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Negative symptoms in schizophrenia show association with amygdala volumes and neural activation during affective processing

Published online by Cambridge University Press:  17 March 2015

Christoffer Rahm ,
Benny Liberg ,
Greg Reckless ,
Olga Ousdal ,
Ingrid Melle ,
Ole A. Andreassen  and
Ingrid Agartz
Christoffer Rahm*
Affiliation:
Department of Medicine, Karolinska Institutet, Stockholm, Sweden Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia
Benny Liberg
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
Greg Reckless
Affiliation:
Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway
Olga Ousdal
Affiliation:
Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway
Ingrid Melle
Affiliation:
Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway
Ole A. Andreassen
Affiliation:
Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway
Ingrid Agartz
Affiliation:
Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway
*
Dr. Christoffer Rahm, Melbourne Neuropsychiatry Centre, National Neuroscience Facility, Level 3, Alan Gilbert Building, 161 Barry St, Carlton, VIV 3053, Australia. Tel: +61 3 9035 8628; Fax: +61 3 9348 0469; E-mail: christoffer.rahm@sll.se
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Abstract

Objectives

Negative symptoms in schizophrenia have been associated with structural and functional alterations of the amygdala. We hypothesised that there would be between-group differences in amygdala volume and neural activation patterns during processing of affective stimuli among patients with schizophrenia and healthy controls. We further hypothesised correlations between neuroimaging metrics and clinical ratings of negative symptoms in patients with schizophrenia.

Methods

We used structural and functional magnetic resonance imaging to assess volume and neural activation of the amygdala in 28 patients with schizophrenia and 28 healthy controls.

Results

We found no between-group differences in amygdala volume or neural activation. However, we found a significant negative correlation between emotional blunting and neural activation in the left amygdala during processing of positive affect. We also found a significant negative correlation between stereotyped thinking and the volume of right amygdala.

Conclusion

Our findings implicate the amygdala in a subgroup of negative symptoms in schizophrenia that are characterised by reduced expression with blunted affect and stereotyped thinking.

Keywords

amygdalafunctional magnetic resonance imagingmagnetic resonance imagingschizophrenia
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 4 , August 2015 , pp. 213 - 220
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1.Earnst, KS, Kring, AM. Construct validity of negative symptoms: an empirical and conceptual review. Clin Psychol Rev 1997;17:167–189.CrossRefGoogle ScholarPubMed
2.Keefe, RS, Harvey, PD, Lenzenweger, MFet al. Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: negative symptoms. Psychiatry Res 1992;44:153–165.CrossRefGoogle ScholarPubMed
3.Milev, P, Ho, BC, Arndt, S, Andreasen, NC. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry 2005;162:495–506.CrossRefGoogle Scholar
4.Bow-Thomas, CC, Velligan, DI, Miller, AL, Olsen, J. Predicting quality of life from symptomatology in schizophrenia at exacerbation and stabilization. Psychiatry Res 1999;86:131–142.CrossRefGoogle ScholarPubMed
5.Murphy, BP, Chung, YC, Park, TW, McGorry, PD. Pharmacological treatment of primary negative symptoms in schizophrenia: a systematic review. Schizophr Res 2006;88:5–25.CrossRefGoogle ScholarPubMed
6.Hovington, CL, Lepage, M. Neurocognition and neuroimaging of persistent negative symptoms of schizophrenia. Expert Rev Neurother 2012;12:53–69.CrossRefGoogle ScholarPubMed
7.Bora, E, Fornito, A, Radua, Jet al. Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophr Res 2011;127:46–57.CrossRefGoogle ScholarPubMed
8.Gur, RE, Turetsky, BI, Cowell, PEet al. Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiatry 2000;57:769–775.CrossRefGoogle ScholarPubMed
9.Koutsouleris, N, Gaser, C, Jager, Met al. Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study. Neuroimage 2008;39:1600–1612.CrossRefGoogle ScholarPubMed
10.Sanfilipo, M, Lafargue, T, Rusinek, Het al. Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms. Arch Gen Psychiatry 2000;57:471–480.CrossRefGoogle ScholarPubMed
11.Wible, CG, Anderson, J, Shenton, MEet al. Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study. Psychiatry Res 2001;108:65–78.CrossRefGoogle ScholarPubMed
12.Wolkin, A, Choi, SJ, Szilagyi, S, Sanfilipo, M, Rotrosen, JP, Lim, KO. Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. Am J Psychiatry 2003;160:572–574.CrossRefGoogle ScholarPubMed
13.Yoshida, T, McCarley, RW, Nakamura, Met al. A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala-hippocampal complex in chronic schizophrenia. Schizophr Res 2009;113:84–94.CrossRefGoogle ScholarPubMed
14.Ousdal, OT, Reckless, GE, Server, A, Andreassen, OA, Jensen, J. Effect of relevance on amygdala activation and association with the ventral striatum. Neuroimage 2012;62:95–101.CrossRefGoogle ScholarPubMed
15.Honea, R, Crow, TJ, Passingham, D, Mackay, CE. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005;162:2233–2245.CrossRefGoogle ScholarPubMed
16.Levitt, JJ, Bobrow, L, Lucia, D, Srinivasan, P. A selective review of volumetric and morphometric imaging in schizophrenia. In: Swerdlow NR, editor. Behavioral neurobiology of schizophrenia and its treatment. Berlin: Springer-Verlag, 2010. pp. 243–282.CrossRefGoogle Scholar
17.Velakoulis, D, Wood, SJ, Wong, MTet al. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Arch Gen Psychiatry 2006;63:139–149.CrossRefGoogle ScholarPubMed
18.Rajarethinam, R, DeQuardo, JR, Miedler, Jet al. Hippocampus and amygdala in schizophrenia: assessment of the relationship of neuroanatomy to psychopathology. Psychiatry Res 2001;108:79–87.CrossRefGoogle ScholarPubMed
19.Aleman, A, Kahn, RS. Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia? Prog Neurobiol 2005;77:283–298.Google ScholarPubMed
20.Rauch, AV, Reker, M, Ohrmann, Pet al. Increased amygdala activation during automatic processing of facial emotion in schizophrenia. Psychiatry Res 2010;182:200–206.CrossRefGoogle ScholarPubMed
21.Fahim, C, Stip, E, Mancini-Marie, Aet al. Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study. Psychiatry Res 2005;140:1–15.CrossRefGoogle ScholarPubMed
22.Gur, RE, Loughead, J, Kohler, CGet al. Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia. Arch Gen Psychiatry 2007;64:1356–1366.CrossRefGoogle ScholarPubMed
23.Lepage, M, Sergerie, K, Benoit, A, Czechowska, Y, Dickie, E, Armony, JL. Emotional face processing and flat affect in schizophrenia: functional and structural neural correlates. Psychol Med 2011;41:1833–1844.CrossRefGoogle ScholarPubMed
24.Hariri, AR, Mattay, VS, Tessitore, Aet al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400–403.CrossRefGoogle ScholarPubMed
25.Spitzer, RL, Williams, JBW, Gibbon, M, First, MB. Structured clinical interview for DSM-III-R- Patient version. New York: Biometrics Research Department, New York State Psychiatric Institute, 1988.Google Scholar
26.Engh, JA, Friis, S, Birkenaes, ABet al. Delusions are associated with poor cognitive insight in schizophrenia. Schizophr Bull 2010;36:830–835.CrossRefGoogle ScholarPubMed
27.Spitzer, RL, Williams, JB, Kroenke, Ket al. Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. JAMA 1994;272:1749–1756.CrossRefGoogle ScholarPubMed
28.Kay, SR, Fiszbein, A, Opler, LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle ScholarPubMed
29.Rush, AJ, Giles, DE, Schlesser, MA, Fulton, CL, Weissenburger, J, Burns, C. The Inventory for Depressive Symptomatology (IDS): preliminary findings. Psychiatry Res 1986;18:65–87.CrossRefGoogle ScholarPubMed
30.Addington, D, Addington, J, Schissel, B. A depression rating scale for schizophrenics. Schizophr Res 1990;3:247–251.CrossRefGoogle ScholarPubMed
31.Ousdal, OT, Anand Brown, A, Jensen, Jet al. Associations between variants near a monoaminergic pathways gene (PHOX2B) and amygdala reactivity: a genome-wide functional imaging study. Twin Res Hum Genet 2012;15:273–285.CrossRefGoogle Scholar
32.Carre, JM, Murphy, KR, Hariri, AR. What lies beneath the face of aggression? Soc Cogn Affect Neurosci 2013;8:224–229.CrossRefGoogle ScholarPubMed
33.Tottenham, N, Tanaka, JW, Leon, ACet al. The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Res 2009;168:242–249.CrossRefGoogle ScholarPubMed
34.Jenkinson, M, Beckmann, CF, Behrens, TE, Woolrich, MW, Smith, SM. Fsl. Neuroimage 2012;62:782–790.CrossRefGoogle ScholarPubMed
35.Jenkinson, M, Smith, S. A global optimisation method for robust affine registration of brain images. Med Image Anal 2001;5:143–156.CrossRefGoogle ScholarPubMed
36.Jenkinson, M, Bannister, P, Brady, M, Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002;17:825–841.CrossRefGoogle ScholarPubMed
37.Smith, SM. Fast robust automated brain extraction. Hum Brain Mapp 2002;17:143–155.CrossRefGoogle ScholarPubMed
38.Woolrich, MW, Ripley, BD, Brady, M, Smith, SM. Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 2001;14:1370–1386.CrossRefGoogle ScholarPubMed
39.Worsley, KJ. Statistical analysis of activation images. In: Jezzard P, Matthews PM, Smith SM, editors. Functional MRI: an introduction to methods (PMMaSMS). Oxford: Oxford University Press, 2001. pp. 251--270.Google Scholar
40.Beckmann, CF, Jenkinson, M, Smith, SM. General multilevel linear modeling for group analysis in FMRI. Neuroimage 2003;20:1052–1063.CrossRefGoogle Scholar
41.Woolrich, M. Robust group analysis using outlier inference. Neuroimage 2008;41:286–301.CrossRefGoogle ScholarPubMed
42.Woolrich, MW, Behrens, TE, Beckmann, CF, Jenkinson, M, Smith, SM. Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage 2004;21:1732–1747.CrossRefGoogle ScholarPubMed
43.Woolrich, MW, Jbabdi, S, Patenaude, Bet al. Bayesian analysis of neuroimaging data in FSL. Neuroimage 2009;45:S173–S186.CrossRefGoogle ScholarPubMed
44.Scherk, H, Falkai, P. Effects of antipsychotics on brain structure. Curr Opin Psychiatry 2006;19:145–150.CrossRefGoogle ScholarPubMed
45.Patenaude, B, Smith, SM, Kennedy, DN, Jenkinson, M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 2011;56:907–922.CrossRefGoogle ScholarPubMed
46.Whalen, PJ. The uncertainty of it all. Trends Cogn Sci 2007;11:499–500.CrossRefGoogle Scholar
47.Kubicki, M, Shenton, ME, Salisbury, DFet al. Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 2002;17:1711–1719.CrossRefGoogle ScholarPubMed
48.Salgado-Pineda, P, Baeza, I, Perez-Gomez, Met al. Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients. Neuroimage 2003;19:365–375.CrossRefGoogle ScholarPubMed
49.Malchow, B, Hasan, A, Schneider-Axmann, Tet al. Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci 2013;263(Suppl. 2):S155–S168.CrossRefGoogle ScholarPubMed
50.Phelps, EA, LeDoux, JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005;48:175–187.CrossRefGoogle ScholarPubMed
51.Schaefer, A, Gray, JR. A role for the human amygdala in higher cognition. Rev Neurosci 2007;18:355–363.CrossRefGoogle ScholarPubMed
52.Ousdal, OT, Jensen, J, Server, A, Hariri, AR, Nakstad, PH, Andreassen, OA. The human amygdala is involved in general behavioral relevance detection: evidence from an event-related functional magnetic resonance imaging Go-NoGo task. Neuroscience 2008;156:450–455.CrossRefGoogle ScholarPubMed
53.Stevenson, RA, Mikels, JA, James, TW. Characterization of the affective norms for English words by discrete emotional categories. Behav Res Methods 2007;39:1020–1024.CrossRefGoogle ScholarPubMed
54.Birn, RM, Cox, RW, Bandettini, PA. Detection versus estimation in event-related fMRI: choosing the optimal stimulus timing. Neuroimage 2002;15:252–264.CrossRefGoogle ScholarPubMed
55.Schafer, A, Schienle, A, Vaitl, D. Stimulus type and design influence hemodynamic responses towards visual disgust and fear elicitors. Int J Psychophysiol 2005;57:53–59.CrossRefGoogle ScholarPubMed