Combined dexamethasone/corticotropin-releasing hormone test in patients with schizophrenia and in normal controls: II

Lammers, C.-H.; Garcı́a-Borreguero, Diego; Schmider, Jürgen; Gotthardt, U.; Dettling, Michael; Holsboer, Florian; Heuser, Isabella

doi:10.1016/0006-3223(95)00065-8

Cited by 142 publications

(77 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have found raised cortisol and ACTH levels in patients with first-episode schizophrenia (Ryan et al, 2003(Ryan et al, , 2004aSachar et al, 1970), together with increased intra-abdominal fat (Ryan et al, 2004a) and impaired glucose tolerance (Ryan et al, 2003), thus suggesting that these endocrine abnormalities could have important metabolic consequences (Dinan, 2004). Studies of patients in the acute relapse phase of a psychotic disorder (with florid symptoms, newly hospitalized or unmedicated) have also found elevated cortisol levels that correlate with the severity of psychotic and arousal symptoms (Lammers et al, 1995;Tandon et al, 1991;Walder et al, 2000), nonsuppression of cortisol secretion by dexamethasone in the dexamethasone suppression test and in the dexamethasone/CRH test (Coryell and Tsuang, 1992;Herz et al, 1985;Lammers et al, 1995), and elevated levels of CRH in the cerebrospinal fluid (Banki et al, 1987). Finally, patients with bipolar disorder also show HPA axis hyperactivity (Kunzel et al, 2003;Linkowski et al, 1994;Watson et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Pariante

Dazzan

Danese

et al. 2005

Neuropsychopharmacol

142

View full text Add to dashboard Cite

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamicpituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age-and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls ( þ 22%, po0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p ¼ 0.028), 17% larger in patients receiving atypicals (p ¼ 0.01), and 30% larger in patients receiving typicals (po0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( þ 11%, p ¼ 0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n ¼ 40, po0.001), 19% larger in depressed patients (n ¼ 13, p ¼ 0.022), 16% larger in bipolar patients (n ¼ 16, p ¼ 0.037), and 12% larger in those with other psychoses (n ¼ 9, p ¼ 0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Pariante

Dazzan

Danese

et al. 2005

Neuropsychopharmacol

142

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that the altered HPA axis activity is usually corrected during a clinically effective therapy with antipsychotic drugs (Lammers et al, 1995;Tandon et al, 1991;Wik et al, 1986). Also, in the transgenic mice overexpressing CRH, some antipsychotic drugs alleviated sensorimotor gating deficits (Dirks 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

View full text Add to dashboard Cite

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.

show abstract

“…29 In psychiatric disorders, such as schizophrenia, stress susceptibility and dopaminergic hyper-reactivity have also been observed. 30,31 According to the developmental hypothesis of schizophrenia, the pathophysiology and etiology of the disorder are related to an affected development or maturation of the brain. Epidemiological studies have provided a solid basis for this hypothesis, for example during early life schizophrenic individuals have shown a retarded motor and cognitive development.…”

Section: Discussionmentioning

confidence: 99%

Ontogenic reduction of Aph-1b mRNA and γ-secretase activity in rats with a complex neurodevelopmental phenotype

et al. 2006

View full text Add to dashboard Cite

Selectively bred apomorphine susceptible (APO-SUS) rats display a complex behavioral phenotype remarkably similar to that of human neurodevelopmental disorders, such as schizophrenia. We recently found that the APO-SUS rats have only one or two Aph-1b gene copies (I/I and II/II rats, respectively), whereas their phenotypic counterpart has three copies (III/III). Aph-1b is a component of the c-secretase enzyme complex that is involved in multiple (neuro)developmental signaling pathways. Nevertheless, surprisingly little is known about csecretase expression during development. Here, we performed a longitudinal quantitative PCR study in embryos and the hippocampus of I/I, II/II and III/III rats, and found gene-dosage dependent differences in Aph-1b, but not Aph-1a, mRNA expression throughout pre-and postnatal development. On the basis of the developmental mRNA profiles, we assigned relative activities to the various Aph-1a and -1b gene promoters. Furthermore, in the three rat lines, we observed both tissue-specific and temporal alterations in c-secretase cleavage activity towards one of its best-known substrates, the amyloid-b precursor protein APP. We conclude that the low levels of Aph-1b mRNA and c-secretase activity observed in the I/I and II/II rats during the entire developmental period may well underlie their complex phenotype.

show abstract

Combined dexamethasone/corticotropin-releasing hormone test in patients with schizophrenia and in normal controls: II

Cited by 142 publications

References 15 publications

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

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

Ontogenic reduction of Aph-1b mRNA and γ-secretase activity in rats with a complex neurodevelopmental phenotype

Contact Info

Product

Resources

About