Relationship between amygdala volume and emotion recognition in adolescents at ultra-high risk for psychosis

https://doi.org/10.1016/j.pscychresns.2014.10.005Get rights and content

Highlights

  • The study explored whether amygdala volumes were related to emotion-recognition impairments in individuals at ultra-high risk (UHR) for psychosis, and whether volumes differed by sex.

  • The amygdala was manually delineated from magnetic resonance images for 39 UHR individuals who had also completed facial and prosody emotion-recognition tasks.

  • Amygdala volume was positively correlated with sadness emotion recognition, in particular prosody, for females only.

  • Left amygdala volume mediated the effect of sadness recognition on depressive symptoms, negative symptoms, overall psychopathology, and global functioning in females.

  • Further research is needed to determine illness specificity and to confirm the reported sex- and emotion-specific results.

Abstract

Amygdala volume has been proposed as a neural risk biomarker for psychotic illness, but findings in the ultra-high risk for psychosis (UHR) population have been somewhat inconsistent, which may be related to underlying social cognitive abilities. The current study investigated whether amygdala volumes were related to emotion-recognition impairments in UHR individuals, and whether volumes differed by sex. Secondary aims were to assess whether (a) emotion-recognition performance was associated with interhemispheric amygdala volume asymmetry and (b) amgydala volume and volume asymmetry acted as a mediator between emotion-recognition and outcome measures. The amygdala was manually delineated from magnetic resonance images for 39 UHR individuals who had also completed facial and prosody emotion-recognition tasks. Partial correlations were conducted to examine associations between amydgala volume/asymmetry and recognition of negative emotions. Mediation analyses were conducted using regression and bootstrapping techniques. Amygdala volume was positively correlated with sadness emotion recognition, in particular prosody, for females only. Left amygdala volume mediated the effect of sadness recognition on depressive symptoms, negative symptoms, overall psychopathology, and global functioning in females. Findings suggest a complex relationship between emotion recognition, the structure of the amygdala and illness outcome, where recognition of sadness appears to be the precipitator of this relationship in UHR females. Further research is needed to determine illness specificity and to confirm our sex- and emotion-specific results.

Introduction

The amygdala is essential for emotion recognition (ER; Adolphs, 2001) and is most prominently linked to negatively valenced emotions, namely sadness, anger and fear (Adolphs et al., 1999, Adolphs and Tranel, 2004). Reduced amygdala volumes are generally found to be associated with poorer ER (Adolphs and Tranel, 2004, Nacewicz et al., 2006). There is solid evidence of impaired ER, particularly for negative emotions, in established schizophrenia (Edwards et al., 2002, Hoekert et al., 2007, Chan et al., 2010) and first episode psychosis (FEP; Edwards et al., 2001, Thompson et al., 2012), and there is also emerging evidence in individuals at ultra-high risk (UHR) of psychosis (Thompson et al., 2011, Amminger et al., 2012a, Amminger et al., 2012b, Green et al., 2012, Thompson et al., 2012). Given these findings, researchers have begun to investigate the structure of the amygdala as a possible neural risk biomarker for psychotic illness (e.g., van Winkel et al., 2013).

The UHR approach identifies a unique ‘clinical’ help-seeking population composed of individuals who are at increased risk of developing psychosis (approximately 17% will transition to a psychotic disorder within an average of 22 months) (Wiltink et al., 2013). The UHR age range is typically 14–30 years, the life period with the highest risk for psychosis onset. Findings of the limited number of studies that have investigated amygdala volumes in UHR patients have been inconclusive, with some studies suggesting amygdala volumes are normal in this population (Velakoulis et al., 2006, Witthaus et al., 2010), and others finding decreases bilaterally (Bechdolf et al., 2012). A number of factors could account for the inconsistent findings, including individual differences in ER impairment within samples, which may bias group findings one way or another. However, no study to date has investigated the relationship between amygdala structure and ER ability in UHR individuals. Only one published study has investigated this relationship in schizophrenia, and it found that smaller left amygdala volumes were associated with deficits in facial recognition of sadness (Namiki et al., 2007). If such a relationship were found in UHR individuals, it would provide the first evidence for putative premorbid structural abnormalities that correspond to difficulties in recognising specific emotions, and would support the suggestion that the amygdala has a potential role in the development of psychotic disorders.

Sex differences in ER are well established in the healthy population, with females being consistently more accurate than males in processing and interpreting facial expressions (e.g., McClure, 2000, Williams et al., 2009). A recent meta-analysis concluded that females have increased activation, particularly in the left amygdala, in relation to negative emotion processing in comparison to males (Stevens and Hamann, 2012). This is in line with the previously reported sex-dependent lateralization of amygdala involvement in emotional memory (Cahill et al., 2001). Interestingly, several studies have found female schizophrenia patients to outperform their male counterparts on emotion-recognition tasks (Scholten et al., 2005, Van׳t Wout et al., 2007, Erol et al., 2013), but the limited ER research in UHR has not yet specifically explored the effects of sex. Given these findings, and evidence of sex-specific amygdala volume abnormalities in first episode psychosis (Frazier et al., 2008) and established schizophrenia (Gur et al., 2004, Niu et al., 2004), the current study will explore associations in each sex, separately. In addition, a reduction in the normal pattern of brain regional asymmetries has been noted in psychotic disorders (e.g. Yucel et al., 2002). Also, amygdala asymmetry has been found to be sex-dependent in patients with first episode psychosis, whereby only females have been shown to have a higher degree of asymmetry compared with healthy controls (Gibbs et al., 2008). Therefore, we will also explore the association between amygdala asymmetry and ER performance for males and females.

The primary aim of the present study was to investigate the possible relationship between recognition of negatively valenced emotions (sadness, anger, fear) and amygdala volumes in male and female UHR individuals. It was hypothesised that smaller amygdala volumes would be associated with larger ER deficits for both facial and prosodic emotion, and that this would be more pronounced in females. Secondary aims were to (a) examine whether ER was associated with interhemispheric amygdalae volume asymmetry and (b) explore the relationship between amygdala volume and symptomatology/functioning, and, where significant correlations are found, the potential mediating role of amygdala volume between ER and these illness dimensions.

Section snippets

Participants

UHR participants were recruited from the Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria, for a larger randomised controlled study, described previously (Amminger et al., 2010). Of the 81 participants recruited for this larger study, a subsample of 43 underwent magnetic resonance imaging (MRI) and behavioural assessment as part of the current study׳s protocol. Of these participants, three were excluded from analyses due to movement artefacts/poor image

Demographic characteristics and emotion recognition

Table 1 shows details of demographic data. The sample comprised 14 males and 25 females, who generally displayed mild levels of positive and negative symptoms and moderate levels of general symptoms. The sample overall was mildly to moderately impaired in global functioning. There was a significant sex difference in age (p=0.018), where on average the males were older than the females. There were no other differences between males and females other than for the measure of ICA (p=0.005). ER data

Discussion

This is the first study to investigate the association between amygdala volume and ER in UHR individuals. Left amygdala volume showed a significant positive correlation with prosody sadness recognition in females only. Secondary analyses revealed that (a) greater asymmetry, where the left amygdala volume was incrementally larger than the right, was significantly correlated with better recognition of sadness in voices, and fear in faces, for males only; and (b) larger left amygdala volumes in

Acknowledgements

This work was supported by the Stanley Medical Research Institute (03T-315 to G.P.A.), two National Health and Medical Research Council (NHMRC) of Australia Australian-based Clinical Research Fellowships (567042 to C.B., 628884 to K.A.), a NHMRC Career Development Fellowship (1007716 to S.L.W.), aNHMRC Senior Principal Research Fellowship (628386 to C.P.), a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Award(C.P.), and a NHMRC Grant (566529) to G.P.A. Neuroimaging

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