J.G. Goekoop

Anxious–Retarded Depression: Relation with Plasma Vasopressin and Cortisol

Dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis is related to melancholic or endogenous depression; however, the strength of this relationship depends on the definition of the specific depression subcategory. A two-dimensionally defined subcategory, anxious–retarded depression, is related to melancholic depression. Since arginine vasopressin (AVP) activates the HPA axis, and both major depression and the melancholic subcategory are associated with elevated plasma AVP levels, we investigated whether the plasma AVP level is also elevated in anxious–retarded depression, melancholic depression and anxious–retarded melancholic depression, and whether plasma AVP and cortisol levels are correlated in these subcategories. A total of 66 patients with major depression not using oral contraception were investigated. Patients with anxious–retarded depression had a highly significant AVP–cortisol correlation, while no such correlation was found in patients with nonanxious–retarded depression. Log-transformed mean plasma AVP values were higher in patients with anxious–retarded depression than in patients with nonanxious–retarded depression. Patients with anxious–retarded melancholic depression also had a significantly elevated level of plasma AVP and a highly significant correlation between plasma AVP and cortisol levels. The correlation was low in patients with melancholic depression. Anxious–retarded depression may be a useful refinement of the melancholic subcategory with regard to dysregulation of the HPA axis and plasma AVP release.

Clinical use of the determination of serotonin in whole blood

Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whole-blood 5-HT concentration of patients was strongly reduced. After treatment with tranylcypromine, an unspecific monoamine oxidase inhibitor (MAOI), the 5-HT content was increased. Determination of whole blood 5-HT in patients treated with fluvoxamine presents a measure of drug compliance. Furthermore, the method may have clinical potential for finding an adequate dose when a 5-HT reuptake inhibitor or an MAOI is used.

Depression with above-normal plasma vasopressin: Validation by relations with family history of depression and mixed anxiety and retardation

An anxious-retarded subtype of depression has been derived from the DSM-IV category of melancholia. It is defined by combined high scores for anxiety and retardation, and is related to family history of depression and increased plasma vasopressin (AVP) levels. Central problems concerning this hypothesized subcategory are whether elevated plasma AVP is related to family history, whether it would be better operationalized by a cut-off level for plasma AVP than as continuous variable, and whether the anxious-retarded phenotype would be better described in terms that account for full variability of mixed anxiety and retardation. A previous study suggested that above-normal plasma AVP was a more useful endophenotypic parameter than plasma AVP as a continuous variable. To answer these and related questions, 81 patients were investigated. Receiver Operating Characteristic analyses yielded a cut-off value of 5.56 pg/ml for above-normal plasma AVP, log-transformed plasma AVP (ln (AVP)) was used as continuous variable, and the correlation between anxiety and retardation was used to account for full variability of the anxious-retarded phenotype. Family history was related to above-normal plasma AVP (n = 16) and non-significantly to ln (AVP). Depression with above-normal plasma AVP, as well as familial depression with above-normal plasma AVP, showed a high correlation between anxiety and retardation, and this correlation was significantly higher than that found in the depressed patient control groups. The data support the delimitation of a largely familial depression with above-normal plasma AVP, vasopressinergic activation of the hypothalamus-pituitary-adrenal axis and a variable anxious-retarded phenotype.

A Network View on Psychiatric Disorders: Network Clusters of Symptoms as Elementary Syndromes of Psychopathology

Introduction The vast number of psychopathological syndromes that can be observed in clinical practice can be described in terms of a limited number of elementary syndromes that are differentially expressed. Previous attempts to identify elementary syndromes have shown limitations that have slowed progress in the taxonomy of psychiatric disorders. Aim To examine the ability of network community detection (NCD) to identify elementary syndromes of psychopathology and move beyond the limitations of current classification methods in psychiatry. Methods 192 patients with unselected mental disorders were tested on the Comprehensive Psychopathological Rating Scale (CPRS). Principal component analysis (PCA) was performed on the bootstrapped correlation matrix of symptom scores to extract the principal component structure (PCS). An undirected and weighted network graph was constructed from the same matrix. Network community structure (NCS) was optimized using a previously published technique. Results In the optimal network structure, network clusters showed a 89% match with principal components of psychopathology. Some 6 network clusters were found, including DEPRESSION, MANIA, “ANXIETY”, PSYCHOSIS, RETARDATION, and BEHAVIORAL DISORGANIZATION. Network metrics were used to quantify the continuities between the elementary syndromes. Conclusion We present the first comprehensive network graph of psychopathology that is free from the biases of previous classifications: a ‘Psychopathology Web’. Clusters within this network represent elementary syndromes that are connected via a limited number of bridge symptoms. Many problems of previous classifications can be overcome by using a network approach to psychopathology.

Recall performance, plasma cortisol and plasma norepinephrine in normal human subjects

This study investigated hypothalamic-pituitary-adrenal (HPA)-axis and sympathetic nervous system (SNS) correlates of recall performance in normal human subjects. Twenty-two normal human subjects were given one memory task: short-term recall of unrelated non-organizable lists of neutral words, in immediate recall conditions. Two types of memory were individualized: measures reflecting effortful processing and measures reflecting automatic processing, which were related to 3 daytime plasma cortisol (CORT) and plasma NE values, and assessed after venipuncture. It was hypothesized that plasma CORT is positively related and plasma norepinephrine (NE) is negatively related to effortful processing. Pearson correlation was computed and regression analysis was performed. Positive correlation appeared between plasma CORT values and negative correlation appeared between plasma NE values and measures reflecting effortful processing. However, stepwise multiple regression analysis showed that only morning plasma CORT values are functionally positively and afternoon plasma NE values are functionally negatively related to effortful processing. This suggests that morning HPA-axis activities enhance and afternoon SNS activities inhibit effortful processing.

Anxious-retarded depression: relation to family history of depression.

Anxious-retarded depression is a two-dimensionally defined subcategory of depression based on high scores for both anxiety and retardation. The anxious-retarded subcategory is related to melancholia as defined by DSM-IV. Patients with this diagnosis exhibit elevated plasma arginine vasopressin (AVP) and a high correlation between plasma vasopressin and cortisol, which suggests vasopressinergic overactivation of the hypothalamus-pituitary-adrenal (HPA) axis. In this report, we present the multidimensional derivation of the anxious-retarded subcategory from DSM-IV melancholia, and a second step in the validation of this anxious-retarded subcategory by exploring its relation to family history of depression. The patient sample comprised 89 patients with major depression and encompassed 66 patients investigated previously regarding plasma AVP and cortisol. All patients were rated for the following three dimensions of psychopathology: autonomic dysregulation (anxiety), motivational inhibition (retardation), and emotional dysregulation, as well as for family history of depression. The dependence of DSM-IV melancholia on the sum scores and the dichotomized scores on the three dimensions was investigated by multiple logistic regression. Thereafter, the dependence of the family history for depression on the same parameters was also investigated. The melancholic subcategory depended on the interaction between the sum scores, as well as on the interaction between the dichotomized scores for anxiety and retardation that constitute the anxious-retarded subcategory. Family history for depression depended only on the interaction of the dichotomized scores, and thus on the anxious-retarded subcategory.

The Network Structure of Human Personality According to the NEO-PI-R: Matching Network Community Structure to Factor Structure

Introduction Human personality is described preferentially in terms of factors (dimensions) found using factor analysis. An alternative and highly related method is network analysis, which may have several advantages over factor analytic methods. Aim To directly compare the ability of network community detection (NCD) and principal component factor analysis (PCA) to examine modularity in multidimensional datasets such as the neuroticism-extraversion-openness personality inventory revised (NEO-PI-R). Methods 434 healthy subjects were tested on the NEO-PI-R. PCA was performed to extract factor structures (FS) of the current dataset using both item scores and facet scores. Correlational network graphs were constructed from univariate correlation matrices of interactions between both items and facets. These networks were pruned in a link-by-link fashion while calculating the network community structure (NCS) of each resulting network using the Wakita Tsurumi clustering algorithm. NCSs were matched against FS and networks of best matches were kept for further analysis. Results At facet level, NCS showed a best match (96.2%) with a ‘confirmatory’ 5-FS. At item level, NCS showed a best match (80%) with the standard 5-FS and involved a total of 6 network clusters. Lesser matches were found with ‘confirmatory’ 5-FS and ‘exploratory’ 6-FS of the current dataset. Network analysis did not identify facets as a separate level of organization in between items and clusters. A small-world network structure was found in both item- and facet level networks. Conclusion We present the first optimized network graph of personality traits according to the NEO-PI-R: a ‘Personality Web’. Such a web may represent the possible routes that subjects can take during personality development. NCD outperforms PCA by producing plausible modularity at item level in non-standard datasets, and can identify the key roles of individual items and clusters in the network.

pH-dependent behaviour of erythrocyte membrane elevations

Freeze-etch electron microscopy of human erythrocytes from heparinized normal blood reveals membrane elevations. These elevations disappear at low pH values and reappear under normal pH conditions in vitro, both in the absence and the presence of plasma. This pH-dependent behaviour is discussed as an intrinsic membrane event.

Osmotic behavior of erythrocytes from patients with a major affective disorder: A freeze-fracture electron microscopic study

Previously we have demonstrated a state-dependent decrease in the number of membrane vesicles in erythrocytes from patients with a major depressive episode. We now report an increase in the number of membrane vesicles during a manic episode as well as a reduction during lithium treatment and we also present data suggesting that the number of erythrocyte membrane vesicles in the affective disorders is dependent on osmotic shrinkage due to the freezing for freeze-etch electron microscopy. Although caution is required since the interrater reliability of the measurement of osmotic strain was insufficient in the mid range where it was tested, we do not think this invalidates the differences in osmotic strain found in the low and high ranges during depressive and manic episodes respectively. These findings warrant the use of more precise techniques in studies of the osmotic behavior of erythrocytes from patients with a major affective disorder.

The appearance of erythrocyte membrane elevations Effects of cooling rates

Low cooling rates during the freezing procedure of normal human blood reveals red cell membrane elevations in freeze-etch electron microscopy. When high cooling rate is applied, these morphological changes are present, if the blood samples are quenched from 5 degrees C. The number of elevations is strongly reduced by low pH and glycerol. Elevations are not observed in ghosts. The formation of intramembrane particle aggregation is differently affected by many conditions.