Biomarkers in Neuropsychiatry最新文献

Background

Retinal health indices were suggested to be related to psychopathological symptoms, such as depressive symptoms. However, large-scale studies using optical coherence tomography (OCT) are missing to investigate the associations among them.

Methods

In the META-KLS cohort study, 1456 participants (mean age [standard deviation]= 54.6 [11.91] years; n= 680 [47.8%] women) completed the Patient Health Questionnaire (PHQ-9) to measure depressive symptoms and underwent OCT. Poor-quality OCTs and multivariate outliers were excluded, and principal component analysis was performed to obtain retinal health indices separately for macular (n= 930) and optic nerve head (ONH) thicknesses (n= 800). Linear regressions were run controlling for covariates. Exploratory interaction models were run with demographic, lifestyle and health markers.

Results

Although there were no direct significant associations between the retinal indices and depressive symptoms (macular: B= −0.05, 95% CI= [-0.15, 0.05], p= 0.32; ONH index: B= -0.02, 95% CI= [-0.11, 0.08], p= 0.71), their associations were moderated by demographic and health factors, e.g., C-reactive protein (CRP) (macular index: B= −0.03, 95% CI= [-0.05, −0.01], p= 0.002; ONH index: B= 0.05, 95% CI= [0.02, 0.08], p= 0.002).

Limitations

Study was cross-sectional and there were no functional assessments of vision.

Conclusions

In a large cohort, we observed associations between retinal indices and self-reported depressive symptoms depending on demographic and health factors, notably CRP. Following up, the study will investigate the prospective prediction of retinal health on depressive symptoms, especially in persons who may have chronic inflammation.

Adverse childhood experiences (ACEs) are associated with developing systemic diseases and mental illnesses, affecting multiple body systems, including those that affect allostasis, such as the immune, endocrine, and nervous systems. Numerous different biomarkers reflect the biological manifestations of ACEs across these systems and point to possible mechanisms of pathology following early adversity. Retinal layer thickness values and retinal microvasculature parameters, which may reflect central nervous system structure and function, have scarcely been explored in relation to early life stress in humans but could potentially be valuable indicators of early life adversity sequelae. Animal models of early life stress using rodents demonstrate that early adversity is associated with structural and functional alterations of the retina. Thus, given the widespread impact of ACEs across several different allostatic systems in the body, including the central nervous system of which the retina is a part, and evidence in animal models suggesting a relationship between early life stress and retinal alterations, the retina is likely to be affected by ACEs in humans. Retinal biomarkers may also represent especially feasible methods for exploring the effects of early adversity on the body, as they can be examined in vivo using optical coherence tomography (OCT), OCT angiography (OCTA), and electroretinography (ERG), which are quick and noninvasive retinal imaging and electrophysiological techniques. Therefore, future research should focus on the impact of ACEs on the retina in humans and what retinal changes predict in terms of symptoms, course, and functional impairment associated with negative physical and mental health outcomes. This can further our understanding of the pathological mechanisms of diseases and disorders that individuals with ACEs are at risk of developing.

Background

Despite the disproportionate impact of Alzheimer’s disease (AD) dementia on Black/African-American and American Indian/Alaska Native groups, they have been underrepresented in biomarker research. Research investigating underrepresented groups’ willingness to engage in research has primarily relied on qualitative research and/or specialized samples (e.g., patients’ first-degree relatives). Similarly, extant quantitative studies include disproportionately small numbers of these participants. This investigation aimed to understand preclinical biomarker and genetic AD research participation in underrepresented groups to facilitate greater diversity in future biomarker research and clinical trials.

Method

We administered an online questionnaire to 599 Black/African-American, 120 American Indian/Alaska Native, and 725 NonHispanic White adults and assessed demographic characteristics and participants’ views on dementia, research, and genetic and preclinical biomarker testing. Attitudes toward research were examined using the standardized 7-item Research Attitudes Questionnaire (RAQ) measure. Using structural equation modeling, we tested a priori hypotheses regarding willingness to engage in AD preclinical biomarker testing. The specific survey item used as the outcome measure asked for agreement with the statement: “I would be willing to undergo any type of testing necessary if it was the only way to find out if I was at risk for AD before there were any symptoms,” answered on a Likert scale (1=strongly disagree – 7=strongly agree).

Results

The three groups differed significantly in their attitudes toward research, as measured by total RAQ scores. Despite no differences in opinion regarding the overall usefulness of biomarkers, the ethnoracial groups differed in their willingness to engage in preclinical biomarker testing for dementia. Path analysis revealed an excellent model fit, indicating that attitudes toward research, as measured by the RAQ, influenced biomarker testing willingness. These findings suggest the need for outreach and engagement programs to occur before attempting research recruitment, particularly with BIPOC populations.

Subconcussive head hits (SHH) are common in contact sport athletes and are predictive of the later development of cognitive and brain changes, including chronic traumatic encephalopathy. In this pilot study we determined whether a history of concussion, and SHH acquired during a single season of college football, were associated with changes on retinal biomarkers of central nervous system (CNS) structure and function. College football players with a history of concussion (FB+C; n=9) or without a concussion history (FB-C; n=11), and non-contact sport collegiate athletes (Track/Swim; n=12) underwent visual and cognitive testing, retinal imaging (optical coherence tomography (OCT) and OCT angiography (OCTA)), and electroretinography (ERG) at three time points: pre-season, post-season and 4-month follow-up. The FB+C group demonstrated thicker maculae and exaggerated ERG waveforms (from all retinal neural cell types) compared to the other groups. These changes were generally observed at all timepoints, suggesting long-term changes associated with concussions, rather than effects of recent football activity. However, we also observed significant relationships between the number of head impacts during the season and stronger ERG responses, degree of macula thickening, enlargement of optic disc parameters, and increases in the density of retinal microvasculature relative to controls. These data suggest that retinal biomarkers are sensitive to both long- and short-term CNS changes related to participation in football, even in young athletes.

Introduction

Psychostimulants are FDA-approved for treating attention deficit hyperactivity disorder (ADHD). They are often prescribed off-label for mood disorders (in the majority of cases for augmentation of major depressive disorder [MDD] or treatment-resistant cases) with particular concerns in patients with comorbid ADHD and bipolar disorder (BD). We aimed to systematically appraise the current knowledge on genetic associations of psychostimulant treatment responses for mood disorders and ADHD.

Methods

A comprehensive search was conducted from database inception until March 21st, 2023. We included randomized controlled studies and non-randomized studies of intervention in adults (>18 years) with a DSM-IV/DSM-5 diagnosis of MDD, BD, or ADHD. We specifically included studies that reported the use of psychostimulants (e.g., methylphenidate [MPH]) and explored genetic associations with dopamine receptors and transporters (DRD4, DRD2, SLC6A3) reuptake inhibitors, norepinephrine transporters (SLC6A2) and serotonin transporters (SLC6A4).

Results

We identified and screened 1,479 abstracts and selected 17 articles for full-text review. Five studies met the inclusion criteria (N=498; mean age 37.13±12.26), including two randomized controlled trials (n= 121, mean age 41.16±14.86) which analyzed genetic polymorphisms in SLC6A3 and SLC6A4. Three non-randomized intervention studies were included: one study (n=171, mean age 35±11) analyzed several SLC6A3 variants, and two studies (n=206, mean age 36.5±11.01) analyzed DRD4, SLC6A3, and SLC6A4 variants. Evidence from the selected studies did not consistently show statistically significant differences in treatment response for either MDD or ADHD in association with genetic polymorphisms. No studies evaluating BD were found, and MPH was the only psychostimulant assessed in the selected articles. The most reported adverse events were moderate nausea, anxiety, and polyuria, with a higher percentage for headaches (38.1%), gastrointestinal complaints (21.2%), and decreased appetite (19.08%). None of the included studies reported serious adverse events which required discontinuation.

Conclusion

Further research is necessary to determine the implications of genetic polymorphisms on clinical response to stimulants with mood disorders and ADHD. Moreover, studies examining a broader range of stimulant medications as well as duration/dose of treatment, including individuals with BD, are crucial to understanding possible genetic influences on treatment response with the potential to inform personalized treatment strategies-optimization of interventions for individuals with mood disorders and ADHD.

Objective markers which can reliably predict psychosis transition among individuals with at-risk mental state (ARMS) are warranted. In this study, sixty-five ARMS subjects [of whom 17 (26.2%) later developed psychosis] were recruited, and we performed supervised linear support vector machine (SVM) with a variety of combinations of.modalities (clinical features, cognition, structural magnetic resonance imaging, eventrelated.potentials, and polyunsaturated fatty acids) to predict future psychosis onset. While single-modality SVMs showed a poor to fair accuracy, multi-modal SVMs revealed better predictions, up to 0.88 of the balanced accuracy, suggesting the advantage of multi-modal machine-learning methods for forecasting psychosis onset in ARMS.

Background

Electroretinographic dysfunction is observed in psychosis, with a-wave and b-wave amplitudes potentially serving as biomarkers. Insulin resistance (IR) and childhood trauma (CT) have also been associated with psychosis-spectrum disorders, particularly schizophrenia. Electroretinographic dysfunction in early-course psychosis (EP) lacks exploration. This case-control exploratory study aimed to understand electroretinographic dysfunction in EP and its relationship with IR and CT.

Methods

The study involved healthy controls (n=13) and EP individuals (n=14) and included photopic and scotopic flash-electroretinography (fERG), blood collection for IR assessment, and the Childhood Trauma Questionnaire (CTQ). Data were analyzed using SPSS v.29.0. Case-control differences across fERG conditions were explored using repeated-measures ANCOVA (3 flash conditions X 2 groups) adjusted for gender and age. Sub-analyses included Fisher’s, Mann-Whitney, partial correlations, and logistic and linear regressions.

Results

Compared to controls, EP participants showed (1) lower photopic a-wave and b-wave amplitudes, specifically in the left eye and under the P₁ condition, (2) greater odds for IR, and (3) higher CTQ scores. IR was associated with a higher CTQ score and a lower P_2b amplitude. A higher CTQ score was associated with lower P_2b amplitude in the left eye when adjusting for its interacting effect with IR.

Conclusion

These findings suggest lower photopic a-wave and b-wave amplitudes, IR, and CT are explanatory markers in EP. CT may dysregulate the hypothalamic-pituitary-adrenal axis, increasing the risk of experiencing later-life psychosis. IR might be a biomarker in psychosis, contributing to electroretinographic dysfunction and neurodegeneration of cone post-synaptic cells. Further investigations are needed.

Suicide is a health problem associated with a number of genetic factors. Genetics polymorphisms in several signaling pathways have been shown in the pathophysiology of suicidal behavior. Variants of the angiotensin converting enzyme (ACE) have been demonstrated to affect risk of some neuropsychiatric conditions and suicide attempt. In the current study, we assessed association between ACE rs4646994, rs1799752 and rs4359 polymorphisms and risk of suicide behavior in a population of Iranian patients attempted suicide (320 individuals who attempted suicide with soft methods and 230 suicide victims) and 300 healthy controls. Polymorphisms were genotyped using tetra-ARMS-PCR method. Data was analyzed using SPSS v.22.0. The rs4359 was associated with successful suicide under co-dominant model in a way that TC genotype was identified as a risk genotype (OR (95% CI)= 1.86 (1.26–2.75), P value=-0.02). In dominant model, TT+TC genotypes were associated with higher risk of successful suicide in comparison with CC genotype (OR (95% CI)= 1.71 (1.18–2.47), P value=-0.04). In over-dominant model, TT+CC genotypes were associated with lower risk in comparison with TC genotype (OR (95% CI)= 0.58 (0.41–0.83), P value=-0.03). rs1799752 was associated with higher risk of successful suicide under co-dominant, recessive and over-dominant models. In co-dominant model, while ID genotype increased the risk (OR (95% CI)= 2 (1.37–2.99), P value=0.003), II genotype decreased the risk (OR (95% CI)= 0.2 (0.09–0.45), P value<0.0001) in comparison with DD genotype). In recessive model, II genotype was associated with lower risk in comparison with total sum of the other genotypes (OR (95% CI)= 0.14 (0.07–0.28), P value<0.0001). The rs4646994 was not associated with risk of successful suicide. Besides, rs4359 was associated with risk of suicide attempt under over-dominant model in a way that TT+CC genotypes decreased risk of suicide attempt (OR (95% CI)= 0.67 (0.48–0.93), P value=0.04). rs1799752 was associated with risk of suicide attempt under co-dominant and recessive models in a way that II genotype conferred lower risk of suicide attempt (OR (95% CI)= 0.53 (0.34–0.83), P value=0.03). Finally, rs4646994 was associated with risk of suicide attempt in all models except for recessive model. I allele of this SNP increased risk of suicide attempt (OR (95% CI)= 1.47 (1.15–1.88), P value=0.018). Taken together, ACE1 gene can be considered as a risk locus for suicide behavior among Iranians.

The insula is a significant neural region associated with the development and clinical symptoms of schizophrenia. Here, we provide an overview of the role of the insula in a non-pathological context, as well as its function in schizophrenia, discussing how structural and functional changes to the insula can provide insight into the etiology of schizophrenia and contribute to potential therapeutic intervention.

Technological advances in nucleic acid sequencing in recent years effectively launched and propelled a new age of the microbiome. A mechanism known as the gut-brain axis has been adopted by psychiatric and neurological researchers, as another possible way to reconcile gene-by-environmental and other hypotheses of how serious brain disorders develop. Toward this end, the microbiome, may represent an informative biomarker, or series of biomarkers, of cellular, molecular, and metabolic pathways that are altered in disease. As with any field projected to be an enormous influence on the future of medicine, early studies of the microbiome are numerous and sometimes afflicted with study design and data quality issues. Some progress in these areas is underway, and here we provide a brief update of the current state of the microbiome with a focus on clinical studies and the quests to better understand mechanistically what functional outcomes in neuropsychiatric disorders might be mediated by microbes. We also review the concept of the microbiome biomarker as a dynamic and evolving measure that keeps improving as technology flourishes. In vitro gut systems that merge innervation and vascularization of epithelial organoids exemplify next-generation microbiome biomarkers.