Hengeveld, M.W.

Drug-free patients with major depression show an increased electrophysiological response to valid and invalid feedback (Article)

2011-12-01T00:00:00Z

Background Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients.Method Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured.Results Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback.Conclusions The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.

Randomised clinical trial: Escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C (Article)

2011-12-01T00:00:00Z

Background Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. Aim To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and ribavirin treatment in a randomised, double-blind, placebo-controlled trial. Methods Seventy-nine hepatitis C patients were treated with peginterferon and ribavirin. Patients received escitalopram (n = 40, 10 mg) or placebo (n = 39), which was initiated together with peginterferon and ribavirin. Primary outcomes were an increase of two points or more on the items reported sadness, inner tension and impaired concentration of the Montgomery-Asberg Depression Rating Scale, and hostile feelings of the Brief Anxiety Scale. Secondary outcome was the development of depression diagnosed by the Mini-International Neuropsychiatric Interview. Measurements were performed at baseline, week 4, 12 and 24 during anti-viral treatment, and 24 weeks thereafter. Results The incidence of psychiatric side-effects was significantly lower in patients treated with escitalopram compared with placebo for all primary and secondary outcomes, except for impaired concentration: reported sadness 27.5 vs. 48.7% (P = 0.052), inner tension 17.5 vs. 38.5% (P = 0.038), impaired concentration 55.0 vs. 66.7% (P = 0.288) and hostile feelings 22.5 vs. 43.6% (P = 0.046) (escitalopram vs. placebo, Chi-squared test). The sum scores of all four endpoints showed an overall beneficial effect of escitalopram (P = 0.009, Mann-Whitney U-test). Depression occurred in 12.5% of the patients in the escitalopram-group vs. 35.9% in the placebo-group (P = 0.015, Chi-squared test). Conclusions Prophylactic treatment with escitalopram is effective in the prevention of psychiatric side-effects during interferon-based treatment of hepatitis C.

Cardiac and electrophysiological responses to valid and invalid feedback in a time-estimation task (Article)

2011-07-13T00:00:00Z

This study investigated the cardiac and electrophysiological responses to feedback in a time-estimation task in which feedbackvalidity was manipulated. Participants across a wide age range had to produce 1 s intervals followed by positive and negative feedback that was valid or invalid (i.e., related or unrelated to the preceding time estimate). Performance results showed that they processed the information provided by the feedback. Negative feedback was associated with a transient cardiac slowing only when feedback was valid. Correct adjustments after valid negative feedback were associated with a more pronounced cardiac slowing. Validity did not affect the feedback-related negativity (FRN), except when remedial action was taken into account. The FRN and cardiac response to feedback decreased with advancing age, but performance did not. The current pattern of findings was interpreted to suggest that the FRN and cardiac response signal "alert" and that the cardiac response, but not the FRN, is implicated in the mechanisms invoked in remedial action.

The anterior cingulate cortex responds differently to the validity and valence of feedback in a time-estimation task (Article)

2011-06-15T00:00:00Z

This study examined the role of the medial frontal cortex in the processing of valence and validity of performance feedback using a time-estimation paradigm. Participants had to produce 1. s intervals followed by positive and negative feedback that could be valid or invalid (i.e., related or unrelated to task performance). Performance results showed that participants used the validity information to adjust their time estimations to negative feedback. The rostral cingulate zone (RCZ) was more active after valid feedback than after invalid feedback, but was insensitive to the valence of the feedback. The rostral anterior cingulate cortex (rACC), posterior cingulate and right superior frontal gyrus, however, appeared to be primarily sensitive to the valence of the feedback; being more active after positive feedback. The results are discussed along the lines of the ACC's cognitive and affective subdivisions and their structural and functional connections.

Treatment adherence therapy in people with psychotic disorders: randomised controlled trial (Article)

2010-12-01T00:00:00Z

Interventions to improve adherence to treatment in people with psychotic disorders have produced inconclusive results. We developed a new treatment, treatment adherence therapy (TAT), whose intervention modules are tailored to the reasons for an individual's non-adherence. Aims To examine the effectiveness of TAT with regard to service engagement and medication adherence in out-patients with psychotic disorders who engage poorly. METHOD: Randomised controlled study of TAT v. treatment as usual (TAU) in 109 out-patients. Most outcome measurements were performed by masked assessors. We used intention-to-treat multivariate analyses (Dutch Trial Registry: NTR1159). RESULTS: Treatment adherence therapy v. TAU significantly benefited service engagement (Cohen's d = 0.48) and medication adherence (Cohen's d = 0.43). Results remained significant at 6-month follow-up for medication adherence. Near-significant effects were also found regarding involuntary readmissions (1.9% v. 11.8%, P = 0.053). Symptoms and quality of life did not improve. CONCLUSIONS: Treatment adherence therapy helps improve engagement and adherence, and may prevent involuntary admission.

Diurnal cortisol patterns of young male patients with schizophrenia (Article)

2010-10-01T00:00:00Z

Aims: It has been suggested that schizophrenic patients are more vulnerable to stress than healthy persons, and that stressors can trigger a psychotic episode or worsen symptoms. The biological system often studied in relation to stress is the hypothalamic-pituitary-adrenal (HPA) axis, which controls the release of cortisol. We investigated whether the diurnal basal activity of the HPA axis differed between young male patients with schizophrenia and healthy controls. Methods: Twenty-seven male patients (mean age 22 ± 5 years) and 38 healthy male control subjects (mean age 22 ± 3 years) were included in the present study. Saliva was sampled at five time points during the day: directly after awakening, 30 min thereafter, and at 12.00 hours, 16.00 hours and 22.00 hours. Results: The cortisol concentration decreased significantly more during the day in the patient group thanin the control group. Patients also showed a significantly decreased area under the curve with respect to the increase, again indicating that the cortisol concentrations decreased more during the day in patients than in controls. Both the morning increase and the area under the curve with respect to the increase were significantly negatively correlated with negative symptom severity. Conclusions: Patients with schizophrenia showed a different daytime sensitivity of the HPA axis. Our findings further suggest that an increase in negative symptom severity is related to a decreased HPA axis sensitivity.

Predictors of perceived benefit among patients committed by court order in the Netherlands: One-year follow-up (Article)

2010-10-01T00:00:00Z

Objective: This study identified predictors of perceived benefit resulting from court-ordered hospitalization in the Netherlands. Methods: This prospective study included 174 psychiatric inpatients committed under court order. Logistic regression was used to examine the relationship between predictor variables and perceived benefit. Results: At one year, 52% of patients evaluated their involuntary hospitalization as beneficial. These patients were more likely to be homeless (odds ratio [OR]=4.13, 95% confidence interval [CI]=1.33-12.84), to have been previously hospitalized voluntarily (OR=2.30, CI=1.18-4.48), and to have high service engagement (OR=2.79, CI=1.19-6.53) or more illness insight (OR=2.78, 95% CI=1.13-6.89). Having a psychotic disorder or higher severity of symptoms at baseline was correlated with an improved perception of benefit. Conclusions: Perceived benefits were predicted by living condition, hospitalization history, service engagement, and illness insight. Clinical characteristics were associated with improvement in perceived benefit. Additional research should focus on causality of associations before effective intervention programs can be developed.

Genome-wide linkage analysis in a Dutch multigenerational family with attention deficit hyperactivity disorder (Article)

2010-02-01T00:00:00Z

Abstract: Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder. Genetics has an important role in the aetiology of this disease. In this study, we describe the clinical findings in a Dutch family with eight patients suffering from ADHD, in whom five had at least one other psychiatric disorder. We performed a genome-wide (parametric and nonparametric) affected-only linkage analysis. Two genomic regions on chromosomes 7 and 14 showed an excess of allele sharing among the definitely affected members of the family with suggestive LOD scores (2.1 and 2.08). Nonparametric linkage analyses (NPL) yielded a maxNPL of 2.92 (P=0.001) for marker D7S502 and a maxNPL score of 2.56 (P=0.003) for marker D14S275. We confirmed that all patients share the same haplotype in each region of 7p15.1-q31.33 and 14q11.2-q22.3. Interestingly, both loci have been reported before in Dutch (affected sib pairs) and German (extended families) ADHD linkage studies. Hopefully, the genome-wide association studies in ADHD will help to highlight specific polymorphisms and genes within the broad areas detected by our, as well as other, linkage studies.

Reactie op ‘Protocol voor complementaire en alternatieve geneeswijzen; naar een verantwoorde toepassing binnen de ggz’ (Article)

2010-01-01T00:00:00Z

Domestic homicide followed by parasuicide: A comparison with homicide and parasuicide (Article)

2009-10-01T00:00:00Z

Homicide-suicides are a rare yet very serious form of interpersonal violence that occur mainly in partnerships and families. As both perpetrator and victim die in a homicideĝ€" suicide, data sources in previous studies typically lack detailed information. This study overcomes this limitation by making use of homicides followed by a suicide attempt of the perpetrator (homicide-parasuicides). The authors examine to what extent these homicide-parasuicides can be understood as being primarily an expression of homicidal or of suicidal behavior. In total, 77 homicide-parasuicides are compared to 430 homicides and 161 parasuicides. The results show that homicide-parasuicides constitute a different category of lethal violence with regard to demographic, individual, and event-related characteristics. Subanalyses of homicide-parasuicides involving women and children reveal similar differences. The finding that a large majority of the perpetrators were mentally ill, dependent on the victim, and killed when faced with separation from the victim may suggest that increased monitoring of this group might have preventive value.

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-a therapy (Article)

2009-10-01T00:00:00Z

Abstract Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H(2)O(2) generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance.

Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia (Article)

2009-08-01T00:00:00Z

This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects

Paternal depressive symptoms during pregnancy are related to excessive infant crying (Article)

2009-07-01T00:00:00Z

OBJECTIVE: Excessive infant crying, or infantile colic, is a common and often stress-inducing problem for parents that can ultimately result in child abuse. From previous research it is known that maternal depression is related to excessive crying, but so far little is known about the influence of paternal depression. METHODS: In a prospective, population-based study, we obtained information on both maternal and paternal depressive symptoms at 20 weeks of pregnancy by using the Brief Symptom Inventory. Parental depressive symptoms were related to excessive crying in 4426 two-month-old infants. The definition of excessive crying was based on the widely used Wessel's criteria (ie, crying >3 hours for >3 days in the past week). RESULTS: After adjustment for depressive symptoms of the mother and relevant confounders, we found a 1.29 (95% confidence interval: 1.09-1.52) higher risk of excessive infant crying per SD of paternal depressive symptoms. CONCLUSIONS: Our findings indicate that paternal depressive symptoms during pregnancy might be a risk factor for excessive infant crying. This finding could be related to genetic transmission, interaction of a father with lasting depressive symptoms with the infant, or related indirectly through contextual stressors such as marital, familial, or economic distress. Copyright

Screening methods for delirium: Early diagnosis by means of objective quantification of motor activity patterns using wrist-actigraphy (Article)

2009-03-01T00:00:00Z

Delirium after cardiac surgery is a risk factor for adverse outcome and even death. Disturbance of motor activity is a core feature of delirium, but hypoactive delirium often remains unrecognized. We explored wrist-actigraphy as a tool to objectively quantify postoperative recovery of 24-h rest-activity patterns to improve the early recognition of delirium after surgery. Motor activity was recorded by wristactigraphy after cardiac surgery in 88 patients over 65 years of age. Patients were assessed daily by using the CAM-ICU. Our final analyses were based on 32 non-delirious patients and 38 patients who were delirious on the first day after surgery. The delirious patients showed lower mean activity levels during the first postoperative night (P<0.05), reduced restlessness during the first day (P<0.05), and a lower mean activity of the 5 h with lowest activity within the first 24 h (P=0.01), as compared to the non-delirious patients. Already at a very early stage after cardiac surgery, a difference in motor activity was observed between patients with and without a delirium. As an unobtrusive method, actigraphy has the potential to be a screening method that may lead to early diagnosis and treatment of delirium.

Disturbed circadian motor activity patterns in postcardiotomy delirium (Article)

2009-02-01T00:00:00Z

Aims: More than 20% of patients of 65 years or older may develop a delirium after cardiac surgery. Patients with delirium frequently show a disturbed 24-hr motor activity pattern, but objective and quantitative data are scarce. Our aim was to quantify motor activity patterns in elderly patients with or without a postcardiotomy delirium after elective cardiac surgery. Methods: Wrist-actigraphy was used to quantify 24-hr motor activity patterns for a 5-day period following cardiac surgery in 79 patients of 65 years or older. Clinical state was monitored daily by means of the Confusion Assessment Method-Intensive Care Unit and the Delirium Rating Scale-Revised 98. Results: The activity Amplitude, and the daytime Activity/minute and Restlessness index were significantly higher and the daytime number of Immobility minutes significantly lower for the patients without delirium or with short delirium episodes, as compared to patients with a sustained delirium (>3 days). Conclusions: Actigraphy proves to be a valuable instrument for evaluating motor activity patterns in relation to clinical state in patients with a postcardiotomy delirium.

Kinderdoding gevolgd door een ernstige poging tot zelfdoding (Article)

2009-01-01T00:00:00Z

Het doden van kinderen is een dramatische gebeurtenis. Deze dodingen krijgen een versterkt dramatisch karakter als de dader ook nog zichzelf doodt of een poging daartoe doet. In deze studie wordt onderzocht of kinderdoding gevolgd door een ernstige poging tot zelfdoding een variatie op doding vormt, een variatie op zelfdoding vormt, of als een aparte categorie van dodelijk geweld moet worden beschouwd. Suïcidale ouders die hun kinderen doodden, verschillen in sociaaldemografische, individuele en daadgebonden karakteristieken van niet-suïcidale ouders die hun kind doodden, en van suïcidale ouders die hun kind(eren) niet doodden. Deze verschillen zijn zodanig, dat kinderdoding gevolgd door (een ernstige poging tot) zelfdoding als aparte groep kan worden beschouwd.

Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-α: Course and relationship with psychiatric status (Article)

2008-10-01T00:00:00Z

Aims: Immunotherapy with interferon-α (IFN-α) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-α induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT). In addition, the production of neurotoxic metabolites of KYN such as 3-hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN-α-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties. Methods: In a group of 24 patients treated with standard IFN-α for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months. Results: No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN. Conclusions: The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-α-based immunotherapy, is neither supported nor rejected.

Plasma activity of prolyl endopeptidase in relation to psychopathology during immunotherapy with IFN-α in patients with renal cell carcinoma (Article)

2008-05-01T00:00:00Z

Abnormal activity in peripheral blood of the cytosolic enzyme prolyl endopeptidase (PEP, EC 3.4.21.26, post prolyl cleaving enzyme, prolyl oligopeptidase) has been found in patients with a variety of psychiatric disorders, most consistently in mood disorders. Mood disturbance is a well-known side effect of immunotherapy with interferon-α (IFN-α). Earlier, we documented a decrease in serum PEP activity in the first 4 weeks of treatment with IFN-α. In 24 patients (16 men, 8 women, median age 60.5 years, range 47-72 years) with metastatic renal cell carcinoma (RCC), psychiatric assessment and blood sampling were performed before and at 4 and 8 weeks and at 6 months after initiation of treatment with IFN-α. No episodes of depression were observed, and the sum score and the scores on the subscales for depression and hostility of the Symptom Check List-90 (SCL-90) did not change during follow-up, whereas the anxiety scores were somewhat lower at 4 and 8 weeks compared with baseline. No change in plasma PEP activity and no relationships between change in psychiatric parameters and change in plasma PEP activity were found. As more subtle relationships between PEP activity and psychiatric status could have easily been obscured, a role for PEP in the pathophysiology of IFN-α-induced mood disturbance can neither be confirmed nor excluded.

Interferon-alpha in oncology patients: fewer psychiatric side effects than anticipated (Article)

2008-01-01T00:00:00Z

Interferon-alpha (IFN-alpha) treatment in both oncological and hepatological settings is associated with depression. If IFN-alpha treatment induces depression in high numbers, it could serve as a model for studying the pathophysiology of depression, in general. The authors therefore studied 43 oncology patients treated with standard or pegylated IFN-alpha with baseline psychiatric assessment and at regular time-points in the first 6 months of treatment. Apart from a severe depression because of brain metastases, authors observed only two clinically relevant depressive states. Contrary to findings in most of the literature, most depressive episodes in this study were self-limiting and short-lasting and were associated with either episodes of flu-like symptoms common at the start of the treatment or with concurrent psychosocial events. In the group as a whole, scores on both observer-based and self-report rating scales did not show clinically relevant changes. The results of this study indicate that IFN-alpha treatment is not suitable as a study model for depression in general.

The effect of antipsychotic medication on facial affect recognition in schizophrenia: A review (Article)

2008-01-01T00:00:00Z

Patients with schizophrenia suffer from impairments in facial affect recognition and social functioning. Since antipsychotic medication affects different areas in the brain, they may also affect target areas involved in emotional processing mechanisms. In this article, we review the findings of the effect of antipsychotic medication on facial affect recognition in schizophrenia. We searched PubMed for articles in English with the keywords schizophrenia, facial, affect, emotion, antipsychotic and medication, published till January 2008. Eight relevant articles were found describing original studies. No substantial improvements in facial affect recognition were found after treatment with either typical or atypical antipsychotic drugs. Facial affect recognition was not related to neuropsychological functioning, and it was unclear whether improvement of symptom severity was related to performance on the facial affect recognition tasks. It is recommended that future research should focus on measuring social skills and social functioning more directly, and by investigating the effects of additional behavioural treatments on facial affect recognition and social functioning relative to treatment with antipsychotic medication alone.

Interferon-α influences tryptophan metabolism without inducing psychiatric side effects (Article)

2007-10-01T00:00:00Z

Background: Interferon-α (IFN-α) treatment is often associated with psychiatric side effects and has been found to lower the amount of tryptophan (TRP) available to the brain. The alterations in tryptophan metabolism might underlie the psychiatric side effects during treatment with IFN-α. Methods: In this study, 43 oncology patients treated with IFN-α were included. In order to study de novo depressions, depressed patients at baseline were excluded. Psychiatric evaluation comprising clinical judgment combined with a structured psychiatric interview and observer-based and self-report rating scales was performed at baseline and at 4 weeks, 8 weeks and 6 months after the start of treatment with IFN-α, and in the case of emerging psychopathology. Blood samples were drawn at the same evaluation times and assessed for concentrations of TRP, large neutral amino acids, kynurenine, 5-hydroxyindole acetic acid, neopterin and biopterin. Results: During treatment with IFN-α, several alterations in laboratory parameters occurred that were consistent with an increased degradation of peripheral TRP. Psychometric ratings revealed hardly any psychiatric changes. No consistent associations were found between changes in the laboratory assessments determined and the diverse psychiatric measures. Conclusion: In this study, IFN-α was found to alter TRP metabolism without inducing psychiatric side effects. Therefore, a possible relationship between TRP metabolism and depression was not substantiated by this study. Copyright

Subjective and physiological responses to emotion-eliciting pictures in male schizophrenic patients (Article)

2007-05-01T00:00:00Z

Several studies have shown that schizophrenic patients have difficulties in their ability to recognize emotional facial expressions, whereas other research indicated that they subjectively report the same emotional experience as healthy controls. The purpose of this study was to investigate whether the physiological responses that accompany emotions differ between schizophrenic patients and controls, which would suggest a different basic emotional processing mechanism in these patients. We presented 40 emotion-eliciting pictures to male patients (n = 26) and controls (n = 21), while measuring heart rate (HR), breathing rate (BR), skin conductance response (SCR) and systolic blood pressure (SBP). Each subject rated each picture for its degree of valence and arousal. Mixed-effects regression models were used to investigate the relationships between the subjective ratings and the physiological responses. In both groups, BR and SCR increased with increasing arousal ratings, suggesting sympathetic activation. The SBP of both groups increased with increases in both the valence and the arousal ratings. However, whereas the patients' HR first decreased with decreasing pleasure ratings and subsequently increased with higher arousal and valence ratings, the HR in the control group was influenced by a complex interaction between valence and arousal ratings. Thus, the schizophrenic patients showed similar relationships between subjective ratings and SCR, BR, and SBP, but a different relationship between subjective ratings and HR compared with the healthy controls.

Physician-assisted death in psychiatric practice in the Netherlands (Article)

1997-01-01T00:00:00Z

BACKGROUND: In 1994 the Dutch Supreme Court ruled that in exceptional instances, physician-assisted suicide might be justifiable for patients with unbearable mental suffering but no physical illness. We studied physician-assisted suicide and euthanasia in psychiatric practice in the Netherlands. METHODS: In 1996, we sent questionnaires to 673 Dutch psychiatrists - about half of all such specialists in the country - and received 552 responses from the 667 who met the study criteria (response rate, 83 percent). We estimated the annual frequencies of requests for physician-assisted suicide by psychiatrists and actual instances of assistance. RESULTS: Of the respondents, 205 (37 percent) had at least once received an explicit, persistent request for physician-assisted suicide and 12 had complied. We estimate there are 320 requests a year in psychiatric practice and 2 to 5 assisted suicides. Excluding those who had ever assisted, 345 of the respondents (64 percent) thought physician-assisted suicide because of a mental disorder could be acceptable, including 241 who said they could conceive of instances in which they themselves would be willing to assist. The most frequent reasons for refusing were the belief that the patient had a treatable mental disorder, opposition to assisted suicide in principle, and doubt that the suffering was unbearable or hopeless. Most, but not all, patients who had been assisted by their psychiatrists in suicide had both a mental disorder and a serious physical illness, often in a terminal phase. Thirty percent of the respondents had been consulted at least once by a physician in another specialty about a patient's request for assisted death. The annual number of such consultations was estimated at 310, about 3 percent of the estimated 9700 requests for euthanasia or physician-assisted suicide in medical practice. CONCLUSIONS: Explicit requests for physician-assisted suicide are not uncommon in psychiatric practice in the Netherlands, but these requests are rarely granted. Psychiatric consultation for medical patients who request physician-assisted death is relatively rare.