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 author describes the development of a neurotoxicity syndrome in a 68 year old women treated for 1½ years with lithium for recurrent depressions. The syndrome developed after 10 mgr. haloperidol per day was added, during a manic episode, for 10 days. The lithium levels were 0.71 ± 0.19 MEq/L. After 19 days all medications were discontinued. The neurotoxicity consisted succes-sivily of confusion, somnolence, agitation, extrapyramidal symptoms, cerebellair ataxia and EEG abnormalities. After 10 weeks memory impairmments were still present. At four months, memory function was restored. After five months, the patient was discharged without residual symptoms. The patient reported amnesia for the first six weeks of the syndrome. The author points out that while patients may develop tolerance to lithium maintenance after several years, they still may develop a neurotoxicity syndrome when haloperidol is added to treat a manic episode.

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).

Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.

Toxicology is one of the eldest areas of special attention in medicine and pharmacy. In the past, forensic toxicology was the most important part, but nowadays, at least in the Netherlands, the clinical, occupational and environmental toxicology have the centre of attention.

The brain plays its own role in the clinical toxicology. There the intoxication can take place, it can be the basis of the peripheral symptoms of the intoxication or it can be the cause of the intoxication, e.g. at a suicidal attempt or the hospital addiction syndrome.

The somatic treatment of an intoxicated patient includes in the first place the stabilization of the patient (cardio-vascular, ventilation and central effects); then the removal of the poison from the surroundings and out of the patient by different suitable methods and finally the symptomatic treatment, sometimes with antidotes.

In the Netherlands, hardly any intoxication is fatal, when the patient arrives in the hospital in time, or euthanasia took place on purpose.

Recently, some investigators have reported blunted natural killer cell activity (NKCA) in patients with major depression. In addition, there were some reports on negative relationships between NKCA and the occurence of negative life events. In order to replicate the above findings, the present study investigates NKCA and negative life events in 11 normal and 35 unipolar (minor, simple major, melancholic) depressed subjects. NKCA has been determined by all subjects. They completed the Questionnaire on Recently Experienced Events with scores on number and impact factor of events related to a) illness, b) working conditions, c) social relationships, d) housing problems, e) loss of possession. Depressed subjects reported higher scores on number and/or impact factor of events related to illness, social relationships and housing problems. In our investigation NKCA was significantly blunted in depressed subjects and, particularly in melancholies. So NKCA is negative correlated to the severity of depression. We were unable to detect any significant relationship between NKCA, and life events ( number of impact factors ), Our results do not corroborate the thesis that life events may affect immune function, as assessed by NKCA.

This article describes the use of non-invasive magnetic resonance (MR) methods for the characterization and monitoring of the pathophysiology of experimental brain injury in laboratory animals as a function of time and treatment. The impact of MR in brain research is primarily due to its non-invasive nature, thereby enabling repeated measurements in long-term studies, and due to the type of information that it provides. MR imaging (MRI) enables the measurement of the morphology/anatomy as well as the functional status of tissues under in vivo conditions. Compared to other in vivo imaging modalities, MRI has a high spatial resolution and allows for a remarkable soft tissue differentiation. MR spectroscopy (MRS) provides information on the biochemical/metabolic status of tissues. MR methods which have proven valuable in animal studies, can be readily translated to the clinical situation where MR-based diagnosis and treatment planning play a rapidly increasing role.

After a short introduction into the principles of MR, we will illustrate the remarkable versatility of MR in research on brain injury from recent animal studies. Examples will be mainly drawn from experiments on early injury in focal cerebral ischemia and from research on mechanical brain trauma and excitotoxic lesions. The article ends with a brief description of the perspectives of MR in neuropsychiatry.

Peripheral markers of psychiatric illness provide a potentially important window into the pathophysiology of a number of psychiatric illnesses. Direct access to pathophysiological processes is fraught with difficulty. However, receptor-regulated second messenger-mediated calcium shifts are an accessible and practical method by which to examine changes in a clinical population. This is possible because platelets and neurons share some physiological features. The platelet intracellular calcium response to receptor stimulation has previously been used as a peripheral marker of psychiatric illness across a range of neurotransmitters, including serotonin, dopamine and glutamate. This review considers the specificity and selectivity of this response and its use in psychotic and mood disorders.

Réus GZ, Stringari RB, Rezin GT, Pezente DP, Scaini G, Maggi DD, De-Nês BT, Streck EL, Quevedo J, Feier G. Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain.

Objective: Electroconvulsive therapy is used efficacious treatment for a variety of complicated psychiatric disorders and evidences have indicated that energy metabolism impairment may be involved in pathophysiology and treatment of mood disorders. This work was performed to determine creatine kinase and mitochondrial respiratory chain activities at different times after the maintenance electroconvulsive shock (ECS).

Methods: Male Wistar rats received a protocol mimicking therapeutic of maintenance or simulated ECS (sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance ECS. We measured creatine kinase and mitochondrial respiratory chain activities in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum.

Results: Our results showed that maintenance ECS alter respiratory chain complexes and creatine kinase activities in the rat brain, but these effects were related to brain area and time after the ECS, in which the animal were killed.

Conclusion: Finally, these findings further support the hypothesis that alteration on the energy metabolism could be involved in the therapeutic or adverse effects of ECS.

De dexamethason-corticotrofin-releasing-hormoon (DEX-CRH)-test is de meest gevoelige test voor veranderingen in de regulatie van de hypothalamus-hypofyse-bijnier-as bij stemmingsstoornissen. Zowel in de premorbide toestand als tijdens de acute episoden van stemmingsstoornissen komt onder deze conditie een verhoogde cortisolreactie voor. Een irreversibele lage GAHA-concentratie kan aan dit regulatietekort een bijdrage leveren. Verhoogde noradrenerge en vasopressinerge activiteiten kunnen in de overgang naar hogere DEX-CRH-reacties tijdens de acute episode een rol spelen. De dexamethason-suppressie-test verschilt van de DEX-CRH-test door de afwezigheid van een externe CRH-belasting en ‘early escape’ in deze test is op specifieke wijze geassocieerd met het melancholische subsyndroom. Dit suggereert dat een endogeen verhoogde CRH-activiteit bij de overgang naar deze subcategorie is betrokken. Verhoogde CRH-activiteit is aangetoond en toenames van noradrenerge activiteit en 5-HT2a-receptoren en afnames van glucocorticoïd-receptor-functie, tryptofaan-concentratie en serotonine-afgifte kunnen een bijdrage leveren. De uiteindelijk resulterende hoge cortisol-concentraties lijken de ontwikkeling te kunnen bevorderen van een resttoestand met ‘early escape’ na herstel.

Herman van Praag has made major contributions to the scientific and conceptual development of psychiatry. Despite progress in delineating reliable diagnostic criteria, our classification system ignores clinical insights available from patients' subjective experiences of illness. Hence a ‘coarsening of diagnosis’ has occurred, weakening the nosologic infrastructure of scientific psychiatry. This paper will discuss these ideas and emphasize the central role of psychopharmacology in advancing psychiatry, with lithium's discovery as a paradigm.

Advances towards the understanding of the etiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome, specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. Other studies have reported the presence of anticipation in BPAD. This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (Trinucleotide Repeat Sequences) and may represent a genetic factor involved in the transmission of the disorder. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions. While significant advances have been made in this major field of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders.

This, then, is what it has been all about. Today I mark the end of an academic career that ranged over 45 years. 1952 was the starting point. In that year, as a medical student, I was accepted as a research assistent by Prof. G.G.J. Rademaker, a neurophysiologist and at the time head of the Department of Neurology at the Academic Hospital in Leiden. The neurological research period was followed by a mycological one. Having received my MD degree and doing my military service, I was asked to carry out a study into the prevalence, prevention and treatment of mycological infections in military personel. For this reason I worked for more than 1, 5 years in Baarn at the section Medical Mycology of the Phytopathological Laboratory, an interacademic institution of the Universities of Amsterdam and Utrecht (1956-1958). Immediately after the military service I became a resident in psychiatry and started – together with the biochemist Prof. B. Leijnse – a research program into the biological determinants of depression. The period of psychiatric investigation lasted until this very day, albeit in different locations, i.e. Rotterdam, Groningen, Utrecht, New York and Maastricht respectively.