Naast de gangbare indicaties voor ECT op het gebied van de affectieve stoornissen, zijn ook positieve effecten van deze behandeling beschreven bij enkele neurologische ziektebeelden. De auteurs geven een overzicht van gepubliceerde onderzoeksresultaten en ziektegeschiedenissen met betrekking tot de effectiviteit van ECT bij de behandeling van motorische symptomen van Parkinson-patiënten met of zonder coëxistente depressieve stoornis. Het enige prospectieve gecontroleerde onderzoek maakt melding van een positief resultaat op de motorische symptomen dat tot zes weken na behandeling aanhoudt. Dit komt overeen met de resultaten van vrijwel alle open onderzoeken en gepubliceerde casus, waarbij verbeteringen beschreven worden, variërend van enkele weken tot vier juar. Twee open onderzoeken (één retrospectief en één prospectief) vinden geen effect op de motoriek.

De aangehaalde literatuur rechtvaardigt volgens de auteurs het opzetten van groter prospectief onderzoek naar de waarde van deze behandeling voor Parkinson-patiënten, en wel met name bij die groep patiënten waarbij de medicamenteuze behandelmogelijkheden uitgeput zijn.

Deze artikelen (deel I en deel II) bevatten een overzicht van de literatuur van de laatste vijftien jaren over psychomotorische stoornissen bij depressieve patiënten, zoals ze gemeten worden met behulp van de volgende meetmethoden:

1. 1. observatieschalen (deel I);

2. 2. de meting en de analyse van specifiek non-verbaal gedrag (deel I);

3. 3. spraakonderzoek (deel I);

4. 4. (keuze) reactietijdmetingen (deel II);

5. 5. metingen van grove motoriek (deel II);

6. 6. onderzoek van fijne motoriek (deel II).

De onderzoeksresultaten warden per methode samengevat. Onderzocht wordt of (a) bij depressieve patiënten een vertraging vastgesteld werd, (b) waaruil deze bestond, (c) welke de aard van de vertraging was, (d) of er correlaties gevonden werden met andere meetmethodes, en (e) welke effecten van behandeling er werden gemeten.

With the introduction of major tranquillizers more than three decades ago symptom rating scales were soon accepted as the method of evaluating their clinical effects. The Mini-compendium is a collection of rating scales for measuring outcome of antianxiety drugs, antidepressants, antimanics, and anti-psychotics. The scales have been selected by their “cash values”, i.e. the scales most frequently used for the respective dimensions. These scales have been further developed in terms of strict item definitions. The simple sum of the individual scale items has been considered as a sufficient statistic if they fulfilled latent structure analysis of shared phenomenology.

Oince the discovery in the late 1950's of imipramine (Tofranil®), the first tricyclic antidepressant (TCA), and iproniazid, the first monoamine oxidase inhibitor (MAOI), many other TCAs and MAOIs, now being considered the classical antidepressants, have become available. Their effectiveness has been shown in numerous studies, although according to nowadays standards well designed studies (placebo-controlled, defined diagnostic groups, the use of standardized rating scales) with these compounds are relatively scarce.

From the early 1980's the so called modern antidepressants have been introduced: the selective serotonin re-uptake inhibitors (SSRIs), the reversible selective monoamine oxidase-A inhibitors (RIMAs) and a variety of other compounds. All these drugs have been registered after their effectiveness had been shown in well designed, placebo-controlled studies. In defining the efficacy of antidepressants, registration authorities consider two aspects important: statistical evidence and clinical relevance.

In this review article, based on a literature study, present ideas upon the relation between M. Parkinson and concomittant depression are dicussed. After a short introduction, it is demonstrated that epidemiological studies show that a common pathophysiological basis can be assumed. Briefly pheno-menological aspects are mentioned, whereafter the changes in the different neurotransmittersystems are discussed in greater detail. The ratio of dopaminergic and serotonergic activities in the basal ganglia constitute an important determinant for the severity of motor symptoms in Parkinson's disease. Reduced serotonergic metabolism may be a compensatory mechanism for the reduced dopaminergic activity. At the same time, a reduced serotonergic activity can predispose to a depression. Lower activities in parts of the dopaminergic, serotonergic and noradrenergic systems may each be responsible for part of the affective symptomatology in depressed Parkinson patients.

Aim: Translation of a specific instrument to measure psychomotor retardation, the “Widlöcher Retardation Rating Scale” and validation of this Dutch translation (Widlöcher remmingsschaal, WRS). Method: In three separate studies, we studied reliability (n = 26), concurrent and divergent validity (n = 25) and predictive validity (n = 28) of the WRS. In- and outpatients with a depressive disorder or schizophrenia participated, and scores on the WRS were compared with those on the Montgomery Asberg Depression Rating Scale (MADRS) and retardation items of the Comprehensive Psychopathological Rating Scale (CPRS).

Results: The internal consistency was good (Cronbach alpha = 0.86), interrater reliability was sufficient to good, the correlation between the sumscores of both raters was r = 0.84, n = 23, p <0.01 and the kappa's were between 0.23 and 0.80. Convergent and divergent validity showed in comparing the correlation between the sum scores on the WRS and the CPRS retardation items (r = 0.91, n = 25, p < 0.01 ) with the correlation between the sumscores on the WRS and the MADRS (r = 0.40, n = 25, p = 0.1). The decrease of the sum scores on the WRS after two weeks of treatment with antide-pressants predicted remission after six weeks. A subgroup of the patients who were not in remission after six weeks, showed a predominance of retardation signs over mood disturbances. The same clinical picture was seen in a group of patients with a chronic disorder.

Conclusion: De Widlöcher Retardation Rating Scale in this Dutch translation is a usefull instrument to measure psychomotor retardation. The connection between remaining retardation symptoms and longterm prognosis deserves further investigation.

The growing populations of the elderly is frequently regarded as a homogeneous entity. In this retrospective study 140 patients above 60 years, first admitted to a psychiatric hospital, were screened for individual psychiatric symptoms. This was done according to the D.S.M.-III-R criteria and with the european ADMP-IV scoring system.

As expected dementia and related disorders are characteristic of the “older” categories, depressieve disorders were seen more frequently in the “younger” categories. Screening the elderly for psychiatric symptoms also shows differentiation within the group of the older patients.

Symptoms related to dementia increase in frequency, also increasing are e.g. visual hallucinations. A decrease was found for hypochondriasis and phobia. So, the group patients above 60 years is clearly heterogeneous.

Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches should operate in close interaction, each providing additional information to the other approach. However, in practice the animal model approach seems to be rather independent from the human studies. In a critical evaluation of the available animal models of depression, Willner concluded that none of the models fulfilled the criteria of a sufficient face, construct and predictive validity. Although this evaluation was made ten years ago, we feel that the situation has improved very little since that time. Most animal models fail to sufficiently mimic both the etiology and the symptomatology of human depressive disorders. With respect to the etiology, stress and major life events are generally considered to be an important factor in the development of depression. Most of the animal models however use stressors which bear little or no relationship to the biology of the species, i.e. to the situations an animal may meet in its everyday life in a natural habitat. Moreover, these models do not pay attention to the temporal dynamics of the disease. In humans, the disease is characterized by its gradual onset, which is often preceded by symptoms of anxiety. Moreover, a relatively large number of patients suffers from recurrent episodes of depression, which tend to occur with decreasing intervals and increasing duration and severity. If we want to improve our knowledge of the causal mechanisms of depression, animal models which allow an experimental analysis of the temporal dynamics of the disease are essential.

The elucidation of sleep regulation is not an easy task. On one side, there is a multitude of solid yet disparate data, on the other side, the topic is tempting for engaging in wild speculation, particularly with respect to the functions of sleep. Models may exert a moderating influence by mediating between the two extremes. However, also they navigate between the risk of banality in reformulating the obvious, and the peril of fancy in losing touch with empirical reality.

Many of the dramatic seasonal changes that occur in animals are triggered by changes in the length of night. Changes in the duration of melatonin secretion, which usually occurs exclusively at night and therefore lasts longer in winter than in summer, often act as a chemical transducer of the effects of seasonal changes in night-length on animals' behavior and physiology. Cells in sites that regulate seasonal behaviors, such as those associated with breeding, appear to possess melatonin receptors and interval timing mechanisms that enable them to detect melatonin and measure the duration of the nightly interval when it is present. These sites then trigger changes that are appropriate for the season that is indexed by the measured length of the interval.

In this article the value of the tyramine conjugation test (TCT) as a predictor of the response to antidepressive medication is reviewed. The TCT seems of little discomfort for the patient, is easy to perform and is suggested to have a high sensitivity and specificity. In addition, there are indications that a decreased tyamine conjugation could be a traitmarker for the vulnerability of depression. Hypotheses concerning the, as yet unclear etiology of the decreased tyramine are reviewed.

The mitogen induced lymphocyte responses were measured in 33 depressed patients categorized according to the DSM-III into minor (300.40, 309.00), simple major (296.X2) and major depression with melancholia and/or psychotic features (296.X3, 296.X4). Three distinct mitogens were used, i.e. phytohemaglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (CON A). We found that major depressives with associated features showed significantly lower mitogen induced lymphocyte responses to PHA and PWM as compared to all other depressed patients. The severity of illness was significantly inversely related to the lymphocyte responses to PHA. Cortisol nonsuppressors exhibited significantly lower PHA and PWM induced lymphocyte responses as compared with suppressors. There were significant and negative correlations between the postdexamethasone Cortisol values and the PHA and PWM stimulated lymphocyte responses.

Serotonin (5-HT) plays an important role in depression and specific 5-HT reuptake blockers appear to be clinically important antidepressants. It is unclear however, which serotonergic mechanism is involved in the antidepressant effect, certainly when regarding the existence of at least seven 5-HT receptor subtypes. By testing different 5-HT ligands in two animal models of depression (forced swimming and DRL72-S test) and comparison with data from literature, evidence is provided for potential antidepressant qualities of 5-HT1A receptor-agonists and 5-HT1C receptor-antagonists. Compounds binding to 5-HT1B, 5-HT2 and 5-HT3 receptors do not have an antidepressant profile. Results of clinical research support the predicted antidepressive effects of 5-HT1A receptor-agonists.

An attempt is made to relate drug and non-drug antidepressive interventions to brain processes. In the present context two concepts are proposed: vulnerability towards depressogenic factors and depression as a state of the brain. Accordingly, it is assumed that the current antidepressants make the brain less vulnerable by inhibiting monoaminergic neurons and by reducing the number or efficacy of their postsynaptic receptors. In contrast, electroconvulsive therapie and sleep-deprivation affect primarily the state of the brain and can produce spectacular (but often short lasting) improvements. It is proposed that the combination of the two aspects may lead to fast and lasting antidepressive effects.

This paper reviews the relationship between cholesterol and psychological functioning. Possibly a relationship exists between the lowering of cholesterol, low serum cholesterol concentration and mood and/or impulse control disorders. This might be associated with a disregulated cerebral serotonin metabolism. These hypotheses are based on (meta-analyses of) epidemiologic research investigating the lowering of cholesterol. One of the findings was an increased mortality due to suicide, homicide and accidents. Much is still unknown about the matters mentioned above. However, recommendations for research and clinical psychiatric practice are formulated.

The dexamethasone suppression test has been carried out in 111 depressed inpatients. Fasting, 8 a.m. plasma levels of Cortisol and adrenocorticotropic hormone (ACTH) were determined before and after administration of 1 mg dexamethasone. In 64 subjects multisequential (1-17,1-24,1-39) ACTH, and in 47 subjects intact (1-39) ACTH has been determined. Patients with melancholia exhibited significantly higher postdexamethasone Cortisol and intact ACTH values as compared with minor and simple major depressives. Severity of illness was significantly and positively related to postdexamethasone intact ACTH - but not to multisequential ACTH. Cortisol nonsuppressors showed higher postdexamethasone (only intact) ACTH values than Cortisol suppressors. Both postdexamethasone ACTH values were significantly and positively related with the postdexamethasone Cortisol values. We have established that Cortisol nonsuppression during melancholia is determined by an augmented escape of ACTH from suppression by dexamethasone. Intact ACTH showed the most significant clinical relevance for depression and Cortisol nonsuppression. In the clinical practice we advize the use of postdexamethasone intact ACTH in stead of plasma Cortisol or multisequential ACTH.

In an introduction the evolution of a neuropsychological and neuropsychiatrie approach in the two last decades is discussed. The role of the basal ganglia, the thalamus and their cortical connections in aphasia is discussed. This review is given as a paradigm to demonstrate a neuropsychiatrie approach of psychiatric disorders. The role of corticosubcortical relations in depression is discussed.

The TRH-test in depression: a review

This paper reviews the literature on the thyrotropin releasing hormone (TRH)-test in depressive patients. The TRH-test appears to exhibit some use as an external validating criterion for the clinical diagnosis of major depression and, in particular melancholia versus minor depression once the clinical diagnosis depression is made. However, the clinical use of this test is hampered by the low sensitivity (±50%) and by the fact that abnormal tests occur in non-depressive states such as borderline personality disorder, schizophrenia, and anxiety disorders. The TRH-test may be used as a predictor for a positive response to biological therapies. In addition, the test has some value for the outcome of a depressive episode. The pathophysiology underpinning an abnormal TRH-test may be determined by noradrenergic (central and peripheric) or serotonergic (central) dysfunctions, thyroid hormone and cortisol hypersecretion, phenomena that are pertinent to severe depression. Recently, it has been established that an abnormal depression-linked TRH-test reflects lower basal thyroid secreting hormone (TSH) secretion. The determination of basal TSH may, in the future, replace TRH-testing.

In this review we discuss the results of studies about the effect of stress, depression, anxiety, social support and various psychosocial treatments on numbers and activity of Natural Killer (NK) cells. In general a suppressive effect is observed among depressive persons and persons who react to stressfull events with feelings of helplessness and anxiety. Lack of social support also seems to engender immunosuppression including NK suppression. Various forms of psychosocial care seem to be able to undo these negative consequences. However, the real clinical relevance of these findings is still a matter of dispute.

People with Parkinson's disease often suffer from depressions. Treatment of these depressions requires the use of antidepressants. The advanced age of most patients, however, can put limitations on the range of suitable antidepressants. Moreover, the drug should not aggravate Parkinson's disease. Many patients suffering from Parkinson's disease are currently prescribed selegiline. This drug is commonly considered to be a contraindication for antidepressants.

In this article, criteria for the choice of a suitable psychofarmacon are discussed. In particular suggestions are offered for the treatment of patients who are already taking selegiline.