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IJABS 2015: 2:1 © 2015 Behavioral Research Center of SBMU Arbabi Hashempour, Brief Article Hyperaldosteronism and bipolar mixed episode: A case report Hashempour Sarah1, Arbabi Mohammad*2 1 . Psychiatrist, University of Welfare and Rehabilitation Sciences, Tehran, Iran. . Associate Professor, Department of Psychiatry, Tehran University, Tehran, Iran.(Corresponding Author: Mohammad Arbabi, [email protected], Roozbeh Hospital, South Kargar Street, Tehran-Iran) 2 (Received: 8 Mar 2015; Revised: 12 May 2015; 10 Jan 2015) Abstract Introduction: Aldosterone is a steroid hormone produced by the outer section of the adrenal cortex. Both glucocorticoids and mineralocorticoids receptors are present in brain structures (e.g. hippocampus and amygdala) that are involved in behavior such as fear and anxiety. Methods: We report a 54 year old male who was referred from the endocrine ward presented with a dysphoric mood, irritability, insomnia, decreased in appetite, talkativeness, anhedonia, hopelessness, worthlessness, recurrent thought of death, somatic symptoms, which include palpitation and sweating. Mental status examination revealed bipolar 1 disorder, single episode mixed, severe, without psychotic feature based on diagnostic statistical manual of mental disorder (DSM4TR) The aldosterone was high and renin was low. Other clinical examination was normal. Conclusion: The age of onset, no history of mood episodes, atypical feature of this episode and associated hyperaldosteronism suggest the causal role of aldosterone in this episode. The patient was treated with Depakin 500m/d, Quetiapine 50mg/d and Haloperidol 5mg/d. His mental and somatic symptoms improved in 4 weeks. This case can show the relationship between hyperaldosteronism and mood episodes. For future studies, it is decent to do more investigation to find the role of aldosterone in mood regulation. Declaration of Interest: None. Keywords: Hyperaldosteronism, Bipolar mood disorder, mixed episode Introduction Aldosterone is a steroid hormone produced by the outer section of the adrenal glands, which had an important role in reabsorption of sodium ions and chloride ions, secretion of potassium and hydrogen ions, thus preserving the extracellular fluid (1). As a result of overproduction of aldosterone secretion unrelated to renin, the primary hyperaldosteronism is diagnosed (2-4). Sodium and potassium are two important ions in action potential of neurons in the central nervous system (4). Mineralocorticoid receptors (such as glucocorticoid receptors) are scattered in brain structures, which are involved in anxiety and fear and selection of targeted behaviors (as hippocampus and amygdala structures) (5, 8). Aldsterone is secreted due to response of hypotalamopituitary- adrenal (HPA) axis. In the past, this combination effect of behavior was not attractable but recent studies have shown more attention to this hormone and its correlation with patients' behavior (3,9). Recent studies have shown a higher prevalence of anxiety and International Journal of Applied Behavioral Sciences (IJABS) volume 2 number 1 Spring 2015. Journals. smbu.ac.ir/ijabs 41 Hyperaldosteronism and bipolar mixed episode: A case report... depression in primary hyperaldosteronism patients (6, 9). In a study by Sonino et al. in 2006, clinical manifestation have been evaluated in 10 psychiatric patients with primary hyperaldosteronism. The result of this study is indicated that generalized anxiety disorder, obsessive compulsive disorder, physical and irritable mood was seen in 6 patients with primary hyperaldosteronism (7). Another study by Kunzel, Sonino, Apostolopoulouk and Hendler were shown that higher levels of aldosterone in patients with depression, anxiety and mania (6-9). Another study conducted by Hallberg has demonstrated that the lower levels of aldosterone had a positive relationship with suicide in depressed patients (12). In 1995, a study was conducted by Walton et al. on two groups of students presented that students who learned and used the anxiety reduction method, the result had lower level serum aldosterone and also lower appearance of mood and anxiety disorders than others (14). Therefore, the aim of this case report is to introduce a case with hyperaldosteronism and mixed mood disorder episode. The present case indicates that the mood symptoms coincided with the increased aldosterone appears to be related to his symptoms. Case report A 54 year old male was admitted to the endocrine ward and referred to our hospital for psychiatric consult due to symptoms of malaise, dysphoric mood, irritability, insomnia, loss of appetite, increasing the amount of speech, lack of enjoyment of life, hopelessness, thoughts of worthlessness, and thoughts of death. These symptoms were started from 4 months ago, after change in his career. Other symptoms such as sweating and palpitations were seen as well. According to DSM4TR criteria, he was admitted in the psychiatric ward with diagnosis of bipolar disorder single mixed episode, severe, without psychotic feature. There was no history of mood episodes in this patient. He had a history of cigarette smoking 42 and opioid consumption but has been in abstinence from four years ago. In family history, there was a depressive mood episodes and suicide behavior was seen in his sons. Laboratory studies on this patient demonstrated high aldosterone and low renin levels, which represented the primary Hyperaldosteronism. Sodium and potassium serum levels were normal. This patient had been treated in hospital for two weeks by Depakin 500 mg, haloperidol 5 mg and 50 mg daily of Quetiapine for control of symptoms, then he was discharged. Conclusion Since sodium ions have an important role in action potentials of neurons, so, increased levels of aldosterone can be made by increasing the sodium ion level, which can cause nerve cell excitability (4). The mineralocorticoid receptor changes in the brain such as the hippocampus and amygdala, which could be a result of changes in aldosterone level, and could account for changes in mood and anxiety levels (5-15). In this case, according to symptoms in upper age with no previous history of mood disorder, atypical and mixed manifestations with increased aldosterone level can be discussed. Studies by Hlavacova and Gripo in 2008 and 2006 presented that the result of stress can be created by increasing the aldosterone exacerbation cycle (10, 15). In a study by Handler et al. and sonio et al. in 2006 and 1975 demonstrated that an increase in aldosterone can change the mood in depression and anxiety in manic patients. In these studies, obsessive and panic irritable mood had been noted, but the present patient presented mixed episodes, and irritability (7, 11). In a study in 2014 by Apostopoulou indicated that women are more affected of aldosterone level than men, but mixed episode are usually more common in women than man (9). Therefore, this presentation in this patients can be seen as a result of patient's endocrine etiology. In a study by kunzel in 2012, more improve in physical symptoms than anxiety and depression symptoms were noted (6), so in our patients, International Journal of Applied Behavioral Sciences (IJABS) volume 2 number 1 Spring 2015. Journals. smbu.ac.ir/ijabs Hashempour, Arbabi the physical symptoms such as sweating, palpitations and headache were more improved. The presence of a positive family history may point to the role of independent genetic factors in endocrine disease incidence. It seems that aldosterone level can be evaluated in patients with a family history of mood disorder. Thus, more studies are needed around this issue. Also, more study on aldosterone levels during treatment is more needed. Knowing the physiopathology of aldosterone level and its relation with mood disorders can help to find more completed treatment approaches such as using aldosterone antagonists and so on. Acknowledgment We would like to thank to our colleagues and the organizations for all provided insight and expertise that greatly assisted this research and patients who helped us kindly in the project. We also tried to consider all ethical issues in this study. 11. Hendler N. Lithium-responsive hyperaldosteronism in manic patients. Journal of Nervous and Mental Disease. 1975; 161(1):49-54. 12. Hallberg L. Decreased aldosterone in the plasma of suicide attempters with major depressive disorder. Psychiatry Research. 2011; 187(1-2): 135-9. 13. Murck H, Held K, Zigenbein M, Kunzel H, Kokh K, Steiger A. The rennin–angiotensin–aldosterone system in patients with depression compared to controls—a sleep endocrine study. Biomedical center of Psychiatry. 2003; 3:15. 14. Walton KG, Pugh ND, Gelderloos P, Macrae P. Stress reduction and preventing hypertension: preliminary support for a psychoneuroendocrine mechanism. The Journal of Alternative and Complementary Medicine. 1995; 1(3):263–283. 15. Grippo AJ. Sadness and broken hearts: neurohumoral mechanisms and co-morbidity of ischemic heart disease and psychological depression. Journal of Physiology and Pharmacology. 2006; 57:5–29. References 1. Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14 2. Conn JW, Louis LH. Primary aldosteronism: a new clinical entity. Transactions of the Association of American Physicians.1955, 68: 215–31; 3. Selye H. Stress and disease. Science. 1955; 122 (3171):625–631. 4. Barnett MW, Larkman PM."The action potential". Practical Neurology. 2007, 7 (3): 192–7. 5. Korte SM. Corticosteroids in relation to fear, anxiety and psychopathology. Neuroscience and biobehavioral reviews. 2001; 25 (2):117–142. 6. Künzel h. Anxiety and depressive symptoms in patients with primary aldosteronism in a longitudinal study. Endocrine Abstracts. 2012; 29 .74-78 7. Sonino N, Fallo F, et al. Psychological aspects of primary aldosteronism. Psychotherapy and psychosomatics. 2006;75 (5):327 8. Hlavacova N, Wes P, Ondrejcakova M, Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder. International Journal of Neuro psychopharmacology. 2012; 15, 247–265 9. Apostolopoulou k. gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: a cross sectional study. The world journal of biological psychiatry. 2014; 15(1):26-35. 10. Hlavacova N, Jezova D. Chronic treatment with the mineralocorticoid hormone aldosterone results in increased anxiety-like behavior. Hormones and behavior. 2008;54 (1):90–97 International Journal of Applied Behavioral Sciences (IJABS) volume 2 number 1 Spring 2015. Journals. smbu.ac.ir/ijabs 43