Affective Illnesses: Organic Theories

I have written hundreds of articles on schizophrenia, but I am also interested in various affective disorders including bipolar disorder and depression.

The Drug Companies

Very serious allegations have been made against drug companies (1). There are severe ethical issues involved.

Manic-Depressive Illness

There is a very thick academic book by this title. I read the second edition, which was published in 2007 by Oxford Press. the book is by Goodwin & Jamison. Despite the title, the book deals with both bipolar illness and unipolar depression. I found the illustrations very interesting, particularly the ones about brain glucose metabolism, which is low in these diseases. Plate 9 in Chapter 15 (Neuroanatomy and Neuroimaging) caught my attention. It shows a striking localization of the diseases in the subgenual prefrontal cortex. Glucose metabolism was decreased in bipolar and unipolar "familial" depressives. Other parts of the brain did not show much of a decrease.

This data is very similar to results for schizophrenia in terms of reduced brain glucose metabolism.

Also reported in this book are "frontotemporoparietal white matter deficits in schizophrenia and bipolar disorder patients compared with controls". These are shown in Plate 10 in the same chapter.

Depression

There are any types of affective disorders (2, 3). there are also many different theories (4, 5). The serotonin theory has been popular, but it has been challenged. Unfortunately psychiatric drugs are thought to cause birth defects if taken by a pregant Mother (6).

Interferon

Unfortunately the drug interferon can produce depression as a side effect (7, 8).

Antidepressants

"Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance."

Irving Kirsch,1* Brett J Deacon,2 Tania B Huedo-Medina,3 Alan Scoboria,4 Thomas J Moore,5 and Blair T Johnson3

1 Department of Psychology, University of Hull, Hull, United Kingdom

2 University of Wyoming, Laramie, Wyoming, United States of America

3 Center for Health, Intervention, and Prevention, University of Connecticut, Storrs, Connecticut, United States of America

4 Department of Psychology, University of Windsor, Windsor, Ontario, Canada

5 Institute for Safe Medication Practices, Huntingdon Valley, Pennsylvania, United States of America

Phillipa Hay, Academic Editor

University of Western Sydney, Australia

This quote is from Ref. 9, which is an open-access article. This means that it can be quoted as long as the citation is given. This article is available free full text on the Internet at Pubmed Central.

Tryptophan Metabolism

Ref. 10 has implicated tryptophan in depression. This is related to Refs. 7 & 8 because interferon is a cytokine.

"In addition to correlative data linking inflammatory markers with depressive symptoms, several lines of evidence demonstrate that both acute and chronic administration of cytokines (or cytokine inducers such as lipopolysaccharide [LPS] or vaccination) can cause behavioral symptoms that overlap with those found in major depression."

Andrew H. Miller, Vladimir Maletic, and Charles L. Raison

Department of Psychiatry and Behavioral Sciences (AHM, CLR), Emory University School of Medicine, Atlanta, Georgia; and Department of Neuropsychiatry and Behavioral Sciences (VM), University of South Carolina School of Medicine, Columbia, South Carolina

The above quote is from Ref. 10.

"There is a rich animal literature demonstrating that administration of cytokines or cytokine inducers can profoundly affect the metabolism of serotonin, norepinephrine, and dopamine (DA)." Ref. 10

More information is given in Refs. 11-14 including treatments.

Conclusions

Monoamine theories of depression are very strong (15). Sorting out the wheat from the chaff is difficult, though. False theories are a dime a dozen. However, there is a strong link to tryptophan metabolism (16, 17).

The academic references I have given are tedious to read. Ref. 18, which is about psychosocial treatment, is much easier to digest. Ref. 19 is about schizophrenia, which has similarities to depression.

References

1. http://libertynewsradio.com/wire/news/2009/09/00228_Merck_employees_had_hit_list_of_doctors_they_sought_to_neutralize_court_documents_reveal_opinion_092025.php

2. Cox JL, Murray D, Chapman G. A controlled study of the onset, duration and prevalence of postnatal depression. Br J Psychiatry 1993;163:27-31.

3. Brandes M, Soares CN, Cohen LS. Postpartum onset obsessive-compulsive disorder: diagnosis and management. Arch Womens Ment Health 2004;7:99-110.

4. Meltzer HY. Role of serotonin in depression. [discussion 499-500]. Ann N Y Acad Sci 1990;600:486-99.

5. Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 1994;40: 288-95.

6. Wogelius P, Norgaard M, Gislum M, et al. Maternal use of selective serotonin reuptake inhibitors and risk of congenital malformations. Epidemiology 2006;17:701-4.

7. Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001;344:961-966.

8. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58:445-452.

9. Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. Irving Kirsch, Brett J Deacon, Tania B Huedo-Medina, Alan Scoboria, Thomas J Moore, and Blair T JohnsonPLoS Med. 2008 February; 5(2): e45. Published online 2008 February 26.

10. Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Andrew H. Miller, Vladimir Maletic, and Charles L. Raison. Biol Psychiatry. Author manuscript; available in PMC 2009 June 1.

11. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: Inflammation and the pathogenesis of major depression. Trend Immunol. 2006;27:24-31.

12. Motivala SJ, Sarfatti A, Olmos L, Irwin MR. Inflammatory markers and sleep disturbance in major depression. Psychosom Med. 2005;67:187-194.

13. Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: Results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006;11:680-684.

14. Godbout JP, Berg BM, Krzyszton C, Johnson RW. Alpha-tocopherol attenuates NFkappaB activation and pro-inflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior. J Neuroimmunol. 2005;169:97-105.

15. Raison CL, Borisov AS, Majer M, Drake DF, Pagnoni G, Woolwine BJ, et al. Activation of central nervous system inflammatory pathways by interferon-alpha: Relationship to monoamines and depression. Biol Psychiatry. 2008 [published online ahead of print September 16].

16. O'Connor JC, Lawson MA, Andre C, Moreau M, Lestage J, Castanon N, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 2008 [published online ahead of print January 15].

17. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon-alpha-induced changes in tryptophan metabolism: Relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54:906-914.

18. http://www.associatedcontent.com/article/141020/the_fountain_house_standards_are_they.html

19. www.associatedcontent.com/article/2215925/the_glutamateglutamine_theory_for_schizophrenia.html