Biomarkers in Neuropsychiatry最新文献

Pharmacological treatment, imaging, and neurochemistry studies identify altered dopamine signaling in bipolar disorder. Our previous work has shown higher concentration of homovanillic acid (HVA), the end metabolite of dopamine, in cerebrospinal fluid (CSF) from individuals with bipolar disorder compared to healthy controls. Here, we analyzed HVA concentrations from a follow-up visit in 103 adults with bipolar disorder and 57 controls from our first cohort. Further, we analyzed CSF monoamine metabolite concentrations in a second cohort of 152 adults with bipolar disorder and 55 controls. At the follow-up visit for the first cohort, HVA was higher in individuals with bipolar disorder (278 ± 102 nmol/L, p = 0.003) compared with controls (232 ± 83 nmol/L). In the second cohort, individuals with bipolar disorder had higher HVA (272 ± 97 nmol/L, p = 0.001) and lower 3-methoxy-4-hydroxyphenylglycol (MHPG, 40 ± 9 nmol/L, p = 0.002) concentrations than controls (HVA, 231 ± 71 nmol/L and MHPG, 45 ± 9 nmol/L). Baseline and follow-up measures of monoamine metabolites showed medium to high correlation to each other but did not predict course of illness. We failed to replicate the association of HVA concentration and psychotic symptoms but confirmed lower 5-hydroxyindoleacetic acid (5-HIAA) concentration in individuals treated with antidepressants. In conclusion, we confirmed high HVA concentration in CSF in patients with bipolar disorder compared to a control group. Previous work suggest that this is a feature shared with ADHD but distinct from schizophrenia and major depressive disorder. The role of increased HVA concentration in the course of illness in bipolar disorder remains unclear.

Cognitive Impairment (CI) is one of the most common and devastating manifestations in patients with Multiple Sclerosis (MS), which directly impacts the quality of life (QOL) and increases the burden of the disease. Years ago, CI was underrated but recently has gained far more attention from scientists in this field. The baseline pathophysiology and exact brain changes leading to CI are yet to be known. Both inflammatory and neurodegenerative processes could be contributing to CI. As a result, the diagnosis of subtle changes, especially in the early phases of the disease, along with the detection of changes throughout the disease course, is of utmost challenging debate among healthcare providers. Conventional Imaging techniques and usual neuropsychiatric screening tests may not detect early CI, rendering some cases missed. Serum or cerebrospinal fluid biomarkers are promising surrogates to detect the CI in these patients. The field of biomarkers in MS is evolving, and growing evidence indicates its applicability in decision-making. In this review, we focused on serum and CSF biomarkers that correlate with the CI in MS. In the end, we briefly discussed the future path in this regard.

Background

Published reports have suggested associations between ABO blood type and various medical conditions such as duodenal ulcers or stomach carcinomas. Studies have also linked this blood type to preoperative anxiety, indicating a possible psychiatric connection. This prompted us to review the literature for possible associations between blood types and one or more psychiatric disorders in controlled studies.

Methods

Using search engines including PubMed and Google Scholar, we used the key words “ABO blood types”, “depression”, “anxiety”, “schizophrenia”, “bipolar disorder”, “dementia” and “psychiatric disorder” to collect published controlled studies on this topic.

Results

Eighteen reports were identified, which investigated the association between blood types and various psychiatric disorders. Some studies reported that the AB blood type was correlated with higher levels of anxiety and cognitive impairment. Another study found that individuals with bipolar or unipolar affective disorder had a higher prevalence of type O blood and a significantly lower rate of type A blood. However, patients with involutional depression were reported to have a higher rate of type A blood and significantly lower rate of type O. None of the blood types were found to have any significant association with risk for dementia, nor were there any significant differences in blood type between those with schizophrenia and healthy controls. Several studies also reported negative findings between blood type and the occurrence of different affective disorders.

Discussion

The studies in this review suggest a possible connection between ABO blood types and certain psychiatric disorders, as well as highlight the controversy in this field of research. How blood types predispose to some mental disorders has not been fully explored and warrants further investigation.

Over the past decade, a considerable number of biomarkers have been evaluated in neurological disorders. In this review we provide a summary of various clinical, biological, genetic, and imaging biomarkers of multiple sclerosis with a focus on their clinical significance and utility.

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.