Symptomatology and cognitive impairment associate independently with post-dexamethasone cortisol concentrations in unmedicated schizophrenic patients

Newcomer, John W.; Faustman, William O.; Whiteford, Harvey; Moses, James A.; Csernansky, John G.

doi:10.1016/0006-3223(91)90052-n

Cited by 61 publications

(32 citation statements)

References 38 publications

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“…Cortisol secretion has been associated with more severe positive symptoms (Kaneko et al, 1992;Walder et al, 2000), whereas in others it was associated with higher ratings of negative symptoms (Newcomer et al, 1991;Tandon et al, 1991). Some investigators purport that in SCH, there is an association of DST nonsuppression with negative symptoms (Altamura et al, 1989;Newcomer et al, 1991;Tandon et al, 1991). Taken together, these results suggest that HPA axis dysregulation/activation and hypercortisolemia are frequent present in SCH patients.…”

Section: Introductionmentioning

confidence: 93%

“…Studies also suggest a relationship between HPA activity and symptomatology in SCH. Cortisol secretion has been associated with more severe positive symptoms (Kaneko et al, 1992;Walder et al, 2000), whereas in others it was associated with higher ratings of negative symptoms (Newcomer et al, 1991;Tandon et al, 1991). Some investigators purport that in SCH, there is an association of DST nonsuppression with negative symptoms (Altamura et al, 1989;Newcomer et al, 1991;Tandon et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Zhang

Zhou

Cao

et al. 2005

Neuropsychopharmacol

178

110

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The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of cytokines and stress-related mediators. Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia. We determined the relationship between cortisol, cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6), and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs. Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients. SCH were randomly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum cortisol and IL-2 levels were assayed by radioimmunometric assay, and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay. Following a 2-week washout period, serum levels of cortisol, IL-2, and IL-6 were increased in patients with schizophrenia compared to HC. Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH. Moreover, elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms. In all, 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms, but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol. The improvement of negative symptoms was related to the change in cortisol. Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms, and is improved with atypical antipsychotic treatment.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Zhang

Zhou

Cao

et al. 2005

Neuropsychopharmacol

178

110

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“…Clinical studies have shown that some patients with schizophrenia have an increased concentration of cortisol in plasma and/or increased release of cortisol after pretreatment with dexamethasone or dexamethasone with corticotropin-releasing hormone (CRH) (Lammers et al, 1995;Ryan et al, 2004;Tandon et al, 1991). Moreover, an association between postdexamethasone cortisol level and negative symptoms of schizophrenia was found (Newcomer et al, 1991). Diminished negative feedback regulation of the HPA axis activity in schizophrenia has been demonstrated also by a postmortem study, which showed a decreased level of glucocorticoid receptors (GR) mRNA in the hippocampus, frontal cortex, and temporal cortex (Webster et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic Drugs Inhibit the Human Corticotropin-Releasing-Hormone Gene Promoter Activity in Neuro-2A Cells—an Involvement of Protein Kinases

Basta‐Kaim

Budziszewska

Jaworska-Feil

et al. 2005

Neuropsychopharmacol

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Antipsychotic drugs can regulate transcription of some genes, including those involved in regulation of hypothalamic-pituitary-adrenal (HPA) axis, whose activity is frequently disturbed in schizophrenic patients. However, molecular mechanism of antipsychotic drug action on the corticotropin-releasing hormone (CRH) gene activity has not been investigated so far. This study was undertaken to examine the influence of conventional and atypical antipsychotic drugs on the CRH gene promoter activity in differentiated Neuro-2A cell cultures stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It has been found that chlorpromazine (0.1-5.0 mM), haloperidol (0.5-5.0 mM), clozapine (1.0-5.0 mM), thioridazine (1.0-5.0 mM), promazine (5.0 and 10 mM), risperidone (5.0 and 10.0 mM), and raclopride (only at the highest used concentrations, ie 30 and 100 mM) present in culture medium for 5 days inhibited the CRH-CAT activity. Sulpiride and remoxipride had no effect. Since CRH gene activity is most potently enhanced by cAMP/protein kinase A pathway, the effect of antipsychotics on the forskolin-induced CRH-CAT activity was determined. Chlorpromazine (1.0-5.0 mM), haloperidol (1.0-5.0 mM), clozapine (1.0-5.0 mM), thioridazine (3.0 and 5.0 mM), and raclopride (30 and 100 mM), but not promazine, sulpiride, risperidone, and remoxipride, inhibited the forskolin-stimulated CRH gene promoter activity. A possible involvement of protein kinases in chlorpromazine and clozapine inhibitory action on CRH activity was also investigated. It was found that wortmannin (0.01 and 0.02 mM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K), significantly attenuated the inhibitory effect of chlorpromazine and clozapine on CRH gene promoter activity. In line with these results, a Western blot study showed that these drugs increased phospho-Ser-473 Akt level, had no effect on total Akt, and decreased glycogen synthase kinase-3b level. Additionally, we found that clozapine decreased protein kinase C (PKC) level and that its action on CRH activity was attenuated by PKC activator (TPA, 0.1 mM). The obtained results indicate that inhibition of CRH gene promoter activity by some antipsychotic drugs may be a molecular mechanism responsible for their inhibitory action on HPA axis activity. Clozapine and chlorpromazine action on CRH activity operates mainly through activation of the PI3-K/Akt pathway. Moreover, PKC-mediated pathway seems to be involved in clozapine action on CRH gene activity.

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“…Authors of some previous studies found positive correlation between cortisol levelsand negative symptoms [7,17,26,30]. In contrast, some other studies found a correlation between serum cortisol and positive symptoms [2,5,25,31].…”

Section: Discussionmentioning

confidence: 92%

Serum Cortisol and DHEA-S Levels in Schizophrenic Patients with Different Response to Antipsychotic Therapy: Association with Psychopathology / Серумски Концентрации На Кортизол И DHEA-S Кал Пациенти Со Шизофренша Со Различен Одговор На Антипсихотичната Терапша Асоци.1Аци.1А Со Психопатологшата

Babinkostova

Stefanovski

Janicevic-Ivanovska

et al. 2015

Prilozi

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Background: Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Imbalance in serum cortisol and DHEA-S levels may be related to responsivity to antipsychotic treatment. Aim: To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with psychopathology in schizophrenic patients with different response to antipsychotic treatment. Material and Methods:This clinical prospective study included 60 patients with schizophrenia and 40 healthy age and sex matched controls. All patients experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥ 4). Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measuredat baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. Results: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels comparedwith control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. Responders group had significant correlation between serum cortisol and PANSS positive scale score as well as between hostility and serum DHEA-S. Conclusion: Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Serum cortisol and DHEA-S are associated with psychopathology in schizophrenic patients with different response to antipsychotic therapy.

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Symptomatology and cognitive impairment associate independently with post-dexamethasone cortisol concentrations in unmedicated schizophrenic patients

Cited by 61 publications

References 38 publications

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Antipsychotic Drugs Inhibit the Human Corticotropin-Releasing-Hormone Gene Promoter Activity in Neuro-2A Cells—an Involvement of Protein Kinases

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