Table of Contents  
CASE REVIEW
Year : 2013  |  Volume : 4  |  Issue : 5  |  Page : 94-98  

Corticosteroid-related central nervous system side effects


1 Department of Science of Health, School of Medicine, University of Catanzaro and Pharmacovigilance's Centre Calabria Region, University Hospital Mater Domini, Italy
2 Geriatry Unit, General Hospital Pugliese-Ciaccio, Catanzaro, Italy
3 Presidio Ospedaliero Unico, Soverato, Catanzaro, Italy

Date of Web Publication2-Nov-2013

Correspondence Address:
Emilio Russo
Chair of Pharmacology, Department of Science of Health, School of Medicine, University of Catanzaro, Via T. Campanella, 115; 88100 Catanzaro
Italy
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.120975

Rights and Permissions
   Abstract 

Corticosteroids have been used since the 50s as anti-inflammatory and immunosuppressive drugs for the treatment of several pathologies such as asthma, allergy, rheumatoid arthritis, and dermatological disorders. Corticosteroids have three principal mechanisms of action: 1) inhibit the synthesis of inflammatory proteins blocking NF-kB, 2) induce the expression of anti-inflammatory proteins by IkB and MAPK phosphatase I, and 3) inhibit 5-lipoxygenase and cyclooxygenase-2. The efficacy of glucocorticoids in alleviating inflammatory disorders results from the pleiotropic effects of the glucocorticoid receptors on multiple signaling pathways. However, they have adverse effects: Growth retardation in children, immunosuppression, hypertension, hyperglycemia, inhibition of wound repair, osteoporosis, metabolic disturbances, glaucoma, and cataracts. Less is known about psychiatric or side effects on central nervous system, as catatonia, decreased concentration, agitation, insomnia, and abnormal behaviors, which are also often underestimated in clinical practice. The aim of this review is to highlight the correlation between the administration of corticosteroids and CNS adverse effects, giving a useful guide for prescribers including a more careful assessment of risk factors and encourage the use of safer doses of this class of drugs.

Keywords: Adverse effects, corticosteroids, central nervous system, mood, psychosis


How to cite this article:
Ciriaco M, Ventrice P, Russo G, Scicchitano M, Mazzitello G, Scicchitano F, Russo E. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother 2013;4, Suppl S1:94-8

How to cite this URL:
Ciriaco M, Ventrice P, Russo G, Scicchitano M, Mazzitello G, Scicchitano F, Russo E. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother [serial online] 2013 [cited 2019 Dec 11];4, Suppl S1:94-8. Available from: http://www.jpharmacol.com/text.asp?2013/4/5/94/120975


   Introduction Top


Glucocorticoids (GCs) are a class of steroid hormones released from the adrenal cortex and their plasma concentration is controlled by the hypothalamic-pituitary-adrenal axis. [1] GCs are mediators of stress response and the derived drugs (also named corticosteroids) are widely used as pharmacological agents for the treatment of inflammatory disease, asthma, and immune/rheumatologic diseases. [2] However, approximately 20% of patients receiving high doses of corticosteroids develop psychiatric disorders including depression, mania, and psychosis [3] requiring pharmacological treatment, while 75% report psychiatric symptoms reversible upon discontinuation of therapy. [4]

Glucocorticoid activity: An overview

Endogenous glucocorticoids affect biological processes including growth, metabolism, development, immune function, and stress response. [5] The production of corticosteroid hormones is under the control of the hypothalamic-pituitary-adrenal axis, activated by mental and physical stimuli. [6]

They are lipophilic hormones crossing the cytoplasmic membrane and binding to specific cytosolic receptors, mineralocorticoid receptors (MR), and glucocorticoid receptors (GR) that regulate gene expression. The drug-receptor complex can trigger the transcription of anti-inflammatory genes such as NF-kB, AP-1, STAT, NFTA, c-Jun, Fos, and inhibit the production of cytokines and pro-inflammatory proteins such as chemotactic proteins and adhesion molecules. [7],[8],[9]

There are approximately 550 polymorphisms identified for the gene coding for the glucocorticoid receptors related to sensitivity to their effects. [10]

Glucocorticoids possess several endocrinological properties being involved in several physiological and pathological processes; they have known effects on glucose metabolism, lipid metabolism, bone and cartilage, protein metabolism, muscular function, hydro-electrolytic balance, gastric secretion, cardiovascular system, hemolymphopoietic tissue, and reproductive physiology. [11]

Endogenous glucocorticoids also control the feeling of hunger, sleep-wake cycle and affect the processes of learning and memory through interaction with specific receptors located in the prefrontal cortex, hippocampus, and basolateral amygdala. [12]

Steroid receptors are expressed in different areas of the brain and their role is related to the regulation of various neurotransmission, including serotonin and dopamine. [13] In particular, in the CNS, glucocorticoids exert their potential effects at hippocampal level, a structure intimately involved in the limbic system, which provides the processing of emotional information and memory. [14] Various studies show a correlation between high levels of endogenous cortisol and hippocampal atrophy resulting in damage and cognitive dysfunction. [15] Negative feedback ensures the activation of the hypothalamic-pituitary-adrenal axis by inducing the overproduction of cortisol and increasing the damage to brain structures. [16]

CNS adverse events

Besides their very common therapeutic use, several well-known adverse effects including weight gain, osteoporosis, and hyperglycemia are often observed. [17] Less-reported adverse events are that involving the central nervous system (CNS) such as psychiatric and cognitive disturbances [Table 1].
Table 1 Corticosteroid dependent adverse effects


Click here to view


Behavioral effects

Studies showed that following the chronic intake of cortisone, 70% of patients report increased appetite with resulting increase of body weight; a 4 to 8% increase is estimated after two years of therapy. [18] Sleep disorders characterized by restlessness and insomnia were observed in 73% of cases. [19] Swinburn et al. in 1988 [20] reported a study showing that patients with Chronic Obstructive Pulmonary Disease, treated with oral prednisolone, develop a sense of well-being called "steroid euphoria" characterized by a reduced sense of anxiety and depression when compared with patients receiving placebo and this occurred even in the absence of improvement in lung function. There are cases, in literature, that describe the appearance of altered behavior with states of agitation and insomnia as a result of intra-articular injection of methylprednisolone. [21]

Recently, in a set of psychiatric symptoms attributed to prolonged treatment or high-dose corticosteroids, catatonia was assessed with muscle stiffness, insomnia, and abnormal behaviors such as silence and stillness. [22]

Psychic effects

Literature reports several cases of depression related to the use of corticosteroid therapy with an incidence of 40.5%; mania, psychosis, and delirium are also very frequent with an incidence of 27.8%, 13.9%, and 10.1%, respectively. [23] Emotional lability and irritability are common symptoms sometimes accompanied by auditory hallucinations and paranoia. [22] Rarely, altered consciousness and disorientation may be observed.

The mechanism by which the corticosteroid induces symptoms such as mania, depression, and psychosis is not clear. [22] The administration of prednisone is associated with decreased levels of corticotrophin, norepinephrine, and beta-endorphin in the cerebrospinal fluid. Furthermore, corticosteroids induce an increased release of glutamate that induces neuronal toxicity due to accumulation effect. [23]

Cognitive effects

In some cases, cognitive deficits, difficulty to maintain concentration, and poor memory, especially after prolonged treatment with high doses of corticosteroids, were observed. [23] Neuroimaging studies in patients taking corticosteroids have related a decrease of hippocampal volume and brain atrophy due to a reduced blood flow in areas of the brain responsible for cognitive functions. [24]

The cognitive effects of corticosteroids appear to be occasional and include disorders, which consist of dementia or delirium. The type of deficiency coincides with the dysfunction at hippocampal level, which is rich in glucocorticoid receptors. [25]

Incidence

A small percentage (2-4%) of patients develop depression, anxiety, or becomes apathetic. [26] While another small percentage (3%) shows psychosis with hallucinations. These adverse events are dose and time dependent and remission results from the suspension of the treatment or decreasing the dose of cortisone. [27] The incidence of neuropsychiatric effects due to assumption of corticosteroid ranges from 2 to 60%, reflecting the variability of dose, the duration of administration, and risk factors identified including genetic predisposition based on polymorphisms of the GR. [28]

The incidence rate of psychiatric disorders is directly correlated to dose and time of glucocorticoids exposure. A study shows that the incidence rate was 22.2% person-years at risk for first courses, 14.0% person-years at risk for second glucocorticoid courses, and 11.7% person-years at risk for third and later courses. [29]

Onset

The beginning of the appearance of symptoms induced by corticosteroids is variable. They may arise in the first phases of treatment, during, or even at the end of therapy. [30] In most cases (86%), they occur within the first 5 days of treatment. The analysis of several studies leads to an average of 11.5 days after the beginning of corticosteroid treatment to the onset of psychiatric symptoms. [31] 89% of patients develop symptoms in the first six weeks, 62% within two weeks, and 39% in the first week. The duration of the neuropsychiatric effects is highly variable and depends on the severity, treatment discontinuation, and by other drug therapies. [31]

Risk factors

Side effects of psychiatric type have been reported following different routes of administration, e.g., intra-articular injection, epidural, topical, and systemic.

Psychiatric side effects due to corticosteroids appear to be dose dependent; they occur in 1.3% of the cases when the dose is less than 40 mg daily and reaches 18.4% for doses of 80 mg daily. [32]

It is not entirely clear whether gender affects the ability to manifest psychiatric symptoms, but some studies suggest that women are more prone. [33]

Other studies show that 73% of the pediatric population receiving steroid therapy develops hyperactivity, irritability, insomnia as well as showing deficits of attention and memory, especially those under 10 years of age and/or high doses of the drug. [32]

Treatment

Generally, symptoms related to administration of corticosteroids disappear after therapy discontinuation. [34] However, some patients require therapeutic treatment. The management of psychiatric symptoms due to administration of corticosteroids includes the reduction of the dose or treatment discontinuation. [35] The patient can be treated with medications normally used in patients with psychiatric or neurological disorders. Mood-stabilizing drugs, such as lithium and valproic acid, are able to control the symptoms caused by corticosteroids. Carbamazepine, inducing steroids metabolism, reduces their neurotoxic effects; atypical antipsychotics, such as olanzapine and fluoxetine (SSRI), are active on this symptoms. [36] The effect of anti-depressive drugs are different, i.e., tricyclic antidepressants could lead to a significant worsening of symptoms, [35] while a selective serotonin reuptake inhibitors, such as fluoxetine, [37] may improve symptoms of depression during corticosteroid therapy as well as phenytoin, lamotrigine, risperidone, quetiapine, and gabapentin. [37]


   Case Report Top


In 2012, in our Pharmacovigilance's Center (Regione Calabria, University Hospital Mater Domini of Catanzaro) a suspected adverse reaction of paraphasia, a language disorder manifested by a difficulty to order words in periods, induced by intramuscular administration of betamethasone was reported.

Regarding this case, the correlation was very high since the patient was not taking other drugs in that period and the adverse reaction appeared 2 hours after the first injection.

Unfortunately, amnesic information is limited since it is an ambulatory patient. We know that it is a middle-aged man, without family history of mental illness and under therapy with angiotensin receptor blocker for hypertension since few years. Reporting low back pain for few months and suspecting a herniated disc, the physician prescribed computerized tomography, documenting bulging lumbar, and steroid therapy was prescribed. Since the beginning of betamethasone (Bentelan®) therapy, the patient was noted to have phenomena characterized by inversion of the letters while talking. Discontinuation of treatment was advised; after treatment interruption, the phenomena disappeared.

In literature, similar cases have not been previously reported; however, many studies show a correlation between psychiatric disorders and corticosteroids use.

Psychiatric disorders secondary to corticosteroids-use are classified as mood disorders substance-induced according to the Diagnostic and Statistical Manual of Disorders Fourth Edition (DSM-IV). [38]


   Discussion and Conclusions Top


Many scientific and literature evidences highlight how the administration of corticosteroids results in a high incidence of mood elevation, satisfaction, and optimism. [39] Less frequently, euphoria, insomnia, and increase in motor activity may occur. [40]

The use of corticosteroids is strongly associated to the development of psychiatric/neurological side effects. These effects are due to the wide expression of GR in the brain, and their long-term modulation can lead to functional and anatomical alterations, which might be responsible for the observed side-effects. The incidence and the onset of such symptoms are quite variable depending on several factors and the type of study; in any case, all healthcare professionals should be aware of such a possibility. Furthermore, such events should be early recognized and treated.

Despite of the known numerous side effects, the use of corticosteroid is widely spread considering the broad spectrum of clinical indications. Psychiatric adverse reactions are under-estimated and therefore it is not always possible to identify the effective dose and at the same time the most secure. It seems only right to recall how the spontaneous reporting of adverse reactions by health professionals and patients is the easiest way to integrate the missing information on the potential and dangers of drugs.


   Acknowledgement Top


The Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) is kindly acknowledged for its financial and technical support.

 
   References Top

1.Rhen T, Cidlowski JA. Antinflammatory action of glucocorticoids Antiinflammatory Action of Glucocorticoids - New mechanisms for old drugs. N Engl J Med 2005;353:1711-23.  Back to cited text no. 1
    
2.Rhen T, Cidlowski JA. Nuclear factor-kB and glucocorticoid receptors. In: Martini L, editor. Encyclopedia of endocrine diseases. Vol. 3. Boston: Elsevier Academic Press; 2004. p. 391-8.  Back to cited text no. 2
    
3.The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972;13:694-8.   Back to cited text no. 3
    
4.Wolkowitz OM. Prospective controlled studies of the behavioral and biological effects of exogenous corticosteroids. Psychoneuroendocrinology 1994;19:233-55.   Back to cited text no. 4
    
5.Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000;21:55-89.   Back to cited text no. 5
    
6.Marques-Deak A, Cizzaand G, Sternberg E. Brain-immune interactions and disease susceptibility. Mol Psychiatry 2005;10:239-50.   Back to cited text no. 6
    
7.Duma D, Jewell CM, Cidlowski JA. Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. J Steroid Biochem Mol Biol 2006;102:11-21.  Back to cited text no. 7
    
8.Bladh LG, Liden J, Dahlman-Wright K, Reimers M, Nilsson S, Okret S. Identification of endogenous glucocorticoid repressed genes differentially regulated by a glucocorticoid receptor mutant able to separate between nuclear factor-kappaB and activator protein-1 repression. Mol Pharmacol 2005;67:815-2.  Back to cited text no. 8
    
9.Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids - new mechanisms for old drugs. N Engl J Med 2005;353:1711-23.  Back to cited text no. 9
    
10.Van Rossum EF, Lamberts SW. Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res 2004;59:333-57.  Back to cited text no. 10
    
11.Lewis DA, Smith RE. Steroid-induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord 1983;5:319-32.  Back to cited text no. 11
    
12.Fietta P, Fietta P, Delsante G. Central nervous system effects of natural and synthetic glucocorticoids. Psychiatry Clin Neurosci 2005;63:613-22.  Back to cited text no. 12
    
13.Schacke H, Docke WD, Asadullah K, Ganda JC. Mechanisms of disease 1723 Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 2002;96:23-43.  Back to cited text no. 13
    
14.Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry 2012;169:491-7.  Back to cited text no. 14
    
15.Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA 1979;241:1011-2.  Back to cited text no. 15
    
16.Hall RCW, Popkin MK, Kirkpatrick B. Tricyclic exacerbation of steroid psychosis. J Nerv Ment Dis 1978;166:738-42.  Back to cited text no. 16
    
17.Halper JP. Corticosteroids and behavioral disturbances, In: Lin AN. Paget SA, editor. Principles of Corticosteroids Therapy. London: Arnold; 2002. p. 174-201.  Back to cited text no. 17
    
18.Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: Published evidence and prospective trial data. Ann Rheum Dis 2006;65:285-93.  Back to cited text no. 18
    
19.Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum 2006;55:420-6.  Back to cited text no. 19
    
20.Swinburn CR, Wakefield JM, Newman SP, Jones PW. Evidence of prednisolone induced mood change ('steroid euphoria') in patients with chronic obstructive airways disease. Br J Clin Pharmacol 1988;26:709-13.  Back to cited text no. 20
    
21.Robinson DE, Harrison-Hansley E, Spencer RF. Steroid psychosis after an intra-articular injection. Ann Rheum Dis 2000;59:927.  Back to cited text no. 21
    
22.Benyamin RM, Vallejo R, Kramer J, Rafeyan R. Corticosteroid induced psychosis in the pain management setting. Pain Physician 2008;11:917-20.  Back to cited text no. 22
    
23.Wolkowitz OM, Rubinow D, Doran AR, Breier A, Berrettini WH, Kling MA. Prednison effects on neurochemistry and behavior. Preliminary findings. Arch Gen Psychiatry 1990;47:963-8.  Back to cited text no. 23
    
24.Ioannou N, Liapi C, Sekeris CE, Palaiologos G. Effects of dexamethasone on K(+)-evoked glutamate release from rat hippocampal slices. Neurochem Res 2003;28:875-81.  Back to cited text no. 24
    
25.Coluccia D, Wolf OT, Kollias S, Roozendaal B, Forster A, de Quervain DJ. Glucocorticoid therapy-induced memory deficits: Acute versus chronic effects. J Neurosci 2008;28:3474-8.  Back to cited text no. 25
    
26.Bolanos S, Khan D, Hanczyc M, Bauer M, Dhanani N, Brown E. Assessment of mood stat in patients receiving long-term corticosteroid therapy and in controls with patient-rated and clinician-rated scales. Ann Allergy Asthma Immunol 2004;92:500-5.  Back to cited text no. 26
    
27.Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972;13:694-8.  Back to cited text no. 27
    
28.Lewis GP, Jusko WJ, Burke CW, Graves L, Boston collaborative drug surveillance program. Prednisolone side effects and serum protein levels. A collaborative study. Lancet 1971;298:778-81.  Back to cited text no. 28
    
29.Bender BG, Lerner JA, Kollasch E. Mood and memory changes in asthmatic children receiving corticosteroids. J Am Acad Child Adolesc Psychiatry 1988;27:720-5.  Back to cited text no. 29
    
30.McEwen BS. Allostasis, allostatic load, and the aging nervous system: Role of excitatory amino acids and excitotoxicity. Neurochem Res 2000;25:1219-31.  Back to cited text no. 30
    
31.Ling MH, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiatric aspects. Arch Psychiatry 1981;38:471-7.  Back to cited text no. 31
    
32.Goldstein ET, Preskorn SH. Mania triggered by a steroid nasal spray in a patient with stable bipolar disorder. Am J Psychiatry 1989;146:1076-7.  Back to cited text no. 32
    
33.George ME, Sharma V, Jacobson J, Simon S, Nopper AJ. Adverse effects of systemic glucocorticosteroid therapy ininfants with hemangiomas. Arch Dermatol 2004;140:963-9.  Back to cited text no. 33
    
34.Kahn D, Stevenson E, Douglas CJ. Effect of sodium valproate in three patients with organic brain syndromes. Am J Psychiatry 1988;145:1010-1.  Back to cited text no. 34
    
35.Wada K, Yamada N, Sato T, Suzuki H, Miki M, Lee Y, et al. Corticosteroid-induced psychotic and mood disorders: Diagnosis defined by DSM-IV and clinical pictures. Psychosomatics 2001;42:461-6.  Back to cited text no. 35
    
36.Hall RC, Popkin MK, Kirkpatrick B. Tricyclic exacerbation of steroid psychosis. J Nerv Ment Dis 1978;166:738-42.   Back to cited text no. 36
    
37.Wyszynski AA, Wyszynski B. Treatment of depression with fluoxetine in corticosteroid dependent central nervous system Sjogren's syndrome. Psychosomatics 1993;34:173-7.  Back to cited text no. 37
    
38.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4 th ed. Text Revision. Washington, DC: American Psychiatric Press; 2000.  Back to cited text no. 38
    
39.Lewis DA, Smith RE. Steroid-induced psychiatric syndromes: A report of 14 cases and a review of the literature. J Affect Disord 1983;5:319-33.  Back to cited text no. 39
    
40.Varney NR, Alexander B, Macindoe JH. Reversible steroid dementia in patients without steroid psychosis. Am J Psychiatry 1984;141:369-72.  Back to cited text no. 40
    



 
 
    Tables

  [Table 1]


This article has been cited by
1 Prescribing options for ulcerative colitis
Benjamin Wakefield,Cath Stansfield
Nurse Prescribing. 2018; 16(Sup7): 9
[Pubmed] | [DOI]
2 Role of Dendritic Cells and Inflammatory Cells in Herpetic Endotheliitis
Ting Wang,Muchen Dong,Yin Jiang,Shuting Wang,Weiyun Shi
Cornea. 2018; 37(6): 748
[Pubmed] | [DOI]
3 Increased prevalence of eating disorders as a biopsychosocial implication of food allergy
Barbara Wróblewska,Anna Maria Szyc,Lidia Hanna Markiewicz,Magdalena Zakrzewska,Ewa Romaszko,Vladimir Brusic
PLOS ONE. 2018; 13(6): e0198607
[Pubmed] | [DOI]
4 Metabolomics Based Profiling of Dexamethasone Side Effects in Rats
Abeer K. Malkawi,Karem H. Alzoubi,Minnie Jacob,Goran Matic,Asmaa Ali,Achraf Al Faraj,Falah Almuhanna,Majed Dasouki,Anas M. Abdel Rahman
Frontiers in Pharmacology. 2018; 9
[Pubmed] | [DOI]
5 The effects of a combination of intravenous dexamethasone and ketamine on postoperative mood in patients undergoing laparoscopically assisted-gynecologic surgery
Cheol Lee,Juhwan Lee,Gilho Lee,Hayeong Lee,Zhou Shicheng,Jihyo Hwang
Psychopharmacology. 2018;
[Pubmed] | [DOI]
6 The protective effect of adrenocorticotropic hormone treatment against noise-induced hearing loss
Ahmet Mutlu,Fatma Ceyda Akin Ocal,Seyra Erbek,Levent Ozluoglu
Auris Nasus Larynx. 2018;
[Pubmed] | [DOI]
7 Melatonin as an anti-inflammatory agent in radiotherapy
M. Najafi,A. Shirazi,E. Motevaseli,A. H. Rezaeyan,A. Salajegheh,S. Rezapoor
Inflammopharmacology. 2017;
[Pubmed] | [DOI]
8 Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer–lipid hybrid nanoparticles
Md. Zahangir Hosain,Kazuki Yuzuriha,Khadijah Khadijah,Masafumi Takeo,Akihiro Kishimura,Yoshihiko Murakami,Takeshi Mori,Yoshiki Katayama
Med. Chem. Commun.. 2017;
[Pubmed] | [DOI]
9 The effect of laserpuncture at the LI4 Hegu point on the plasma levels of ß-endorphin in healthy subjects
H Mihardja,A Srilestari,S A Budianto
Journal of Physics: Conference Series. 2017; 884: 012065
[Pubmed] | [DOI]
10 Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators
Gloria S. Forkuo,Amanda N. Nieman,Nina Y. Yuan,Revathi Kodali,Olivia B. Yu,Nicolas M. Zahn,Rajwana Jahan,Guanguan Li,Michael Rajesh Stephen,Margaret L. Guthrie,Michael M. Poe,Benjamin D. Hartzler,Ted W. Harris,Gene T. Yocum,Charles W. Emala,Douglas A. Steeber,Douglas C. Stafford,James M. Cook,Leggy A. Arnold
Molecular Pharmaceutics. 2017;
[Pubmed] | [DOI]
11 Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
Sangwoo Ham,Yun-Il Lee,Minkyung Jo,Hyojung Kim,Hojin Kang,Areum Jo,Gum Hwa Lee,Yun Jeong Mo,Sang Chul Park,Yun Song Lee,Joo-Ho Shin,Yunjong Lee
Scientific Reports. 2017; 7(1)
[Pubmed] | [DOI]
12 Advances in patent applications related to allergen immunotherapy
Eduardo Santos da Silva,Carina Silva Pinheiro,Cristina Maria Quintella,Fatima Ferreira,Luis Gustavo C. Pacheco,Neuza Maria Alcântara-Neves
Expert Opinion on Therapeutic Patents. 2016; 26(6): 657
[Pubmed] | [DOI]
13 Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells
Bingqing Zeng,Yiwen Li,Bo Niu,Xinyi Wang,Yufang Cheng,Zhongzhen Zhou,Tingting You,Yonggang Liu,Haitao Wang,Jiangping Xu
Journal of Molecular Neuroscience. 2016;
[Pubmed] | [DOI]
14 Efficacy of tocilizumab for psychiatric symptoms associated with relapsing polychondritis: the first case report and review of the literature
Lijun Liu,Shengyun Liu,Wenjuan Guan,Lei Zhang
Rheumatology International. 2016; 36(8): 1185
[Pubmed] | [DOI]
15 Synergy between phenotypic modulation and ROS neutralization in reduction of inflammatory response of hypoxic microglia by using phosphatidylserine and antioxidant containing liposomes
Md Zahangir Hosain,Takeshi Mori,Akihiro Kishimura,Yoshiki Katayama
Journal of Biomaterials Science, Polymer Edition. 2016; 27(3): 290
[Pubmed] | [DOI]
16 Treatments affecting dog behaviour: something to be aware of
Carlo Siracusa
Veterinary Record. 2016; 179(18): 460
[Pubmed] | [DOI]
17 Neuropsychiatric manifestations in rheumatoid arthritis
Andrei F. Joaquim,Simone Appenzeller
Autoimmunity Reviews. 2015; 14(12): 1116
[Pubmed] | [DOI]
18 Sustained corticosteroid- induced mania and psychosis despite cessation
Mary Gable,Dwayne Depry
The International Journal of Psychiatry in Medicine. 2015; 50(4): 398
[Pubmed] | [DOI]
19 The incidence and prevalence of psychiatric disorders in multiple sclerosis: A systematic review
Ruth Ann Marrie,Stephen Reingold,Jeffrey Cohen,Olaf Stuve,Maria Trojano,Per Soelberg Sorensen,Gary Cutter,Nadia Reider
Multiple Sclerosis Journal. 2015; 21(3): 305
[Pubmed] | [DOI]
20 Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis
Rossana Aiello,Rosalia Crupi,Antonio Leo,Serafina Chimirri,Vincenzo Rispoli,Rosario Marra,Rita Citraro,Salvatore Cuzzocrea,Giovambattista De Sarro,Emilio Russo
Behavioural Brain Research. 2014;
[Pubmed] | [DOI]
21 Psychiatric comorbidity in multiple sclerosis: It’s not the genes
Ruth Ann Marrie
Multiple Sclerosis Journal. 2014; 20(14): 1803
[Pubmed] | [DOI]
22 Pediatric inflammatory bowel disease and depression
Divya Keethy,Christine Mrakotsky,Eva Szigethy
Current Opinion in Pediatrics. 2014; 26(5): 561
[Pubmed] | [DOI]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Case Report
    Discussion and C...
   Acknowledgement
    References
    Article Tables

 Article Access Statistics
    Viewed4752    
    Printed146    
    Emailed1    
    PDF Downloaded1008    
    Comments [Add]    
    Cited by others 22    

Recommend this journal