[Narcissistic personality disorder]. / Narzisstische Persönlichkeitsstörung.

Narcissism is a multifaceted term which encompasses traits of normal personality as well as a specific personality disorder. While much research has been concerned with narcissism as a trait there are only few empirical studies available on narcissistic personality disorder (NPS). The current diagnostic of NPS according to DSM-IV-TR focuses on grandiose type narcissism whereas vulnerable narcissism, which has been described by clinicians and researchers has not yet been recognised. Psychotherapy of narcissistic patients through different psychotherapeutic schools focuses mainly on processes in the therapeutic relationship, the analysis and change of grandiose and vulnerable schemas, emotion regulation techniques and correction of narcissistic behavior in favor of prosocial interactions.

Dissociative symptoms are positively related to stress in borderline personality disorder.

OBJECTIVE: According to DSM-IV criteria, dissociative symptoms in borderline personality disorder (BPD) occur in response to stress. Empirical evidence is, however, lacking. METHOD: Using ambulatory monitoring, we assessed dissociative symptoms and subjective ratings of stress every 60 min for 48 h on a palmtop computer in BPD-patients (n = 51), clinical controls (CC; major depression n = 25; panic disorder n = 26), and healthy controls (HC; n = 40). Data analyses were primarily based on hierarchical linear models. RESULTS: In all groups, states of increased stress were paralleled by increased scores of dissociation, thus confirming the hypothesized association between stress and dissociation. The increase in dissociation was more pronounced in BPD-patients when compared with CC and HC. Additionally, BPD-patients reported heightened dissociative experience compared with CC and HC, even after controlling for stress. CONCLUSION: Our data suggest that BPD-patients might be prone to dissociation when experiencing stress and are characterized by a generally heightened level of dissociation.

[Nacissistic personality disorder]. / Narzisstische Persönlichkeitsstörung. Immer Arger mit Mr. Bombastic.

The narcissistic personality disorder is the extreme form of the so-called narcissistic personality style, which is characterized by exaggerated self-importance coupled with an inordinate desire to be admired, ideas of grandiosity and a strong sense of entitlement, an absence of empathy and feelings of envy. In contact with others, the narcissist appears arrogant, readily feels injured, and takes advantage of other to achieve his own ends. A central psychodynamic role in the development of the condition is a labile sense of self-worth and its overcompensation. Psychotherapeutic treatment aims initially to develop an awareness of the problem in the patient, correction of cognitive dysfunction and a reduction in aggressive or disdainful behavior. Impulsive and aggressive behavior and attacks of depression may be reduced through the use of selective serotonin reuptake inhibitors.

Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls.

There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.

Combined dexamethasone/corticotropin-releasing hormone test in acute and remitted manic patients, in acute depression, and in normal controls: I.

Hypothalamic-pituitary-adrenal system (HPA)-function in patients with mania (n = 11), depression (n = 11, unipolar) and in control subjects (n = 11) was studied; six of the acutely manic patients were reevaluated after a symptom-free interval of at least 6 months. The combined dexamethasone-suppression/human CRH-challenge test was used to probe HPA-system function. After CRH and dexamethasone pretreatment, ACTH and cortisol release were significantly increased in both manic and depressed patients in comparison to the control group. In the remitted patients with mania, a significant decrease in hormonal release after DEX and CRH was evident when compared to the acute manic episode, but the degree of CRH-stimulated hormone secretion in these remitted patients was still significantly larger than in normal controls. This study demonstrates that acute and remitted manic episodes are associated with a profoundly dysregulated HPA-system activity.

The combined dexamethasone/corticotropin-releasing hormone stimulation test is more closely associated with features of diurnal activity of the hypothalamo-pituitary-adrenocortical system than the dexamethasone suppression test.

BACKGROUND: The dexamethasone suppression test (DST) is a widely used endocrine test in psychiatry, but was reported to not allow reliable inferences with regard to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system. We compared the association of the standard DST and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters of diurnal cortisol profiles. METHODS: We performed a DEX/CRH challenge and 24-hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years) and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). RESULTS: A path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH status) to be dependent upon minimal 24-hour cortisol and evening frequency of pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST status) was related to 24-hour mean cortisol. Simple linear regressions supported an association of cortisol AUC with several parameters of the diurnal cortisol profiles, which was not true for the standard DST. CONCLUSIONS: We conclude that the combined DEX/CRH challenge test is more closely associated with the activity of the HPA system than the standard DST in healthy and depressed subjects.

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

Hypothalamic-pituitary-adrenal system (HPA) function was tested in 24 patients with schizophrenia and compared to 24 age-matched healthy volunteers using the combined dexamethasone-suppression (DST/CRH) corticotropin-releasing hormone stimulation test (DST/CRH). After stimulation with CRH, the dexamethasone-pretreated patients released significantly more cortisol, but a similar amount of adrenocorticotropic hormone (ACTH) in comparison to controls. No association between DST status and degree of severity of illness and/or current medication was found. However, in comparison to unmedicated patients, those patients currently receiving antipsychotics, who were also those with a lesser degree of severity of illness, showed a decreased release of CRH-stimulated cortisol and ACTH. This study demonstrates that schizophrenic patients have a dysregulation of the HPA system as assessed with the DEX/CRH test. Overall, however, the degree of HPA-system dysfunction in schizophrenic patients seems to be of a lesser magnitude than in patients with affective disorders.

Age-associated changes of pituitary-adrenocortical hormone regulation in humans: importance of gender.

In the present study the hypothesis was tested that in normal human aging an insensitivity of the glucocorticoid feedback signals is acquired. Thus, 40 healthy elderly (mean age: 69 +/- 5 years) and 20 younger (mean age: 34 +/- 8 years) individuals underwent a combined dexamethasone suppression/CRH-stimulation test. Cortisol secretion after dexamethasone (DEX) pretreatment and before CRH was increased in the older age group, but none of the subjects escaped DEX-induced suppression of cortisol. However, after additional CRH administration to the DEX-pretreated volunteers, the older group released significantly more cortisol than their young counterparts. Within the group of the elderly only, a positive correlation between BASAL, DEX-pretreated cortisol concentration and post-CRH steroid responses was found. Gender profoundly affected DEX/CRH-test outcome: females, regardless of age, had an increased hormonal secretion in comparison to males. It is concluded that, during human aging, adaptive changes in glucocorticoid receptors take place, allowing for the system to maintain "peripheral" glucocorticoid homeostasis, but that more sophisticated challenge procedures such as the DEX/CRH test reveal an age-related increase in HPA system activity.

Pituitary-adrenal-system regulation and psychopathology during amitriptyline treatment in elderly depressed patients and normal comparison subjects.

OBJECTIVE: This study was done to compare the effects of 6-week treatment with amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) regulation in elderly depressed patients and age-matched comparison subjects. METHOD: A combined dexamethasone-suppression/CRH-stimulation (dexamethasone/CRH) test was administered before initiation of amitriptyline treatment and at the end of weeks 1, 3, and 6 of treatment. Thirty-nine depressed inpatients, mean age = 69 years, completed the study. Fourteen normal volunteers, mean age = 67 years, served as comparison subjects. RESULTS: In relation to the comparison subjects, the depressed patients had a profoundly abnormal HPA response, in particular an exaggerated cortisol release in the dexamethasone/CRH test. This abnormality began to disappear after 1 week of treatment with amitriptyline. In contrast, amitriptyline did not affect neuroendocrine regulation in the comparison subjects at any time during the test period. CONCLUSIONS: The data suggest that amitriptyline affects HPA regulation in hypercortisolemic depression only, and they raise the possibility that normalization of its feedback control is related to the antidepressive effect of amitriptyline.

Low lumbar bone mineral density in patients with major depression.

Major depression is associated with hypercorticoidism, a risk factor for osteoporosis. However, it is unknown whether depressive disorders are associated with alterations in bone mineral density. The authors measured the density of trabecular bone from the first to the third lumbar vertebra by quantitative computerized tomography in 80 depressed inpatients older than 40 years and in 57 healthy comparison subjects. An analysis of covariance model with age as a covariate showed a significant effect of diagnosis on the dependent variable spinal bone mineral density: depressed patients had lower values. Other factors could not explain the finding. The authors conclude that major depression is a significant risk factor for osteoporosis.

In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid.

A putative transcription factor induced in vitro by glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta was recently cloned and characterized [Yajima S. et al. (1997) J. Neurosci. 17, 8657-8666]. The messenger RNA of this protein, termed murine GDNF-inducible transcription factor (mGIF, hereafter referred to as GIF), is localized within cortical and hippocampal regions of brain, suggesting that GIF might be regulated by perturbations of these brain regions. In an effort to learn more about the role of GIF in vivo, we examined GIF messenger RNA in the brains of rats treated with the glutamatergic agonist kainic acid. This treatment is known to induce seizures and alter the messenger RNA expression of several growth factors, including GDNF, in several brain regions. Rats were given intraperitoneal saline (1 ml/kg) or kainic acid (15 mg/kg) and were killed at various time-points for in situ hybridization of brain sections with a GIF messenger RNA riboprobe. In saline-treated rats, GIF messenger RNA was present at low levels in cerebral cortex, hippocampus and hippocampal remnants such as the taenia tecta. Kainic acid treatment induced robust increases in GIF messenger RNA in several brain regions, including cerebral cortex, hippocampus, caudate-putamen, nucleus accumbens, and several nuclei of the amygdala and hypothalamus. Most brain regions showed the greatest increase in GIF messenger RNA 4-6 h after kainic acid administration and a return towards normal levels at 48 h. The CA3 region of hippocampus, however, showed a more rapid increase in GIF messenger RNA that was also evident 48 h after kainic acid administration. These results demonstrate that GIF messenger RNA can be regulated in vivo, and that this novel factor warrants further study as a central mediator of GDNF and perhaps other neurotrophic factors.

Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain.

We have established the cellular distribution of the dopamine D3 receptor using tritiated 7-hydroxy-N-N-di-n-propyl-2-aminotetralin and a complementary RNA probe to visualize autoradiographically the protein in binding studies and the gene transcripts by in situ hybridization, respectively. Studies with these two markers confirm the restricted expression of the D3 receptor in few brain areas, i.e. mainly the ventral striatal complex, the substantia nigra-ventral tegmental area and the cerebellum. In nucleus accumbens, the D3 receptor was mainly expressed in medium-sized neurons of the rostral pole and ventromedial shell subdivisions, but not of the core or septal pole, i.e. accumbal subdivisions expressing the D2 receptor. In the ventromedial shell, about 60% of the D3 receptor-expressing neurons were neurotensin neurons, presumably projecting to the ventral pallidum. In the islands of Calleja, both D3 receptor binding and messenger RNA were abundant in the entire population of granule cells. These cells are known to make sparse contacts with dopaminergic axons and also to express the D1 receptor. In the mesencephalon, low levels of D3 messenger RNA were detected in few dopamine neurons of substantia nigra pars lateralis and ventral tegmental area. In addition, some D3 receptor binding but not messenger RNA was detected in medial substantia nigra and lateral ventral tegmental area, where the receptor is presumably located presynaptically on afferents. In the archicerebellum, Purkinje cell perikarya in lobules 9 and 10 expressed the D3 receptor messenger RNA, whereas binding sites were found in the molecular layer, where corresponding dendrites but no known dopaminergic projection from mesencephalon are found. The occurrence of D3 receptor gene expression in some brain areas receiving low dopamine innervation supports the hypothesis that this receptor may mediate non-synaptic actions of dopamine.

Regulation of striatal dopamine receptors by corticosterone: an in vivo and in vitro study.

The effects of chronic corticosterone administration and adrenalectomy on the expression of brain dopamine receptors were studied in rats. In situ hybridization and receptor binding autoradiography were carried out to determine D1, D2 and D3 receptor expression in dorsal and ventral striata. Except for down-regulation of D2 mRNA in dorsal striatum after 2 week corticosterone treatment, no other significant changes were detected. In addition, the transcriptional regulation of D1 and D2 gene promoters by glucocorticoids was studied in neuroblastoma cell lines using transient transfections. While a small segment of the D2-promoter could be activated three-fold by dexamethasone, large fragments of neither D1 or D2 promoters were regulated by this treatment. Glucocorticoids do not appear to have direct overall effects on striatal dopamine receptor expression. The observed down-regulation of D2 receptor mRNA in the dorsal striatum in vivo is likely secondary to increased striatal dopamine release induced by corticosterone.

With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.

There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.02) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.005) and ACTH (p < 0.006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.01) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.

In situ hybridization on brain tissue.

ABSTRUCT: In situ hybridization (ISH) is an important method for determining the distribution of mRNA within cells or tissue preparations by hybridization of a nucleic acid probe (either DNA or RNA) with a specific target nucleic acid (usually mRNA) (1,2). Thus, ISH enables the localization of transcripts within cells, tissues, and whole body and allows a neuroanatomic comparison of specific mRNA expression with the respective protein expression. Furthermore, ISH can serve as a tool to detect quantitative changes in gene expression in distinct neuroanatomic areas under various experimental conditions.

[Psychopharmacologic treatment of personality disorders]. / Psychopharmakologische Behandlung von und bei Persönlichkeitsstörungen.

There is only a paucity of studies concerning the pharmacological treatment of personality disorders per se. On the other hand the clinical use of medication in these conditions is quite high, although there is no effective psychopharmacological treatment of distinct personality disorders. The psychopharmacological treatment of patients suffering from a personality disorder focuses on distinct symptoms and its comorbidity. Some symptoms could also be associated with other disorders like depression or psychosis, which often makes an exact differentiation of these disorders and a personality disorder difficult. Since symptoms of personality disorders are ego-syntonic, chronic and very often dependent on psychosocial factors, it is unlikely that a solely psychopharmacological treatment will be successful in most patients with a personality disorder. However, severe syndromes like depressive, impulsive, aggressive, dissociative, anxious or psychotic features may render a pharmacotherapy necessary. For the treatment of depressive syndromes or impulsivity a medical therapy with serotonin reuptake inhibitors, for the treatment of psychotic syndromes a medication with atypical antipsychotics is recommended. Impulsive or aggressive behaviour could be treated with mood stabilizers as well. Furthermore, there are indications for the use of alpha2-agonists, micro-opiate-antagonists and omega-3 fatty acid. The general use of benzodiazepines should be avoided as well as polypragmasy. Advantages versus potential damage of a high dose pharmacotherapy should be carefully weighed against each other. This article gives an overview over the today's most common psychopharmacological treatment possibilities in patients with a personality disorder.

Preliminary evidence of improvement of depressive symptoms but not impulsivity in cluster B personality disorder patients treated with quetiapine: an open label trial.

INTRODUCTION: Atypical antipsychotics might become a new treatment option for patients with an impaired impulse regulation as seen in cluster B personality disorders (PD). The aim of the present study is to investigate the efficacy and tolerability of quetiapine in patients with cluster B PD. METHODS: Fifteen in-patients with a DSM-IV diagnosis of borderline, histrionic, or narcissistic PD were treated for 8 weeks with quetiapine at a dose of 400 mg/day in an open-label fashion. Effects on impulsivity (Barratt Impulsiveness Scale, BIS), depressive symptoms (Hamilton Depression Scale, HAMD, and Beck Depression Inventory, BDI) and side effects (Dosage Record and Treatment Emergent Symptom Scale, DOTES) were assessed. RESULTS: Twelve patients completed the study. No positive effect on impulsivity (BIS) was found, but a significant improvement on depression scores (HAM-D and BDI) was noted. Adverse effects that might have been due to study medication were mainly anticholinergic and mild-to-moderate. DISCUSSION: The data of our preliminary open-label study do not argue for a general recommendation of quetiapine for the treatment of impulsivity in cluster B PD, but indicate positive effects on depressive symptoms.

[Significance of emotion-focused concepts to cognitive-behavioral therapy]. / Bedeutung emotionsfokussierter Konzepte und Interventionen für die kognitive Verhaltenstherapie.

Emotions are the central process of motivation and play a key role in adaptive behavior in humans. Although cognitive-behavioral therapy stresses the importance of changing both cognition and behavior, there is growing emphasis on direct therapeutic work on emotions and emotional processing, as problematic emotional processes are at the core of nearly all psychic disorders. This type of work is the goal of emotion-focused psychotherapy, which centers on direct change of problematic emotions, especially those which are usually suppressed resp. overregulated by the patient. This paper examines the basic phobic/emotional conflict, the problematic emotional processes arising from this conflict, and the importance to cognitive-behavioral therapy of their potentially integrative role.