In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN-Related Parkinson's Disease

Background

Alterations in mitochondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism, and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be performed.

Objectives

The objectives of this study were to explore glucose production, gluconeogenesis, and the contribution of gluconeogenesis to glucose production in idiopathic and PRKN PD compared with healthy controls with state-of-the-art biochemical methods.

Methods

We applied a dried-blood sampling/gas chromatography/mass spectrometry approach to monitor fluxes in the Cori cycle in vivo.

Results

The contribution of gluconeogenesis to total glucose production is increased in idiopathic PD patients (n = 33), but not in biallelic PRKN mutation carriers (n = 5) compared with healthy controls (n = 13).

Conclusions

We provide first-time in vivo evidence for alterations in glucose metabolism in idiopathic PD, in keeping with the epidemiological evidence for an association between PD and diabetes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Speech and gait abnormalities in motor subtypes of de-novo Parkinson's disease

Aim

To investigate the presence and relationship of temporal speech and gait parameters in patients with postural instability/gait disorder (PIGD) and tremor-dominant (TD) motor subtypes of Parkinson's disease (PD).

Methods

Speech samples and instrumented walkway system assessments were acquired from a total of 60 de-novo PD patients (40 in TD and 20 in PIGD subtype) and 40 matched healthy controls. Objective acoustic vocal assessment of seven distinct speech timing dimensions was related to instrumental gait measures including velocity, cadence, and stride length.

Results

Compared to controls, PIGD subtype showed greater consonant timing abnormalities by prolonged voice onset time (VOT) while also shorter stride length during both normal walking and dual task, while decreased velocity and cadence only during dual task. Speaking rate was faster in PIGD than TD subtype. In PIGD subtype, prolonged VOT correlated with slower gait velocity (r = −0.56, p = 0.01) and shorter stride length (r = −0.59, p = 0.008) during normal walking, whereas relationships were also found between decreased cadence in dual task and irregular alternating motion rates (r = −0.48, p = 0.04) and prolonged pauses (r = −0.50, p = 0.03). No correlation between speech and gait was detected in TD subtype.

Conclusion

Our findings suggest that speech and gait rhythm disorder share similar underlying pathomechanisms specific for PIGD subtype.     

Postoperative confusion and basilar artery stroke

Introduction  

Non-focal postoperative mental status changes can be challenging.     

Statins and cognition in late‐life bipolar disorder

Objectives

Recent data suggests that statins have positive effects on cognition in older adults. Studies in patients with mood disorders have found contradicting positive and negative effects of statins on mood and cognition, with limited data in bipolar disorder (BD). The objective of this study was to assess the association between statin use and cognition in older adults with BD.

Methods

In a cross‐sectional sample of 143 euthymic older adults with BD (age ≥ 50), statin users (n = 48) and nonusers (n = 95) were compared for cognitive outcomes: Global and cognitive domain z‐scores were calculated from detailed neuropsychological batteries using normative data from healthy comparators (n = 87).

Results

The sample had a mean age of 64.3 (±8.9) years, 65.0% were female, with an average of 15.1 (±2.79) years of education. Statin users did not differ from nonusers on global (?0.60 [±0.69] vs ?0.49 [±0.68], t[127] = 0.80, P = .42) or individual cognitive domains z‐score.

Conclusions

In older patients with BD, statin use is not independently associated with cognitive impairment. This suggests that in older BD patients, the cognitive dysfunction associated with BD trumps the potential cognitive benefit that is associated with statins in older adults without a psychiatric disorder. Further, statins do not seem to exacerbate this cognitive dysfunction. Future longitudinal studies are needed to confirm these findings.     

Individual and parental psychiatric history and risk for suicide among adolescents and young adults in Denmark

Background  

Both individual and familial histories of mental illness are substantial risk factors for suicide in young people.     

Recent substance use among clients with early psychosis and the potential to graduate from New Journeys

Aim

This study examined the relationship between recent substance use prior to intake and program graduation among young adults with early psychosis enrolled in coordinated specialty care.

Methods

Participants (N = 248) were from New Journeys, a network of coordinated specialty care programs in Washington State. Recent (i.e., past 30 days) alcohol, cannabis, and other substance use was collected at intake and process data (e.g., contact) was collected by clinicians across a 2-year period.

Results

At intake, 32% of participants reported alcohol use only, 26% cannabis use only, and 15% both alcohol and cannabis use. Participants who reported alcohol use only (p = .02), cannabis use only (p = .03), and any substance use (p = .02) had significantly lower chances of graduating from coordinated specialty care than individuals who do not use substances.

Conclusions

Unlike prior work, recent substance use influences clients' potential to graduate from New Journeys. Additional focus on the implementation of substance use treatment, with an emphasis on alcohol use, in coordinated specialty care programs is needed improve program completion rates.     

Analysis of positron emission tomography hypometabolic patterns and neuropsychiatric symptoms in patients with dementia syndromes

Aims

To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI).

Methods

This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. ¹⁸F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models.

Results

Patients with clinical Alzheimer's disease (AD, 81.6%, 605/741) and dementia with Lewy bodies (67.9%, 19/28) mostly had AD-pattern hypometabolism, and 76/137 (55.5%) of patients with frontotemporal lobar degeneration showed frontal and anterior temporal pattern (FT-P) hypometabolism. Besides corticobasal degeneration, patients with behavioral variant frontotemporal dementia (36/58), semantic dementia (7/10), progressive non-fluent aphasia (6/9), frontotemporal lobar degeneration and amyotrophic lateral sclerosis (3/5), and progressive supranuclear palsy (21/37) also mostly showed FT-P hypometabolism. The proportion of FT-P hypometabolism was associated with the presence of hallucinations (R = 0.171, p = 0.04), anxiety (R = 0.182, p = 0.03), and appetite and eating abnormalities (R = 0.200, p = 0.01) in AD.

Conclusion

Specific hypometabolic patterns in FDG-PET are associated with NPS and beneficial for the early identification and management of NPS in patients with CI.     

Childhood and juvenile meningiomas

Purpose  

The purpose of this paper was to study the clinical characteristic, treatment, and prognosis of childhood meningioma.     

The association between transient childhood psychotic experiences and psychosocial outcomes in young adulthood: Examining the role of mental disorders and adult attachment

Aim

Evidence suggest individuals with mental disorders and psychotic experiences (PE), even transient PE, show poorer psychosocial outcomes relative to those with mental disorders. The concept of “attachment” is hypothesized as the mechanism by which people seek support in times of need. This can be measured as discrete styles or as positive (low avoidance/anxiety)/negative (high avoidance/anxiety) dimensions. Adult attachment has previously been examined on PE risk factors, but not outcomes. This study aimed to examine the relationship between transient childhood PE and adult psychosocial outcomes, comparing those with and without mental disorders. Second, to examine the role of adult attachment.

Method

Participants (n = 103) attended baseline (age 11–13) and 10-year follow-up. PE and mental disorders were measured using the Schedule for Affective Disorders and Schizophrenia for School-aged Children. Attachment and outcomes were measured using self-report measures. Analysis compared those with PE (with/without mental disorders), and mental disorders without PE, to controls, using linear and Poisson regression.

Results

PE was associated with lower self-esteem (β = −2.28, p = .03), perceived social support from friends (β = −2.80, p = .01), and higher stress in platonic relationships (IRR = 1.64). PE and mental disorders were associated with lower self-esteem (β = −5.74, p = .002), higher stress in romantic (IRR = 1.40) and platonic (IRR = 1.59) relationships, general stress (β = 5.60, p = .006), and mental distress (β = 5.67, p = .001). Mental disorders alone was not associated with any measure. Adult attachment dimensions attenuated some results.

Conclusions

This paper illustrates the association between transient PE and adult psychosocial outcomes, with & without co-occurring mental disorders, and demonstrates the role of adult attachment.     

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.     

Correlations between psychopathology and self‐reported quality of life among adolescents in youth correctional facilities in Lagos,Nigeria: A short report

Background

The relationship between psychopathology and quality of life (QoL) and well‐being among young incarcerated offenders has hardly been explored.

Aims

Our aim was to test the hypothesis that higher self‐rated psychopathology would be associated with lower QoL among adolescents resident within youth correctional facilities in Lagos.

Methods

Psychopathology was assessed using the Strength and Difficulty Questionnaire (SDQ), while QoL was measured by using the Paediatric Quality of Life .

Results

One hundred and sixty‐five adolescents completed the study, mostly boys (n = 124; 75%) with a mean age of 14.3 ± 2.1 years. Nearly, a fifth (30, 18%) of respondents had abnormal total SDQ scores (≥17), suggestive of definite psychiatric disorder, while another 44 (27%) had highly probable psychopathology (total SDQ scores 15–16). There was strong negative correlation (r = ?0.51, p < 0.001) between total SDQ scores and overall self‐reported QoL among respondents.

Conclusions and implications for practice

Although we were unable to infer direction of relationship between psychopathology and QoL among these adolescents, it is plausible to suppose that treatment of mental health problems could have a positive impact on rehabilitation and reintegration. Given the rate of likely psychopathology, mental health screening within young offender institutions should be routine, and followed, as necessary with full assessment and resultant treatment. Copyright © 2017 John Wiley & Sons, Ltd.     

Gut microbial signatures and differences in bipolar disorder and schizophrenia of emerging adulthood

Introduction

Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed.

Methods

In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed.

Results

We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified.

Conclusion

This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.     

Suicide and mental illness in parents and risk of suicide in offspring

Background  

A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide.     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

A Review and Meta-Analysis of Affective Judgments and Physical Activity in Adult Populations

Background  

Popular theories of health behavior have often been criticized for neglecting an affective component to behavioral engagement.     

Hope,despair and transformation: Climate change and the promotion of mental health and wellbeing

Background  

This article aims to provide an introduction to emerging evidence and debate about the relationship between climate change and mental health.     

Specialized Versus Generic Allied Health Therapy and the Risk of Parkinson's Disease Complications

Background

Specialized versus generic physiotherapy (PT) reduces Parkinson's disease (PD)–related complications. It is unclear (1) whether other specialized allied heath disciplines, including occupational therapy (OT) and speech and language therapy (S<), also reduce complications; (2) whether there is a synergistic effect among multiple specialized disciplines; and (3) whether each allied health discipline prevents specific complications.

Objectives

To longitudinally assessed whether the level of expertise (specialized vs. generic training) of PT, OT, and S< was associated with the incidence rate of PD-related complications.

Methods

We used claims data of all insured persons with PD in the Netherlands between January 1, 2010, and December 31, 2018. ParkinsonNet-trained therapists were classified as specialized, and other therapists as generic. We used mixed-effects Poisson regression models to estimate rate ratios adjusting for sociodemographic and clinical characteristics.

Results

The population of 51,464 persons with PD (mean age, 72.4 years; standard deviation 9.8) sustained 10,525 PD-related complications during follow-up (median 3.3 years). Specialized PT was associated with fewer complications (incidence rate ratio [IRR] of specialized versus generic = 0.79; 95% confidence interval, [0.74–0.83]; P < 0.0001), as was specialized OT (IRR = 0.88 [0.77–0.99]; P = 0.03). We found a trend of an association between specialized S< and a lower rate of PD-related complications (IRR = 0.88 [0.74–1.04]; P = 0.18). The inverse association of specialized OT persisted in the stratum, which also received specialized PT (IRR = 0.62 [0.42–0.90]; P = 0.001). The strongest inverse association of PT was seen with orthopedic injuries (IRR = 0.78 [0.73–0.82]; P < 0.0001) and of S< with pneumonia (IRR = 0.70 [0.53–0.93]; P = 0.03).

Conclusions

These findings support a wider introduction of specialized allied health therapy expertise in PD care and conceivably for other medical conditions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Intraoperative neurophysiology for surgery in and around the brainstem: role of brainstem mapping and corticobulbar tract motor-evoked potential monitoring

Introduction  

New advancements of intraoperative neurophysiology for surgery in and around the brainstem have been described.     

White matter microstructure in habit and reward circuits in anorexia nervosa: Insights from a neurite orientation dispersion and density imaging study

Background

Behavioral features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN.

Methods

In this brain imaging study, 29 female adolescents with partially or fully weight-restored AN and 27 healthy controls, all between 10 and 19 years, underwent whole-brain multi-shell diffusion tensor imaging. Utilizing neurite orientation dispersion and density imaging methods, we investigated group differences in white matter neurite density, orientation dispersion, and myelin density in tracts between prominent nodes of the reward circuit (ventral tegmental area (VTA) to nucleus accumbens (NAcc)) and the habit circuit (sensory motor area [SMA] to putamen).

Results

Findings revealed reduced neurite (F = 5.20, p = 0.027) and myelin density (F = 5.39, p = 0.025) in the left VTA-NAcc tract, and reduced orientation dispersion in the left (F = 7.00, p = 0.011) and right (F = 6.77, p = 0.012) VTA-NAcc tract. There were no significant group differences in the SMA-putamen tract. Significant relationships, after corrections, were not evident between tract microstructure and reward responsiveness, compulsive behaviors, illness duration, or BMI.

Conclusions

Adolescents with AN exhibit less dense, undermyelinated, and less dispersed white matter tracts connecting prominent reward system nodes, which could potentially signify underutilization of this part of the reward circuit. These results provide a detailed examination of white matter microstructure in tracts underlying instrumental behavioral phenotypes contributing to illness in AN.     

MR imaging and prognosis of hypoxic-ischemic leukoencephalopathy

Objective  

To correlate prognosis of hypoxic-ischemic white-matter injury with magnetic resonance imaging (MRI).