[The Charles Bonnet syndrome and dementia]. / Het syndroom van Charles Bonnet en dementie.

An 83-year-old visually impaired woman was admitted to the hospital because of complex visual hallucinations. Her symptoms were indicative of the Charles Bonnet syndrome (CBS). On the basis of this case we explore the relationship between CBS and dementia and discuss the different opinions on this topic.

Left and right High Frequency repetitive Transcranial Magnetic Stimulation of the dorsolateral prefrontal cortex does not affect mood in female volunteers.

OBJECTIVE: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) has yielded divergent results concerning its effect on mood in normal volunteers. In a former study, we were unable to demonstrate negative mood effects after one session of HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) in a large group of healthy female volunteers: researchers had focused mainly on negative mood changes, overlooking a possible positive mood induction, while no studies had yet examined mood effects of HF-rTMS delivered on the right prefrontal cortex. In this study, we have tried to replicate our previous HF-rTMS findings on the left DLPFC in a new (large) group of healthy female subjects, and we focused especially on positive mood changes. We also extended our former research by stimulating the right DLPFC in a different but comparable (large) group of healthy female volunteers with the same HF-rTMS parameters. METHODS: In this sham-controlled, single blind, crossover HF-rTMS study, stimulus parameters were an exact copy of our previous healthy volunteer study. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic resonance (MRI) guidance. To examine subjective mood changes we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS), and the Positive Affect and Negative Affect Schedule (PANAS), the latter to assure assessment of positive emotions. To detect any delayed mood changes, assessments were also re-administered 30min post-HF-rTMS. RESULTS: We were unable to demonstrate immediate or delayed mood changes after one single active HF-rTMS session on the left or right DLPFC. CONCLUSIONS: Although we took into account several methodological problems which might have confounded previous rTMS mood induction studies, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence mood in healthy female volunteers was not supported. SIGNIFICANCE: One HF-rTMS session has no effect on subjective mood in healthy female volunteers.

[Mild mental retardation and complex psychiatric symptoms are accompanied by submicroscopic sub-telomeric deletion of a long arm of chromosome 3. A case study]. / Matige zwakzinnigheid en complexe psychiatrische symptomatologie die gepaard gaan met een submicroscopische subtelomerische deletie van een lange arm van chromosoom 3.

A 34-year-old woman presented with complex symptoms of unknown origin. Because she suffered from a co-existing learning disability (mental retardation) and dysmorphic disorders a genetic examination was carried out. This revealed a submicroscopic terminal deletion of the long arm of chromosome 3. The contribution that clinical genetics make to the diagnosis of mental retardation is discussed on the basis of a review of the recent literature.

Lack of impact of repetitive High Frequency Transcranial Magnetic Stimulation on mood in healthy female subjects.

BACKGROUND: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) is currently used as an experimental tool to induce mood changes in normal volunteers and as a treatment option for depression. However, HF-rTMS, mostly performed on the left dorsolateral prefrontal cortex (DLPFC), has yielded divergent results and effects on mood which seem to be oppositely lateralized between these two groups. The inconsistent results that have been reported might be explained by methodological heterogeneity and drawbacks. METHODS: In this sham-controlled, single blind, crossover study, we tried to reproduce previous HF-rTMS findings of a negative mood induction in 28 healthy female subjects. To exclude individual anatomical differences, the left DLPFC was localised under magnetic resonance guidance (MRI). Mood assessment was performed before and just after HF-rTMS with Visual Analogue Scales and the Profile of Mood States. To detect possible delayed mood changes, ratings were also performed 30 min post HF-rTMS. RESULTS: We were unable to demonstrate significant mood changes from baseline after one single active HF-rTMS session on the left DLPFC. CONCLUSIONS: Although this study controlled for several methodological problems, the hypothesis that one single session of HF-rTMS on the left DLPFC has negative mood effects in healthy female volunteers was not supported.

Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study.

Agomelatine (S 20098) has a unique and new pharmacological profile. It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder (DSM-IV criteria). The methodology used was a conventional double-blind design comparing three different doses of agomelatine (1, 5 and 25 mg once a day) with placebo over an 8-week treatment period. Paroxetine was used as the study validator. Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were included. On the pivotal analysis, the mean final HAM-D total score (Full Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more effective than placebo. This was confirmed by other analyses and criteria (responders, remission, subpopulation of severely depressed patients, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness). Agomelatine 25 mg alleviated the anxiety associated with depression, as measured on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to validate the study methodology and population. Agomelatine, whatever the dose, showed good acceptability with a side-effects profile close to that of placebo. In conclusion, this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.

Positron emissie tomografie (PET) bij stemmingsstoornissen: een overzicht.

Positron emission tomography is one of the most important techniques of functional imaging in psychiatry. This paper gives a synopsis of the findings in mood disorders: determination of brain glucose metabolism, cerebral blood flow and receptor studies. Investigation in a resting state as well as after activation are discussed. Although findings are somewhat discrepant hypometabolism, and/or hypoperfusion, most often in frontal and limbic areas are frequently described. Further research is needed, and standardization of the methodology would be most wellcome.

123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects.

5-HT2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT2A receptors, 123iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (123I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42% +/- 7% was found. These results are in agreement w in vitro and positron emission tomography findings of a decline in 5-HT2A receptor binding with age. The findings confirm the suitability of 123I-5-I-R91150 for SPET imaging of 5-HT2A receptors, and highlight the necessity for age-matched controls in clinical studies.

Cerebral blood flow related to induction of a depressed mood within and out of the realm of attention in normal volunteers.

The effects of a depressed mood on regional cerebral blood flow (rCBF) were measured after a mood-induction procedure (MIP) in normal volunteers. The MIPs were administered 'within the realm of attention' and 'out of the realm of attention'. A modified Velten procedure, which consisted of tape-recorded self-referent depressive statements, was used for mood induction. For the induction out of the realm of attention, a combination of dichotic listening and subliminal stimulation was used. A neutral induction procedure served as a control condition. CBF was measured with Tc-99m HMPAO single photon emission computed tomography (SPECT) with regard to 14 healthy female students. Scores on mood rating scales showed negative changes after both MIPs. Statistical analyses revealed lateralized changes in rCBF in the thalamus. Decreased thalamic CBF in the right hemisphere was demonstrated after both MIPs compared with the neutral induction condition. Moreover, hippocampal rCBF increased significantly, but only after induction out of the realm of attention. These findings suggest both hippocampal and thalamic involvement in the regulation of mood experience.

Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow.

An explorative analysis of the relationship between symptomatology and cerebral blood flow in the chronic fatigue syndrome (CFS) as assessed with 99mTc HMPAO SPECT scan reveals statistically significant positive correlations between frontal blood flow on the one hand and objectively and subjectively assessed cognitive impairment, self-rating of physical activity limitations and total score on Hamilton Depression Rating Scale on the other. A pathophysiological role of frontal blood flow in the cognitive impairment and physical activity limitations in CFS is hypothesized. A comparison of cerebral blood flow between CFS, major depression (MD) and healthy controls (HC) has been performed. A lower superofrontal perfusion index is demonstrated in MD as compared with both CFS and HC. There is neither a global nor a marked regional hypoperfusion in CFS compared with HC. Asymmetry (R > L) of tracer uptake at parietotemporal level is demonstrated in CFS as compared with MD.

Measurement of anhedonia.

Instruments developed to measure anhedonia are reviewed and their psychometric properties and conceptual framework discussed. Most instruments were designed considering anhedonia to be a symptom either of schizophrenia or of depression. Only the Physical and Social Anhedonia Scales of Chapman et al, designed to measure a lifelong pleasure deficiency, considered to be related to schizophrenia, and, to a lesser extent, the Pleasure Scale of Fawcett et al, designed to evaluate a state dependent deficit, considered to identify a subtype of depression, have been psychometrically extensively investigated. Since we were interested in studying anhedonia in depression, we made a Dutch translation of the Fawcett-Clark Pleasure Scale and report here on the psychometric properties of this translated version. Using the Rasch model for testing the homogeneity and transferability of the scale, we demonstrated that the original scale did not fit the model. A subscale of 14 items was constructed which did.

[Ethics and research: ethical considerations in clinical research]. / Ethique et recherche: Considérations éthiques en recherche clinique.

Two subjects are discussed: the use of placebo controls in clinical trials and informed consent. Particularly in trials of drugs for disorders for which there exist effective treatments, the use of placebo is still controversial, although anyhow in violation of the Declaration of Helsinki. Informed consent aims at giving a subject all the necessary information to allow him to decide, with full knowledge, whether to accept a particular treatment or experimental protocol. Its importance would seem, albeit essential, to be rather illusory.

Propofol and methohexitone anaesthesia: effects on the profile of mood state.

The influence on mood of anaesthesia by infusion with propofol or methohexitone was evaluated in 80 female patients assessed with the Profile of Mood State preoperatively and at 30 min, 1, 2 and 4 h after anaesthesia. Patients given propofol were more elated and continuously less anxious than those given methohexitone from 1 to 4 h after anaesthesia (54.3, SEM 1.1 vs. 50.7 SEM 1.2). They also felt more agreeable after 2 h (45.4 SEM 1.4 vs. 48.4 SEM 1.2). All patients felt more tired and more confused post-operatively than pre-operatively. Propofol has different and more favourable influences on the post-operative mood state than does methohexitone.

Dopamine D2 receptors in depression measured with single photon emission computed tomography.

Psychobiological theories of mood disorders have been concerned mainly with noradrenaline and serotonin. There exists, however, a recent upsurge of interest in dopamine. We have used single photon emission computed tomography and 123I-iodobenzamide, a high-affinity ligand for D2 receptors, to study these receptors in depression. Subjects were 21 (unipolar) depressed inpatients and 11 normal controls. The mean basal ganglia/cerebellum uptake ratio was 1.94 (+/- 0.27) in the depressed patients versus 1.74 (+/- 0.17) in the controls. This difference was statistically significant (Mann-Whitney U test, p = 0.025). These data could indicate an increase of D2 receptor density in depression.

Inhibition of the pituitary-adrenal axis with dexamethasone and cortisol in depressed patients and healthy subjects: a dose-response study.

Different doses dexamethasone (0.25, 0.5, and 1 mg) or cortisol (30, 60, and 120 mg) were administered PO at 2230h to 39 depressed patients and 20 healthy subjects on nonsuccessive days. The inhibiting capacity of the two steroids on hypothalamo-pituitary axis (HPA) function was evaluated by measuring the plasma levels of cortisol, ACTH, and beta-endorphin at 0900h and 1530h each day following treatment. Baseline levels of the hormones were measured before starting treatment. A dose-dependent suppressive effect of both steroids on the plasma levels of cortisol, ACTH, and beta-endorphin was found both in patients and controls, except for the 0900h levels of cortisol after cortisol treatment. The effects were most profound in the morning. Differences between patients and controls were observed after cortisol treatment, but not dexamethasone, with respect to cortisol, ACTH, and beta-endorphin plasma levels in the morning. Cortisol treatment discriminated dexamethasone nonsuppressors from suppressors (patients and controls) and patients categorized as dexamethasone suppressors from controls in a way that dexamethasone treatment could not. The data favour the idea of impaired corticosteroid feedback beyond the pituitary level as part of HPA dysfunction.

SPECT imaging of serotonin2 receptors in depression.

Changes of serotonin2 (5HT2) receptors have been described in depression, and long-term antidepressant treatment has been shown to decrease the number of 5HT2 receptors. In this study, single photon emission computed tomography (SPECT), with 2-123I-ketanserin as a ligand, was used to investigate 5HT2 receptors in vivo in the brain of depressed patients and normal volunteers. A higher uptake of the tracer was observed in the parietal cortex of the patients, and there was a right greater than left asymmetry in the infero-frontal region of the depressed subjects and not in that of the control subjects. These findings could indicate changes in 5HT2 receptors in major depression.

Influence of Propofol on the Mood - a comparative study.

The influence of propofol on mood was evaluated, considering the potential use of propofol as an anesthetic for electroconvulsive therapy. The mood state of 80 psychologically healthy subjects was assessed before and from 1/2 hour till 4 hours after surgery under anesthesia with either propofol or methohexitone. The mood was assessed with the Profile of Mood States (POMS). The propofol group was more elated from one hour until 4 hours after anesthesia (p<0,01 )(factor 1). 1 hour after anesthesia the propofol group was continuously more composed than the methohexitone group (p<0,01) (factor 4) and after two hours the propofol group was more agreeable (p<0,05) (factor 2). Moreover, patients, who received propofol, were less tired (factor 3) and confused (factor 5). It can be concluded that, compared with methohexitone, propofol has a favorable influence on different aspects of mood.

Predictive value of two endogenicity measures.

Endogenicity has been considered to have a major predictive value as to the therapeutic response to antidepressants. Two recently introduced measures of endogenicity (the Michigan Discriminant Index and the Hamilton Endogenomorphy Subscale) were investigated regarding their potential predictive value. It was concluded that, in a group of selected depressive patients, neither the Michigan Discriminant Index, nor the Hamilton Endogenomorphy Subscale, had a predictive value concerning short-term response to antidepressants.