In this first part of a review on biological psychiatric aspects of obsessive-compulsive disorder (OCD), firstly a short introduction is given about historical, diagnostic and epidemiological issues concerning OCD. Subsequently pharmacologic treatment-studies are discussed. Only serotonin (5-HT) reuptake blockers are proven to be effective. There is accumulating evidence that this therapeutic effect is not due to antidepressant effects. The results of the treatment-studies strongly suggests that 5-HT is involved in OCD. CSF-studies seem to confirm this. Possibly the therapeutic effect is related with adaptive changes of 5-HT receptors. There is evidence that in a subgroup of O CD-patients the dopaminergic system is involved.

In this second part of a review on OCD, challenge-tests are discussed and an overview is given of neuro-imaging studies. Subsequently some hypotheses concerning the pathogenesis of OCD are reviewed. The serotonin (5-HT) agonist metachloro-phenylpiperazine (mCPP) was found to lead to an increase in obsessive-compulsive symptoms. These studies revealed a dissociation between the behavioral and the neuroendocrine responses: OCD-patients showed a blunted hormonal respons compared to controls. Possibly different receptor subtypes are involved. One study is reported with a 5-HT1a agonist as a probe. This study lends no support to an involvement of the 5-HT1a receptor. Tests with noradrenergic probes showed unequivocal results.

Research on the neuroanatomic substrate of OCD is critically reviewed. PET-scan studies point to a possible role of the (orbito-)frontal cortex and the basal ganglia in OCD. Keywords: obsessive-compulsive disorder, OCD, challenge-test, serotonin (5-HT), mCPP, PET-scan.

Two subjects are described suffering from longlasting behavioral disorders, who appeared to have both an abnormal karyotype, 47XXY and 47XYY respectively. The relationship between psychopathological disorders and the type of karyotypes is discussed. It is concluded that both biological and environmental factors are involved in the development of behavioral disorders that are observed frequently in this kind of subjects.

In this paper a case history is described of a young male patient who gradually developed progressive personality changes and psychiatric complaints. This was subsequently followed by neurological symptoms and dementia. The patient appeared to be suffering from the adult form of metachromatic leucodystrophy (MLD). MLD is a rare disease with an autosomal-recessive mode of inheritance. The pathogenesis involves a deficiency of the enzyme arylsulfatase-A, causing sulfatide accumulation in (among others) nervous tissue.

Based upon a review of the literature several subtypes of MLD are mentioned. Both diagnostic aspects and therapeutic possibilities are critically discussed. It is argued that in cases of psychiatric complaints which do not easily fit in the diagnostic framework of the DSM-III-R in adolescence, the existence of neuropsychiatric diseases should be evaluated.