Biomarkers in Neuropsychiatry最新文献

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.

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.