Jaap G. Goekoop

Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

BACKGROUND High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity due to an enhanced corticotropin-releasing hormone (CRH) drive and glucocorticoid feedback resistance. In humans, PTSD and MDD are associated with decreased and increased resistance to glucocorticoid feedback, respectively, which might reflect persistent changes in neuroendocrine sequelae following childhood abuse. METHODS We investigated the relationship between childhood abuse and HPA axis function using a combined dexamethasone/CRH (DEX/CRH) test in 39 BPD patients with (n = 24) and without (n = 15) sustained childhood abuse and comorbid PTSD (n = 12) or MDD (n = 11) and 11 healthy control subjects. RESULTS Chronically abused BPD patients had a significantly enhanced corticotropin (ACTH) and cortisol response to the DEX/CRH challenge compared with nonabused subjects. Comorbid PTSD significantly attenuated the ACTH response. CONCLUSIONS Hyperresponsiveness of the HPA axis in chronically abused BPD subjects might be due to the enhanced central drive to pituitary ACTH release. Sustained childhood abuse rather than BPD, MDD, or PTSD pathology accounts for this effect. Possibly due to an enhanced efficacy of HPA suppression by dexamethasone, PTSD attenuates the ACTH response to DEX/CRH.

Three- to 5-year prospective follow-up of outcome in major depression

BACKGROUND A Dutch cohort of predominantly out-patient DSM-III-R major depressive patients was followed for 3 to 5 years after start of treatment in a psycho-neuro-endocrinological prediction study. The study design permitted description of the course of remissions, relapses and recurrences. METHODS Pharmacological treatment was standardized, psychotherapy was tailored to the needs of the patient, follow-ups were done monthly until 3 years or more after the initial recruitment. RESULTS After 9 months 49% of the patients had reached full remission and 45% were in partial remission. During the following 3 to 5 years 82% of the patients had reached a period of full remission. Sixteen per cent of the patients needed 2 years or more before full remission. A relapse or recurrence rate of 41% within 5 years was found. Patients with residual symptoms relapsed particularly in the first 4 months after remission, while patients without residual symptoms recurred mainly after 12 months after remission. Previous depressive episodes and psychoticism predicted relapse. Psychomotor retardation at inception predicted a longer time to partial remission. CONCLUSION In most cases, major depression is a seriously impairing episodic disease. This is also true for a sample of predominantly out-patients treated at a university clinic.

The dutch temperament and character inventory (TCI): dimensional structure, reliability and validity in a normal and psychiatric outpatient sample

Abstract In this study 170 psychiatric outpatients and 399 community-based adults completed a Dutch translation of the Temperament and Character Inventory (TCI). Factor structure, internal consistency and relationship with age and psychiatric status were investigated. Also comparisons were made between the TCI scores of the Dutch community sample and Cloninger’s US normative data. Confirmatory factor analyses were used to examine the relationship between subscales and their corresponding personality domain. Both the result of our patient and normal control group indicated a high similarity with the seven theoretical dimensions of Cloninger’s biosocial model of personality. The internal consistencies of the seven scales were remarkably comparable, both across patient and normal samples, and across culturally different samples of normal volunteers. The most conspicuous difference between the Dutch normal sample and Cloninger’s normative sample was a much lower Self-Transcendence score for our sample. As a whole the patient group had lower Self-Directedness and Cooperativeness and higher Harm-Avoidance scores than the normal controls. The findings of this study suggest that the TCI can be applied in the investigation of psychiatric and normal populations.

Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression

BACKGROUND The aim of the study was to search for the existence of, and define, a possible relationship between performance in neuropsychological tests and baseline concentrations of plasma cortisol, vasopressin and oxytocin in medication-free patients with a major depressive episode. METHODS Measures of depression and anxiety were obtained and a neuropsychological battery was presented. Blood for neuropeptide analysis was drawn by venepuncture at 8.00, 16.00 and 23.00 h. RESULTS The melancholic patients performed less well on the neuropsychological battery than did the non-melancholic patients, but these differences could be accounted for by the severity of the illness. Global intellectual functioning was negatively correlated with mean baseline plasma concentrations of cortisol. Patients with high mean plasma vasopressin concentrations remembered more auditory presented words in the delayed recall test and produced more intrusions in the visual word learning list than did patients with low or normal mean plasma vasopressin concentrations. No association was found between neuropsychological performance and plasma concentrations of oxytocin. CONCLUSIONS Our findings support the hypothesis that elevated baseline plasma cortisol concentrations are related to cognitive impairment in depressed patients and the hypothesis that the neuropeptide vasopressin independently enhances memory, directly or indirectly through increasing arousal and attention.

Plasma Arginine Vasopressin and motor activity in major depression

BACKGROUND Previously, we found that mean plasma concentrations of arginine vasopressin (AVP), but not of oxytocin (OT), were higher in depressed patients than in healthy controls. Plasma AVP concentrations were positively correlated to clinically rated psychomotor retardation. To further explore this previously reported relation we studied psychomotor retardation by means of an activity monitor, which is a more fine-focused and more objective instrument to analyze motor retardation than a clinical rating scale. METHODS Plasma AVP and OT concentrations, and day- and nighttime wrist activity were measured in 48 in- and outpatients with major depression and 30 healthy controls during a period of 5 consecutive days and nights. RESULTS Principal components analysis revealed three components of motor activity: motor activity during wakefulness, motor activity during sleep, and the awake/sleep time ratio. In patients and controls an inverse relationship between plasma AVP concentrations and motor activity during wakefulness was found. Patients with elevated AVP plasma levels showed increased motor activity during sleep. CONCLUSIONS These results suggest that high plasma AVP levels are related to the clinical picture of daytime psychomotor retardation and nighttime motor activity in major depression. Mean plasma OT concentrations were not related to measures of motor activity.

Fluvoxamine reduces responsiveness of HPA axis in adult female BPD patients with a history of sustained childhood abuse

The aim of the study is to test whether fluvoxamine affects the function of the hypothalamic pituitary adrenal (HPA) axis in female borderline (borderline personality disorder, BPD) patients with and without a history of sustained childhood abuse. Special attention is given to the presence of comorbid major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The HPA axis of 30 female BPD patients with (n=17) and without (n=13) a history of sustained childhood abuse was challenged with a combined dexamethasone and corticotropin releasing hormone test (DEX/CRH test) before and after 6 (n=14) and 12 (n=16) weeks of fluvoxamine treatment (150 mg/day). Both 6- and 12-week fluvoxamine treatments were associated with a significant and robust reduction of the adrenocorticotrophic hormone (ACTH) and cortisol response to the DEX/CRH test. The magnitude of the reduction was dependent on the presence of sustained childhood abuse, but not on the presence of comorbid MDD or PTSD: patients with a history of sustained childhood abuse showed the strongest reduction in ACTH and cortisol. In conclusion, Fluvoxamine treatment reduces the hyperresponsiveness of the HPA axis in BPD patients with a history of sustained childhood abuse. This effect is likely to be obtained in the first 6 weeks of treatment.

The interrater reliability of a Dutch version of the comprehensive psychopathological rating scale

To apply the Comprehensive Psychopathological Rating Scale (CPRS) in the Netherlands we translated the English version into Dutch and examined its interrater reliability. Three patient groups were investigated. Kappa coefficients were generally comparable with those reported in a study of the German version of the CPRS and in a Dutch study measuring the present state by means of the Present State Examination.

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. Forty-one patients with major depression and twenty-five controls participated in a case-control design under natural circumstances in a field study to investigate plasma vasopressin levels three times daily, circadian motor activity, and the 24-h periodicity of body temperature for five consecutive 24-h periods. Temperature measurements consisted of at least five, but mostly six or more measurements every 24 h. Twenty-two percent of the patients, but none of the controls lacked 24-h periodicity of body temperature. In melancholic patients increased vasopressin levels in plasma correlated with a weak 24-h periodicity of body temperature. The role of vasopressin is discussed in the light of the present findings.

Multidimensional hierarchic ordering of psychopathology : Rasch analysis in factor-analytic dimensions

Both the classification based on independent psychiatric categories as well as the concept of an underlying 1‐dimensional hierarchy of syndromes are insufficiently valid. At symptom level we previously found 5 factor‐analytical components representing 6 dimensions of psychopathology. Rasch analysis based on the prevalence of signs and symptoms now demonstrates the presence of hierarchic patterns in each of these dimensions. Manic, psychotic and rare neurotic symptoms, being the negative instances of the 1‐dimensional hierarchy, contribute to high rates of hierarchic patterns in this multidimensional hierarchic model. Depending on the dimension tested, 5% to 13% of the patterns were nonhierarchic.

Support for two increased vasopressinergic activities in depression at large and the differential effect of antidepressant treatment

Animal models of depression support a pathogenetic role for vasopressinergic activation involving increased arginine vasopressin (AVP) release and AVP receptor (V1b) synthesis. Evidence of this has been found particularly in patients with highly anxious-retarded (HAR) and above-normal AVP (ANA) depression. A general pathogenetic theory however predicts vasopressinergic activities to play a role in at least all major depressive disorders, and antidepressant (AD) treatment to be mediated by vasopressinergic reduction. We tested these hypotheses by re-analysing the data of 66 depressed patients; 27 with and 39 without AD treatment. The plasma AVP concentration and the AVP-cortisol correlation were used as presumed parameters of AVP release and pituitary V1b receptor function. A high AVP-cortisol correlation (r = 0.72; p < 0.001) was found in the non-AD group, and no correlation in the AD treatment group. AD treatment did not relate to plasma AVP concentration. The AVP-cortisol correlation in HAR and ANA depression was not explained by a low rate of AD treatment. These human data support the hypothesis of increased AVP release and receptor function as pathogenetic characteristics of major depression, and show selective normalization of the AVP-cortisol correlation, which is supposed to reflect the receptor function, by AD treatment.