The mediating effect of brain-derived neurotrophic factor levels on childhood trauma and psychiatric symptoms in patients with first-episode schizophrenia

Background: Previous studies have implicated childhood trauma and abnormal brain-derived neurotrophic factor in the pathogenesis of schizophrenia. Here, we explored whether brain-derived neurotrophic factor levels mediated the relationship between childhood trauma and psychopathological symptoms in patients with first-episode schizophrenia. Methods: Patients with first-episode schizophrenia ( n = 192) and healthy controls ( n = 136) were enrolled. Childhood traumatic experiences and psychopathology were assessed by Childhood Trauma Questionnaire and Positive and Negative Syndrome Scale, respectively. Enzyme-linked immunosorbent assay was used to quantify brain-derived neurotrophic factor levels. Results: The patients with first-episode schizophrenia experienced more severe childhood trauma and had lower serum brain-derived neurotrophic factor levels than healthy controls. Emotional abuse and Childhood Trauma Questionnaire total score showed positive correlation with Positive and Negative Syndrome Scale positive, general psychopathological subscore and total score. Emotional neglect showed positive correlation with Positive and Negative Syndrome Scale positive subscore. Physical neglect was positively associated with Positive and Negative Syndrome Scale negative subscore. Emotional neglect and Childhood Trauma Questionnaire total score were negatively correlated with serum brain-derived neurotrophic factor levels. The serum brain-derived neurotrophic factor levels mediated the relationship between both Childhood Trauma Questionnaire total score and Positive and Negative Syndrome Scale total score and negative symptoms in the patients. The brain-derived neurotrophic factor levels also mediated the relationship between emotional neglect and Positive and Negative Syndrome Scale total score in the patients. Conclusion: Childhood trauma might contribute to the clinical symptoms of schizophrenia by affecting brain-derived neurotrophic factor levels. Perhaps we can prevent schizophrenia by reducing childhood traumatic experiences.

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The relationship of childhood trauma and DNA methylation of NMDA receptor genes in first-episode schizophrenia

Epigenomics ◽

10.2217/epi-2020-0451 ◽

2021 ◽

Author(s):

Camila M Loureiro ◽

Helene A Fachim ◽

Fabiana Corsi-Zuelli ◽

Rosana Shuhama ◽

Paulo R Menezes ◽

...

Keyword(s):

Dna Methylation ◽

Childhood Trauma ◽

Genomic Dna ◽

First Episode ◽

Childhood Trauma Questionnaire ◽

History Of Childhood ◽

History Of ◽

First Episode Schizophrenia ◽

Relationship Of ◽

The Relationship

Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials & methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results: GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls.

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The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study

Translational Psychiatry ◽

10.1038/s41398-019-0627-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Tarik Dahoun ◽

Matthew M. Nour ◽

Robert A. McCutcheon ◽

Rick A. Adams ◽

Michael A. P. Bloomfield ◽

...

Keyword(s):

Childhood Trauma ◽

Dopamine Release ◽

Striatal Dopamine ◽

Psychotic Symptoms ◽

Childhood Trauma Questionnaire ◽

Mediation Analyses ◽

Positron Emission ◽

Syndrome Scale ◽

Negative Syndrome ◽

The Relationship

Abstract Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.

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Effects of Risperidone and Paliperidone on Brain-Derived Neurotrophic Factor and N400 in First-Episode Schizophrenia

Chinese Medical Journal ◽

10.4103/0366-6999.241802 ◽

2018 ◽

Vol 131 (19) ◽

pp. 2297-2301 ◽

Cited By ~ 4

Author(s):

Rong-Qin Wu ◽

Chong-Guang Lin ◽

Wei Zhang ◽

Xiao-Dong Lin ◽

Xing-Shi Chen ◽

...

Keyword(s):

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

First Episode ◽

First Episode Schizophrenia

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Comparison of brain N-acetylaspartate levels and serum brain-derived neurotrophic factor (BDNF) levels between patients with first-episode schizophrenia psychosis and healthy controls

European Psychiatry ◽

10.1016/j.eurpsy.2009.10.001 ◽

2011 ◽

Vol 26 (1) ◽

pp. 57-63 ◽

Cited By ~ 17

Author(s):

N. Goto ◽

R. Yoshimura ◽

S. Kakeda ◽

J. Moriya ◽

K. Hayashi ◽

...

Keyword(s):

Basal Ganglia ◽

Neurotrophic Factor ◽

Plasma Levels ◽

Brain Derived Neurotrophic Factor ◽

First Episode ◽

Resonance Spectroscopy ◽

Control Subjects ◽

First Episode Schizophrenia ◽

Age Range ◽

Plasma Mhpg

Abstract:Background:N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups.Method:Eighteen patients (nine males, nine females; age range: 13–52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15–49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls.Results:Levels of NAA/Cr in the left basal ganglia (p = 0.0065) and parieto-occipital lobe (p = 0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects.Conclusions:These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.

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Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study

CNS Spectrums ◽

10.1017/s1092852913000849 ◽

2013 ◽

Vol 19 (5) ◽

pp. 374-381 ◽

Cited By ~ 21

Author(s):

Jan Volavka ◽

Pál Czobor ◽

Leslie Citrome ◽

Richard A. Van Dorn

Keyword(s):

Aggressive Behavior ◽

Antipsychotic Drugs ◽

Phase 1 ◽

The Other ◽

First Episode ◽

Intervention Effectiveness ◽

Primary Analysis ◽

Syndrome Scale ◽

First Episode Schizophrenia ◽

Negative Syndrome

IntroductionAggressive behavior can be a dangerous complication of schizophrenia. Hostility is related to aggression. This study aimed to compare the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone on hostility in schizophrenia.MethodsWe used the data that were acquired in the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at least minimal hostility (a score ≥ 2) at baseline.ResultsThe primary analysis of hostility indicated an effect of difference between treatments (F4,1487 = 7.78, P < 0.0001). Olanzapine was significantly superior to perphenazine and quetiapine at months 1, 3, 6, and 9. It was also significantly superior to ziprasidone at months 1, 3, and 6, and to risperidone at months 3 and 6.DiscussionOur results are consistent with those of a similar post-hoc analysis of hostility in first-episode subjects with schizophrenia enrolled in the European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine demonstrated advantages compared with haloperidol, quetiapine, and amisulpride.ConclusionOlanzapine demonstrated advantages in terms of a specific antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE trial.

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Relationship of Personality to Dissociation and Childhood Trauma in Borderline Personality Disorder

CNS Spectrums ◽

10.1017/s109285290001912x ◽

2003 ◽

Vol 8 (10) ◽

pp. 755-762 ◽

Cited By ~ 29

Author(s):

Daphne Simeon ◽

Dorothy Nelson ◽

Rachela Elias ◽

Jennifer Greenberg ◽

Eric Hollander

Keyword(s):

Borderline Personality Disorder ◽

Personality Disorder ◽

Childhood Trauma ◽

Short Form ◽

Small Sample Size ◽

Borderline Personality ◽

Small Sample ◽

Emotional Neglect ◽

Childhood Trauma Questionnaire ◽

The Relationship

ABSTRACTBackground:Dissociation is a prominent feature in some individuals with borderline personality disorder (BPD), yet our understanding of the meanings and implications of prominent dissociation in BPD remains limited. The purpose of this study was to investigate the relationship between dissociation and childhood trauma in BPD and to explore the relationships of dissociation and trauma to various personality features of BPD.Methods:Twenty BPD subjects and 24 healthy comparison subjects of similar age and gender were administered the Dissociative Experiences Scale, the Childhood Trauma Questionnaire—short form, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the Relationship Style Questionnaire, and the Schema Questionnaire.Results:The BPD group exhibited greater dissociation and childhood trauma, as well as greater pathology in most personality variables, compared with the healthy group. Dissociation in BPD was not significantly related to total childhood trauma, but only to emotional neglect, which accounted for 23% of the variance in dissociation scores.Conclusion:Within the BPD group, dissociation was associated with fearful attachment and immature defenses, while total childhood trauma and emotional neglect were associated with overconnection and disconnection schemata. This is a preliminary study with a small sample size, yet the correlates of dissociation in BPD merit further investigation.

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An early improvement threshold to predict response and remission in first-episode schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.bp.109.069328 ◽

2010 ◽

Vol 196 (6) ◽

pp. 460-466 ◽

Cited By ~ 30

Author(s):

R. Schennach-Wolff ◽

F. H. Seemüller ◽

A. Mayr ◽

W. Maier ◽

S. Klingberg ◽

...

Keyword(s):

Predictive Validity ◽

Area Under The Curve ◽

First Episode ◽

Early Improvement ◽

Score Improvement ◽

Syndrome Scale ◽

Definition Of ◽

First Episode Schizophrenia ◽

Negative Syndrome ◽

First Episode Of Schizophrenia

BackgroundEarly improvement with treatment is thought to be important in patients with first-episode schizophrenia, yet a valid definition is still outstanding.AimsTo develop a valid definition of early improvement and test its predictive validity regarding response and remission.MethodWe examined 188 in-patients with first-episode schizophrenia. Early improvement was defined as improvement in Positive and Negative Syndrome Scale (PANSS) total score at week 2, response as a 40% PANSS total score improvement at end-point, and remission according to consensus criteria.ResultsReasonable predictive validity of early improvement was found for a 46% PANSS total score improvement at week 2 and a 50% improvement for remission (area under the curve: response 0.707, remission 0.692). Estimated confidence intervals ranged from 26 to 62% PANSS reduction for response and remission.ConclusionsPatients with a first episode of schizophrenia should improve by at least 30% in PANSS total score at week 2 to achieve response and remission.

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