Dexamethasone suppression test in schizophrenia: Relationship to symptomatology, ventricular enlargement, and outcome

Abstract

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p less than 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was associated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

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

“…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).…”

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

“…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).…”

“…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).…”

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

“…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].…”

“…In some studies cortisol secretion was primarily associated with more severe positive symptoms [2,5,25], whereas in others it was associated with higher ratings of negative symptoms [7,17,26]. It has been suggested that the relation between cortisol levels and symptoms severity is due to the augmenting effects of cortisol on dopamine activity [27].…”