scholarly journals Interaction between adverse childhood experiences and polygenic risk in patients with bipolar disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Young-Min Park ◽  
Tatyana Shekhtman ◽  
John R. Kelsoe
Keyword(s):  
Bipolar Disorder ◽  
Clinical Outcomes ◽  
Adverse Childhood Experiences ◽  
Age At Onset ◽  
Polygenic Risk Score ◽  
Childhood Experiences ◽  
Polygenic Risk ◽  
Adverse Childhood ◽  
Genes And Environment ◽  
Genomic Study

Abstract The interaction between genes and environment often occurs when they depend on one another. We hypothesized that adverse childhood experiences (ACEs) would interact with genetic predispositions to bipolar disorder (BD), demonstrating earlier age at onset (AAO) and worse clinical outcomes. We aimed to clarify the effects of the interaction between ACEs and genetic susceptibility using polygenic risk score (PRS) on AAO and clinical outcomes. Single nucleotide polymorphisms and clinical data, including ACEs, were obtained from the Bipolar Genomic Study, which contains a large sample of BD participants. A total of 1615 subjects with BD I were obtained and divided into two groups according to the presence or absence of ACEs and an additional four groups based on the number of ACEs (none versus one versus two versus ≥ three types). ACEs was evaluated using the childhood life events scale (CLES). BD–PRS was obtained from the Psychiatric Genomics Consortium, which compared BD patients and healthy controls. The BD–PRS was higher in the group with ACEs than without ACEs at most p-value thresholds. In multivariate linear regression analyses, both groups with more ACEs and higher BD–PRS were independently and interactively associated with an earlier AAO of BD; however, only greater ACEs were associated with worsened clinical outcome. These findings highlight the clinical importance of evaluating ACEs and polygenic risk in research of the etiology of BD.

scholarly journals Effect of the Type and Number of Adverse Childhood Experiences and the Timing of Adverse Experiences on Clinical Outcomes in Individuals with Bipolar Disorder

2020 ◽  
Vol 10 (5) ◽  
pp. 254 ◽  
Author(s):  
Young-Min Park ◽  
Tatyana Shekhtman ◽  
John R. Kelsoe
Keyword(s):  
Bipolar Disorder ◽  
Clinical Outcomes ◽  
Adverse Childhood Experiences ◽  
Suicide Attempts ◽  
Age At Onset ◽  
Diagnostic Interview ◽  
Childhood Experiences ◽  
Adverse Experiences ◽  
Adverse Childhood ◽  
Negative Effect

Studies have reported an association between adverse childhood experiences (ACEs) and the clinical outcomes of bipolar disorder (BD). However, these studies have several limitations; therefore, we aimed to clarify the effect of the type and number of ACEs and the timing of adverse experiences on clinical outcomes in patients with BD. We analyzed the data of patients with BD (N = 2675) obtained from the National Institute of Mental Health: Bipolar Disorder Genetic Association Information Network, Translational Genomic Institute-I, and Translational Genomic Institute-II. All patients had been diagnosed using the Diagnostic Interview for Genetic Studies. ACEs were evaluated using the Childhood Life Events Scale (CLES). We analyzed the relationship between childhood trauma and clinical outcome in patients with and without exposure to ACEs. We found that ACEs had a robust negative effect on clinical outcomes, including earlier age at onset, presence of psychotic episodes, suicide attempts, mixed symptoms or episodes, substance misuse comorbidity, and worse life functioning. Specifically, the number of ACEs had the most significant effect on clinical outcomes; however, specific ACEs, such as physical abuse, had a considerable influence. Moreover, post-childhood adverse experiences had a weaker effect on clinical outcomes than ACEs did. There was an association of ACEs with negative clinical outcomes in patients with BD. This indicates the importance of basic and clinical research on ACEs in patients with BD.

scholarly journals Case-control study of adverse childhood experiences and multiple sclerosis risk and clinical outcomes

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262093
Author(s):  
Mary K. Horton ◽  
Shannon McCurdy ◽  
Xiaorong Shao ◽  
Kalliope Bellesis ◽  
Terrence Chinn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Adverse Childhood Experiences ◽  
Multiple Testing ◽  
Multiple Testing Correction ◽  
Latent Factors ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Rich Data ◽  
Control Study

Background Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study’s objective was to test for the association between ACEs and MS risk and several clinical outcomes. Methods We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California. Eighteen ACEs were assessed including parent divorce, parent death, and abuse. Outcomes included MS risk, age of MS onset, Multiple Sclerosis Severity Scale score, and use of a walking aid. Logistic and linear regression estimated odds ratios (ORs) (and beta coefficients) and 95% confidence intervals (CIs) for ACEs operationalized as any/none, counts, individual events, and latent factors/patterns. Results Overall, more MS cases experienced ≥1 ACE compared to controls (54.5% and 53.8%, respectively). After adjusting for sex, birthyear, and race, this small difference was attenuated (OR = 1.01, 95% CI: 0.87, 1.18). There were no trends of increasing or decreasing odds of MS across ACE count categories. Consistent associations between individual ACEs between ages 0–10 and 11–20 years and MS risk were not detected. Factor analysis identified five latent ACE factors, but their associations with MS risk were approximately null. Age of MS onset and other clinical outcomes were not associated with ACEs after multiple testing correction. Conclusion Despite rich data and multiple approaches to operationalizing ACEs, no consistent and statistically significant effects were observed between ACEs with MS. This highlights the challenges of studying sensitive, retrospective events among adults that occurred decades before data collection.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes

2016 ◽  
Vol 189 ◽  
pp. 290-297 ◽  
Author(s):  
Sara Poletti ◽  
Benedetta Vai ◽  
Enrico Smeraldi ◽  
Roberto Cavallaro ◽  
Cristina Colombo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Adverse Childhood Experiences ◽  
Grey Matter ◽  
Detrimental Effect ◽  
Childhood Experiences ◽  
Adverse Childhood

Adverse childhood experiences influence white matter microstructure in patients with bipolar disorder

2014 ◽  
Vol 44 (14) ◽  
pp. 3069-3082 ◽  
Author(s):  
F. Benedetti ◽  
I. Bollettini ◽  
D. Radaelli ◽  
S. Poletti ◽  
C. Locatelli ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Adverse Childhood Experiences ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Adult Life ◽  
Mean Diffusivity ◽  
Childhood Experiences ◽  
Axial Diffusivity ◽  
Adverse Childhood

BackgroundBipolar disorder (BD) is associated with adverse childhood experiences (ACE), which worsen the lifetime course of illness, and with signs of widespread disruption of white matter (WM) integrity in adult life. ACE are associated with changes in WM microstructure in healthy humans.MethodWe tested the effects of ACE on diffusion-tensor imaging (DTI) measures of WM integrity in 80 in-patients affected by a major depressive episode in the course of BD. We used whole-brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity, and fractional anisotropy.ResultsACE hastened the onset of illness. We observed an inverse correlation between the severity of ACE and DTI measures of axial diffusivity in several WM fibre tracts contributing to the functional integrity of the brain and including the corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus and uncinate fasciculus.ConclusionsAxial diffusivity reflects the integrity of axons and myelin sheaths, and correlates with functional connectivity and with higher-order abilities such as reasoning and experience of emotions. In patients with BD axial diffusivity is increased by lithium treatment. ACE might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.

scholarly journals Neurocognition and its association with adverse childhood experiences and familial risk of mental illness

2021 ◽  
Author(s):  
Sai Priya Lakkireddy ◽  
Srinivas Balachander ◽  
Pavithra Dayal ◽  
Mahashweta Bhattacharya ◽  
Mino Susan Joseph ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Mental Illness ◽  
Theory Of Mind ◽  
Psychiatric Disorders ◽  
Processing Speed ◽  
Adverse Childhood Experiences ◽  
Familial Risk ◽  
Childhood Experiences ◽  
Adverse Childhood

Background: Neurocognitive deficits are considered an endophenotype for several psychiatric disorders, typically studied in unaffected first-degree relatives (FDRs). Environmental factors such as adverse childhood experiences (ACEs) may also affect neurocognition. This study examines the effect of ACEs on neurocognitive performance in FDRs of patients with severe mental illness in order to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Methods: The sample consists of a total of 512 individuals composed of unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder or alcohol use disorder) and healthy controls (with no familial risk). Neurocognitive tests included processing speed (Color Trails), new learning (Auditory Verbal Learning Test), working memory (N-Back), and Theory of Mind (SOCRATIS). ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models adjusted for age, gender and education were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Total Score and the interaction (familial risk x ACE-IQ Total score). Results: When all FDRs were examined as a group, the main effect of familial risk predicted poor performance in all domains of neurocognition (p <0.01), and the ACEs x familial risk interaction had a significant negative association with global neurocognition, processing speed & working memory. This interaction effect was driven predominantly by the familial risk of AUD. In FDRs of schizophrenia & bipolar disorder, only the main effects of familial risk were significant (working memory, theory of mind & global neurocognition), with no impact of ACEs or its interaction in both these sub-groups. Conclusions: The impact of childhood adversity on neurocognition is moderated by familial risk of psychiatric disorders. Genetic or familial vulnerability may play a greater role in disorders such as schizophrenia and bipolar disorder, while the interaction between ACEs and family history may be more relevant in the case of disorders with greater environmental risk, such as substance use.

scholarly journals Adverse childhood experiences and postpartum depression in bipolar disorder

2020 ◽  
Vol 263 ◽  
pp. 661-666
Author(s):  
Amy Perry ◽  
Katherine Gordon-Smith ◽  
Arianna Di Florio ◽  
Christine Fraser ◽  
Nick Craddock ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Postpartum Depression ◽  
Adverse Childhood Experiences ◽  
Childhood Experiences ◽  
Adverse Childhood

Brain and pain: old assumptions and new science about chronic pain

2020 ◽  
Vol 26 (3) ◽  
pp. 156-158
Author(s):  
George Ikkos ◽  
Parashar Pravin Ramanuj
Keyword(s):  
Chronic Pain ◽  
Nucleus Accumbens ◽  
Clinical Outcomes ◽  
Adverse Childhood Experiences ◽  
Gabaergic Neurons ◽  
Behavioural Inhibition ◽  
Childhood Experiences ◽  
New Science ◽  
Psychopharmacological Treatment ◽  
Adverse Childhood

SUMMARYThe authors summarise the evolving understanding of the neuropsychophysiology of chronic pain, including the relevance of adverse childhood experiences in facilitating it and similarities between the central physiology of chronic pain and opioid addiction. Emerging understanding highlights the importance of dopamine-expressing GABAergic neurons in the nucleus accumbens and suggests that D1 expression is associated with a sense of pleasure and approach behaviour and D2 with a sense of punishment and behavioural inhibition. Regulation of D1 and D2 expression may be mediated by nigrostriatal and medial frontal striatal pathways within the increasingly understood brain as a ‘predictive’ organ. The distinction between the predictive brain and personal ‘expectations’ and the importance of the latter for clinical outcomes are emphasised. The relevance of findings for possible future psychopharmacological treatment avenues is also presented.

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