Amygdala response to self-critical stimuli and symptom improvement in psychotherapy for depression.
BACKGROUND
Cognitive-behavioural therapy is efficacious in the treatment of major depressive disorder but response rates are still far from satisfactory.


OBJECTIVE
To better understand brain responses to individualised emotional stimuli and their association with outcome, to enhance treatment.


METHODS
Functional magnetic resonance imaging data were collected prior to individual psychotherapy. Differences in brain activity during passive viewing of individualised self-critical material in 23 unmedicated out-patients with depression and 28 healthy controls were assessed. The associations between brain activity, cognitive and emotional change, and outcome were analysed in 21 patients.


RESULTS
Patients showed enhanced activity in the amygdala and ventral striatum compared with the control group. Non-response to therapy was associated with enhanced activity in the right amygdala compared with those who responded, and activity in this region was negatively associated with outcome. Emotional but not cognitive changes mediated this association.


CONCLUSIONS
Amygdala hyperactivity may lessen symptom improvement in psychotherapy for depression through attenuating emotional skill acquisition.
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland nadja.
Nadja
N
Doerig
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Tobias
T
Krieger
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
David
D
Altenstein
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Yolanda
Y
Schlumpf
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Simona
S
Spinelli
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Jakub
J
Späti
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Janis
J
Brakowski
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Boris B
BB
Quednow
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Erich
E
Seifritz
Nadja Doerig, PhD, Neuroscience Centre, University and ETH Zurich, and Department of Psychology, University of Zurich; Tobias Krieger, PhD, Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, and Department of Psychology, University of Zurich; David Altenstein, PhD, Department of Psychology, University of Zurich; Yolanda Schlumpf, PhD, Division of Neuropsychology, Department of Psychology, University of Zurich; Simona Spinelli, PhD, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, Zurich Centre for Integrative Human Physiology, University of Zurich, Switzerland; Jakub Späti, PhD, Department of Psychophysiology, National Institute of Mental Health, National Centre of Neurology and Psychiatry, Tokyo, Japan, and Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Janis Brakowski, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; Boris B. Quednow, PhD, Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Erich Seifritz, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Neuroscience Centre, University and ETH Zurich, and Zurich Centre for Integrative Human Physiology, University of Zurich; Martin grosse Holtforth, PhD, Department of Psychology, University of Zurich, and Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Bern, Switzerland.
Martin Grosse
MG
Holtforth
D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000628:therapy*; D004644:Emotions; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011613:Psychotherapy / Q000379:methods*; D012044:Regression Analysis; D012647:Self-Assessment; D055815:Young Adult