Discordant changes in plasma ACTH and β-lipotropin/β-endorphin levels in Clshing's disease patients with depression

Abstract

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and 13-1ipotropin/13-endorphin ([~-LPH/13-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+ SD] depressed mood score = 0.17+ 0.4; modified Hamilton Depression scale score = 7.6 + 4.5) and five as severely depressed (mean depressed mood score = 2.4 + 0.5; modified Hamilton Depression scale score = 15 + 5.6) (p< 0.05). ACTH and ~-LPI-I/[3-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and [3-LPI-I/~I-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed=90.0+ 16.7; severely depressed=34.6 + 8.7 (p<0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration. These initial findings, taken together with data in related areas, suggest that greater diversity in regulation and cosecretion of ACTH and ~-LPH/13-E may occur than is currently suspected. Such diversity may play a role in the relationship between HPA axis dysregulation and mood disorders.

Clinical Correlates of Major Depression in Cushing’s Disease

“…The severity was both in terms of cortisol production and clinical presentation (e.g., diabetes, hypertension, etc.). Despite the large patient population (n = 162), we could not confirm the findings suggesting a relationship between depression and plasma ACTH levels [3,4].…”

“…A relationship between severity of depression and ACTH plasma levels was observed in Cushing's syndrome [3,4].…”

Chronic treatment with corticosterone increases the number of tyrosine hydroxylase-expressing cells within specific nuclei of the brainstem reticular formation

“…Cushing's syndrome is due to increased glucocorticoid levels in the body, and it is characterized by several clinical alterations which concern vegetative and behavioral functions (Starkman et al, 1992 ). For instance, altered metabolism (including diabetes), increased blood pressure, sleep disorders, increased feeding, aggressiveness, anxiety, and psychosis have been described in patients suffering from Cushing's syndrome (Krieger and Glick, 1974 ; Shipley et al, 1992 ; Ntali et al, 2015 ).…”

Estudo do fator de transcrição Max no hipocampo de camundongos adolescentes submetidos a um modelo de submissão social prolongada.

“…As mudanças estruturais induzidas pelo estresse parecem ter caráter transitório, e algumas vezes acabam desaparecendo espontaneamente, quando os animais são submetidos a um período de recuperação (Heine et al, 2004a, b), ou quando os níveis elevados de corticosteroides são normalizados (Starkman et al, 1992 (Kosten et al, 2008), sugerem fortemente um papel importante para esta proteína, como um fator de resistência ao desenvolvimento da depressão induzida pelo estresse. Além disso, o estresse imprevisível também reduziu a expressão do RNAm para Bcl-2, uma proteína de membrana com propriedade antiapoptótica, em estruturas límbicas de ratos (Jiao et al, 2005;Kosten et al, 2008).…”