Is there a link between childhood trauma, cognition, and amygdala and hippocampus 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)
- et al.
Childhood trauma and cognitive function in first-episode affective and non-affective psychosis
Schizophr. Res.
(2011) - et al.
The relationship between brain structure and neurocognition in schizophrenia: a selective review
Schizophr. Res.
(2004) - et al.
Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia
Schizophr. Res.
(1995) - et al.
Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis
Schizophr. Res.
(2011) - et al.
The human amygdala: a systematic review and meta-analysis of volumetric magnetic resonance imaging
Brain Res. Rev.
(2002) - et al.
Amygdala volume in patients receiving chronic corticosteroid therapy
Biol. Psychiatry
(2008) - et al.
Reduced cortical thickness as an outcome of differential sensitivity to environmental risks in schizophrenia
Biol. Psychiatry
(2011) - et al.
The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma
Biol. Psychiatry
(2008) - et al.
Amygdala circuitry in attentional and representational processes
Trends Cogn. Sci.
(1999) - et al.
Structural and cognitive deficits in remitting and non-remitting recurrent depression: a voxel-based morphometric study
Neuroimage
(2010)
The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition
Brain Cogn.
Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment
Schizophr. Res.
Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis
Schizophr. Res.
Childhood victimization and long-term intellectual and academic outcomes
Child Abuse Negl.
The veridicality of punitive childhood experiences reported by adolescents and young adults
Child. Abuse Negl.
Histories of childhood maltreatment in schizophrenia: relationships with premorbid functioning, symptomatology, and cognitive deficits
Schizophr. Res.
Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis
Psychol. Med.
Functional MRI mapping of category-specific sites associated with naming of famous faces, animals and man-made objects
Neurosci. Bull.
Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity
Br. J. Psychiatry
The childhood experience of care and abuse questionnaire (CECA.Q): validation in a community series
Br. J. Clin. Psychol.
Aging and brain activation with working memory tasks: an fMRI study of connectivity
Int. J. Geriatr. Psychiatry
The amygdala: vigilance and emotion
Mol. Psychiatry
The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study
Brain
Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study
Neuropsychopharmacology
Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment
Arch. Pediatr. Adolesc. Med.
The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder
Psychol. Med.
Reliability and comparability of psychosis patients' retrospective reports of childhood abuse
Schizophr. Bull.
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These authors contributed equally as first author.