Is the acquired hypothyroidism a risk factor for developing psychiatric disorders?
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ABSTRACT:
SUBMITTER: Osnaya-Brizuela N
PROVIDER: S-EPMC11294236 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders. 21 samples, consisting of 3 replicates harvested at 7 different time-points of RA+BDNF-induced neuronal differentiation
2016-06-01 | E-GEOD-69838 | biostudies-arrayexpress
Project description:BackgroundLoneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood.MethodsThis study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6674 observations; 1993-2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes.ResultsBoth self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status.ConclusionChildhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness - even in childhood - might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.
| S-EPMC9874978 | biostudies-literature
Project description:Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02-1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81-1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19-1.74) and without (OR, 1.88; 95% CI: 1.26-2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.
| S-EPMC6848186 | biostudies-literature
Project description:Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders.
2016-06-01 | GSE69838 | GEO
Project description:BackgroundEpidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear.MethodsWe assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis.ResultsWe found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, P=7.35×10-12; HDL: rg=0.304, P=4.14×10-17). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ (P values are 6.59×10-11 and 2.10×10-12, respectively) and the 6p22.1 locus was identified in both MDD and SCZ (P values are 1.05×10-8 and 5.75×10-14, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (P<0.05/18776 = 2.66×10-6). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels.ConclusionsOur findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.
| S-EPMC11187243 | biostudies-literature
Project description:Genetics provides two major opportunities for understanding human disease-as a transformative line of etiological inquiry and as a biomarker for heritable diseases. In psychiatry, biomarkers are very much needed for both research and treatment, given the heterogenous populations identified by current phenomenologically based diagnostic systems. To date, however, useful and valid biomarkers have been scant owing to the inaccessibility and complexity of human brain tissue and consequent lack of insight into disease mechanisms. Genetic biomarkers are therefore especially promising for psychiatric disorders. Genome-wide association studies of common diseases have matured over the last decade, generating the knowledge base for increasingly informative individual-level genetic risk prediction. In this review, we discuss fundamental concepts involved in computing genetic risk with current methods, strengths and weaknesses of various approaches, assessments of utility, and applications to various psychiatric disorders and related traits. Although genetic risk prediction has become increasingly straightforward to apply and common in published studies, there are important pitfalls to avoid. At present, the clinical utility of genetic risk prediction is still low; however, there is significant promise for future clinical applications as the ancestral diversity and sample sizes of genome-wide association studies increase. We discuss emerging data and methods aimed at improving the value of genetic risk prediction for disentangling disease mechanisms and stratifying subjects for epidemiological and clinical studies. For all applications, it is absolutely critical that polygenic risk prediction is applied with appropriate methodology and control for confounding to avoid repeating some mistakes of the candidate gene era.
| S-EPMC6599546 | biostudies-literature
Project description:ImportanceIncreased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention.ObjectiveTo assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality.Design, setting, and participantsThis prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021.ExposuresMild or moderate to severe head trauma.Main outcomes and measuresCardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed.ResultsA total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality.Conclusions and relevanceThese findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.
| S-EPMC9051987 | biostudies-literature
Project description:In this narrative review, we examine biological processes linking psychological stress and cognition, with a focus on how psychological stress can activate multiple neurobiological mechanisms that drive cognitive decline and behavioral change. First, we describe the general neurobiology of the stress response to define neurocognitive stress reactivity. Second, we review aspects of epigenetic regulation, synaptic transmission, sex hormones, photoperiodic plasticity, and psychoneuroimmunological processes that can contribute to cognitive decline and neuropsychiatric conditions. Third, we explain mechanistic processes linking the stress response and neuropathology. Fourth, we discuss molecular nuances such as an interplay between kinases and proteins, as well as differential role of sex hormones, that can increase vulnerability to cognitive and emotional dysregulation following stress. Finally, we explicate several testable hypotheses for stress, neurocognitive, and neuropsychiatric research. Together, this work highlights how stress processes alter neurophysiology on multiple levels to increase individuals' risk for neurocognitive and psychiatric disorders, and points toward novel therapeutic targets for mitigating these effects. The resulting models can thus advance dementia and mental health research, and translational neuroscience, with an eye toward clinical application in cognitive and behavioral neurology, and psychiatry.
| S-EPMC10714507 | biostudies-literature
Project description:It has recently been proposed that a single dimension, called the p factor, can capture a person's liability to mental disorder. Relevant to the p hypothesis, recent genetic research has found surprisingly high genetic correlations between pairs of psychiatric disorders. Here, for the first time, we compare genetic correlations from different methods and examine their support for a genetic p factor. We tested the hypothesis of a genetic p factor by applying principal component analysis to matrices of genetic correlations between major psychiatric disorders estimated by three methods-family study, genome-wide complex trait analysis, and linkage-disequilibrium score regression-and on a matrix of polygenic score correlations constructed for each individual in a UK-representative sample of 7 026 unrelated individuals. All disorders loaded positively on a first unrotated principal component, which accounted for 57, 43, 35, and 22% of the variance respectively for the four methods. Our results showed that all four methods provided strong support for a genetic p factor that represents the pinnacle of the hierarchical genetic architecture of psychopathology.
| S-EPMC6168558 | biostudies-literature
Project description:The treatment of psychiatric disorders presents three major challenges to the research and clinical community: defining a genotype associated with a disorder, characterizing the molecular pathology of each disorder and developing new therapies. This Review addresses how cellular and animal systems can help to meet these challenges, with an emphasis on the role of the zebrafish. Genetic changes account for a large proportion of psychiatric disorders and, as gene variants that predispose to psychiatric disease are beginning to be identified in patients, these are tractable for study in cellular and animal systems. Defining cellular and molecular criteria associated with each disorder will help to uncover causal physiological changes in patients and will lead to more objective diagnostic criteria. These criteria should also define co-morbid pathologies within the nervous system or in other organ systems. The definition of genotypes and of any associated pathophysiology is integral to the development of new therapies. Cell culture-based approaches can address these challenges by identifying cellular pathology and by high-throughput screening of gene variants and potential therapeutics. Whole-animal systems can define the broadest function of disorder-associated gene variants and the organismal impact of candidate medications. Given its evolutionary conservation with humans and its experimental tractability, the zebrafish offers several advantages to psychiatric disorder research. These include assays ranging from molecular to behavioural, and capability for chemical screening. There is optimism that the multiple approaches discussed here will link together effectively to provide new diagnostics and treatments for psychiatric patients.
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