Thierry D'AMATO | Université Claude Bernard Lyon 1 (original) (raw)

Papers by Thierry D'AMATO

Psychiatry Research, 2018

Background. Guidelines have been edited for the treatment of schizophrenia (SZ) and bipolar disor... more Background. Guidelines have been edited for the treatment of schizophrenia (SZ) and bipolar disorders (BD). Background regimen is currently recommended for both illnesses (antipsychotic drug for SZ and mood stabilizer for BD). The recommendations are less clear for major depression in these disorders. Long-term anxiolytic and hypnotic prescriptions may have potential side effects and should be withdrawn as soon as possible. Objective. The aim of this study was to investigate the prevalence and associated factors of Potentially Inappropriate Psychotropic drugs (PIP) in a large multicenter sample of Homeless Schizophrenia (SZ) and Bipolar Disorder (BD) (HSB) patients. Methods. This multicenter study was conducted in 4 French cities: Lille, Marseille, Paris and Toulouse. PIP was defined by at least one item among: (i) absence of background regimen (antipsychotic for SZ or mood stabilizer for BD), (ii) absence of antidepressant for major depressive disorder and (iii) daily long-term anxiolytic or (iv) hypnotic prescription. Results. Overall, 703 HSB patients, mean aged 38 years and 82.9% men were included, 487 SZ (69.3%) and 216 BD (30.7%). 619 (88.4%) of the patients reported at least one PIP. 386 (54.9%) patients had an inappropriate background regimen prescription (209(43.4%) of SZ had no antipsychotic prescription and 177(81.9%) of BD no mood stabilizer), 336 (48%) had an inappropriate antidepressant prescription (with no significant difference between SZ and BD), 326 (46.4%) had an inappropriate prescription of anxiolytics and 107 (15.2%) had an inappropriate prescription of hypnotics. 388(55%) of the subjects were diagnosed with major depression but only 52(13%) of them were administered antidepressants. In multivariate analysis, PIP was associated with bipolar disorder diagnosis (aOR=4.67 [1.84-11.89], p=0.001), current major depressive disorder (aOR=27.72 [9.53-80.69], p<0.0001), lower rate of willingness to ask for help (aOR=0.98[0.96-0.99], p=0.001). Potentially inappropriate background regimen prescription was associated with bipolar disorder diagnosis (aOR=6.35 [3.89-10.36], p<0.0001), lower willingness to ask for help (aOR=0.99[0.98-0.99], p=0.01) and lack of lifetime history of psychiatric care (aOR=0.30[0.12-0.78], p=0.01). Inappropriate antidepressant prescription was associated with antisocial personality disorder (aOR=1.58 [1.01-2.48], p=0.04) and current substance use disorder (aOR=2.18[1.48-3.20], p<0.0001). Conclusion. The present findings suggest that almost 9 on 10 HSB subjects may receive a PIP including inappropriate prescriptions or absence of appropriate prescription. Bipolar disorder 3 and/or major depression should be targeted in priority and treated with mood stabilizers and/or antidepressants in this population, while anxiolytics and hypnotics should be withdrawn as much as possible. Major depression should be particularly explored in subjects with comorbid antisocial personality disorder and substance use disorder. The psychiatric care has been associated with better appropriate psychotropic prescriptions and should be reinforced in this population.

Psychiatry Research: Neuroimaging, 2004

Patients with first-rank symptoms (FRS) of schizophrenia do not experience all of their actions a... more Patients with first-rank symptoms (FRS) of schizophrenia do not experience all of their actions and personal states as their own. FRS may be associated with an impaired ability to correctly attribute an action to its origin. In the present study, we examined regional cerebral blood flow (rCBF) with positron emission tomography during an actionattribution task in a group of patients with FRS. We used a device previously used with healthy subjects that allows the experimenter to modulate the subject's degree of movement control (and thus action attribution) of a virtual hand presented on a screen. In healthy subjects, the activity of the right angular gyrus and the insula cortex appeared to be modulated by the subject's degree of movement control of the virtual hand. In the present study, the schizophrenic patients did not show this pattern. We found an aberrant relationship between the subject's degree of control of the movements and rCBF in the right angular gyrus and no modulation in the insular cortex. The implications of these results for understanding pathological conditions such as schizophrenia are discussed.

Progress in neuro-psychopharmacology & biological psychiatry, Jan 13, 2018

Little is known about perception of physical pain in schizophrenia (SZ). Some studies have sugges... more Little is known about perception of physical pain in schizophrenia (SZ). Some studies have suggested that patients with SZ may have an increased pain threshold, while others have suggested that patients with SZ may suffer from undetected and untreated high physical pain levels. The objectives of this study were (i) to investigate the prevalence of self-reported physical pain in stabilized SZ subjects, and (ii) to determine whether physical pain was associated with psychiatric characteristics and somatic comorbidities (iii) to determine whether antidepressants and benzodiazepine administration were associated with lower self-reported pain. 468 community-dwelling stable SZ subjects (73% men, mean aged 32 years) were recruited in the Schizophrenia Expert Center national network. Patients with moderate to extreme pain, assessed with the EQ5D-5L questionnaire, were classified as belonging to the "pain group". 104 (22.2%) reported moderate to extreme pain levels. In multivariate...

The British journal of psychiatry : the journal of mental science, 2018

Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been... more Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD. Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6. 613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however,...

Psychiatry research, Aug 12, 2017

The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is w... more The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort. 389 participants (73% males, mean aged 32.7 years, mean illness duration 10.8 years) formed the study sample, with each comprehensively evaluated, clinically and neuropsychologically, over 2 days. 118 participants (30.3%) were defined as APA+ according to their father's age at birth (≥35 years). APA+ was associated with a wide range of cognitive dysfunctions in univariate analyses. In multivariate analyses, the only significant difference was th...

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Presse médicale (Paris, France : 1983), 2016

Switching antidepressant medication may be helpful in depressed patients having no benefit from t... more Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

Schizophrenia research, 2002

Depressive symptoms frequently occur during the course of schizophrenia. This study explored the ... more Depressive symptoms frequently occur during the course of schizophrenia. This study explored the relationships between the schizophrenia symptomatology and three measures of depression. Eighty-one drug-free inpatients with acute schizophrenia were assessed with the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia (CDSS), and the Hamilton rating scale for depression (HAM-D). The depressive subscale of PANSS (PANSS-D) was also considered as a third scale for measuring depression. A principal component analysis (PCA) of PANSS items identified five clinical dimensions of schizophrenia called 'negative', 'positive', 'anxio-depressive', 'excitement', and 'disorganisation and others'. Our anxio-depressive dimension (PANSS-ad) was strictly identical with the PANSS-D. Scores on CDSS and HAM-D were highly inter-correlated and highly correlated with the PANSS-ad. Furthermore, while scores on CDSS were correlate...

The American journal of psychiatry, 1994

This study was performed to assess the possible involvement of the dopamine D3 receptor gene (DRD... more This study was performed to assess the possible involvement of the dopamine D3 receptor gene (DRD3) in the etiology of schizophrenia. The authors' approach included a population study and a family study using both parametric (lod score) and nonparametric (affected pedigree member) methods of linkage analysis. Two different DNA markers were studied at the DRD3 locus. The family study included 35 multiplex families of schizophrenic subjects for the linkage analyses. The population study involved 50 unrelated schizophrenic subjects and 50 normal comparison subjects from the same ethnic and geographic origin. Whichever clinical classification was used to define the pathological phenotype (schizophrenia or schizophrenia spectrum), the results of the lod score and affected pedigree member studies did not provide any evidence of linkage of the DRD3 gene to the illness. The negative results of the association study reinforce these results. The hypothesis that the DRD3 gene has a predisp...

Psychiatry research, Jan 30, 2003

Left temporoparietal repetitive transcranial magnetic stimulation (rTMS) reportedly diminishes ve... more Left temporoparietal repetitive transcranial magnetic stimulation (rTMS) reportedly diminishes verbal hallucinations. A 21-year-old schizophrenic man, who had killed his mother in the belief that she was a demon, failed to respond to combined treatment with a variety of antipsychotic agents. His persistent hallucinations consisted of two voices (God and the Devil). As an adjunct to continued antipsychotic medication, the patient received a course of rTMS: 10 sessions of 1-Hz stimulations near Wernicke's area. After rTMS, the patient's hallucinations grew less intrusive and he no longer required isolation. Although the improvement could be a delayed effect of medication, further trials of rTMS in cases of this type appear justified.

Psychiatry research, 2003

Hippocampus, 2009

Rat with excitotoxic neonatal ventral hippocampal lesions (NVHL rats) is considered as a heuristi... more Rat with excitotoxic neonatal ventral hippocampal lesions (NVHL rats) is considered as a heuristic neurodevelopmental model for studying schizophrenia. Extensive study of this model is limited by the lack of clear validity criteria of such lesions and because ascertaining of the lesions is realized postmortem with histological examination after completing experiments. Here, in a first experiment, by assessing the locomotor response to amphetamine in adult NVHL rats, we further specify that the lesions must be bilateral and confined to the ventral hippocampus to obtain the validated behavioral phenotype. We then show a longitudinal magnetic resonance imaging (MRI) protocol suitable for the detection of brain structural changes in NVHL rats. The T 2-weighted images acquired in adult NVHL rats reveal the same structural changes as those appraised with histological protocol. Moreover, we demonstrate that the lesion status in adulthood can be accurately predicted from the T 2-weighted images acquired in the juvenile period. As technical advantages, our MRI protocol makes possible to select animals according to lesion criteria as soon as in the juvenile period before long-lasting experiments and gives access in vivo to a quantitative parameter indicative of the lesion extent. Finally, we show that the lesion size increases only slightly between juvenile and adult periods. These latter results are discussed in the context of the specific postpubertal emergence of the behavioral deficits in NVHL rats. V

Synapse, 2007

Overt schizophrenia is preceded by a prodromal phase during which juvenile patients display atten... more Overt schizophrenia is preceded by a prodromal phase during which juvenile patients display attenuated schizophrenia-related symptoms. Here, we have looked for evidence of a prodromal phase in juvenile STOP null mice, which, during adulthood, imitate features of schizophrenia. We have principally examined locomotor activity, which is abnormal in adult STOP null mice, and its apparent relationship with perturbed glutamatergic and dopaminergic transmission. When compared to corresponding wild-type mice, juvenile STOP null mice did not exhibit the basal hyperlocomotion or locomotor hypersensitivity to mild stress observed in adult mice. Juvenile STOP null mice also lacked disturbed locomotor sensitivity to MK-801, which was evident in adult mice. In contrast, juvenile STOP null mice exhibited a similar hypersensitivity to amphetamine as that found in adult mice. Thus, STOP null mice exhibited both a progression of locomotor activity defects over time and subtle alterations in the prepubertal period. We suggest that the pattern of locomotor disturbances observed in this study is related to altered dopaminergic reactivity in juvenile mice without major disturbance in glutamatergic transmission, whereas both neurotransmitter systems are impaired in adult mice.

Schizophrenia Research, 1995

Psychiatry Research, 2002

Psychiatry Research, 2001

Since the findings concerning the Wisconsin Card Sorting Test WCST performance of healthy first-d... more Since the findings concerning the Wisconsin Card Sorting Test WCST performance of healthy first-degree relatives of patients with schizophrenia are equivocal, it still remains unclear whether the WCST may serve as a neuropsychological indicator of vulnerability to schizophrenia. The aim of this study was to evaluate whether the first-degree relatives' schizotypal features could account for these discrepancies. The subjects were 24 schizophrenic probands, 49 of their first-degree relatives and 41 normal controls. The computerized version of the WCST was used and schizotypy features were assessed using four of Chapman's scales. The patient group performed worse on the WCST and had higher scores of schizotypy than the control group. The relatives group did not significantly differ from the control, neither on the WCST performance nor on the scores of schizotypy. However, the subgroup of relatives and the subgroup of patients with high scores on the negative dimension of schizotypy showed a worse performance on the WCST than the subgroups with low scores. There were no differences on the WCST performance between the subgroups with high vs. low scores on the positive dimension of schizotypy. Thus, discrepancies across studies could be explained by a confounding factor represented by the negative dimension of schizotypy.

Psychiatry Research, 1992

The role of the human histocompatibility complex (HLA) in the pathogenesis of schizophrenia has b... more The role of the human histocompatibility complex (HLA) in the pathogenesis of schizophrenia has been suggested in previous reports. We conducted a genetic study in 33 new families. Our linkage analysis, which used the affected sib-pair method, did not provide evidence for nonrandom assortment. Moreover, the results of an association study using the "haplotype relative risk" method failed to confirm the positive association between HLA A9 and schizophrenia. Taken together, our data did not support any relationship of HLA type to schizophrenia.