Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk.
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SUBMITTER: Versace A
PROVIDER: S-EPMC6135796 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy offspring having a parent with BD were compared with those in healthy controls.A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity were examined using whole-brain analyses, co-varying for age.Group-by-age interactions showed a linear increase in FA and a linear decrease in RD in CONT in the left corpus callosum and right inferior longitudinal fasciculus. In HBO, there was a linear decrease in FA and an increase in RD with age in the left corpus callosum and no relation between FA or RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed linear and showed nonlinear relations between FA and RD and age in these regions in CONT and HBO.This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO compared with CONT in the corpus callosum and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO.
| S-EPMC2996850 | biostudies-literature
Project description:ObjectivesEmotion regulation deficits are a core feature of bipolar disorder. However, their potential neurobiological underpinnings and existence beyond bipolar I disorder remain unexplored. Our main goal was to investigate whether both individuals with bipolar I and bipolar II disorder show deficits in emotion regulation during an attention control task, and to explore the neurophysiological underpinnings of this potential deficit.MethodsTwenty healthy controls, 16 euthymic participants with bipolar I disorder, and 19 euthymic participants with bipolar II disorder completed psychometric and clinical assessments, a neuroimaging emotion regulation paradigm, and an anatomical diffusion-weighted scan. Groups were matched for age, gender, and verbal IQ.ResultsDuring the presence of emotional distracters, subjects with bipolar I disorder showed slowed reaction times to targets, and increased blood oxygenation level-dependent (BOLD) responses in the amygdala, accumbens, and dorsolateral prefrontal cortex, but not increased inverse functional connectivity between these prefrontal and subcortical areas, and altered white matter microstructure organization in the right uncinate fasciculus. Subjects with bipolar II disorder showed no altered reaction times, increased BOLD responses in the same brain areas, increased inverse functional connectivity between the prefrontal cortex and amygdala, and no abnormalities in white matter organization.ConclusionsParticipants with bipolar I disorder showed abnormalities in functional and anatomical connectivity between prefrontal cortices and subcortical structures in emotion regulation circuitry. However, these deficits did not extend to subjects with bipolar II disorder, suggesting fundamental differences in the pathophysiology of bipolar disorder subtypes.
| S-EPMC4672703 | biostudies-literature
Project description:The relationship between the p factor and cognition in youth has largely focused on general cognition (IQ) and executive functions (EF). Another cognitive construct, processing speed (PS), is dissociable from IQ and EF, but has received less research attention despite being related to many different mental health symptoms. The present sample included 795 youth, ages 11-16 from the Colorado Learning Disabilities Research Center (CLDRC) sample. Confirmatory factor analyses tested multiple p factor models, with the primary model being a second-order, multi-reporter p factor. We then tested the correlation between the p factor and a latent PS factor. There was a significant, negative correlation between the p factor and PS (r(87) = -0.42, p < .001), indicating that slower processing speed is associated with higher general mental health symptoms. This association is stronger than previously reported associations with IQ or EF. This finding was robust across models that used different raters (youth and caregiver) and modeling approaches (second-order vs. bifactor). Our findings indicate that PS is related to general psychopathology symptoms. This research points to processing speed as an important transdiagnostic construct that warrants further exploration across development.
| S-EPMC10368543 | biostudies-literature
Project description:Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework.
| S-EPMC9289457 | biostudies-literature
Project description:Evidence suggests that early pubertal timing may operate as a transdiagnostic risk factor (i.e., shared across syndromes of psychopathology) for both genders. The current study examined associations between pubertal timing and dimensional psychopathology, structured across different levels of three organizational models: 1) DSM-based syndrome model, 2) traditional model of internalizing and externalizing factors, and 3) bifactor (p-factor) model, which includes a general psychopathology factor as well as internalizing- and externalizing- specific factors. For study analyses, 567 youth-parent pairs completed psychopathology measures when youth (55.5% female) were 13.58 (SD = 2.37, range = 9-17). Findings across all models revealed that early pubertal timing served as a transdiagnostic risk factor and also displayed some syndrome specific associations. Gender did not moderate any relationships between pubertal timing and psychopathology. Study findings reinforce the importance of examining risk across different levels of psychopathology conceptualization and analysis.
| S-EPMC6550487 | biostudies-literature
Project description:BackgroundInternalizing disorders (IDs), consisting of syndromes of anxiety and depression, are common, debilitating conditions often beginning early in life. Various trait-like psychological constructs are associated with IDs. Our prior analysis identified a tripartite model of Fear/Anxiety, Dysphoria, and Positive Affect among symptoms of anxiety and depression and the following constructs in youth: anxiety sensitivity, fearfulness, behavioral activation and inhibition, irritability, neuroticism, and extraversion. The current study sought to elucidate their overarching latent genetic and environmental risk structure.MethodsThe sample consisted of 768 juvenile twin subjects ages 9-14 assessed for the nine, abovementioned measures. We compared two multivariate twin models of this broad array of phenotypes.ResultsA hypothesis-driven, common pathway twin model reflecting the tripartite structure of the measures were fit to these data. However, an alternative independent pathway model provided both a better fit and more nuanced insights into their underlying genetic and environmental risk factors.ConclusionsOur findings suggest a complex latent genetic and environmental structure to ID phenotypes in youth. This structure, which incorporates both clinical symptoms and various psychological traits, informs future phenotypic approaches for identifying specific genetic and pathophysiological mechanisms underlying ID risk.
| S-EPMC7656112 | biostudies-literature
Project description:Bipolar disorder is a highly heritable illness that onsets in adolescence and young adulthood. We examined gene expression (mRNA) and protein levels of candidate immune and neurotrophic markers in well-characterized offspring of bipolar parents in order to identify reliable indicators of illness risk status and the early clinical stages of illness development. We measured mRNA expression and protein levels in candidate immune (TNF-?, IL-1?, IL-10, IFN-?) and neurotrophic (brain-derived neurotrophic factor (BDNF)) markers from plasma. High-risk offspring were identified from families in which one parent had confirmed bipolar disorder. Control offspring were identified from families in which neither parent met lifetime criteria for a major psychiatric disorder. All parental Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses were based on Schedule for Affective Disorders - Lifetime Version (SADS-L) interviews and blind consensus review. As part of an ongoing study, all offspring were prospectively assessed using KSADS-PL format interviews and diagnoses confirmed on blind consensus review. High-risk offspring had significantly increased IL-6 (p?=?0.050) and BDNF (p?=?0.006) protein levels compared to controls. Those high-risk offspring in earlier compared to later clinical stages of illness development had higher IL-6 (p?=?0.050) and BDNF (p?=?0.045) protein levels. After adjustments, only differences in BDNF protein levels remained significant. There was a moderating effect of the BDNF genotype on both gene expression and protein levels in high-risk compared to control offspring. The BDNF genotype also moderated the association between clinical stage and gene expression levels in high-risk offspring. These findings provide support for detectable differences in candidate immune and neurotrophic markers in individuals at high risk of developing bipolar disorder and for detectable changes over the clinical stages of illness development. These associations appear to be moderated by genetic variants.
| S-EPMC4447739 | biostudies-literature
Project description:There is considerable covariation between externalizing and internalizing problems across the lifespan. Partitioning general and specific psychopathology is crucial to identify (a) processes that confer specific risk for externalizing versus internalizing problems and (b) transdiagnostic processes that confer risk for the covariation between externalizing and internalizing problems. The oddball P3 event-related potential (ERP) component, thought to reflect attentional orienting, has been widely examined in relation to psychopathology. However, prior studies have not examined the P3-or other aspects of neural functioning-in relation to general versus specific psychopathology in children. The present study examined whether children's (N = 124, ages 3-7 years) P3 amplitudes were associated with general versus specific psychopathology. Children's electroencephalography data were recorded during an oddball task. Parents rated their children's externalizing and internalizing problems. Using bifactor models to partition variance in parents' ratings of children's psychopathology symptoms, we examined children's P3 amplitudes in relation to three latent factors: (1) the general factor of psychopathology-the covariation of externalizing and internalizing psychopathology, (2) unique externalizing problems-the variance in externalizing problems after controlling for the general factor, and (3) unique internalizing problems. Results indicated that smaller P3 amplitudes were associated with unique externalizing problems at ages 3-5, and with general psychopathology at ages 6-7. Findings suggest that smaller P3 amplitudes may be associated with externalizing problems from a very young age. Moreover, there may be a developmental shift in the functional significance of the P3 in relation to general and specific psychopathology in childhood.
| S-EPMC10543161 | biostudies-literature
Project description:Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.
| S-EPMC5290348 | biostudies-literature
Project description:ObjectiveBipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR).MethodDuring functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth.ResultsWe found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction).ConclusionIf replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177.
| S-EPMC9382574 | biostudies-literature