Biomarkers in Neuropsychiatry最新文献

Biomarkers in Parkinson’s disease are widely researched in the field of neuropsychiatry. Though Parkinson’s disease is diagnosed clinically, biomarkers prove to be a promising means to identify disease in early stages, track disease progression, and distinguish Parkinson’s disease from other conditions like dementia with Lewy bodies. There is debate on the level of clinical utility specific Parkinson’s disease biomarkers have. This state of the art review discusses recent advances in the search for Parkinson’s disease biomarkers and delves into the clinical value of each, exploring biomarkers obtained through different modalities like cerebrospinal fluid, serum, genetics and imaging.

This study presents the findings of the magnetic resonance morphometric analysis of brain subcortical structures in patients with remitting relapsing multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) phenotypes in comparison with the control group. The study revealed significant differences between the volume of the left nucleus accumbens [control:RRMS= 570,108 ± 100,024:487,851 ± 124,174; F(p) ANOVA= <0001] and the volume of the left globus pallidus [control:RRMS= 2076,247 ± 290,695: 1855,851 ± 280,476; F(p) ANOVA= <0001] in patients with the relapsing remitting phenotype. Patients with the secondary progressive phenotype showed a statistically valid decrease in volume for multiple subcortical structures: the left caudate nucleus [control:SPMS= 3686,500 ± 501,966:3108,946 ± 565,138; F(p) ANOVA= 0.001], right caudate nucleus [control:SPMS= 3772,550 ± 508,087:3242,292 ± 650,215; F(p) ANOVA= 0003], left putamen [control:SPMS= 5130,781 ± 547,844: 4164,967 ± 1076,993; F(p) ANOVA= <0001], right putamen [control:SPMS= 5096,303 ± 611,397: 4281,046 ± 1100,752; F(p) ANOVA= 0001], left globus pallidus [control:SPMS= 2076,247 ± 290.696:1800,913 ± 296,609; F(p) ANOVA= <0001], left nucleus accumbens [control:SPMS= 570,108 ± 100,024;458,904 ± 131,690; F(p) ANOVA= 0001], right nucleus accumbens [control:SPMS= 587,567 ± 100,542: 447,375 ± 103,687; F(p) ANOVA= <0001]. The increase in EDSS was significantly correlated with the decrease in right nucleus accumbens in both RRMS and SPMS. The investigation revealed potential subcortex structures (nucleus accumbens) that could be considered as markers for the transition of RRMS to SPMS.

Major depressive disorder (MDD) is a disabling and severe psychiatric disorder with high risk of suicide, and adulthood is one of the most probable period for the onset. The neural basis underlying the young adults with MDD remains underexplored. In this study, we have investigated the cortical and subcortical alterations of neuroanatomical structures and functional activation in twenty-three young depressive patients with suicide attempt versus forty-five healthy controls. Significant disruptions of regional gray matter volume at left middle frontal extending to superior frontal involved with cognitive processing were found correlated with anxiety scores in MDD patients. Increased cortical thickness at right orbital frontal responsible for decision making was correlated with severity of suicide. Further, increased functional activation at left auditory association cortex was a hallmark of hallucinations in MDD, which was directly associated with depression severity. Moreover, decreased spontaneous brain activity at right inferior frontal was also found, reflecting lower inhibition control in MDD patients. The abnormal structural and functional findings at fronto-cortical areas implied the dysfunctional cognitive control and emotion regulation in MDD. The alterations correlated with clinical scores might indicate the reliable neural markers for MDD.

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible disease characterized by gait disturbance, a frontal-subcortical pattern of cognitive impairment, and urinary incontinence with disproportionately enlarged ventricles. Its prevalence rises with aging. Patients with iNPH are treated with shunt placement, and predicting the surgical outcome is not always easy. Cerebrospinal fluid (CSF) has inevitably been an attractive matrix for biomarker identification in both the diagnosis and treatment of iNPH and the disease may have individual CSF composition changes. Additionally, in order to detect iNPH earlier, implement treatment faster, and have better therapeutic effects, the incorporation of CSF biomarkers in the diagnostic and treatment process is essential. In this review, CSF biomarkers of Alzheimer’s disease pathology, axonal damage, neuronal damage, astroglial dysfunction, myelin damage, inflammation, and extracellular matrix protein remodeling have been evaluated and tried to emphasize those of which have highly consistent findings in the studies. CSF samples collected only at a single time point may not be sufficient to identify a promising marker in such a dynamic and used to be a common comorbid condition to other neurodegenerative diseases. These confounders demonstrate the limitations of using solely biomarkers to diagnose the disease and to foresee the outcome of the shunt surgery. Therefore, CSF samples collected antemortem at different time points and biopsy-confirmed iNPH patients with and without other neurodegenerative diseases would fill the gaps in identifying a valid biomarker. Longitudinal observations of shunt responders and non-responders in multicenter with well-defined cohorts are also needed to understand iNPH-specific markers. Finally, biomarkers of a bioinformatic approach that includes micro-RNAs, extracellular vesicles, metabolomics, the microbiome, or else are warranted to identify novel and useful diagnostic and prognostic biomarker tools in iNPH.

Objective

Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery.

Methods

We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6 +/−8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart.

Results

Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability.

Conclusion

These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS.

Significance

The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS.

The challenge to find the best predictors of conversion from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) has been ongoing at least for the last decade. Nonetheless, clinicians still lack, to date, a robust predictive tool for identifying individuals who will go through this conversion. In this narrative review, we reported the sensitivity and specificity of biomarkers and neurocognitive assessment in predicting the progression from MCI to AD. Given that biomarkers do not necessarily provide a better predictive accuracy as showcased by the numbers in this study, cognitive tests seem like a more cost-effective, less invasive, and easily accessible option. They also offer the added benefit of measuring functional cognitive impairment. However, it remains clear that efforts are still needed to come up with more accurate, sensitive, and specific predictors.

Sleep has an important role for long-term memory consolidation. As deficits in learning and memory are clinical characteristics of Alzheimer’s disease (AD), it has been suggested that disruptions in sleep-mediated consolidation processes are related to AD. Indeed, sleep disruptions and sleep disorders are often comorbid with AD and perhaps precede the onset of AD symptoms as a risk factor. Additionally, research has shown that sleep disruptions and disorders are associated with accumulation of β-amyloid (AB), a neuropathologic hallmark and biomarker of AD. However, the studies that have investigated the relationship between sleep disturbances and AB burden have been heterogenous in design and quality, leaving it unclear whether the overall effect is statistically significant. As such, this paper investigated the relationship between sleep disturbances and AB burden by meta-analytically integrating reported correlations that have been published to date. Results revealed that higher levels of cerebral AB (lower AB42/40 ratios) were related to shorter sleep durations, highlighting the importance of total sleep time in supporting the clearance of AB during slow-wave sleep. Herein we also controlled for heterogeneity in the included studies by conducting several moderator analyses, showing an important role for age, sex, cognitive impairment, sleep disorders, and education in influencing the associations between sleep disturbances and AB.

Background

As the need for prompt identification and management of childhood mood. disorders continues to grow, increasing interest has shifted towards potential objective. biomarkers. One modality that has shown promise as a biomarker has been quantitative electroencephalography or qEEG. In this review, we expand on our previous investigation into qEEG biomarker research for child mood disorders and potential challenges faced in ongoing development.

Ongoing research into qEEG:

Since our last systematic review, qEEG biomarker research of childhood major depressive disorder remained sparse, with only one novel awake qEEG investigation in children despite ongoing adult depression qEEG research. For bipolar disorder, previously identified qEEG researchers have continued investigation into Bipolar II diagnosis identification, Bipolar I versus II diagnostic discrimination, and general bipolar biomarker utilization.

Challenges faced by qEEG:

While the nature of qEEG as a data-driven, easily performed, and easily analyzable biomarker is promising, challenges to clinical utilization remain, including direct anatomical correlation and generation of patientfacing clinically tested and usable tools. However, preliminary general utilization of qEEG in clinical settings with childhood mood disorder has shown excellent efficacy, and ongoing research to address these limitations is feasible and ongoing.

Conclusions

While qEEG biomarker research in child mood disorders has remained slow, there is a clear need and strong ongoing potential for future investigations.

Frontotemporal dementia (FTD) is one of the most common neurodegenerative diseases, encompassing a myriad of different, clinically distinct subtypes which all target the frontoinsular region. FTD is characterized by a decline in behavioral, language, and executive functions. Due to its proximity to similar diseases, both in symptomology and mechanism, FTD remains challenging to diagnose conclusively. As a result, searching for distinct biomarkers that allow clinicians to differentiate between FTD and other neurocognitive disorders is extremely important. This review examines studies published in the past decade to evaluate which current biomarkers are the most clinically viable and where future research might lead. Genetic screening for FTD, specifically the three most common mutations to the TDP-43, MAPT, and PGRN genes, show promising predictive ability and could help patients access treatment in the early stages of the disease. In addition, serum and CSF biomarkers can help clinicians track the disease process and show good specificity when differentiating between FTD, primary psychiatric disorders, and other neurodegenerative diseases, especially when coupled with imaging techniques such as MRI and PET. Lastly, recent advances in machine learning may allow future researchers and clinicians to comprehensively analyze FTD's biochemical and imaging fingerprint, leading to increasingly accurate and timely diagnosis. Further work must be focused on transitioning the understanding of FTD biomarkers from research to concrete tools available to clinicians and patients, with the hopes of advancing the quality of care available to those suffering from FTD.

Systemic inflammatory processes can cause changes in cognition and functional capacity in the general population. Currently there are no accessible biomarkers capable of early detection and monitoring of such pathologies, and only few studies involving older than 80 years-old population were done. The C-reactive protein (CRP) and blood counts are low-cost tests that are often performed in routine basis. From the blood counts it is possible to evaluate the absolute count of neutrophils and lymphocytes, which are peripheral blood inflammatory markers. With these results, it is also possible to evaluate the neutrophils to lymphocytes ratio (NLR). Therefore, these tests may be potential biomarkers in the evaluation of the development of dementia, mild cognitive disorder, and functional dependence, with the possibility of assisting in the clinical management and prevention of such pathologies.

Objective

To evaluate the association between cognition and functional capacity with C-reactive protein, absolute neutrophil count, lymphocyte count, and NLR in a population of elderly people aged 80 years and older.

Methods

Observational analytical cross-sectional study conducted in the cohort of the Longevous Project of the Discipline of Geriatrics and Gerontology of UNIFESP. Complete blood counts (CBC) and CRP were collected from 244 patients included in the study between 2010 and 2013. Gender and the presence of hypertension and diabetes mellitus were also characterized. Associations between the absolute values of neutrophils and lymphocytes and the NLR with cognitive tests (mini mental state examination, MMSE, and clock drawing test, CDT) and with functional capacity (basic activities of daily living, BADL or Katz score, and instrumental activities of daily living, IADL or Lawton score) were performed using nonparametric Mann-Whitney and Kruskall-Wallis statistical tests.

Results

We found no associations between the markers obtained by the CBC and the cognitive assessment tests. We also found no association between the CRP and the MMSE. However, we obtained a statistically significant difference between the CRP marker and the CDT, with P = 0.003. There was no statistically significant difference between markers obtained by CBC or CRP with the BADLs. But we observed a statistically significant association between the IADLs and the absolute count of neutrophils and lymphocytes, respectively P = 0.0379 and 0.0190.

Conclusion

The presented results contribute to the hypothesis that serum inflammatory biomarkers can be useful in the assessment of health outcomes. We identified that patients with lower functional capacity for IADLs have higher absolute neutrophil and lymphocyte counts when compared to patients with higher functional capacity. In addition, we identified that patients with low performance on CDT have CRP at higher levels when compared to patie