E. Sherwood Brown

Association of depression with medical illness: Does cortisol play a role?

Elevated cortisol in a subset of depressed patients is an enduring and well-replicated finding. Much interest has focused on the possible effects of depression on the hippocampus; however, an emerging body of evidence suggests an association between depression and non-central nervous system illnesses. In this review, data on the effects of depression on the brain and other organ systems sensitive to elevated cortisol are discussed. From searches of the MEDLINE, PSYCHINFO, and Current Contents databases, and other sources, articles were found specifically related to depression and physical changes or medical conditions associated with corticosteroid excess in patients with Cushings disease, including cognitive impairment, hippocampal atrophy, increased waist-to-hip ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density. Some evidence suggests an association between depression and hypertension, peptic ulcers, and diabetes. Depression does not appear to be associated with hyperlipidemia. The data provide some support for similar health effects in depressed patients and patients with Cushings disease or the metabolic syndrome; however, additional studies are needed relating systemic effects of depression to cortisol. Limitations of the current literature, treatment implications, and possible directions for future research are discussed.

Hippocampal remodeling and damage by corticosteroids : Implications for mood disorders

Mood disorders are common, recurrent and disabling illnesses which are frequently associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and memory loss. The hippocampus provides negative feedback to the HPA axis and has an important role in key aspects of spatial and declarative memory. Thus, hippocampal dysfunction could account for both the memory impairment and neuroendocrine abnormalities found in mood disorders. The critical role of the hippocampus in declarative memory, emotional processing, and vulnerability to stress has been demonstrated in both animal and human studies. Cellular processes in the hippocampus including long-term potentiation, neurogenesis, and dendritic remodeling are currently areas of intense study. Human studies report cognitive impairment consistent with hippocampal dysfunction in depression, bipolar disorder, Cushings disease, and in those individuals receiving exogenous corticosteroids. This review examines data on the role of corticosteroids in hippocampal remodeling and atrophy in patients with mood disorders. Interventions to prevent or reverse the damaging effects of corticosteroids on the hippocampus are discussed.

Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy

BACKGROUND Hippocampal volume reduction, declarative memory deficits, and cortisol elevations are reported in persons with major depressive disorder; however, data linking cortisol elevations with hippocampal atrophy are lacking. Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans. METHODS Seventeen patients on long-term prescription corticosteroid therapy and 15 controls of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging and proton magnetic resonance spectroscopy, the Rey Auditory Verbal Learning Test, Stroop Color Word Test and other neurocognitive measures, the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS Compared with controls, corticosteroid-treated patients had smaller hippocampal volumes and lower N-acetyl aspartate ratios, lower scores on the Rey Auditory Verbal Learning Test and Stroop Color Word Test, and higher Hamilton Rating Scale for Depression and Brief Psychiatric Rating Scale scores. CONCLUSIONS Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes, lower N-acetyl aspartate ratios, and declarative memory deficits compared with controls. These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans.

Effects of Glucocorticoids on Mood, Memory, and the Hippocampus: Treatment and Preventive Therapy

Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long‐term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long‐term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti‐seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid‐induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment.

Mood Symptoms during Corticosteroid Therapy: A Review

&NA; Corticosteroids such as prednisone are commonly prescribed for a variety of illnesses mediated by the immune system. This paper reviews the available literature on mood symptoms during corticosteroid treatment. Few studies have used well‐recognized measures of symptoms or clearly defined diagnostic criteria to characterize such mood changes. The limited data available suggest that symptoms of hypomania, mania, depression, and psychosis are common during therapy. Symptoms appear to be dose dependent and generally begin during the first few weeks of treatment. Risk factors for the development of mood instability or psychosis are not known. The similarities of the psychiatric symptoms resulting from corticosteroid treatment to the symptoms of bipolar disorder are discussed.

Drug abuse and bipolar disorder: comorbidity or misdiagnosis?

Bipolar disorder is a common, severe and cyclic psychiatric illness. A strong association between alcohol dependence and bipolar disorder has been reported in numerous studies. The abuse of other drugs including cocaine, amphetamines, opiates, cannabis, and prescription medications in bipolar patients is also an important public health concern and has been less extensively investigated. This review examines the abuse of drugs other than alcohol or nicotine in people with bipolar disorder. The high rates of milder affective symptoms but not mania observed in patients in drug abuse treatment settings suggests the symptoms may in many cases be associated with the drug use. However, such patients presenting in psychiatric settings might be suffering from cyclothymic and related attenuated bipolar disorders (type II). Substance abuse may be associated with medication non-compliance, more mixed or dysphoric mania and possibly an earlier onset of affective symptoms and more hospitalizations. The pharmacotherapy of patients with bipolar disorder and drug abuse is examined, including evidence on the use of mood stabilizers, neuroleptics and the newer atypical antipsychotics in this population.

The psychiatric side effects of corticosteroids

LEARNING OBJECTIVES Readers will learn the importance of psychiatric symptomatology with corticosteroid drug therapy, especially when combined with other medications. DATA SOURCES A brief history of corticosteroid use over the last five decades was complied utilizing MEDLINE and PSYCHOINFO as sources of information which include peer-reviewed research articles, case studies, and relevant reviews in English. CONCLUSION Corticosteroids are routinely prescribed for a variety of allergic and immunologic illnesses. Psychiatric side effects from corticosteroids include mania, depression and mood disturbances. Psychiatric symptoms usually occur within the first two weeks of corticosteroid therapy and seem to be dose related. Treatment with lithium or antipsychotics may be helpful. Physicians should carefully monitor patients for psychiatric and cognitive side effects of corticosteroid use.

Mood changes during prednisone bursts in outpatients with asthma

Corticosteroids, such as prednisone and dexamethasone, are frequently prescribed medications sometimes associated with severe systemic side effects. Currently there are limited data regarding the psychiatric side effects of these medications, although mood changes and even psychoses have been reported. This study was designed to quantify psychiatric changes during brief courses of prednisone in patients with asthma. Outpatients with asthma (N = 32) receiving bursts of prednisone (>40 mg/day) were evaluated before, during, and after corticosteroid therapy by use of the Hamilton Rating Scale for Depression, the Young Mania Scale, the Brief Psychiatric Rating Scale, and the Internal State Scale. A Structured Clinical Interview for DSM-IV disorders was also conducted to examine past psychiatric history. Highly significant increases in the Young Mania Scale and Activation subscale of the Internal State Scale (both measures of mania) were observed with no increase in depression measures during the first 3 to 7 days of prednisone therapy. Mood changes were not correlated with improvement in airway obstruction, suggesting that mood elevations may not be in response to improvement in asthma symptoms. Subjects with past or current symptoms of depression had a significant decrease in depressive symptoms during prednisone therapy compared with those without depression. Some patients with posttraumatic stress disorder reported increases in depression and memories of the traumatic event during prednisone therapy. In summary, statistically significant changes in mood were observed even during brief courses of corticosteroids at modest dosages. The symptoms were primarily manic, not depressive. Persons with depression did not become more depressed during prednisone therapy, and, in fact, some showed improvement.

Association Between Low Serum 25-Hydroxyvitamin D and Depression in a Large Sample of Healthy Adults: The Cooper Center Longitudinal Study

OBJECTIVE To investigate the association between serum vitamin D levels and depression in a large database of patients from the Cooper Clinic. PATIENTS AND METHODS We conducted a cross-sectional study of 12,594 participants seen at the Cooper Clinic from November 27, 2006, to October 4, 2010. Serum 25-hydroxyvitamin D [25(OH)D] was analyzed, and depression was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score of 10 or more. Those with and those without a history of depression represented 2 distinct populations with respect to CES-D scores; accordingly, they were analyzed separately. RESULTS In the total sample, higher vitamin D levels were associated with a significantly decreased risk [odds ratio, 0.92 (95% confidence interval, 0.87-0.97)] of current depression based on CES-D scores. The finding was stronger in those with a prior history of depression [odds ratio, 0.90 (95% confidence interval, 0.82-0.98)] and not significant in those without a history of depression [odds ratio, 0.95 (95% confidence interval, 0.89-1.02)]. CONCLUSION We found that low vitamin D levels are associated with depressive symptoms, especially in persons with a history of depression. These findings suggest that primary care patients with a history of depression may be an important target for assessment of vitamin D levels.

Psychiatric Diagnoses in Inner City Outpatients with Moderate to Severe Asthma

Objective: Psychiatric symptoms may be associated with increased asthma morbidity and mortality. However, no investigations have identified syndromal psychiatric diagnoses in asthma patients using current diagnostic criteria or examined treatment received for mental illness. Method: We conducted structured clinical interviews on 32 patients with moderate to severe asthma to identify current and past psychiatric illness. Results: Twenty-five percent of subjects had current major depressive disorder, but only 25 percent of these received antidepressants. Anxiety disorders, including panic disorder (16 percent), and social (13 percent) and specific phobias (28 percent) were also common. All subjects with panic disorder were receiving appropriate therapy. Conclusions: Asthma patients with moderate to severe asthma treated at community health facilities may have high rates of often untreated mood and anxiety disorders. Interventions aimed at identifying and treating psychiatric disorders in this population are needed.