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

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Abstract

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.

Introduction

Recent work by our group and others has investigated childhood trauma as a potential risk factor in psychosis, providing robust evidence of a relationship between abusive childhood experiences and adult psychotic disorders (Bebbington et al., 2004, Fisher et al., 2010, Houston et al., 2011). Interestingly, exposure to childhood trauma is also associated with adverse effects on cognitive function, both in childhood and in adulthood (Perez and Widom, 1994). This is also the case in psychosis, where we and others have shown that a history of childhood trauma is associated with decreased cognitive performance in attention, concentration and mental speed, language, and verbal intelligence (Lysaker et al., 2001, Schenkel et al., 2005, Aas et al., 2011a, Aas et al., 2011b, Shannon et al., 2011). Although the pathophysiological substrate for this association remains unclear, it is possible that these cognitive deficits may well represent the functional correlate of the brain structural changes often observed in relation to trauma exposure.

In fact, both animal and human studies report cortical thinning, especially in frontal and temporal areas, and hippocampal and amygdala volume alterations in relation to childhood trauma (Edmiston et al., 2011, Habets et al., 2011, McCrory et al., 2011). Most importantly, a relationship between childhood trauma and volume reduction in these two brain structures has been recently observed in a small sample of patients with psychosis (Hoy et al., 2011). This is particularly interesting since amygdala and hippocampal changes have been frequently implicated in psychoses, and in the cognitive alterations observed in these disorders (Sumich et al., 2002, Velakoulis et al., 2006, Gur et al., 2007, Zanelli et al., 2010).

In this respect, although the amygdala is classically viewed as a key structure in emotional processing, its role in higher functions has been the focus of renewed interest also in humans. In fact, animal research has extensively shown a general role for the amygdala in attention and vigilance processes, and in working memory (Holland and Gallagher, 1999, Davis and Whalen, 2001, McIntyre et al., 2003). In humans, the amygdala has also been shown to contribute to performance in working memory and executive control in functional imaging studies (Schaefer et al., 2006, Schaefer and Gray, 2007). Furthermore, its volume has been linked to worse performance on immediate and delayed verbal recall in patients with schizophrenia and affective disorders (Killgore et al., 2009), and in the latter group also on acoustic and visual attention (Li et al., 2010). The hippocampus is well known for its role in cognitive function, particularly in memory (Lupien et al., 2007). In schizophrenia, hippocampus and parahippocampus have been correlated with accuracy and performance speed, memory and executive function and abstraction, respectively (Bilder et al., 1995, Antonova et al., 2004). Moreover, a larger anterior hippocampus volume has been associated with better cognitive performance in first-episode psychosis (Bilder et al., 1995).

How could changes in these regions mediate the relationship between childhood trauma and its associated cognitive dysfunction? It has been proposed that childhood trauma may affect cognitive function by interplaying with the major stress response system, the hypothalamic–pituitary–adrenal (HPA) axis (Heim et al., 2008, Aas et al., 2011a). This is intriguing, since the amygdala and the hippocampus are thought to play an important role in regulating HPA axis activity (Lupien et al., 2007). It is therefore conceivable that the effects of childhood trauma on cognitive function may be mediated by changes in these brain structures. This is exactly what we have investigated in this study, which represents the first evaluation of the link between childhood trauma, cognitive function, and amygdala and hippocampus volume in first episode psychosis.

Here, in a sample of patients with first episode psychosis, we predicted that 1) the presence of childhood trauma would be associated with impaired cognitive performance and with smaller amygdala and hippocampus volumes; 2) the association between childhood trauma and impaired cognition would be mediated by smaller amygdala and hippocampus volumes. While we have previously reported data on childhood trauma and reduced cognitive function in this sample (Zanelli et al., 2010, Aas et al., 2011a), hippocampal and amygdala volumes (and their relationship with childhood trauma and cognitive function) have never been investigated and reported.

Section snippets

Subjects

We studied 83 subjects during their first episode of psychosis recruited as part of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ÆSOP) study (Dazzan et al., 2004, Dazzan et al., 2005). Ethical approval for the study was granted by the local Ethical Committee, and participants gave written informed consent. Subjects aged 16–65 years were approached, who consecutively presented for the first time to the local psychiatric services with a functional psychotic illness (ICD-10

Results

Socio-demographic and clinical characteristics of the sample are shown in Table 1. Patients mean age was 27.4 years (SD 7.9; range 18–54). There were more males (p = 0.001) and a lower number of years of education (p = 0.002) among patients than among controls.

Patients had a significantly smaller left (p = 0.001, d = 0.5) and right (p = 0.001, d = 0.4) amygdala than controls (Table 1). Although there was no significant difference in hippocampus volume between patients and controls, we observed a trend level

Discussion

In the first study that has investigated the relationship between childhood trauma, cognitive function, and amygdala and hippocampus volume in first episode psychosis patients, we found that childhood trauma is associated with worse cognitive function and smaller amygdala volume in first-episode psychosis. Moreover, we find that this smaller amygdala volume seems to mediate the relationship between trauma history and cognitive dysfunction.

Our finding of a smaller amygdala volume in the patient

Role of funding source

This work was supported by the Medical Research Council (UK). This specific aspect of the study has been funded also by the British Academy. Dr. Pariante's research is also supported by the South London and Maudsley NHS Foundation Trust & Institute of Psychiatry, NIHR Biomedical Research Centre for Mental Health, the UK Medical Research Council, the NARSAD, and the Commission of European Communities 7th Framework Programme Collaborative Project Grant Agreement no. 22963 (Mood Inflame). Dr.

Contributors

MA and SN conducted the data analyses and wrote the first version of the paper. CMP and PD coordinated and supervised the data analysis and interpretation and finalized the paper. All authors contributed to and have approved the final manuscript.

Conflict of interest

The authors have no conflict of interest to declare.

Acknowledgments

We also thank the Stanley Medical Research Foundation for their support. We thank the AESOP researchers who helped with the data collection and the patients who took part in the study.

References (55)

  • S.J. Lupien et al.

    The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition

    Brain Cogn.

    (2007)
  • V. Mondelli et al.

    Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment

    Schizophr. Res.

    (2010)
  • V. Mondelli et al.

    Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis

    Schizophr. Res.

    (2010)
  • C.M. Perez et al.

    Childhood victimization and long-term intellectual and academic outcomes

    Child Abuse Negl.

    (1994)
  • A. Prescott et al.

    The veridicality of punitive childhood experiences reported by adolescents and young adults

    Child. Abuse Negl.

    (2000)
  • L.S. Schenkel et al.

    Histories of childhood maltreatment in schizophrenia: relationships with premorbid functioning, symptomatology, and cognitive deficits

    Schizophr. Res.

    (2005)
  • M. Aas et al.

    Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis

    Psychol. Med.

    (2011)
  • H.M. Bai et al.

    Functional MRI mapping of category-specific sites associated with naming of famous faces, animals and man-made objects

    Neurosci. Bull.

    (2011)
  • P.E. Bebbington et al.

    Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity

    Br. J. Psychiatry

    (2004)
  • A. Bifulco et al.

    The childhood experience of care and abuse questionnaire (CECA.Q): validation in a community series

    Br. J. Clin. Psychol.

    (2005)
  • I.A. Cook et al.

    Aging and brain activation with working memory tasks: an fMRI study of connectivity

    Int. J. Geriatr. Psychiatry

    (2007)
  • M. Davis et al.

    The amygdala: vigilance and emotion

    Mol. Psychiatry

    (2001)
  • P. Dazzan et al.

    The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study

    Brain

    (2004)
  • P. Dazzan et al.

    Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study

    Neuropsychopharmacology

    (2005)
  • E.E. Edmiston et al.

    Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment

    Arch. Pediatr. Adolesc. Med.

    (2011)
  • H.L. Fisher et al.

    The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder

    Psychol. Med.

    (2010)
  • H.L. Fisher et al.

    Reliability and comparability of psychosis patients' retrospective reports of childhood abuse

    Schizophr. Bull.

    (2011)
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