Fatigue is a common symptom in the community and the commonest associations are with stress or mood disturbance. One in a hundred people complain of unexplained and prolonged fatigue, with half that number meeting the strictest criteria for the chronic fatigue syndrome (CFS). Discrete fatigue syndromes have been described, particularly after Epstein Barr virus infection. The majority of patients with CFS have a syndrome similar to the ICD-10 definition of neurasthenia. Mood and somatoform disorders are common comorbid or differential diagnoses.

The prognosis is poor, particularly in patients attending hospitals and those with comorbid psychiatric disorders. The aetiology of both CFS and chronic unexplained fatigue are essentially unknown, perhaps reflecting the heterogenenous natures of both the symptom and syndrome. There is reasonable evidence to suggest that particular infections may trigger both prolonged fatigue and CFS. Maintaining factors are different from triggering factors and include mood and sleep disorders, illness beliefs and behaviours, and possibly inactivity. Treatments aimed at reversing these maintaining factors show promise.

A psychofysiological study of the cardiac adaptivity to attention-demanding reaction time tasks demonstrated that children with a lesser variant of the pervasive developmental disorder (DSM-IV: PDDNOS) exhibit less cardiac responsiveness to attention tasks than healthy children do. We studied changes in heart rate variability (HRV), which were measured in a frequency band ranging from 0.07 to 0.14Hz. During the performance of an attention task, healthy children exhibited task load-related decreases in HRV. These decreases were found to be significantly smaller and not task load-related in a group of children with a PDDNOS who were judged to be not hyperactive. The decreases in HRV during task performance were almost absent in children with a PDDNOS who were moreover judged to be hyperactive. The magnitude of HRV decreases appeared to be significantly related to one of our task performance measures and to behaviour problems reported by the parents. Our results suggest a diminished vagal adaptivity to attention-demanding task situations in children with a PDDNOS, which is related to their resistance to unexpected changes in their daily routines.

Nature and nurture are not separate. Instead it is important to investigate the interplay between genes and environment and how they influence on another. To an important degree, genetic effects on behavior come about because they either influence the extent to which the individual is likely to be exposed to individual differences in environmental risk or they affect how susceptible the individual is to environmental adversities.

The current inability to explain or predict which genetically predisposed individuals will finally become schizophrenic has forced us to confront our ignorance of the precise mechanism and mode of the transmission of this disorder. Zubin's proposal to view the schizophrenic as a vulnerable individual who develops a temporary episode only under certain provocations can help place the controversy in proper perspective. Vulnerability (predisposition, diathesis) to schizophrenia can be defined as the individual's characteristic treshold beyond which stressful events produce decompensation manifest in the clinically diagnosable symptom picture.

The cytochrome P450 iso-enzyme system plays a key role in the biotransformation of many drugs, including psychotropics. Its activity is determined by both genetic and environmental factors. The most important iso-enzymes for psychiatry in general are P450 IID6, 3A4 and 1A2. Knowledge about the involvement of these enzymes and biotransformation processes is mandatory because of the individual variability in their metabolic capacity. Regular measurement of plasmaconcentrations of (psycho)pharmacological compounds is therefore essential. In addition, the potential value of pheno- and/or genotyping has to be investigated.

Mounting evidence suggests involvement of prenatal factors in the pathogenesis of schizophrenia. The objective of the present study was to provide evidence for the hypothesis on schizophrenia that abnormal fetal brain development leads to impaired sensorimotor gating of acoustic startle stimuli. To this purpose, pregnant rats were treated with methylazoxymethanol acetate on one of four subsequent days of gestation, from E9 to E12. These procedures inhibit early stages of cortical proliferation in the foetuses, resulting in adult brain abnormalities that were mainly found in the entorhinal region. At the adult age, habituation andprepulse inhibition (PPI) of startle responses to acoustic stimuli were investigated. Our results show impaired habituation and PPI in rats treated at embryonic days 10 and 11. It is concluded that sensorimotor gating deficits can result from a developmental abnormality involving the entorhinal region, supporting the hypothesis that similar deficits, often observed in schizophrenic subjects, may be the result of entorhinal cortex dysfunction.

Between 25 and 30% of the victims of a whiplash injury have complaints after one year. This condition is referred to as late whiplash syndrome. This syndrome is characterized by pain of the neck, headache, forgetfulness, poor concentration, mental fatigue, and affective symptoms. The causes of the persistent symptoms are unknown. In all, the evidence that late-whiplash syndrome is a neurological disorder is flimsy. Current opinion holds that the acute basis is the painful injury of the neck. In the months following the accident, pain is the substrate on which psychological and social factors may act. Emotional symptoms such as lability of affect and disturbed mood, or posttraumatic stress disorders are common after whiplash. Although there is definitely a place for psychiatrists and psychologists in the treatment of late whiplash syndrome, these professionals are not involved in late whiplash disorder as much as they should be. Brief psychological treatment has proven to significantly reduce the severity and duration of symptoms. Optimal management must cover the treatment of pain, depression, anxiety, and fatigue; adequate psycho-education, stressing the good long-term outcome; and education of patients and relatives on possible cognitive symptoms.

In the training program for residents in psychiatry, scientific education and participation in research projects are relatively underdeveloped. This may result in a gap between recently acquired scientific knowledge and its implementation in clinical practice.

Since the start of the residency training in psychiatry in 1989 in the Vincent van Gogh Institute for Psychiatry, several research lines have been developed especially concerning dimensional diagnostic procedures, evaluation of treatment effects, stress and psychopathology, pharmacokinetics of psychotropic compounds and disordered impulse and aggression regulation. It is concluded that active participation in research projects by both psychiatrists and residents in psychiatry is increasingly mandatory due to social-economic en scientific developments. Despite several countervailing factors, the Vincent van Gogh Institute for Psychiatry has succeeded in the creation of a scientific orientation in the residency program resulting in a number of publications.

Decades of research into the etiology of schizophrenia on a phenotypic level, i.e. studies of neuroanatomy, neuropathology, neurophysiology and other areas such as immunology have yielded only fragmentary results. A contribution of genetic factors, has been consistently shown, however, beginning with E. Kraepelin's pioneering studies at the turn of the century. Evidence has accumulated from family-, twin-, and adoption studies. Identical twins have a 48% risk of developing schizophrenia if one of them is affected. In contrast, a 17 % risk is reported for nonidentical twins. These rates are similar to other complex genetic disorders such as diabetes, hypertension and asthma. Advances in the genetic analysis of complex traits as well as progress in the Human Genome Project should provide a basis for uncovering the molecular causes of schizophrenic disorders and for investigating the neuropathology of this individually and socially devastating neuropsychiatrie disorder. There is no doubt, that discovery of the genetic variation associated with the illness would help in identifying specific targets for development of more effective, targeted treatments.

With aging, most cognitive functions decline, especially processes concerning memorizing, attention, concentration, organizing, planning and problem solving. Neuropsychology can make an important contribution in early and differential diagnostics. The borderline between normal and pathological cognitive aging is especially important in this respect. The neuropsychologist gains insight in medical, biological, psychological and social factors of the aging person. Has the profile of complaints and deficits a normal background or is a pathological process taking place? It is important to people who are unnecessarily worried about possible dementia.

Neuropsychological assessment also provides information about a patient's disturbed and undisturbed cognitive functions, their personality and their way of coping with problems in every day's life. This is of major importance, because it provides information and possibilities for biological or psychological interventions. Because of the complexity of problems that may occur, it is necessary that the neuropsychologist is experienced and works in a multidisciplinary team in which neurological and psychiatric expertise is present.

The distribution of schizophrenia within populations bears upon the genetic nature of the disorder. From the World Health Organization Ten-Country Study of incidence Jablensky et al concluded that: Schizophrenic illnesses are ubiquitous, appear with similar incidence in different cultures and have clinical features that are more remarkable by their similarity across cultures than by their difference.

The WHO study included populations in Japan, India and Europe that have been separated for tens of thousands of years. Moreover illnesses with essentially the same characteristics are commonplace in the Australian aboriginal population that separated from other human populations 50,000 years ago.

The relationship between epilepsy and behavior disorders will be briefly outlined, and an initial distinction between periictal and interictal disorders made. This paper will concentrate on the periictal disorders. These include the ictally driven psychoses, such as complex partial seizure status and absence status. There will then be a discussion of the postictal psychoses. It will be noted how these form a constant clinical picture, which sometimes goes unrecognized. The phenomenology may be typically paranoid or schizophrenia-like, andpatients often present in a setting of clear consciousness. The fascinating phenomenon of the lucid interval will be noted. Following this there will be some discussions on the management of these disorders. The rest of the paper will discuss the phenomenon of forced normalization, first discovered by Landolt. This often remains unrecognised, but is of interest to both neurology and psychiatry. Essentially this is about patients who, following suppression of seizures, develop an acute psychotic state or some other kind of behavior disorder. With the return of the seizures the behavior disorder resolves. Various theories in relationship to this condition will be noted, and the fascinating paradox that in psychiatry we give a seizure to resolve a psychosis, whereas in epileptology suppression of seizures can lead to a psychosis will be presented.

Med Psych Units (MPU) are neither clear-cut medical nor psychiatric units. This makes it difficult to acquire funding for these often expensive units. Despite this, there are many reasons why MPU's should be a necessary part of any larger scale inpatient service of a general and teaching hospital. It is therefore even more remarkable that such units hardly exist in Europe and that only about twenty exist in the USA. Five main reasons why such units should be opened are:

1. The increasing average age of the population of the Western World, with high co-morbidity and polypharmacy in the elderly and elderly elderly.

2. An increase in the number of chronic physical diseases resulting in co-morbid psychiatric disorders. This increase in chronicity is the consequence of increasingly successful treatment of acute and potentially lethal diseases; for example, acute myocardial infarction and the subsequent development of chronic heart disease.

3. The decreasing duration of hospital admission. On average the duration of stay in a general hospital in The Netherlands is now nine days. The number of day-treatments has doubled in the last decade. This situation means that it is not possible to observe the behavior of patients on a general medical ward or to carry out a psychiatric consultation.

4. Inadequate medical evaluation of psychiatric patients. According to a recent survey by the Dutch Ministry of Health, the care given for physical disease to psychiatric patients in mental hospitals in The Netherlands needs much to be desired for.

5. The psychiatric co-morbidity of somatic diseases is accompanied by a high consumption of medical facilities and high economic losses, unless adequately recognized and treated.

Classical psychiatric taxonomy appears to be increasingly inadequate in the diagnostic process of mentally retarded subjects. The reasons for this are the atypical presentation of classical psychiatric disorders, special diagnostic entities like cycloid psychosis and unstable mood disorder and the existence of so-called behavioural phenotypes related to syndromes with a known genetic etiology. In addition, disturbed behaviour may be the result of somatic or neurologic comorbidity and induced to adverse drug events.

Serotonin 5-hydroxytryptamine (5-HT) is an important regulator of morphogenetic activities during early central nervous system development, including cell proliferation, migration, and differentiation as well as synapto-genesis. Serotonergic raphe neurons diffusely project to a variety of brain regions (e.g. cortex, amygdala, hippocampus) and play known roles in integrating emotion, cognition, motor function as well as in food intake, sleep, pain, and sexual activity. The diversity of physiologic functions is due to the fact that 5-HT acts as a master control neurotransmitter within a highly complex system of neural communication mediated by multiple pre- and postsynaptic 5-HT receptors, thus orchestrating the activity and interaction of several other neurotransmitter systems. Since proteins involved in the regulation of central serotonergic activity (e.g. enzymes, receptors, transporter) play pivotal role in brain 5-HT homeostasis, polymorphisms in the regulatory regions of their genes resulting in variation of expression and function are likely to influence complex traits, such as temperament/personality and psychopathology.

The European psychiatric literature is rich in descriptions and studies of atypical psychotic disorders. Most of these are finally deemed to be varieties of the affective or schizophrenic disorders, which in turn are regarded to be typical.

The acute polymorphic psychotic disorder according to the ICD-10, and the periodic catatonia of Gjessing, although hardly recognized and acknowledged, are good candidates to be considered as separate psychotic disease entities.

Alzheimer disease (AD), the most common form of dementia in the elderly, is rapidly becoming a major health problem in developed countries where the number of elderly people continuously grows due to improved medical care. Consequently, the number of AD patients is increasing and thus far no effective therapies are available. Clinically the disease can be diagnosed with 90% reliability on the basis of neurological examination, neuropsychological testing and brain imaging techniques. A definite diagnosis, however, requires the post-mortem detection of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the brain. The SPs are extracellular deposits mainly composed of amyloid P (Ap) surrounded by dystrophic neurites. NFT are intraneural inclusions of paired helical filaments composed of hyperphosphorylated tau.

Although age is the major risk factor for AD, population survey and family studies have provided substantial evidence that genetic factors are major contributors to the expression of AD.

The common denominator of anxiety disorders is that they share inappropriate levels of emotions and cognitions that affect rather than enable adaptive behaviours. The variety of symptoms include ‘spontaneous’ panic attacks with mental and physical symptoms, stimulus bound anxiety associated with avoidance behaviour, and almost constant ‘generalized’ anxious feelings. According to the DSM-IV criteria the anxiety disorders are classified as shown in Table I.