Restoring the missing person to personalized medicine and precision psychiatry

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Фев. 9, 2023

Precision psychiatry has emerged as part of the shift to personalized medicine and builds on frameworks such U.S. National Institute Mental Health Research Domain Criteria (RDoC), multilevel biological “omics” data and, most recently, computational psychiatry. The is prompted by realization that a one-size-fits all approach inadequate guide clinical care because people differ in ways are not captured broad diagnostic categories. One first steps developing this treatment was use genetic markers pharmacotherapeutics based predictions pharmacological response or non-response, potential risk adverse drug reactions. Advances technology have made greater degree specificity precision potentially more attainable. To date, however, search for largely focused parameters. Psychiatric disorders involve multi-level dynamics require measures phenomenological, psychological, behavioral, social structural, cultural dimensions. This points need develop fine-grained analyses experience, self-construal, illness narratives, interpersonal interactional dynamics, contexts determinants health. In paper, we review limitations arguing it cannot reach its goal if does include core elements processes give rise psychopathological states, which agency experience person. Drawing from contemporary systems biology, epidemiology, developmental psychology, cognitive science, propose cultural-ecosocial integrating with person-centered care.

Язык: Английский

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Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions

Progress in Neurobiology, Год журнала: 2022, Номер 219, С. 102353 - 102353

Опубликована: Сен. 12, 2022

Neurological and neuropsychiatric disorders affect men women differently. Multiple sclerosis, Alzheimer's disease, anxiety disorders, depression, meningiomas late-onset schizophrenia more frequently than men. By contrast, Parkinson's autism spectrum condition, attention-deficit hyperactivity disorder, Tourette's syndrome, amyotrophic lateral sclerosis early-onset are prevalent in Women have been historically under-recruited or excluded from clinical trials, most basic research uses male rodent cells animals as disease models, rarely studying both sexes factoring sex a potential source of variation, resulting poor understanding the underlying biological reasons for gender differences development such diseases. Putative pathophysiological contributors include hormones epigenetics regulators but additional non-biological influences may be at play. We review here evidence underpinning role chromosome complement, X inactivation, environmental epigenetic vulnerability to brain disease. conclude that there is pressing need better genetic, mechanisms sustaining diseases, which critical developing precision medicine approach based on sex-tailored prevention treatment.

Язык: Английский

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Longitudinal Trajectories of Food Insecurity in Childhood and Their Associations With Mental Health and Functioning in Adolescence

JAMA Network Open, Год журнала: 2021, Номер 4(12), С. e2140085 - e2140085

Опубликована: Дек. 20, 2021

Importance

Household food insecurity has been associated with mental health problems in children independently of family income and other confounders. It is unclear whether during childhood also functioning adolescence.

Objective

To evaluate longitudinal trajectories household the first 13 years life, characteristics these trajectories, associations externalizing, internalizing, substance use, social adjustment at 15 age.

Design, Setting, Participants

This cohort study included participants from Québec Longitudinal Study Child Development, a 2120 born Québec, Canada, 1997 1998 followed up annually or biannually 5 months to age (1998-2013). Data were analyzed November 2020 October 2021.

Exposures

When aged 1.5, 4, 8, 10, 12, years, mothers reported member experienced hunger because had run out money buy past 12 months.

Main Outcomes Measures

Group-based trajectory modeling was used identify differential exposure 1.5 according logit functions At age, adolescents completed validated questionnaires assessing problems. Associations between outcomes assessed using linear regressions.

Results

A total 2032 individuals analyses (1026 [50.5%] male) 1441 analysis association (752 [52.2%] female). Two identified age: high risk (73 [3.6%]) low (1959 [96.4%]). months, high-risk low-risk groups differed including insufficiency (58 [80.6%] vs 405 [21.0%]), single parenthood (21 [29.2%] 135 [6.9%]), parental history depression (mothers: 30 [43.5%] 411 [21.7%]; fathers: [32.4%] 209 [13.5%]). The cannabis use (β, 0.47; 95% CI, 0.12-0.81), peer bullying 0.43; 0.08-0.77), dropout potential 0.38; 0.03-0.68) after for sex, insufficiency, health.

Conclusions Relevance

In this study, few persistent insecurity, which psychosocial later adolescence confounders income. Early identification may guide delivery tailored interventions improve

Язык: Английский

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A Mendelian randomization approach for advancing healthcare innovation: From pregnancy hypertension to schizophrenia

Technology and Health Care, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Background Schizophrenia, a severe mental disorder, is strongly associated with perinatal factors, including pregnancy hypertension, which affects fetal neurodevelopment. The causal relationship between hypertension and schizophrenia remains unclear. Objective To investigate the using two-sample Mendelian randomization (MR) study. Methods Pregnancy (cases/controls: 7686/115,8993) was considered as exposure 76755/243,649) outcome. A MR study genetically estimated associations, inverse variance-weighted method primary analysis. two-step explored potential mediators. Sensitivity tests assessed pleiotropy, heterogeneity, stability. Results Four single nucleotide polymorphisms (SNPs) were identified genetic instruments for (P < 5 × 10 -8 , r² 0.001). increased risk of (odds ratio = 1.098, 95% CI 1.025–1.173, P 0.007), while reverse analysis found no significant link 1.03, 0.980–1.082, 0.235). revealed elevated levels 1,4-Dihydroxy-2-naphthoic acid 1.351, 1.097–1.664, 0.004), decreased 0.97, 0.942–0.998, 0.040). Conclusion high-risk factor schizophrenia, potentially mitigating this effect. These findings offer insights prophylaxis highlight need further research into underlying mechanisms.

Язык: Английский

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Monocyte/HDL Cholesterol Ratios as a New Inflammatory Marker in Patients with Schizophrenia

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(2), С. 276 - 276

Опубликована: Янв. 31, 2023

Monocyte/HDL cholesterol ratio (MHR) is a novel inflammatory marker that used as prognostic factor for cardiovascular diseases and has been studied in many diseases. The aim of this study was to investigate the role factors schizophrenia patients by examining MHR levels compare healthy controls terms disease risk.

Язык: Английский

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Environmental Risk Factors and Cognitive Outcomes in Psychosis: Pre-, Perinatal, and Early Life Adversity

Current topics in behavioral neurosciences, Год журнала: 2022, Номер unknown, С. 205 - 240

Опубликована: Янв. 1, 2022

Язык: Английский

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Scars and PARs in a close relative

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(12)

Опубликована: Март 11, 2024

Язык: Английский

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The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood

BMC Immunology, Год журнала: 2024, Номер 25(1)

Опубликована: Май 3, 2024

Abstract Background Early-onset schizophrenia (EOS) is a type of (SCZ) with an age onset < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development SCZ. We aimed to identify characteristic genes cells EOS further explore pathogenesis from perspective immunology. Methods obtained microarray data whole-genome mRNA expression peripheral blood mononuclear (PBMCs); 19 patients (age range: 14.79 ± 1.90) healthy controls (HC) 15.67 2.40) were involved. screened for differentially expressed (DEGs) using Limma software package modular weighted gene co-expression network analysis (WGCNA). In addition, cells, we performed enrichment analysis, infiltration receiver operating (ROC) curve analysis; also used random forest (RF), support vector machine (SVM), LASSO-Cox algorithm. Results selected following genes: CCL8, PSMD1, AVPR1B SEMG1. employed RF, SVM, identified cells: activated mast CD4 + memory resting T neutrophils cells. AUC values all > 0.7. Conclusion Our results indicate that function altered SEMG1 regulate EOS. Further, are expected diagnostic markers therapeutic targets

Язык: Английский

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Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study

Psychological Medicine, Год журнала: 2021, Номер 53(6), С. 2609 - 2618

Опубликована: Ноя. 18, 2021

Abstract Background Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal cross-sectional associations a weighted score cumulative for schizophrenia – exposome (ES-SCZ) with functioning in first-episode (FEP). Methods Data were derived from baseline 1-month assessments Athens FEP Research Study enrolled 225 individuals FEP. The Global Assessment Functioning (GAF) Personal Social Performance Scale (PSP) used to measure social, occupational, psychological functioning. ES-SCZ was calculated based on previously validated method. Results associated total scores GAF PSP at assessments. These findings remained significant when accounting several alternative explanatory variables, including other (obstetric complications, migration, ethnic minority), clinical characteristics (duration untreated psychosis, symptom severity, previous antipsychotic use), family history demonstrating association between is over above risk cannot be explained by severity alone. improved assessment, no ES-SCZ-by-time interaction found functioning, indicating changes contingent ES-SCZ. Conclusions Our suggest rather than predictor functional improvement, represents stable indicator captures poor early psychosis. Environmental loading can beneficial characterization incorporated into transdiagnostic staging models.

Язык: Английский

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Examining the psychobiological response to acute social stress across clinical stages and symptom trajectories in the early psychosis continuum

Development and Psychopathology, Год журнала: 2023, Номер 36(2), С. 774 - 786

Опубликована: Фев. 28, 2023

Abstract The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, independently studied clinical high-risk (CHR) first-episode psychosis (FEP) populations. Notable this literature, however, is that there are few studies directly comparing markers stress response across progressive stages illness. Here we examined psychobiological Trier Social Stress Test 28 CHR (mean age 19.1) 61 FEP (age 23.0) patients, order understand stage(s) or trajectories which differences subjective physiological occur. overall sample had greater perceived blunted cortisol (FEP + CHR, n = 89, 21.7) compared with healthy controls ( 45, 22.9). Additional analyses demonstrated elevated heart rate systolic blood pressure but were no further parameters (cortisol, rate, pressure) between stage- trajectory-based groups. Together, suggests individual may differentially emerge at particular en route – demonstrates how stage-based can shed light on emergence evolution neurobiological changes mental

Язык: Английский

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