Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex

The dynorphin system has been associated with the regulation of mood. The expression of the prodynorphin mRNA was currently studied in the amygdaloid complex, a brain region critical for emotional processing, in subjects (14–15 per group) diagnosed with major depression, bipolar disorder, or schizophrenia and compared to normal controls. In situ hybridization histochemistry was used to characterize the anatomical distribution and expression levels of the prodynorphin mRNA within the amygdaloid complex. High prodynorphin mRNA levels were expressed in the parvicellular division of the accessory basal, posterior cortical, periamygdaloid cortex, and amygdalohippocampal area in normal subjects. Individuals with major depression had significantly reduced (41–68%) expression of the prodynorphin mRNA in the accessory basal (both parvicellular and magnocellular divisions; P 0.01) and amygdalohippocampal area (P 0.001) as compared to controls. The bipolar disorder group also showed a significant reduction (37–38%, P 0.01) of the mRNA expression levels in the amygdalohippocampal area and in the parvicellular division of the accessory basal. No other amygdala nuclei studied showed any significant differences for the prodynorphin mRNA levels measured in the major depression and bipolar disorder subjects. Additionally, the prodynorphin mRNA expression levels did not differ significantly between the schizophrenic and normal control subjects in any of the amygdala areas examined. These findings indicate specific prodynorphin amygdala impairment in association with mood disorder. Molecular Psychiatry (2002) 7, 75–81. DOI: 10.1038/ sj/mp/4000930

[1]  E. Azmitia,et al.  The primate serotonergic system: a review of human and animal studies and a report on Macaca fascicularis. , 1986, Advances in neurology.

[2]  S. Rauch,et al.  Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge , 1998, The Journal of Neuroscience.

[3]  L. Lemieux,et al.  Increased amygdala volumes in female and depressed humans. A quantitative magnetic resonance imaging study , 2000, Neuroscience Letters.

[4]  Y. Hurd,et al.  Differential messenger RNA expression of prodynorphin and proenkephalin in the human brain , 1996, Neuroscience.

[5]  D. Terrian,et al.  U-50,488H inhibits dynorphin and glutamate release from guinea pig hippocampal mossy fiber terminals , 1991, Brain Research.

[6]  T. Miyata,et al.  Isolation and structural organization of the human preproenkephalin B gene , 1982, Nature.

[7]  J John Mann,et al.  Role of the Serotonergic System in the Pathogenesis of Major Depression and Suicidal Behavior , 1999, Neuropsychopharmacology.

[8]  R. Adolphs,et al.  The human amygdala in social judgment , 1998, Nature.

[9]  H. Meltzer Role of Serotonin in Depression a , 1990, Annals of the New York Academy of Sciences.

[10]  J. Kleinman,et al.  Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects , 1997, Molecular Psychiatry.

[11]  R. Yolken,et al.  The Stanley Foundation brain collection and Neuropathology Consortium , 2000, Schizophrenia Research.

[12]  Yvette I. Sheline,et al.  Amygdala core nuclei volumes are decreased in recurrent major depression , 1998, Neuroreport.

[13]  P. Skolnick,et al.  Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments. , 1994, The Journal of pharmacology and experimental therapeutics.

[14]  E. Stern,et al.  Linguistic threat activates the human amygdala. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Adolphs,et al.  Fear and the human amygdala , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  D. Price,et al.  Opioid precursor gene expression in the human hypothalamus , 1995, The Journal of comparative neurology.

[17]  T. Robbins,et al.  Amygdala-ventral striatal interactions and reward-related processes. , 1992 .

[18]  E. Mori,et al.  Amygdalar volume and emotional memory in Alzheimer's disease. , 1999, The American journal of psychiatry.

[19]  R. Webber,et al.  Lower CSF level of dynorphin(1–8) immunoreactivity in schizophrenic patients , 1985, Neuropeptides.

[20]  John H Krystal,et al.  Antidepressant effects of ketamine in depressed patients , 2000, Biological Psychiatry.

[21]  J. D. McGaugh,et al.  Localization in the amygdala of the amnestic action of diazepam on emotional memory , 1993, Behavioural Brain Research.

[22]  Joseph E LeDoux Emotion circuits in the brain. , 2009, Annual review of neuroscience.

[23]  P. Skolnick,et al.  Adaptation of the NMDA receptor in rat cortex following chronic electroconvulsive shock or imipramine. , 1993, European journal of pharmacology.

[24]  H. Soininen,et al.  Distribution of parvalbumin‐immunoreactive cells and fibers in the human amygdaloid complex , 1995, The Journal of comparative neurology.

[25]  P. Skolnick,et al.  Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. , 1990, European journal of pharmacology.

[26]  B. Morris,et al.  Regulation of striatal prodynorphin mRNA levels by the raphe-striatal pathway. , 1988, Brain research.

[27]  C. Gambarana,et al.  Dizocilpine antagonizes the effect of chronic imipramine on learned helplessness in rats , 1993, Pharmacology Biochemistry and Behavior.

[28]  E. Lauterbach The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction , 1993 .

[29]  Michael Davis,et al.  Neurotransmission in the rat amygdala related to fear and anxiety , 1994, Trends in Neurosciences.

[30]  L. Goldstein The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction , 1992, The Yale Journal of Biology and Medicine.

[31]  M. Åsberg,et al.  Biological Correlates of Suicidal Behavior , 1984 .

[32]  H. Emrich,et al.  Psychotomimesis mediated by kappa opiate receptors , 1986, Science.

[33]  M. Åsberg,et al.  CSF 5-HIAA predicts suicide risk after attempted suicide. , 1994, Suicide & life-threatening behavior.

[34]  R. Dolan,et al.  Conscious and unconscious emotional learning in the human amygdala , 1998, Nature.

[35]  A. Chiba,et al.  The amygdala and emotion , 1996, Current Opinion in Neurobiology.

[36]  S. Strakowski,et al.  Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. , 1999, Archives of general psychiatry.

[37]  R. Rimón,et al.  Dynorphin A and substance P in the cerebrospinal fluid of schizophrenic patients , 1990, Psychiatry Research.

[38]  R. Whelpton,et al.  Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex—a possible mechanism of neuroprotection in major depression? , 2000, Neuroscience.

[39]  C. Chavkin,et al.  Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus , 1993, Nature.

[40]  T. Chase,et al.  Dynorphin agonist therapy of Parkinson's disease. , 1993, Clinical neuropharmacology.

[41]  Jerome Engel,et al.  The Temporal Lobe and Limbic System , 1998 .