Contingent negative variation and Dex-CRH test in patients with major depression

Abstract

E€ects of corticosteroid secretion on cognitive information processing have been reported in studies with animals (Vicedomini et al., 1990; Oitzl and de Kloet, 1992; Sandi and Rose, 1994), healthy human subjects (Wolkowitz et al., 1990, 1997), patients with Cushing's syndrome (Whelan et al., 1980) or treated with corticosteroids (Ling et al., 1981; Varney et al., 1984). In depression hypothalamic pituitary adrenal (HPA) axis dysregulation is the major neuroendocrine ®nding (Holsboer and Barden, 1996) and cognitive impairment is frequently observed (Weingartner, 1982; Veiel, 1997), however, only a limited number of studies addressed the relationship between HPA axis dysregulation and cognitive dysfunction in depression. Findings of these studies suggest an association between cognitive impairment assessed by neuropsychological tests and nonsuppression of cortisol in the dexamethasone suppression test (DST) (Siegel et al., 1989, Wolkowitz et al., 1990). The contingent negative variation (CNV), an event related potential, provides a tool to evaluate the central neurophysiological activity underlying cognitive processes of attention (McCallum and Walter 1968). In addition, CNV amplitudes were inversely correlated with severity of depression (Papart et al., 1990). Furthermore, nonsuppression in DST was associated with alterations of CNV amplitude and latency in depressed patients (Timsit-Berthier et al., 1986). In a recent study by our group (Heimberg et al., 1999) a complex CNV paradigm was applied which included a variation in the intensity of attention. Compared to healthy controls, depressed patients presented with a slightly decreased CNV in the target, but a substantial CNV in the nontarget-condition, which was not observed in healthy subjects (Heimberg et al., 1999). In eight inpatients of this study [6 females, 2 males, age: 51.8 11.3 years (mean S.D.)] a combined dexamethasone-corticotropin releasing hormone (Dex-CRH) test (Holsboer et al., 1987), which provides an increased sensitivity compared to the DST (Heuser et al., 1994) was additionally performed. All patients were in an acute phase of major depression (between the ®rst and second week after admission to the depression unit) and were treated with a monotherapy of 200 mg trimipramine for at least 5 days before the examination of the CNV and seven days before the Dex-CRH test. Severity of depression was assessed by Hamilton Rating Scale of Depression (HDRS, Hamilton, 1967). The CNV paradigm, a choice-reaction task, which included a preceding warning period of one second, consisted of a series of 72 ®gures of three complex ®gures presented tachistoscopicly. One third of the series consisted of three identical ®gures (response-relevant condition=RR) and had to be con®rmed by button press immediately after the presentation of the third identical condition (target condition). In the two further thirds of the series either two of the ®gures were identical or all ®gures di€ered (response irrelevant condition=RI). In the response-irrelevant condition (RI) no button press was required. Therefore, both conditions (RRand RI-condition) di€er to a large extent in the requirement of attentional demanding processes. CNV prior to the second ®gure served as the baseline. Monopolar EEG was recorded with the electrode positions Fz, Cz, Pz and two connected electrodes at the mastoid position as reference. Maximal amplitude of CNV was measured between 1200 and 1500 ms after onset of the second ®gure (S1) and before the third ®gure (S2); for further details see Heimberg et al. (1999). In depressed patients (HDRS-score, 21.6 5.9) CRH stimulated cortisol in the Dex-CRH test was increased by trend compared to healthy controls matched by age