Pilot study examining the relationship of childhood trauma, perceived stress, and medication use to serum kynurenic acid and kynurenine levels in schizophrenia.
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ABSTRACT:
SUBMITTER: Shovestul BJ
PROVIDER: S-EPMC5833307 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
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Pilot study examining the relationship of childhood trauma, perceived stress, and medication use to serum kynurenic acid and kynurenine levels in schizophrenia.
Shovestul Bridget J BJ Glassman Matthew M Rowland Laura M LM McMahon Robert P RP Liu Fang F Kelly Deanna L DL
Schizophrenia research 20170109
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Project description:Traumatic experiences and fetal development influence tryptophan (TRP) and its neuroactive byproduct, kynurenic acid (KYNA). Maternal TRP metabolite levels during pregnancy vary by fetal sex, with higher concentrations in mothers carrying male fetuses. This pilot study aimed to explore the relationship between offspring sex, maternal childhood trauma, and maternal salivary KYNA and TRP levels during pregnancy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine KYNA and TRP levels in maternal saliva samples collected from 35 late-pregnancy participants. Maternal childhood trauma was assessed using the Childhood Trauma Questionnaire, including subscales for emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. Among mothers pregnant with boys, salivary KYNA significantly correlated with physical and emotional neglect, and salivary TRP with emotional neglect. No significant correlations were found in mothers who delivered female offspring. Significant associations of childhood trauma and offspring sex were found for salivary KYNA but not TRP concentrations. Mothers with higher trauma levels who delivered boys exhibited higher levels of salivary KYNA compared to those with lower trauma levels. Moreover, mothers with higher trauma levels who delivered boys had higher salivary KYNA levels than those with higher trauma levels who delivered girls. This pilot study provides evidence of an association between maternal childhood trauma and TRP metabolism, measured in saliva, especially in mothers pregnant with boys. However, longitudinal studies with larger sample sizes are required to confirm these results.
| S-EPMC11041113 | biostudies-literature
Project description:Background and hypothesisThe role of early adversity and trauma is increasingly recognized in psychosis but treatments for trauma and its consequences are lacking. Psychological treatments need to understand the prevalence of these experiences, the relationship with specific symptoms and identify potentially tractable processes that may be targeted in therapy. It was hypothesized that greater adversity, and specifically abuse rather than neglect, would be associated with positive symptoms and specifically hallucinations. In addition, negative beliefs would mediate the relationship with positive symptoms.Study design292 Patients with treatment resistant psychosis completed measures of early adversity as well as current symptoms of psychosis.Study resultsEarly adversity in the form of abuse and neglect were common in one-third of the sample. Adversity was associated with higher levels of psychotic symptoms generally, and more so with positive rather than negative symptoms. Abuse rather than neglect was associated with positive but not with negative symptoms. Abuse rather than neglect was associated with hallucinations but not delusions. Abuse and neglect were related to negative beliefs about the self and negative beliefs about others. Mediation demonstrated a general relationship with adversity, negative-self, and other views and overall psychotic symptoms but not in relation to the specific experience of abuse and hallucinations. Females were more likely to be abused, but not neglected, than males.ConclusionsWhilst most relationships were modest, they supported previous work indicating that adversity contributes to people with psychosis experiencing distressing symptoms especially hallucinations. Treatments need to address and target adversity.
| S-EPMC11207680 | biostudies-literature
Project description:A greater understanding of why some people are more at risk of developing PTSD is required. We examine the relationship between temperament traits in early childhood and subsequent trauma exposure and risk of PTSD. We used data on 2017 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). Temperament was measured using the Carey Infant Temperament Scale (average score from ages 6 and 24 months). This provided data on 9 individuals traits, and Easy, Medium, and Difficult temperament clusters. Trauma exposure was measured from 0 to 17 years, and PTSD at age 23 years using the PTSD Checklist for DSM-V (PCL-5). Regression models were used to estimate associations between temperament and both trauma and PTSD, and to examine mediation (of temperament to PTSD pathway) and interaction (temperament X trauma on PTSD) effects. 1178 (58.4%) individuals were exposed to a trauma in childhood and 112 (5.5%) had PTSD. Higher levels of Intensity were associated with a small increase in trauma exposure (ORadjusted 1.23, 95% CI 1.12, 1.34; p < 0.001) and PTSD (ORadjusted 1.27, 95% CI 1.05, 1.54; p = 0.012). Higher levels of Activity, Adaptability, Mood and Threshold temperament traits were also associated with trauma exposure. Medium (ORadjusted 1.49, 95% CI 1.21, 1.84; p < 0.001) and Difficult (ORadjusted 1.47, 95% CI 1.18, 1.84; p = 0.001) temperament clusters were associated with increased trauma exposure compared to an Easy cluster, but were not associated with PTSD. The relationship between trait Intensity and adult PTSD was partially mediated by childhood/adolescent trauma (Indirect ORadjusted 1.08, 95% CI 1.01, 1.16, p = 0.024, proportion mediated 26.2%). There was some evidence that trait Intensity modified the relationship between trauma and PTSD (ORadjusted 1.66, 95% CI 1.07, 2.55, p = 0.023). PTSD in early adulthood is more common in those with intense stimuli responsiveness in childhood. Temperament traits might be useful predictors of trauma exposure and mental health outcomes and offer potential targets for supportive interventions.
| S-EPMC8670596 | biostudies-literature
Project description:BackgroundPatients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine pathway, and its formation indirectly depends on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine.MethodsWe analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were selected covering KMO and were analyzed in UNPHASED.ResultsWe included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA.LimitationsGiven the limited sample size, the results are tentative until replication.ConclusionOur results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA.
| S-EPMC3244499 | biostudies-literature
Project description:Tryptophan (TRP) catabolites exert neuroactive effects, with the plethora of evidence suggesting that kynurenic acid (KYNA), a catabolite of the kynurenine pathway (KP), acts as the regulator of glutamate and acetylcholine in the brain, contributing to the schizophrenia pathophysiology. Newer evidence regarding measures of KP metabolites in the blood of schizophrenia patients and from the central nervous system suggest that blood levels of these metabolites by no means could reflect pathological changes of TRP degradation in the brain. The aim of this study was to investigate plasma concentrations of TRP, kynurenine (KYN) and KYNA at the acute phase and remission of schizophrenia in a prospective, case-control study of highly selected and matched schizophrenia patients and healthy individuals. Our study revealed significantly decreased KYN and KYNA in schizophrenia patients (p < 0.001), irrespective of illness state, type of antipsychotic treatment, number of episodes or illness duration and no differences in the KYN/TRP ratio between schizophrenia patients and healthy individuals. These findings could be interpreted as indices that kynurenine pathway might not be dysregulated in the periphery and that other factors contribute to observed disturbances in concentrations, but as our study had certain limitations, we cannot draw definite conclusions. Further studies, especially those exploring other body compartments that participate in kynurenine pathway, are needed.
| S-EPMC10741951 | biostudies-literature
Project description:Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.
| S-EPMC7240182 | biostudies-literature
Project description:BackgroundThe elevated prolactin levels in first-episode drug-naïve (FEDN) schizophrenia patients may correlate with long-term stress caused by childhood trauma. This study aimed to assess the relationship between elevated prolactin levels and childhood trauma in FEDN schizophrenia patients, while also considering sex differences.MethodsUtilizing a cross-sectional design, the study involved 88 FEDN schizophrenia patients and 76 healthy controls (HCs). Evaluations encompassed measuring prolactin levels in peripheral blood and assessing mental health using the Positive and Negative Syndrome Scale (PANSS), the Childhood Trauma Questionnaire - Short Form (CTQ-SF), as well as evaluating resilience with the Connor-Davidson Resilience Scale (CD-RISC), perceived social support with the Perceived Social Support Scale (PSSS), and demographic characteristics to control for confounding factors. A mediation model was constructed using the RMediation package of the R software.MethodsThe results suggested prolactin levels in FEDN schizophrenia patients were higher than in HCs(t=-9.938, p = 0.000). Group classification (HCs vs. FEDN schizophrenia patients) (t = 9.291, p = 0.000) and sex (t = 3.282, p = 0.001) were influential factors for prolactin levels. Elevated prolactin(OR = 1.007, p = 0.000), along with higher scores for childhood emotional(OR = 1.469, p = 0.006)andsexual abuse(OR = 1.592, p = 0.018) and lower social support(OR = 0.946, p = 0.026), were associated with the onset of schizophrenia. Positive correlations were found between prolactin levels and childhood emotional (r = 0.268, p = 0.002) /sexual abuse(r = 0.264, p = 0.002), with no sex differences. No significant relationship was observed between prolactin levels and PANSS scores. Mediation analysis revealed that childhood emotional abuse (95% CI: [0.059 ~ 0.293]) and sexual abuse (95% CI: [0.086 ~ 0.439]) had significant indirect effects on schizophrenia, mediated by elevated prolactin levels.ConclusionThese findings suggest that childhood trauma may be associated with the onset of schizophrenia by influencing prolactin levels, highlighting the complex interplay between hormonal disruptions and early-life stress in the development of schizophrenia.
| S-EPMC11900333 | biostudies-literature
Project description:BackgroundEvidence from high-income countries suggests that childhood trauma is associated with schizophrenia. Studies of childhood trauma and schizophrenia in low and middle income (LMIC) countries are limited. This study examined the prevalence of childhood traumatic experiences among cases and controls and the relationship between specific and cumulative childhood traumatic experiences and schizophrenia in a sample in South Africa.MethodsData were from the Genomics of Schizophrenia in the South African Xhosa people study. Cases with schizophrenia and matched controls were recruited from provincial hospitals and clinics in the Western and Eastern Cape regions in South Africa. Childhood traumatic experiences were measured using the Childhood Trauma Questionnaire (CTQ). Adjusted logistic regression models estimated associations between individual and cumulative childhood traumatic experiences and schizophrenia.ResultsTraumatic experiences were more prevalent among cases than controls. The odds of schizophrenia were 2.44 times higher among those who experienced any trauma than those who reported no traumatic experiences (95% CI 1.77-3.37). The odds of schizophrenia were elevated among those who experienced physical/emotional abuse (OR 1.59, CI 1.28-1.97), neglect (OR 1.39, CI 1.16-1.68), and sexual abuse (OR 1.22, CI 1.03-1.45) compared to those who did not. Cumulative physical/emotional abuse and neglect experiences increased the odds of schizophrenia as a dose-response relationship.ConclusionChildhood trauma is common in this population. Among many other benefits, interventions to prevent childhood trauma may contribute to a decreasing occurrence of schizophrenia.
| S-EPMC7053504 | biostudies-literature
Project description:Cognitive impairments predict poor functional outcomes in people with schizophrenia. These impairments may be causally related to increased levels of kynurenic acid (KYNA), a major metabolic product of tryptophan (TRYP). In the brain, KYNA acts as an antagonist of the of α7-nicotinic acetylcholine and NMDA receptors, both of which are involved in cognitive processes. To examine whether KYNA plays a role in the pathophysiology of schizophrenia, we compared the acute effects of a single oral dose of TRYP (6 g) in 32 healthy controls (HC) and 37 people with either schizophrenia (Sz), schizoaffective or schizophreniform disorder, in a placebo-controlled, randomized crossover study. We examined plasma levels of KYNA and its precursor kynurenine; selected cognitive measures from the MATRICS Consensus Cognitive Battery; and resting cerebral blood flow (CBF) using arterial spin labeling imaging. In both cohorts, the TRYP challenge produced significant, time-dependent elevations in plasma kynurenine and KYNA. The resting CBF signal (averaged across all gray matter) was affected differentially, such that TRYP was associated with higher CBF in HC, but not in participants with a Sz-related disorder. While TRYP did not significantly impair cognitive test performance, there was a trend for TRYP to worsen visuospatial memory task performance in HC. Our results demonstrate that oral TRYP challenge substantially increases plasma levels of kynurenine and KYNA in both groups, but exerts differential group effects on CBF. Future studies are required to investigate the mechanisms underlying these CBF findings, and to evaluate the impact of KYNA fluctuations on brain function and behavior. (Clinicaltrials.gov: NCT02067975).
| S-EPMC10516920 | biostudies-literature
Project description:The pivotal tryptophan (TRP) metabolite kynurenine is converted to several neuroactive compounds, including kynurenic acid (KYNA), which is elevated in the brain and cerebrospinal fluid of people with schizophrenia (SZ) and may contribute to cognitive abnormalities in patients. A small proportion of TRP is metabolized to serotonin and further to 5-hydroxyindoleacetic acid (5-HIAA). Notably, KP metabolism is readily affected by immune stimulation. Here, we assessed the acute effects of an oral TRP challenge (6 g) on peripheral concentrations of kynurenine, KYNA and 5-HIAA, as well as the cytokines interferon-γ, TNF-α and interleukin-6, in 22 participants with SZ and 16 healthy controls (HCs) using a double-blind, placebo-controlled, crossover design. TRP raised the levels of kynurenine, KYNA and 5-HIAA in a time-dependent manner, causing >20-fold, >130-fold and 1.5-fold increases in kynurenine, KYNA and 5-HIAA concentrations, respectively, after 240 min. According to multivariate analyses, neither baseline levels nor the stimulating effects of TRP differed between participants with SZ and HC. Basal cytokine levels did not vary between groups, and remained unaffected by TRP. Although unlikely to be useful diagnostically, measurements of circulating metabolites following an acute TRP challenge may be informative for assessing the in vivo efficacy of drugs that modulate the neosynthesis of KYNA and other products of TRP degradation.
| S-EPMC9416551 | biostudies-literature