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Letters to the Editor   |    
Acute Clinical Deterioration With Increased Systemic Inflammation as a Risk Factor for Depression: An Alternative Interpretation of the Data
G. Umberto Meduri, M.D.; Mei-Chiung Shih, Ph.D.
Am J Psychiatry 2012;169:867-867. doi:10.1176/appi.ajp.2012.12040498
View Author and Article Information
Memphis
Palo Alto, Calif.

The authors report no financial relationships with commercial interests.

Accepted for publication in May 2012.

Copyright © American Psychiatric Association

Accepted May , 2012.

To the Editor: We read with interest the article by Fardet et al. in the May issue of the Journal (1) and wish to raise concerns with the authors' interpretation that glucocorticoid treatment is associated with higher risk for depression and severe neuropsychiatric disorders.

First, some of the definitions used in the study were vague, and symptoms such as “low mood” were used to identify depression. Psychiatric referral, a more precise marker of neuropsychiatric problems, was similar between the exposed and unexposed groups.

Second, the authors reported a “high incidence of neuropsychiatric adverse events in the first 3 months of glucocorticoid treatment.” Most patients received glucocorticoid treatment for acute exacerbation of obstructive lung disease (asthma or chronic obstructive pulmonary disease) or for lower respiratory tract infection. For these conditions, the duration of glucocorticoid treatment is usually less than 14 days. While neuropsychiatric adverse events may occur during treatment, the time to event extended to 3 months. The lack of a clear temporal association is a major limitation of this study since the event could occur from 2 to 10 weeks after the termination of treatment.

Lastly, depression was the most frequently reported neuropsychiatric adverse event reported in this study. The authors failed to address the known association between the clinical conditions requiring glucocorticoid treatment (24) and depression, as well as the association between systemic inflammation (5) and depression. Glucocorticoid treatment (as well as initial daily dose) is a marker of disease severity associated with increased systemic inflammation. This cause-and-effect relationship was not accounted for in the study, and unexposed patients were not matched by disease severity.

For these reasons, we believe that an alternative interpretation should have been presented that takes into account the association of depression and glucocorticoid treatment with increased severity of underlying clinical condition. The alternative interpretation should clarify that for clinical conditions associated with depression, an acute deterioration—associated with increased systemic inflammation and/or glucocorticoid resistance (6)—may worsen symptoms of depression.

Fardet  L;  Petersen  I;  Nazareth  I:  Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care.  Am J Psychiatry 2012; 169:491–497
[PubMed]
 
van Ede  L;  Yzermans  CJ;  Brouwer  HJ:  Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.  Thorax 1999; 54:688–692
[CrossRef] | [PubMed]
 
Opolski  M;  Wilson  I:  Asthma and depression: a pragmatic review of the literature and recommendations for future research.  Clin Pract Epidemiol Ment Health 2005; 1:18
[CrossRef] | [PubMed]
 
Cohen  MD;  Ginsburg  WW:  Polymyalgia rheumatica.  Rheum Dis Clin North Am 1990; 16:325–339
[PubMed]
 
Dowlati  Y;  Herrmann  N;  Swardfager  W;  Liu  H;  Sham  L;  Reim  EK;  Lanctôt  KL:  A meta-analysis of cytokines in major depression.  Biol Psychiatry 2010; 67:446–457
[CrossRef] | [PubMed]
 
Pace  TW;  Hu  F;  Miller  AH:  Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression.  Brain Behav Immun 2007; 21:9–19
[CrossRef] | [PubMed]
 
References Container
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References

Fardet  L;  Petersen  I;  Nazareth  I:  Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care.  Am J Psychiatry 2012; 169:491–497
[PubMed]
 
van Ede  L;  Yzermans  CJ;  Brouwer  HJ:  Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.  Thorax 1999; 54:688–692
[CrossRef] | [PubMed]
 
Opolski  M;  Wilson  I:  Asthma and depression: a pragmatic review of the literature and recommendations for future research.  Clin Pract Epidemiol Ment Health 2005; 1:18
[CrossRef] | [PubMed]
 
Cohen  MD;  Ginsburg  WW:  Polymyalgia rheumatica.  Rheum Dis Clin North Am 1990; 16:325–339
[PubMed]
 
Dowlati  Y;  Herrmann  N;  Swardfager  W;  Liu  H;  Sham  L;  Reim  EK;  Lanctôt  KL:  A meta-analysis of cytokines in major depression.  Biol Psychiatry 2010; 67:446–457
[CrossRef] | [PubMed]
 
Pace  TW;  Hu  F;  Miller  AH:  Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression.  Brain Behav Immun 2007; 21:9–19
[CrossRef] | [PubMed]
 
References Container
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