Biomarkers in Neuropsychiatry最新文献

Background

Progress has been achieved in many fields in understanding the biological mechanisms of depression, including genome-wide association analysis, neurotransmitter system function, brain regions and neural networks, inflammatory response, neuroplasticity, neuroimaging, and neuro electrophysiology. These progresses provide a reliable basis for developing the medical and physical therapies for depression. However, the current treatments developed from biological mechanisms can only address less than 60 % of depressive symptoms and have limited efficacy in improving social functioning and reducing recurrence. Studies have explored the non-biological mechanisms of depression in mental fields. These progresses are helpful to develop more interventions that could alleviate depressive symptoms, improve functional impairments, and reduce recurrence, thereby promoting a more comprehensive recovery in depressed patients. However, there is not a systematic and deep review to highlight the non-biological mechanisms of depression.

Methods

This study summarizes the recent progress in the non-biological fields of depression by searching publications on human studies in PubMed, PMC, and Google Schooler with exclusion of animal studies.

Results

This study reviews the intergenerational transmission characteristics, the relationship between depression and emotional trauma, cognitive deficit, relationship impairment, self-function, sense of the meaning of life, motivation deficit, and psycho-rationality of depression.

Conclusions

This study was clarified the non-biological mechanisms and characteristics of depression and provided a theoretical basis for the development of non-drug interventions.

Objective

Atypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort.

Methods

We conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models.

Results

Among a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups.

Conclusion

Our cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature.

Significance

These findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.

Background

Exposure to childhood trauma may cause several alterations in brain structure and connectivity in adult patients having a major psychiatric disorder. Recent reports have shown that adult patients and young healthy offspring of patients carry similar abnormal retinal response. Because the retina and the brain have the same embryonic origin, the retina gives access to living neuronal tissue that may capture the early neurobiological effect of trauma.

Objective

Evaluate the association between exposure to childhood trauma and anomalies in cone (photopic) and rod (scotopic) responses assessed by electroretinography (ERG) in children and adolescents at familial risk (FHRs) of psychosis or mood disorders.

Methods

ERG recordings (n=194) undertaken on 134 offspring (M_age of 1st recording=15.7, 49% females) enrolled in our longitudinal study and born to a parent having DSM-IV schizophrenia, bipolar disorder or major depressive disorder were analyzed using repeated measures linear mixed models and applying multiple comparisons. The scotopic and photopic a- and b-wave latencies and amplitudes were recorded. Five types of childhood trauma were assessed prospectively and retrospectively in FHRs: physical abuse, sexual abuse, emotional abuse, neglect and witnessing domestic violence.

Results

None of the ERG scotopic or photopic parameters were associated with the global measure of exposure to trauma. However, when analyzing the specific effect of each type of trauma, data suggested that physical abuse in girls would be significantly associated with a prolonged scotopic a-wave latency (p=0.024, ES=0.28) and a trend of association was observed with a prolonged photopic b-wave latency (p=0.099, ES=0.27).

Conclusion

Our study did not suggest a substantial effect of childhood trauma on previously reported ERG anomalies in the cone and rod response in youth at familial risk of psychosis or mood disorder. Only one type of trauma i.e., physical violence toward the child, could have a specific effect on the cone and rod prolonged latencies in girls. Methodological limitations are discussed for consideration in interpreting the findings.

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.