Publications (33)98.27 Total impact
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Article: A three-dimensional model of thoughts: insight into depression.
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ABSTRACT: Thought processing and mood regulation are closely linked, but existing classifications of mood disorders fail to recognize the complex interplay between these two clinical dimensions. Furthermore, existing classifications fail to account for the possibility that depression might be associated with an increased frequency of self-referential thoughts that could in some circumstances be related to creativity processes. Based on recent evidence from clinical phenomenology, experimental psychology and affective neuroscience, we propose a novel comprehensive theoretical framework that incorporates thought processing and emotional valence. This new taxonomy provides insights into the clinical understanding of the spectrum of mood disorders and accounts for the possibility of increased creativity in altered mood states.Psychopathology 05/2012; 45(4):203-14. · 1.82 Impact Factor -
Article: Salivary cortisol profiles in patients remitted from recurrent depression: one-year follow-up of a mindfulness-based cognitive therapy trial.
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ABSTRACT: Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday (-8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.Journal of psychiatric research 01/2012; 46(1):80-6. · 3.72 Impact Factor -
Article: Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample.
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ABSTRACT: This study investigated clinical and genetic predictors of increasing suicidal ideation during antidepressant treatment. A total of 131 depressed outpatients were allocated to four antidepressants (paroxetine, venlafaxine, clomipramine or nefazodone) in a sequential step procedure until remission. Suicidality was assessed using the 10th item of the Montgomery-Asberg Depression Rating Scale (MADRS). A total of 11 candidate genes involved in different mechanisms of antidepressant action were selected for association with increasing suicidality. Increasing suicidality correlated with depression severity and higher antidepressant blood levels. Risk of increasing suicidal ideation was higher in subjects taking antidepressants other than paroxetine (odds ratio: 1.11). The strongest genetic predictor was found to be rs1360780 within the FKBP5 gene (p = 2.9 × 10(-5)), followed by 2677G>T in the ABCB1 gene. The rs130058 SNP within the 5-HTR1B gene demonstrated a differential association with increasing suicidal ideation depending on antidepressant type. Increasing suicidal ideation might be an adverse effect of antidepressants. The involvement of FKBP5 indicates that dysregulation of the hypothalamic-pituitary-adrenal axis is involved in treatment increasing suicidal ideation.Pharmacogenomics 03/2011; 12(3):365-77. · 3.97 Impact Factor -
Article: The cortisol awakening response in patients remitted from depression.
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ABSTRACT: An impressive number of data has been accumulated on dysfunctions of the hypothalamo-pituitary-adrenal (HPA) axis and cortisol hypersecretion in depression. To assess the dynamic HPA functioning, the cortisol awakening response (CAR) is an easily accessible and reliable approach. Some data suggest that elevated CAR in depressed patients has trait-like characteristics. Therefore we investigated whether patients in remission from a depressive episode have elevated CAR compared to control subjects. CAR of thirty-eight patients in remission from depression (11 men, 27 women, age range 24-66) and 52 control participants were analyzed (18 men, 34 women, age range 24-63). All patients had experienced ≥3 previous depressive episodes and were off psychotropic medication since at least 3 months. Saliva samples were collected only once, at home, either on weekend or weekday at 0, 15, 30, 45 and 60 min post-awakening. The area under the curve (AUC) above minimum cortisol concentration displayed large interindividual variability (6.4-fold in remitted patients and 8.1-fold in controls, based on 80% range). Investigation of possible variability factors showed that percent explained variance increased from 3.9% when group was considered alone to 8.8%, 12.3% and 19.2% after adjusting for significant effects of weekday vs. weekend, wake-up time and sleep duration, respectively. According to the latter model, AUC was estimated to be 51% higher in remitted patients than in controls (p = 0.007), while a 21% AUC decrease was associated with a 1-h longer sleep duration (p<0.001). In future studies, detection of between-group differences might benefit from adjusting for sleep duration and other possible confounders.Journal of psychiatric research 12/2010; 44(16):1199-204. · 3.72 Impact Factor -
Article: Early telephone intervention for psychiatric outpatients starting antidepressant treatment.
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ABSTRACT: The article addresses the hypothesis that early telephone intervention for psychiatric outpatients starting antidepressant treatment would increase compliance with pharmacological treatment and retention time in the study, and thus allow for a more favourable clinical outcome. The study focuses on 131 depressed outpatients who participated in a study aiming to obtain full remission. Patients who benefited from three early structured telephone interventions (n=81) were compared with participants who benefited from the usual care (n=50) with no clinical contact before the first clinical assessment at 2 weeks. The intervention proved to have no significant effect on treatment adherence, attrition rate, exclusion rate for adverse events or improvement of depression severity. It was nevertheless associated with increased retention time in the present study. These results suggest that motivational phone calls may reinforce adhesion in psychiatric patients and provide early opportunities to adapt treatment to individual needs. These results suggest that motivational phone calls may reinforce adhesion in psychiatric patients and provide early opportunities to adapt treatment to individual needs.Nordic journal of psychiatry 02/2010; 64(4):265-7. · 0.99 Impact Factor -
Article: Depression relapse prophylaxis with Mindfulness-Based Cognitive Therapy: replication and extension in the Swiss health care system.
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ABSTRACT: Mindfulness-Based Cognitive Therapy (MBCT) is a group intervention that integrates elements of Cognitive Behavioural Therapy (CBT) with components of mindfulness training to prevent depressive relapse. The efficacy of MBCT compared to Treatment As Usual (TAU), shown in two randomized controlled trials indicates a significant decrease in 1-year relapse rates for patients with at least three past depressive episodes. The present study is the first independent replication trial comparing MBCT+TAU to TAU alone across both language and culture (Swiss health care system). Sixty unmedicated patients in remission from recurrent depression (>or=3 episodes) were randomly assigned to MBCT+TAU or TAU. Relapse rate and time to relapse were measured over a 60 week observation period. The frequency of mindfulness practices during the study was also evaluated. Over a 14-month prospective follow-up period, time to relapse was significantly longer with MBCT+TAU than TAU alone (median 204 and 69 days, respectively), although both groups relapsed at similar rates. Analyses of homework adherence revealed that following treatment termination, the frequency of brief and informal mindfulness practice remained unchanged over 14 months, whereas the use of longer formal meditation decreased over time. Relapse monitoring was 14months in duration and prospective reporting of mindfulness practice would have yielded more precise frequency estimates compared to the retrospective methods we utilized. Further studies are required to determine which patient characteristics, beyond the number of past depressive episodes, may predict differential benefits from this therapeutic approach.Journal of affective disorders 09/2009; 122(3):224-31. · 3.76 Impact Factor -
Article: Phenomenology of racing and crowded thoughts in mood disorders: a theoretical reappraisal.
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ABSTRACT: Racing thoughts is a frequent symptom in mood disorders, particularly mixed depressive states. This paper aims to summarize our current knowledge about its phenomenology and frequency in the spectrum of mood disorders, and to offer a new theoretical framework. We made a selective review of original and review papers in Medline and PsychInfo database using the keywords "racing thoughts", "crowded thoughts" and "depressive mixed state" in conjunction with "mood disorders". In the context of a hypomanic state, "racing thoughts" may appear as a result from an excessive production of thoughts, moving quickly from one to the other, and generating a sense of fluidity and pleasantness. In the context of depression, "racing thoughts" are phenomenologically different and better described as "crowded thoughts": they are not only characterized by too many thoughts occurring at the same time in the field of consciousness, but perceived as unpleasant and induce the feeling that ideas are difficult to catch. DISCUSSION AND CLINICAL RELEVANCE: We suggest that crowded thoughts might result from the mixture of a hypomanic component, with an accelerated production of new thoughts (constituting the main source of this symptom in hypomania), and a depressive component, with a deficit of inhibition of previous thoughts (hence making thoughts crowded rather than truly racing). This distinction could help better identify crowded thoughts, and consequently depressive mixed states, which has important implications for therapeutic management. It might also help to further disentangle the psychobiological processes which contribute to the complexity of mood disorders.Journal of affective disorders 07/2009; 121(3):189-98. · 3.76 Impact Factor -
Article: [Psychiatry].
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ABSTRACT: In 2008 there is no major breakthrough in the field of psychopharmacology. Paliperidone, (Invega), or 9-hydroxyrisperidone, the main hydroxylated metabolite of risperidone, is now available in Switzerland. It has the same pharmacodynamic profile and a different pharmacokinetic profile, linked to an extended release preparation. Bupropion, an antidepressant with noradrenergic and dopaminergic activity, is now accepted on the Swiss market for the treatment of depression under the name of Wellbutrin. Until now, its indication was limited to tobacco withdrawal (under the name of Zyban). The article also includes new data issued from the STAR*D study (concerning the efficacy of cognitive behavioural therapy) and a few remarks about the recent debate in the media about the efficacy of antidepressants.Revue médicale suisse 02/2009; 5(186):138-42. -
Article: Is there a place for tricyclic antidepressants and subsequent augmentation strategies in obtaining remission for patients with treatment resistant depression?
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ABSTRACT: Major depressive disorder is a worrying mental health problem and obtaining remission from treatment resistant depression (TRD) remains an important clinical issue. Twenty patients (14 women, 6 men) considered as treatment resistant after the fourth step of a seven-step treatment algorithm to obtain remission in major depression received clomipramine 150 mg/day for 1 month (step 5). In case of failure, two subsequent augmentation strategies with lithium and lithium plus triiodothyronine (T3) were implemented. Median Montgomery-Asberg Depression Rating Scale (MADRS) score at initiation of clomipramine treatment was 29 (range 8-43). Treatment with clomipramine alone allowed five patients to achieve sustained remission (MADRS < or = 8), while three patients were responders (MADRS decrease > or = 50%) and three patients were partial responders (MADRS decrease > 25%). Lithium augmentation in 10 patients led to one additional remission, whereas no additional remission was observed in 6 patients with further T3 augmentation. Tricyclic antidepressants have demonstrated efficacy in TRD. The present study suggests that treatment with clomipramine might allow obtaining remission in some patients who do not fully respond despite multiple interventions.Pharmacological Research 11/2008; 59(3):202-6. · 4.44 Impact Factor -
Article: CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response.
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ABSTRACT: Paroxetine is characterized by large interindividual pharmacokinetic variability and heterogeneous response patterns. The present study investigates plasma concentration and therapeutic response to paroxetine for the influence of age, sex, and CYP2D6 and ABCB1 polymorphisms, the latter gene encoding for the permeability glycoprotein. Genotyping for CYP2D6 (alleles *3, *4, *5, *6, and *xN) and ABCB1 polymorphisms (61A>G, 2677G>T, and 3435C>T) was performed in 71 depressed patients who started 20 mg paroxetine per day and had plasma concentration measured after 2 weeks at a fixed dose. A dose increase to 30 mg per day was possible starting at week 2. For 63 patients, severity of depression (Montgomery-Asberg Depression Rating Scale) was assessed at weeks 0, 2, and 4 and every 2 weeks thereafter until discontinuation. Persistent response was defined as 50% improvement from baseline score sustained from the first occurrence to study end point. Paroxetine concentration significantly differed between female and male patients (median, 28 versus 16 ng/mL; P = 0.001). Differences were not significant between CYP2D6 heterozygous and homozygous extensive metabolizers (median, 27 versus 22 ng/mL; P = 0.074) and between ABCB1 genotypes (P > 0.10). When considered in a multivariate model, CYP2D6 heterozygous extensive metabolizer phenotype (P = 0.062) and female gender (P = 0.001) predicted 1.3-fold and 1.6-fold higher paroxetine concentration, respectively, but fraction of explained variability was modest (21%). Frequency of persistent response at study end point did not significantly differ according to CYP2D6 heterozygous extensive metabolizer versus homozygous extensive metabolizer phenotype and ABCB1 polymorphisms in univariate analyses. After adjusting for age, sex, paroxetine concentration at week 2, and daily dose at study end point, ABCB1 genotype contributed to improving the model significantly for 61A>G (P = 0.043), but not 2677G>T (P = 0.068) and 3435C>T (P = 0.11). None of two poor metabolizers and four ultrarapid metabolizers showed persistent response to paroxetine. The hypothesis that permeability glycoprotein activity might be a relevant predictor of therapeutic response deserves to be further investigated while controlling for pharmacokinetic variability.Therapeutic Drug Monitoring 08/2008; 30(4):474-82. · 2.49 Impact Factor -
Article: [Electroconvulsive therapy: thoughts on a prohibited treatment].
Revue médicale suisse 04/2008; 4(148):676-9. -
Article: [Trends in psychiatry].
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ABSTRACT: New data confirm that antidepressants have a global protective effect on the risk of suicide even if they very moderately and transiently increase suicide attempts, particularly in young people. We also present recent data about the following topics. (1) The main results of the STAR*D study, an outpatient study about depression treatment following a very complex algorithm. Nearly all the head to head comparisons between treatments showed a lack of significant difference, and the rates of clinical remission for patients non responders to their first two treatments were low. (2) The reintroduction of sertindole, an atypical antipsychotic: cardiac monitoring is necessary, but should not prevent its use as a second line drug. (3) The potential efficacy of dawn simulation and high density negative air ionization in seasonal depression.Revue médicale suisse 02/2008; 4(140):158-60, 162-5. -
Article: The lactate provocation test to investigate the relationships between panic attacks and psychosis: a report of two cases.
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ABSTRACT: It was suspected that the delusional convictions of bewitchment and devil persecution of two female patients (41 and 40-years-old) could be the consequence of an erroneous interpretation of the sensations induced by panic attacks, as several authors have previously suggested. The interest of this case report stems from the manner in which we tested our clinical hypothesis. The patients agreed to the use of a lactate provocation test in double-blind, placebo-controlled conditions during four randomized sessions on consecutive days (two with lactate and two with placebo). The results for patient A strongly supported our hypothesis: patient A developed two full-blown panic attacks during the active lactate sessions, whereas patient B developed one subthreshold and one moderate panic attack during the active lactate sessions. The results of these investigations led to a more specific psychotherapeutic approach for patient A.The World Journal of Biological Psychiatry 02/2008; 9(2):154-8. · 2.38 Impact Factor -
Article: Time course of response to paroxetine: influence of plasma level.
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ABSTRACT: Early improvement of depression severity is considered an important therapeutic goal, predictive of later remission. The present study aimed at testing the hypothesis that plasma concentration might influence the time course of response to paroxetine. Eighty-four patients with a severe depressive episode started paroxetine 20 mg/day, with a possible dose adjustment to 30 mg/day after 2 weeks. Severity of depression (Montgomery-Asberg Depression Rating Scale) was assessed at weeks 0, 2 and 4 for all patients, and every 2 weeks thereafter until discontinuation. Median duration on paroxetine was 6 weeks (range 4-18 weeks). Plasma concentration was measured at steady-state after 2 weeks at 20 mg/day. In a first stage, pattern analysis led to distinguish patients with non-response, non-persistent response, early persistent response (obtained at week 2) and delayed persistent response (week 4 or later). Comparison of patients with (n=29, 34.5%) and without persistent response (n=55, 65.5%) did not reveal any significant difference, whereas focus on patients with persistent response indicated that shorter time to response was significantly associated with shorter duration of current episode (r(S)=0.54, p=0.003) and higher plasma level (r(S)=-0.47, p=0.011). In a second stage, a sigmoid mixed effects model was developed that adequately fitted depression severity versus time profiles among patients with persistent response (n=157 data for 29 patients). Estimated median time to response was 3.2 weeks (range 0.9-6.6). Higher paroxetine concentration, younger age and shorter episode duration were confirmed as significant determinants of a shorter time to response (likelihood ratio tests, p<0.005). The present study supports the hypothesis that higher paroxetine concentration might contribute to hasten relief of depressive symptoms in severely depressed patients.Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2007; 31(4):892-900. · 3.25 Impact Factor -
Article: Pathological Journeys or Help Seeking Behavior: The Case of Travelers to Geneva, An International City
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ABSTRACT: Several international organizations have their headquarters in Geneva and are thus hypothesized to attract both people seeking help for human right abuses and also pathological travelers. The present study aimed at characterizing pathological travelers, a population seldom studied in psychiatry. Patients referred for pathological journeys to the only psychiatric hospital in Geneva were retrospectively identified on the basis of medical certificates. Their medical records were then analyzed. The study covered a 4-year period. Seventy-six patients were identified. They were in majority male, aged less than 50 and single; 62% came from European countries and 84% had some prior psychiatric history; 58% were diagnosed with a psychotic disorder, mainly schizophrenia, acute transient psychotic disorder and delusional disorder. Sixteen patients (21%) had been attracted to Geneva specifically because of its international organizations, while 60 came for other reasons. Prevalence of persecutory delusions was significantly higher among travelers attracted by the "interna-tional Geneva" (88% versus 43%, P<0.005). Pathological journeys represent an identifiable cause of psychiatric hospitali-zation in Geneva. Prospective studies should be conducted using a more precise and restrictive definition of this entity in order to avoid stigmatization of people crossing borders for other motives.The Open Psychiatry Journal 01/2007; 107:26-30. -
Article: No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of psychiatric patients and control subjects.
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ABSTRACT: It was recently reported that a rare functional variant, R441H, in the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk factor for unipolar major depression (UP) since it was originally found in 10% of UP patients (vs. 1.4% in control subjects). We explored the occurrence of this variation in patients with affective disorders (n = 646), autism spectrum disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic panel of control individuals from North Africa, Sub-Saharan Africa, India, China, and Sweden (n = 277). Surprisingly, we did not observe the R441H variant in any of the individuals screened (3188 independent chromosomes). Our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to UP. The absence of the variant from a large cohort of psychiatric patients and control subjects suggests that the findings reported in the original study could be due to a genotyping error or to stratification of the initial population reported. Additional data by other groups should contribute to the clarification of the discrepancy between our results and those previous published.Biological Psychiatry 08/2006; 60(2):202-3. · 8.28 Impact Factor -
Article: Low-dose venlafaxine in three adolescents and young adults with autistic disorder improves self-injurious behavior and attention deficit/hyperactivity disorders (ADHD)-like symptoms.
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ABSTRACT: In our clinical practice, we have had good experiences with venlafaxine in the treatment of self-injurious behavior (SIB) and attention deficit/hyperactivity disorders (ADHD)-like symptoms in patients with pervasive developmental disorders (PDD), and we report here three cases of possible therapeutic response: (A) a 17-year-old boy with autism and severe behavioral symptoms, including aggression toward self or property, SIB and hyperactivity, who appeared to respond to low-dose venlafaxine (18.75 mg/day); (B) a 23-year-old woman with autism hyperactivity who appeared to respond to low-dose venlafaxine (18.75 mg/day); (C) a 17-year-old girl with autism hyperactivity who appeared to respond to low-dose venlafaxine (18.75 mg/day). Follow-ups occurred respectively 18, 36 and 6 months after treatment initiation, making it possible to observe the stability of the clinical improvement in these cases.Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2006; 30(2):312-5. · 3.25 Impact Factor -
Article: Body dysmorphic disorder, psychosis and insight: a report of four cases.
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ABSTRACT: Body dysmorphic disorder is described in the DSM-IV as a single clinical entity, but an additional diagnosis of delusional disorder, somatic type, is allowed when the preoccupation concerning an imaginary defect in appearance is held with delusional intensity. The existence of two clinical forms is implicitly recognized, depending on the presence or absence of psychotic symptoms. Several studies have suggested that these two forms make up a single illness, characterized by different degrees of insight. This supposition is supported by the fact that the symptomatology and the clinical response to the SSRIs are thought to be similar for the two forms. Moreover, certain authors have suggested that categorical nosography (as used by the DSM-IV) should not be the point of reference and that a 'dimensional' point of view is preferable, meaning that the presence of psychotic symptoms would constitute merely a simple phenomenon or state of the same illness.Psychopathology 02/2006; 39(3):130-5. · 1.82 Impact Factor -
Article: Induction of a mixed depressive episode during rTMS treatment in a patient with refractory major depression.
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ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive experimental technique which has mostly been investigated in the treatment of mood disorders with possible efficacy in depression. Among its potential side effects, there have been some reports of rTMS-induced (hypo)mania in the literature but none for rTMS-induced mixed episodes. We report the case of a 39-year-old woman suffering from refractory chronic major depression who developed a depressive mixed episode associated with a mild serotonin syndrome during her second week of rTMS treatment. She was receiving a combination of antidepressants, the doses of which were kept unchanged during rTMS treatment. Mixed as well as manic episodes may be induced by transcranial magnetic stimulation, complications already observed with antidepressants and electroconvulsive therapy. Therefore, caution should be exercised among clinicians using this experimental procedure, particularly in the treatment of bipolar depressed patients.The World Journal of Biological Psychiatry 02/2006; 7(4):261-4. · 2.38 Impact Factor -
Article: Missed Monday appointments.
Psychiatric Services 06/2005; 56(5):613. · 2.38 Impact Factor
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Institutions
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2002–2012
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University of Geneva
- • Department of Psychiatry
- • Department of Clinical Neuroscience
- • Division of Neuropsychiatry
Genève, GE, Switzerland
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