Dissertation committee:
Δημήτριος Αναγνωστόπουλος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Στεφανής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αργύρης Στριγγάρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Κόλλιας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ηλίας Τζαβέλλας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Mαρίνος Κυριακόπουλος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αλέξανδρος Χατζημανώλης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Schizophrenia research over the last decades has shifted the paradigm from finding etiological factors to building a causal model where genetic factors interact with environmental ones. Adverse childhood psycho-traumatic experiences (ACPTEs) such as physical, sexual and emotional abuse, physical and emotional neglect, and bullying have been proposed by several researchers to be some of the most significant environmental factors associated with schizophrenia spectrum disorders, if not the most significant. The present doctoral study aims at the investigation of the role of the aforementioned ACPTEs as potential environmental components in the development of a first-episode psychosis (FEP).
Reviewing the literature regarding the effect of ACPTEs on early psychosis, our primary hypothesis proposes that the severity of psychotic symptoms at baseline is higher among FEP patients reporting a history of ACPTE compared to FEP patients who have not experienced ACPTE, and the early course of the illness is worse among FEP patients reporting a history of ACPTE, as the severity of psychotic symptoms typically persists after the initiation of antipsychotic treatment when assessed at the 1 month follow-up. The second hypothesis proposes that premorbid adjustment is worse among the FEP patients with a history of ACPTE. The third hypothesis proposes that the impairment of cognitive functions, including social cognition, is more severe among FEP patients with a history of ACPTE compared to the FEP patients have not experienced ACPTE. The fourth hypothesis proposes that FEP patients with a history of ACPTE are characterized by increased depressive symptoms and negative schemes for self and others. In addition, the depressive symptoms and negative schemes for self and others mediate both the association between ACPTE and increased psychotic symptoms at baseline and the association between ACPTE and the persistence of the psychotic symptoms at 1 month follow-up.
The research data were collected from a sample of men and women patients of the Greek general population aged 16-45 (N=225) who had experienced a FEP in the context of Athens First Episode Psychosis Study.
ACPTEs were assessed using the Childhood Trauma Questionnaire Short Form (CTQ-SF) and the short version of Retrospective Bullying Questionnaire (RBQ). The positive and negative psychotic symptoms, as well as general symptoms and the total score, were assessed at baseline and 1 month follow-up, using the Positive and Negative Syndrome Scale (PANSS). In the statistical analysis of the data from the clinical assessment with PANSS after one month of treatment with antipsychotics, taking into account clinical severity at baseline, the association of ACPTE with a potential increased PANSS score at follow-up could be an indicator of reduced therapeutic effect in these patients (PANSS 1 month improvement) Clinical remission was assessed based on the baseline and follow-up values of the PANSS and on Andreasen’s symptomatic criteria. Premorbid adjustment was assessed using Premorbid Adjustment Scale and four scores derived; two scores regarding academic and social adjustment in childhood (5-11 years old) and two scores regarding academic and social adjustment in early adolescence (11-15 years old). Social cognition including jumping to conclusion bias and affection recognition assessed using Beads Test and Degraded Faces Affection Recognition Test (DFART). Cognition including sustained attention, visual working memory assessed using Continuous Performance Test (CPT) and Benton Test. In addition, verbal comprehension, working memory, processing speed and perceptual reasoning were assessed using WAIS. Depression was assessed using the depression subscale of Symptom Check List 90 (SCL-90) and finally schemes for self and others were assessed using Brief Core Scheme Scale (BCSS). The psychometric assessment tools mentioned above are compatible with those have been used by the European network of national programs studying the interaction of genetics with environmental factors in pathogenesis of psychosis (European Genes Environment Interaction-EUGEI study).
Regarding the statistical analysis methodology, Pearson's chi square (χ2) test was used to compare ACTPEs between males and females. The Student's t-test or the nonparametric Mann-Whitney test was used to compare quantitative variables between two groups. The nonparametric Kruskal-Wallis test was used to compare quantitative variables between more than two groups. Spearman's correlation coefficient (rho) was used to test the relationship between two quantitative variables. Linear regression analyses were performed to investigate the relationship between ACPTEs and the assessment scales, reporting the corresponding dependence coefficients (β) and their standard errors (SE). Linear regression analyses were performed using logarithmic transformations. To investigate the association between ACPTEs and the variable ‘’remission’’ logistic regression analysis models were performed, and odds ratios with their 95% confidence intervals (95% CI) were obtained adjusting for age, sex, and education level. Finally, Baron and Kenny's analysis technique was performed to test our mediation hypothesis. All statistical analyses were conducted using SPSS 24.0.
According to the results of our analyses, there was no significant association of bullying with increased severity of psychopathology, at baseline; however after one month of treatment as usual there was a significant association with increased negative symptoms (β=1.66; SE=0.70; p=0.018) and total PANSS (1 month improvement) score (β=4.81; SE=2.34; p=0.041). In addition, emotional neglect was associated with increased negative symptoms (β=4.62; SE=1.99; p=0.021), symptoms of general psychopathology (β=6.15; SE=2.98; p=0.040), and PANSS total score (β=12,9; SE=5,13; p=0,019) at baseline, while after one month of treatment as usual there were significant associations across all PANSS (1 month improvement) subscales. [(positive: β=4.60; SE=1.19; p<0.001) (negative: β=2.81; SE=1.12; p=0.013) (general β=6.08; SE=1.89; p=0.002) (total score β=13.64; SE=3.74; p<0.001)]
The premorbid adjustment in childhood educational (β=0.021; SE=0.009; p=0.028) and social activities (β=0.034; SE=0.010; p=0.001) of the individuals who had a history of bulling was found to be reduced compared to patients without a history of bullying. Regarding early adolescence, the patients with a history of sexual abuse and emotional neglect had a reduced premorbid adjustment both in education (β=0.204; SE=0.060; p=0,001) (β=0.216; SE=0.049; p=0,011) and in socialization (β=0.197; SE=0.061; p=0.001) (β=0.151; SE=0.050; p=0.003) compared to the patients without history of the corresponding ACPTEs.
Concerning cognitive functions a significant negative association between bullying and Benton test score (β=-0.030; SE=0.012; p=0.016) as well as between physical neglect and perception reasoning index (β=-7.98; SE=3.49; p=0.023) was found.
Significant association of emotional neglect with negative schemas for self and others (β=0.274; SE=0.091; p=0.003)(β=0.198; SE=0.086; p=0.022) and with depression (β=0.58; SE=0.22; p=0.008) as well as a significant association between bullying and depression was found (β=0.36; SE=0.13; p=0.007). In the mediation analyses, the results demonstrated that depression was a mediating factor in the significant association of emotional neglect with the symptoms of general psychopathology (p=0.033) and with total score of PANSS at baseline (p=0.047). However, at one month follow up both depression and negative self schemas were found to mediate the significant association of emotional neglect with increased positive psychotic symptoms (p=0.041; p:0.021), increased symptoms of general psychopathology (p=0.042, p:0.019), and increased PANSS (1 month improvement) total score. (p=0.041; p: 0.017).
The findings presented in the current work with regard to emotional neglect are consistent with prior evidence supporting the association of ACPTEs with an increased severity of psychotic symptoms and an unfavorable initial clinical course. In addition, it is demonstrated that the effects of ACPTΕs, such as bullying and emotional neglect, may not be apparent at admission but may be substantial, on the course of the FEP through poor symptomatic remission. The findings suggest the mediation role of depression and negative schemes for self between emotional neglect and symptom severity, thereby supporting the hypothesis of the traumatogenic neurodevelomental model of psychosis and further implicate the affective pathway to psychosis etiology. Given that depression and anxiety symptoms are the most frequent among patients diagnosed with early psychosis in early intervention units, the recording and early treatment of ACPTEs, at least in terms of emotional neglect, may contribute to the prevention and the efficient treatment of the first psychotic episode in patients with a history of adverse traumatic experiences.
