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1.
Psychiatry Res ; 337: 115949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795698

RESUMO

Ketamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied. This double-blind study with 30 patients divided into 2 groups of 15 each, aimed to determine if GSH, added to standard ketamine infusion (GSH+K), rendered better outcomes in MDD patients versus patients receiving ketamine infusions with a normal saline placebo (K+NS). There were significant drops in BDI-II scores from day 1 to day 14, PHQ- scores from day 1 to day 14 and PHQ-9 scores day 14 to day 28, suggesting the overall treatment was effective. There were no statistically significant differences between the groups over time. However, a sustained improvement in depressive symptoms was observed for 14 days post-infusion in both groups.


Assuntos
Transtorno Depressivo Maior , Glutationa , Ketamina , Humanos , Ketamina/administração & dosagem , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Masculino , Adulto , Método Duplo-Cego , Pessoa de Meia-Idade , Quimioterapia Combinada , Antidepressivos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Resultado do Tratamento , Infusões Intravenosas , Escalas de Graduação Psiquiátrica
2.
Case Rep Psychiatry ; 2022: 8162871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620411

RESUMO

Our patient Mr. A is a mentally and physically disabled gentleman. He was first diagnosed with bipolar disorder as a teenager. He incurred a lumbar spinal injury due to a motor vehicle incident in his 20s which led to weakness, numbness, and frequent infection over both of his lower extremities. He also developed alcohol addiction over the course of his life. Mr. A presented to our facility with complicated neuropsychiatric symptoms. By adopting various clinical strategies, we were able to control his symptoms of agitation, self-harm, mood swings, and stereotyped behavior. However, we were not able to improve his neurocognitive functioning or speech impairment which seemed to become severe and irreversible in a period of a few months. We felt disappointed and perplexed by the mixed treatment responses. To understand Mr. A's clinical presentation, various laboratory tests and imaging studies were performed. Different psychotropic medications were used to manage his symptoms. Gradually, we felt that we were able to understand this case better clinically and etiologically. His bipolar disorder, alcohol addiction, and physical injury had likely all contributed to his neuropsychiatric symptoms, directly or indirectly. It is highly possible that an alcohol-related progressive dementia along with his chronic bipolar disorder played a key role in the progression of his brain neurodegeneration. Also, Wernicke-Korsakoff syndrome could reasonably be considered having developed during his clinical course. Moreover, the fluctuation of the patient's neuropsychiatric symptoms we observed during his hospitalization reflects the increased vulnerability of the human brain under sustained neurodegeneration.

3.
J Clin Endocrinol Metab ; 89(5): 2228-36, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15126546

RESUMO

Carriers of congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency demonstrate increased secretion of cortisol precursors after ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic CRH secretion. Because both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression, we performed endocrine and psychologic studies in consecutively admitted parents of patients with classic congenital adrenal hyperplasia due to 21-OH deficiency and parents of children with other chronic endocrine disorders. The number of excluded carriers because of pathologic reasons was higher than that of controls (P = 0.05). Carriers of 21-OH deficiency had a lower mean 24-h urinary free cortisol excretion (26.4 +/- 3.4 vs. 42.7 +/- 6.4 microg/d, P = 0.03) and higher peak ACTH (75.7 +/- 8.1 vs. 54.2 +/- 5.9 pg/ml, P = 0.04) and 17-hydroxyprogesterone (224.2 +/- 28.1 vs. 107.1 +/- 12.5 ng/dl, P < 0.001) concentrations post CRH stimulation than control subjects. Cortisol and androstenedione responses were similar in the two groups. Psychometric assessment performed by administering the State-Anxiety Inventory, Beck Depression Inventory, Profile of Mood States, Symptom Checklist-90R, and Temperament and Character Inventory revealed no differences between the two subject groups. Interestingly, a stepwise multiple linear regression model analysis in each population sample revealed that in carriers of 21-OH deficiency but not in the control subjects, a lower mean 24-h urinary free cortisol excretion and a higher ACTH response to ovine CRH stimulation predicted predisposition to obsessive-compulsive behavior, novelty seeking, reward dependence, and harm avoidance. We conclude that carriers of 21-OH deficiency appear to have mild hypocortisolism and compensatory changes of CRH secretion secondary to lower cortisol concentrations. These changes might predict mild predisposition of these subjects to physical and psychologic pathology, suggesting that larger studies are necessary.


Assuntos
Hiperplasia Suprarrenal Congênita/fisiopatologia , Hiperplasia Suprarrenal Congênita/psicologia , Glândulas Endócrinas/fisiopatologia , Heterozigoto , Testes Psicológicos , Estresse Fisiológico/etiologia , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/genética , Adulto , Estudos de Casos e Controles , Doença Crônica , Suscetibilidade a Doenças , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/genética , Doenças do Sistema Endócrino/parasitologia , Doenças do Sistema Endócrino/fisiopatologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Psicometria
4.
Biol Psychiatry ; 54(9): 873-8, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14573313

RESUMO

BACKGROUND: Preclinical data indicate a crucial role of stress in the acute effects of drugs of abuse, maintenance of self-administration, and susceptibility to relapse. Stress system activation may serve as a marker for a neurochemical dysfunction with prognostic significance in patients with addiction. METHODS: We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects without depressive symptoms, and seven subjects with substance abuse and depressive symptoms. No subject met diagnostic criteria for depression or other severe psychiatric disease. RESULTS: Compared with normal control subjects, substance abusers showed significantly lower ACTH and cortisol responses over the course of oCRH stimulation (p <.0001). Substance abusers with depressive symptoms showed similarly blunted responses. CONCLUSIONS: Polysubstance abusers with no past or current diagnosis of other Axis I disorders show blunted ACTH and cortisol responses to oCRH administration. The finding of an activated HPA axis in this population suggests an overlapping role of central CRH and HPA axis activation in affective disorders and substance abuse, which is likely to constitute an endocrine milieu necessary for the maintenance of addictive behavior. These data support the role of future therapeutic trials with nonpeptide CRH receptor 1 antagonists in these patients.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina/administração & dosagem , Depressão/fisiopatologia , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Hormônio Adrenocorticotrópico/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Fatores de Tempo
5.
Neuroendocrinology ; 78(3): 154-62, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14512708

RESUMO

Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks. No differences in prolactin secretion were seen with either thyrotropin-releasing hormone stimulation or L-dopa suppression testing. Basal afternoon cortisol secretion was significantly elevated during weeks 1 and 2 comparing abusers to controls. Elevated afternoon cortisol secretion is a sensitive indicator of central stress activation. These results point to the hypothalamus, not the pituitary gland, as being primarily altered in cocaine withdrawal. The data demonstrate that both the dopamine-prolactin and hypothalamic-pituitary-adrenal (HPA) axes are affected during cocaine cessation. As medications are developed to modulate activation of a dysfunctional stress system, future therapeutic studies of substance abuse, withdrawal, craving and relapse should employ more sophisticated tests of hypothalamic pituitary function, especially the HPA axis, as this information may be a guide in the diagnosis and predict clinical responses.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Prolactina/sangue , Adulto , Análise de Variância , Área Sob a Curva , Transtornos Relacionados ao Uso de Cocaína/terapia , Humanos , Hidrocortisona/metabolismo , Pacientes Internados , Determinação da Personalidade , Prolactina/metabolismo , Valores de Referência , Centros de Tratamento de Abuso de Substâncias , Fatores de Tempo
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