No abstract

No abstract

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, Cushing's 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.

Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient's experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.

BACKGROUND: Physicians in the United States write approximately 10 million new prescriptions for oral corticosteroids each year. Common side effects of corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This article reviews the available literature on psychiatric and cognitive changes during corticosteroid therapy. METHOD: A search of the MEDLINE and psycINFO databases was conducted to find clinically relevant articles on psychiatric and cognitive side effects with corticosteroids using search terms including corticosteroid, prednisone, mania, depression, psychosis, mood, memory, and cognition. RESULTS: Symptoms of hypomania, mania, depression, and psychosis occur during corticosteroid therapy as do cognitive changes, particularly deficits in verbal or declarative memory. Psychiatric symptoms appear to be dose-dependent and generally occur during the first few weeks of therapy. Patients who must remain on corticosteroids may benefit from pharmacotherapeutic approaches, such as lithium and the new antipsychotic medications. CONCLUSION: Mood and cognitive changes with corticosteroids appear to be common but generally mild and reversible side effects. More studies are needed to determine effective treatment for steroid-induced psychiatric disorders.

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.

BACKGROUND: One of the most enduring and replicated findings in biological psychiatry is activation of the hypothalamic-pituitary-adrenal (HPA) axis in a subset of patients with major depressive disorder. This review will discuss some of these findings and their pertinence to the assessment and treatment of depressed patients. METHOD: MEDLINE, PsychINFO, and Current Contents databases were searched for pertinent articles on the HPA axis in patients with depression. In addition, hand searches were conducted of references from these sources and abstracts from meetings and books on this topic. Articles that would provide an overview of major or interesting studies in the field were selected for inclusion. RESULTS: The data support that HPA axis activation is common in depressed patients. Frequently reported findings include elevated cortisol and corticotropin-releasing hormone (CRH), nonsuppression on the dexamethasone suppression test, a blunted adrenocorticotropic hormone (ACTH) response to CRH, and hippocampal volume reduction. Evidence of HPA axis activation appears to have prognostic value and is associated with increased risk of depression relapse and even suicide. CONCLUSION: Future research in this area will focus on a better understanding of the etiology and long-term consequences of HPA axis activation in depressed patients. In addition, medications that act on the HPA axis are currently in development and may be part of the psychiatrist's and primary care physician's pharmacopoeia in the near future.

These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder, and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician. Controlled studies of topiramate's acute and long-term efficacy and side effects in bipolar disorder appear warranted.