, FES = 20, HC = 13). At baseline, semantic similarity was evidently higher in patients compared to healthy individuals, especially when social functioning was impaired; but this was not related to the severity of clinically ascertained thought disorder in patients. Across the study sample, higher semantic similarity at baseline was related to poorer Stroop performance and processing speed. Over time, while semantic similarity was stable in healthy subjects, it increased in patients, especially when they had an increasing burden of negative symptoms. Disruptions in word-level choices made by patients with schizophrenia during short 1-min descriptions are sensitive to interindividual differences in cognitive and social functioning at first presentation and persist over the early course of the illness.
Network modeling has been proposed as an effective approach to examine complex associations among antecedents, mediators and symptoms. This study aimed to investigate whether the severity of ...depressive symptoms affects the multivariate relationships among symptoms and mediating factors over a 2-year longitudinal follow-up.
We recruited a school-based cohort of 1480 primary and secondary school students over four semesters from January 2020 to December 2021. The participants (n = 1145) were assessed at four time points (ages 10-13 years old at baseline). Based on a cut-off score of 5 on the 9-item Patient Health Questionnaire at each time point, the participants were categorized into the non-depressive symptom (NDS) and depressive symptom (DS) groups. We conducted network analysis to investigate the symptom-to-symptom influences in these two groups over time.
The global network metrics did not differ statistically between the NDS and DS groups at four time points. However, network connection strength varied with symptom severity. The edge weights between learning anxiety and social anxiety were prominently in the NDS group over time. The central factors for NDS and DS were oversensitivity and impulsivity (3 out of 4 time points), respectively. Moreover, both node strength and closeness were stable over time in both groups.
Our study suggests that interrelationships among symptoms and contributing factors are generally stable in adolescents, but a higher severity of depressive symptoms may lead to increased stability in these relationships.
Abstract
Progressive reduction in glutamatergic transmission has been proposed as an important component of the illness trajectory of schizophrenia. Despite its popularity, to date, this notion has ...not been convincingly tested in patients in early stages of schizophrenia. In a longitudinal 7T magnetic resonance spectroscopy (1H-MRS), we quantified glutamate at the dorsal anterior cingulate cortex in 21 participants with a median lifetime antipsychotic exposure of less than 3 days and followed them up after 6 months of treatment. Ten healthy controls were also scanned at 2 time points. While patients had significantly lower overall glutamate levels than healthy controls (F(1,27) = 5.23, P = .03), we did not observe a progressive change of glutamate concentration in patients (F(1,18) = 0.47, P = .50), and the group by time interaction was not significant (F(1,27) = 0.86, P = .36). On average, patients with early psychosis receiving treatment showed a 0.02 mM/y increase, while healthy controls showed a 0.06 mM/y reduction of MRS glutamate levels. Bayesian analysis of our observations does not support early, post-onset glutamate loss in schizophrenia. Interestingly, it provides evidence in favor of a lack of progressive glutamate change in our schizophrenia sample—indicating that the glutamate level at the onset of illness was the best predictor of the levels 6 months after treatment. A more nuanced view of glutamatergic physiology, linked to early cortical maturation, may be required to understand glutamate-mediated dynamics in schizophrenia.
Falls are a major health care concern for our aging population. Previous research has identified impaired sustained attention as a risk factor for falls. Recently, meditation has been shown to ...improve different types of attention in various populations. However, there are no studies to date examining whether meditation training can improve sustained attention and mobility in older adults.
We are conducting a 4-week proof-of-concept meditation intervention. We will recruit community-dwelling older adults. Participants will be randomized into one of two groups: (1) meditation training or (2) music listening (control). All participants will complete three 20-min group sessions per week and will be encouraged to continue their practice independently on the remaining days each week. Our primary outcome measure is behavioral performance on the Sustained Attention to Response Task (SART). Our secondary and tertiary outcomes include electroencephalograms (EEG) to assess attention and cognitive processing, mobility, and executive function.
Our proof-of-concept intervention aims to examine whether meditation training can improve sustained attention in older adults, who are known to be susceptible to falls. Importantly, our research has the potential to inform future clinical trials aimed at improving mobility and reducing falls risk in our aging population.
Clinicaltrials.gov ID NCT03417635.
A substantial number of individuals with clinical high-risk (CHR) mental state do not transition to psychosis. However, regardless of future diagnostic trajectories, many of these individuals develop ...poor social and occupational functional outcomes. The levels of glutathione, a crucial cortical antioxidant, may track variations in functional outcomes in early psychosis and prodromal states. Thirteen clinical high-risk and 30 healthy control volunteers were recruited for a 7-Tesla magnetic resonance spectroscopy scan with a voxel positioned within the dorsal anterior cingulate cortex (ACC). Clinical assessment scores were collected to determine if any association was observable with glutathione levels. The Bayesian Spearman’s test revealed a positive association between the Social and Occupational Functioning Assessment Scale (SOFAS) and the glutathione concentration in the clinical high-risk group but not in the healthy control group. After accounting for variations in the SOFAS scores, the CHR group had higher GSH levels than the healthy subjects. This study is the first to use 7-Tesla magnetic resonance spectroscopy to test whether ACC glutathione levels relate to social and occupational functioning in a clinically high-risk group and offers preliminary support for glutathione levels as a clinically actionable marker of prognosis in emerging adults presenting with risk features for various severe mental illnesses.
Dementia literacy is important for risk mitigation and preventative strategies before disease onset. The aim of our study was to investigate dementia literacy and how demographic characteristics ...influence these perceptions in order to provide evidence for how dementia-centered public health initiatives should structure their focus. We conducted a globally administered online survey, through Amazon Mechanical Turk (mTurk). Survey items evaluated: (1) personal perception on the preventability of dementia, and (2) risk awareness of lifestyle factors. Differences in risk scoring between the 598 respondents were compared using Kruskal-Wallis testing factored by demographic categorizations. Most of the sample demonstrated understanding that lifestyle factors contribute some risk toward dementia, though these risk scores were generally low. Differences in risk scoring varied by demographic characteristics. Women, older adults, those with non-post-secondary attainment, below average income, and White background tended to report lower risk scores. Public health education and initiatives for dementia prevention should focus on lifestyle risk factors, in addition to considering the barriers related to the demographic factors identified that may prevent populations from accessing programs and information.
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