Learning as a model for neural plasticity in major depression.
BACKGROUND
The neuroplasticity hypothesis of depression proposes that a dysfunction of neural plasticity-the basic ability of living organisms to adapt their neural function and structure to external and internal cues-might represent a final common pathway underlying the biological and clinical characteristics of the disorder. This study examined learning and memory as correlates of long-term synaptic plasticity in humans to further test the neuroplasticity hypothesis of depression.


METHODS
Learning in three tasks, for which memory consolidation has been shown to depend on local synaptic refinement in areas of interest (hippocampus-dependent declarative word-pair learning, amygdala-dependent fear conditioning, and primary-cortex-dependent visual texture discrimination), was assessed in 23 inpatients who met International Classification of Disease, 10th Revision, criteria for severe unipolar depression and 35 nondepressed comparison subjects.


RESULTS
Depressed subjects showed a significant deficit in declarative memory consolidation and enhanced fear acquisition as indicated by skin conductance responses to conditioned stimuli, in comparison with nondepressed subjects. Depressed subjects demonstrated impaired visual discrimination at baseline, not allowing for valid group comparisons of gradual improvement, the plasticity-dependent phase of the task.


CONCLUSIONS
The results of the study are consistent with the neuroplasticity hypothesis of depression, showing decreased synaptic plasticity in a dorsal executive network that comprises the hippocampus and elevated synaptic plasticity in a ventral emotional network that includes the amygdala in depression. Evaluation of further techniques aimed at modulating synaptic plasticity might prove useful for developing novel treatments for major depressive disorder.
Nissen
Christoph
C
Department of Psychiatry, University Medical Center Freiburg, Germany. christoph.nissen@uniklinikfreiburg.de
Holz
Johannes
J
Blechert
Jens
J
Feige
Bernd
B
Riemann
Dieter
D
Voderholzer
Ulrich
U
Normann
Claus
C
D000328:Adult; D003865:Major Depressive Disorder / Q000523:psychology*; D004192:Discrimination, Psychological; D005239:Fear; D005260:Female; D006801:Humans; D007858:Learning; D008297:Male; D008568:Memory; D008875:Middle Aged; D008960:Models, Psychological; D009473:Neuronal Plasticity; D011597:Psychomotor Performance