W.M.A. Verhoeven

Brain correlates of memory dysfunction in alcoholic Korsakoff's syndrome

OBJECTIVES To investigate the relation between anterograde amnesia and atrophy of brain structures involved in memory processing in alcoholic Korsakoffs syndrome. METHODS The volume of brain structures involved in memory processing was measured with MRI from 13 subjects with Korsakoffs syndrome, 13 subjects with chronic alcoholism without Korsakoffs syndrome, and 13 control subjects. The brain structures analysed were the hippocampus, the parahippocampal gyrus, the mamillary bodies, the third ventricle, and the thalamus. Brain volumes were correlated with the delayed recall of a verbal learning test. RESULTS Compared with subjects with chronic alcoholism and control subjects, subjects with Korsakoffs syndrome had a reduced volume of the hippocampus, the mamillary bodies, and the thalamus, and enlargement of the third ventricle. The impairment of delayed recall correlated with the volume of the third ventricle (r=−0.55, p=0.05) in the Korsakoff group. CONCLUSIONS Anterograde amnesia in alcoholic Korsakoffs syndrome is associated with atrophy of the nuclei in the midline of the thalamus, but not with atrophy of the mamillary bodies, the hippocampus, or the parahippocampal gyrus.

The psychopathological phenotype of Velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) is mostly associated with deletions of chromosome 22q11, and is thought to be characterized by an increased frequency of major psychiatric disorders. Sixteen patients adults with VCFS and psychiatric symptoms were evaluated using a semi-structured investigation of history, symptoms, signs and behaviour. All available data were used in consensus meetings to obtain a classifiable diagnostic category. In contrast to other reports, no categorical diagnosis could be established. Instead, a quite specific psychological, behavioural and psychopathological constellation emerged that should most adequately be denominated as a VCFS-psychiatric syndrome. It is concluded that VCFS is associated with a specific psychopathological syndrome.

Plasma amino acids and neopterin in healthy persons with Down’s syndrome

SummaryIn persons with Down’s syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism.In the present study, 48 older healthy DS persons without signs of dementia, psychiatric or somatic comorbidity and free of medication were analyzed for plasma levels of amino acids, neopterin and monoaminergic metabolites. Data were compared with those obtained from age and sex matched healthy controls.It was found that the spectrum of amino acids showed widespread differences in that levels of nearly all essential amino acids were lower in DS patients as compared to healthy controls. In addition, a significantly lower methionine and higher taurine concentration were observed which is in accordance with a disturbed homocysteine metabolism. With respect to the monoamine metabolites, the concentration of 5-hydroxyindoleacetic acid was not altered whereas that of homovanillic acid was significantly increased. Finally, the concentration of the immune activation marker neopterin was increased in persons with DS.It is concluded that healthy DS persons of older age show extensive biochemical abnormalities suggesting a compromised homocysteine metabolism, an activated cell-mediated immune response and an enhanced turnover of dopamine.

Sanfilippo B in an elderly female psychiatric patient: A rare but relevant diagnosis in presenile dementia

Verhoeven WMA, Csepán R, Marcelis CLM, Lefeber DJ, Egger JIM, Tuinier S. Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia.

Citalopram in mentally retarded patients with depression: A long-term clinical investigation

The effect of citalopram was investigated in 20 mentally retarded patients suffering from a depressive disorder characterized by alterations in the domains of affectivity, motivation, motor activity and vital signs. The study followed a baseline-controlled open design. Citalopram was started in a daily dosage of 20 mg that was kept unchanged for 6 weeks. Thereafter dosage was adjusted to maximally 60 mg per day. Treatment effects were assessed according to the Clinical Global Improvement Scale (CGIS) after at least 6 months. In 12 of the 20 patients a moderate to marked improvement in all domains was observed upon treatment with 20-40 mg citalopram daily. Treatment for one year in the effective dose prevented recurrence of depressive symptomatology. Concomitant use of sedative anticonvulsants reduced responsiveness to treatment. No interactions were observed. It is concluded that citalopram is a well-tolerated, safe and effective antidepressant in mentally retarded subjects with depressive disorders.

Two steps forward, one step back; paradigmatic changes in psychiatry.

Summary. The initial scientification of psychiatry after the European discovery of psychotropic drugs via psychopharmacology and biological psychiatry has gradually ended in an impasse. As a result of at least four developments, psychiatry is re-orientating in a more dimensional and functional direction in order to adapt to the progress in the neurosciences. Rigid adherence to nosological systems should be replaced by a careful observation and description of psychopathology as well as a search for relevant psychological dysfunctions and their putative pathophysiological basis. Psychotropics have to be developed that do not suppress symptoms but promote potentially intact functions. Emphasis should be given to the brain mechanisms that are involved in habit formation and chronicity. Modern genetics will drive the discipline towards early intervention and prevention and will elucidate the relations between genetic disorders and the behavioural phenotype. The basis, however, remains clinical observation, dynamically reshaped by neuroscience.

Neuropsychiatric aspects of patients with hypothalamic hamartomas

Hypothalamic hamartomas (HH) are developmental malformations that are associated with gelastic seizures, other types of seizures, cognitive decline, and symptoms related to hypothalamic dysfunction. Although aggressive behavior is frequently described, data on the neuropsychiatric profile are limited. In this article, five patients with HH are described who displayed a wide variety of psychiatric symptoms that, dependent on the time frame, met the criteria for several categorical diagnoses. Major neuropsychiatric symptoms comprised aggression that is only partial context dependent, compulsive behavior, psychotic symptoms not responding to treatment, and organic mood instability. HH should therefore be considered a neuropsychiatric syndrome with a highly variable expression that can be best captured by a thorough description of behaviors, symptoms, sequelae of epilepsy, and hypothalamic dysfunction.

Prader–Willi syndrome: cycloid psychosis in a genetic subtype?

Prader–Willi syndrome (PWS) is a genetically determined disorder associated with the loss of the paternal contribution to the proximal part of the long arm of chromosome 15. Its pathophysiology is dominated by hypothalamic dysfunctions. The psychopathological phenotype comprises affective and psychotic symptoms as well as an increase of pre-existent obsessive-compulsive behaviors. The present study comprises 19 PWS patients who were referred for neuropsychiatric evaluation because of psychotic deterioration. Patients were assessed by using the elements of semistructured symptom checklists. In the majority a genetic analysis was performed to detect the underlying chromosomal defect. In 16 of the 19 patients a diagnosis of cycloid psychosis could be established. The other three showed a bipolar affective disorder. Of the psychotic patients, 11 were diagnosed as UPD and one as del 15q11–13. The remaining four patients were diagnosed clinically. For various reasons the genetic etiology could not be established. In PWS patients with a psychotic disorder (cycloid psychosis) a disproportional number of UPD is found.

Neurosyphilis in the mixed urban–rural community of the Netherlands

Objective Neurosyphilis is caused by dissemination into the central nervous system of Treponema pallidum. Although the incidence of syphilis in the Netherlands has declined since the mid-1980s, syphilis has re-emerged, mainly in the urban centres. It is not known whether this also holds true for neurosyphilis. Methods The epidemiology of neurosyphilis in Dutch general hospitals in the period 1999–2010 was studied in a retrospective cohort study. Data from the Dutch sexually transmitted infection (STI) clinics were used to analyse the number of patients diagnosed with syphilis in this period. Results An incidence of neurosyphilis of 0.47 per 100 000 adults was calculated, corresponding with about 60 new cases per year. This incidence was higher in the western (urbanised) part of the Netherlands, as compared with the more rural areas (0.6 and 0.4, respectively). The number of patients diagnosed with syphilis in STI clinics increased from 150 to 700 cases in 2004 and decreased to 500 new cases in 2010. The sex ratio was in favour of men, yielding a percentage of 90% of the syphilis cases and of 75% of the neurosyphilitic cases. The incidence of neurosyphilis was highest in men aged 35–65 years, and in women aged 75 years and above. The most frequently reported clinical manifestation of neurosyphilis was tabes dorsalis. In this study, 15% of the patients were HIV seropositive. Conclusion The incidence of neurosyphilis in a mixed urban–rural community such as the Netherlands is comparable to that in other European countries. Most patients are young, urban and men, and given the frequent atypical manifestations of the disease reintroduction of screening for neurosyphilis has to be considered.

Catatonia: The rise and fall of an intriguing psychopathological dimension

Background: For at least 125 years the discussion about the clinical relevance of catatonic symptoms in psychiatry continues. It started from the original description by Kahlbaum and was revived by modern factor analytical studies, that identified the catatonic dimension in about 10% of newly admitted patients. Objective: Over a period of 2 years, four patients with an acute episodic psychosis and prominent catatonic symptoms were examined. Methods: A clinical description is given of the psychopathology and classification is performed according to the various diagnostic instruments. Results: All patients showed a circular fluctuation of their psychoses, with motor symptoms ranging from the excited to the inhibited pole within one episode. Their clinical pictures also comprised mood swings and anxieties as well as hallucinatory and delusional experiences, whereas the course of disease was characterized by complete recovery without residual symptoms. Conclusions: The significance of catatonic symptoms is not recognized in the current taxonomies despite the fact that this has major pharmacological treatment implications.