Biomarkers in Neuropsychiatry最新文献

A subset of individuals with schizophrenia (SZ) are thought to have a microvascular component to their illness with studies demonstrating alterations in retinal superficial, deep, and choroidal microvasculature networks. However, the direction and location of these alterations have differed across studies. In a recent study, we reported that individuals with SZ demonstrated lower superficial layer perfusion density than a healthy control (HC) group. The current study investigated characteristics of the deep vascular layer in SZ. We included 28 individuals with a diagnosis of SZ or schizoaffective disorder, and 37 HCs. Optical coherence tomography angiography (OCTA) data was collected to measure deep retinal layer perfusion density, skeletonized vessel density, vessel diameter index, and fractal dimension. We conducted between-group comparisons to examine differences in these OCTA variables between SZ and HC groups. A trend analysis was conducted to determine if differences reflected a linear trend according to age and illness length, and Spearman correlations were conducted to determine associations between deep and superficial layer density. Individuals with SZ demonstrated significantly lower bilateral perfusion density and vessel diameter index, as well as lower left eye skeletonized vessel density and fractal dimension. There was a significant linear trend in the data indicating that individuals with chronic SZ demonstrated the lowest OCTA values, followed by individuals within two years of their first episode of psychosis who did not differ from older controls, followed by younger controls, who demonstrated the highest values in at least one eye. Lower density values in the deep retinal layer were also significantly associated with lower density values in the superficial layer. Overall, results suggest that microvascular alterations are present in multiple retinal layers in SZ and that they may be useful visual system biomarkers of neurovascular changes in the disorder.

Purpose

The 22q11.2 deletion syndrome (22q11.2DS) has an estimated prevalence of 1:2148 live births and is associated with an increased risk of schizophrenia, cognitive decline and early-onset Parkinson’s disease. Because retinal and cerebral tissue share embryological, physiological and anatomical characteristics, retinal blood vessel morphology and retinal nerve fiber layer (RNFL) thickness have been proposed as non-invasive biomarkers for psychiatric and neurodegenerative disorders. In this exploratory study, we examined these potential biomarkers in adults with 22q11.2DS relative to controls, and in relation to age.

Methods

Central retinal artery and vein equivalent, fractal dimension, and vascular tortuosity, obtained through fundoscopy, and peripapillary RNFL and macular thickness, obtained through optical coherence tomography, were compared between adults with 22q11.2DS and sex- and age-matched controls.

Results

Mean retinal vascular fractal dimension and tortuosity values were significantly higher in the group of adults with 22q11.2DS than in controls (p < 0.001; p < 0.001). RNFL was thicker in the nasal segment (p = 0.002) in 22q11.2DS, and a trend for thinner RNFL in the nasal and temporal inferior segments (p = 0.05 and p = 0.06, respectively) was found. There were significant negative correlations with age for fractal dimension (p < 0.001) and RNFL thickness in the global (p = 0.007), temporal inferior (p = 0.005) and temporal superior (p = 0.04) segments in adults with 22q11.2DS, but not in controls.

Conclusions

Our results indicate higher retinal vascular fractal dimension and tortuosity, and a decrease in fractal dimension and RNFL thickness in relation to age in adults with 22q11.2DS. Our findings support future studies that focus on retinal fractal dimension and RNFL thickness as potential biomarkers for age-related manifestations in 22q11.2 including psychotic and (early) neurodegenerative disorders.

Long non-coding RNAs (lncRNAs) influence pathoetiology of multiple sclerosis (MS). We identified expression levels of three vitamin D receptor-associated lncRNAs, namely SNHG6, SNHG16 and LINC00346 in the blood of MS patients compared with healthy subjects. SNHG6 level was significantly lower in MS cases compared with controls (expression ratio (ER) (95 % CI)= 0.39 (0.22–0.69), P = 0.0015) and in female patients compared with female controls (ER (95 % CI)= 0.28 (0.13–0.59), P = 0.0001). SNHG16 was also under-expressed in total MS patients compared with controls (ER (95 % CI)= 0.24 (0.1–0.57), P = 0.0001). LINC00346 level was lower in entire patients versus controls (ER (95 % CI)= 0.03 (0.009–0.09), P < 0.0001). Such down-regulation was also detected in patients of both sexes compared with corresponding controls (P = 0.0008 and <0.0001 for males and females, respectively). There was no difference in expressions of SNHG6, SNHG16 and LINC00346 between male and female patients. There was no remarkable correlation between expressions of SNHG6, SNHG16 and LINC00346 lncRNAs and age, disease duration, age at onset or EDSS. LINC00346 had the AUC values of 0.84, 0.82 and 0.94 in differentiation of total MS patients from total controls, female patients from healthy females and male patients from healthy males, respectively. SNHG6 could separate female patients from female controls with AUC of 0.79. Finally, female patients from female controls could be separated by SNHG16 levels with AUC of 0.73. Taken together, these lncRNAs might be proposed as putative peripheral markers for MS.

During the 1960 s and 1970 s, questions about the validity of psychiatric diagnoses challenged psychiatry's respectability. Robert Spitzer and the DSM-III project hoped to rescue psychiatry by fixing its diagnoses. However, their choices regarding the schizophrenia diagnosis perhaps hampered psychosis research for 40 years. The defining characteristics of psychosis are perceptions, thoughts, and actions that do not comport with socially shared experience. For Kraepelin and Bleuler, the core features of a schizophrenia-like psychosis syndrome were disturbances of affect, self, and volition. John Wing and the International Pilot Study of Schizophrenia (IPSS) favored the theory of Kurt Schneider and his symptoms of first-rank importance for diagnosing schizophrenia. They reconceptualized schizophrenia as a reality distortion diagnosis. Will Carpenter and John Strauss, using IPSS data, showed that schizophrenia was most like an affect-self-volition disturbance syndrome and that depending on reality distortions for a schizophrenia diagnosis was incompatible with the evidence. Nevertheless, schizophrenia in DSM-III and DSM-IV was championed by John Wing and embraced by the DSM framers. Outcomes from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) are consistent with Carpenter and Strauss's concern that switching from a Kraepelin-Bleuler core to reality distortion was an error. B-SNIP found, replicated, cross- and externally validated neurobiologically distinctive subgroups called psychosis Biotypes. The main clinical characteristics differentiating the Biotypes are thought disturbances, lack of spontaneous speech, and low involvement in social and occupational activities. Psychosis research and clinical care might be different today if Spitzer and the DSM-III framers had made a different choice and listened to Carpenter and Strauss.

Viral infections during childhood can increase susceptibilities to neurodevelopmental and psychiatric disorders. We are currently in the early years following a viral pandemic caused by the rapid evolution of highly transmissible, host-evading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here we place this virus and the disease it generates, Coronavirus Disease 2019 (COVID-19), in the context of inflammatory host phenotypes and psychosocial factors which exacerbate stress to the developing human nervous system. While exposures to pathogens and inflammation during neurodevelopment are well-studied risk factors in psychiatric research, the subtle effects on a child’s physiology of factors such as social isolation, food insecurity, and other social determinants of health are more difficult to identify and quantify. In this post-pandemic era, we have the unique opportunity to initiate in local community healthcare facilities, inclusive longitudinal studies to measure pandemic-mediated mental health outcomes in children of all races, ethnicities, genders, and other groups shaped by social, cultural, and as yet unidentified determinants. Toward this end, the identification of children in need of prompt psychiatric intervention may be accelerated by the use of biomarkers indicating COVID-19 infection status, inflammation, imbalances of the gut-brain axis, and acute and chronic stress. Especially promising are approaches combining these biomarkers with mental health screening tools such as the Child Behavior Checklist (CBCL) and the Epic Patient Healthcare Questionnaire 9 (PHQ9).

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA with important roles in regulation of autophagy, neurite growth and morphogenesis. Polymorphisms within this gene have been associated with some neuropsychiatric conditions. In the current case-control study, we investigated associations between obsessive-compulsive disorder (OCD) and four single nucleotide polymorphism within this gene, namely rs12826786, rs4759314, rs1899663 and rs920778. There was significant difference in genotype distribution of rs920778 between OCD patients and normal controls (P value = 0.01). rs920778 was associated with risk of OCD in co-dominant model (TT versus CC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 0.66 (0.49–0.88), P value = 0.005 and OR (95 % CI) = 0.63 (0.44–0.91), P value = 0.014, respectively). This SNP was associated with OCD in dominant model (TT+TC versus CC) only in un-adjusted analysis (OR (95 % CI) = 0.52 (0.31–0.88), P value = 0.015). Finally, this SNP was associated with OCD in over-dominant model (CC+TT versus TC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 2.38 (1.33–4.25), P value = 0.003 and OR (95 % CI) = 2.78 (1.31–5.89), P value = 0.008, respectively). The current study shows possible impact of rs920778 on risk of OCD in Iranian population.

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.