Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis?

Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
Schizophrenia Research (Impact Factor: 3.92). 02/2012; 137(1-3):73-9. DOI: 10.1016/j.schres.2012.01.035
Source: PubMed


Patients with psychosis have higher rates of childhood trauma, which is also associated with adverse effects on cognitive functions such as attention, concentration and mental speed, language, and verbal intelligence. Although the pathophysiological substrate for this association remains unclear, these cognitive deficits may represent the functional correlate of changes observed in relation to trauma exposure in structures such as the amygdala and the hippocampus. Interestingly, these structures are often reported as altered in psychosis. This study investigated the association between childhood trauma, cognitive function and amygdala and hippocampus volume, in first-episode psychosis. We investigated 83 patients with first-episode psychosis and 63 healthy controls. All participants underwent an MRI scan acquired with a GE Sigma 1.5-T system, and a standardized neuropsychological assessment of general cognition, memory, processing speed, executive function, visuo-spatial abilities, verbal intelligence, and language. In a subsample of the patients (N=45) information on childhood trauma was collected with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). We found that amygdala, but not hippocampus, volume was significantly smaller (p=0.001) in patients compared to healthy controls. There was a trend level interaction for hippocampus volume between group and sex (p=0.056). A history of childhood trauma was associated with both worse cognitive performance and smaller amygdala volume. This smaller amygdala appeared to mediate the relationship between childhood trauma and performance on executive function, language and verbal intelligence in patients with psychosis. This points to a complex relationship between childhood trauma exposure, cognitive function and amygdala volume in first-episode psychosis.

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    • "For example, being abused in childhood may lead to insecure attachment and paranoid world view (Lovatt et al. 2010), low self-esteem (Fowke et al. 2012), behavioural hostility (Lysaker et al. 2002) and perceived discrimination (Addington et al. 2013), all of which could result in difficulties forming relationships and maintaining employment. Childhood maltreatment is also associated with detrimental effects on the developing brain, such as reduced volume of the amygdala (Aas et al. 2012; Hoy et al. 2012), hippocampus (Hoy et al. 2012), ventrolateral prefrontal cortex (Morandotti et al. 2013) and in total grey matter (Sheffield et al. 2013). It may modify sensitivity to stress among patients with psychosis, potentially through dysregulation of the hypothalamicpituitary-adrenal (HPA) axis (Neigh et al. 2009; "
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    ABSTRACT: Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study. Participants were 268 (152 females, 116 males) individuals identified as UHR 2-14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS). Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups. Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia.
    Full-text · Article · Jul 2015 · Psychological Medicine
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    • "They also report increased incidences of childhood trauma compared to the general population (Fisher et al., 2011; Read et al., 2005; Aas et al., 2014). Childhood trauma has been associated with reduction of BDNF levels, both in schizophrenia and bipolar disorders (Kauer-Sant'Anna et al., 2007; Mondelli et al., 2011) and with volumetric changes in the hippocampus and in the amygdala in patients with first-episode psychosis (Aas et al., 2012b; Hoy et al., 2012). The BDNF gene has at least one functional variant with a single nucleotide polymorphism (SNP; rs6265) resulting in a valine to methionine substitution at codon 66 of the proBDNF. "
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    ABSTRACT: Objective: Here we investigated a two hit gene environment model in relation to functional genomic factors (BDNF mRNA), and volume of hippocampal subfields in schizophrenia spectrum and bipolar disorders, focusing on both an environmental (childhood trauma) and genetic risk factor (BDNF val66met). Method: A total of 323 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited. A history of childhood trauma was obtained using the Childhood Trauma Questionnaire. BDNF DNA and RNA were analyzed using standardized procedures. A subsample of n = 108 underwent MRI scanning, and the FreeSurfer was used to obtain measures of hippocampal subfield. All MRI data were corrected for age and gender, with post-hoc analysis correcting for ICV. Results: A history of childhood trauma or being a met carrier of the BDNF val66met was associated with significantly reduced BDNF mRNA level. Additive effects were observed between a history of childhood trauma and BDNF val66met, in the direction of met carriers with high levels of childhood trauma having the lowest BDNF mRNA levels. Lastly, met carriers reporting high levels of childhood trauma (specifically sexual or physical abuse) had significantly reduced hippocampal subfield volumes CA2/3 and CA4 dentate gyrus. Conclusion: The current findings demonstrate that the reduced BDNF mRNA levels found in psychosis may be associated with both a history of childhood trauma and BDNF val66met variants. Further, our study supports a two hit model including a history of childhood trauma as well as genetic vulnerability (met carriers of the BDNF val66met) behind reduced volume of hippocampal subfields in psychosis. This was specifically found for areas important for neurogenesis, the CA2/3 and the CA4 DG.
    Full-text · Article · Aug 2014 · Journal of Psychiatric Research
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    • "Regarding bipolar disorders, one large study (n ¼202) showed that childhood trauma is associated with higher scores on the ALS, with the strongest association for emotional abuse (Etain et al., 2008). Childhood trauma has been linked to increased amygdala activation (van Harmelen et al., 2013), a brain region important for fear and emotions (Gallagher and Chiba, 1996; Aas et al., 2012b), supporting a relationship of childhood trauma with possible changes in emotional regulation. "
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    ABSTRACT: This study aimed to investigate associations between a history of childhood trauma and levels of affective lability in bipolar patients compared to controls. Forty-two patients and 14 controls were assessed using the Affective Lability Scale (ALS) and the Childhood Trauma Questionnaire (CTQ). Affective Lability Score was significantly associated with scores on the Childhood Trauma Questionnaire. A multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability between patients and controls.
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