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Biomedical subjects

J P Olié

Publications and source records attributed to J P Olié.

At least 19 recordsLinked to original sources

Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine.

Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the antidepressant, tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt), a compound with structural similarities to the tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of tianeptine involve the dynamic interplay between numerous neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of tianeptine on central plasticity is the most thoroughly studied of any antidepressants. Effects of tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of tianeptine as an antidepressant, these actions offer insights into how compounds like tianeptine may be useful in the treatment of neurobiological features of depressive disorders.

Affect↗

Antidepressant efficacy and cognitive effects of repetitive transcranial magnetic stimulation in vascular depression: an open trial.

BACKGROUND: Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) were demonstrated by many controlled studies in major depression. Moreover, this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy.Vascular depression is a subtype of late-life depression, associated with cerebrovascular disease and means a poorer response to antidepressant treatment. We employed rTMS over the left prefrontal cortex in 11 patients with late-onset resistant vascular depression. The primary purpose of this two-week open study was to examine antidepressant efficacy of rTMS in vascular depression. The secondary aim was to evaluate cognitive effects of rTMS in our sample. METHODS: Clinical status, as measured with the Hamilton Depression Rating Scale (HDRS), and cognitive effects, as evaluated by neuropsychological tests, were assessed at baseline and after two weeks of rTMS. Brain measurements to obtain an index of prefrontal atrophy were performed at both the motor cortex and prefrontal cortex. RESULTS: Five out of 11 resistant patients with late-onset vascular depression were responders. They showed a clinically meaningful improvement in HDRS scores, with a decrease of 11, 4 points (p<0.01). Antidepressant response is correlated to the relative degree of prefrontal atrophy (p = 0.05). After two weeks, verbal fluency and visuospatial memory improved. No cognitive performance deteriorated except for verbal memory, as the delayed recall decreased significantly in the responders' group. CONCLUSIONS: Our preliminary observations prompt to perform a subsequent controlled study to examine if rTMS may constitute an alternative to electroconvulsive therapy.

Aged↗

Phenomenological and comorbid features associated in obsessive-compulsive disorder: influence of age of onset.

BACKGROUND: To explore clinical features of symptoms and comorbidity according to the age of onset of patients suffering from obsessive-compulsive disorder (OCD). METHODS: The survey involved collecting data from both patient members of an OCD association, and a sample of 175 OCD patients seen in OCD specialty practice. All the patients (n=617) responded to a questionnaire on family and personal psychiatric OCD history, phenomenological features of OCD and comorbidity. They were classified according to OCD age at onset [group early age of onset (EO): under 15, group late age of onset (LO): older than 15]. RESULTS: A higher percentage of patients from Group LO complained of OCD triggering by factors such as professional difficulties and childbirth (P<0.05); also they more often had (P=0.05) a sudden onset of symptoms. On the other hand, clinical features, such as superstition and magic thoughts, parasite obsessions and repeating, counting, hoarding, tapping/rubbing and collecting compulsions were significantly more frequent (P<0.05) in EO; likewise, history of tics was more frequent in this group. The existence of comorbid depression (at least one episode) did not show any significant difference between groups. However, depression preceding OCD was more frequent in LO. There was no significant difference in treatment response according to age of onset OCD. CONCLUSIONS: The results showed a clear association of EO with obsessions of superstition and parasites, repetitive compulsions and motor and vocal tics, whereas a sudden onset, triggering factors and a more frequent depression preceding OCD characterized LO.

Adolescent↗

5HTTLPR polymorphism in schizophrenic patients: further support for association with violent suicide attempts.

Previous studies testing the functional polymorphism in the promoter of the serotonin-transporter gene (5HTTLPR) in various psychiatric conditions have suggested that the association could be with an intermediate phenotype, impulsivity and/or violence rather than with a diagnosis. Schizophrenia is associated with a high risk of suicide, especially in patients with high impulsivity. We examined whether this polymorphism could be associated with violent suicide and/or impulsivity in schizophrenic patients. We genotyped the 5HTTLPR polymorphism in 185 unrelated schizophrenic patients from a French Caucasian population. The genotype frequencies significantly differed between patients who made violent suicide attempts and both, those who attempted suicide with a non-violent method (P = 0.013) and those who never attempted suicide (P = 0.026). The genotypes containing the low activity "short" allele was significantly more frequent in violent suicide attempters (P = 0.007) than in non-violent suicide attempters. No evidence was found for an association either with schizophrenia itself, when compared to gender and ethnically matched controls (n = 159) or with impulsivity, assessed using Barratt's Impulsivity Scale. Although replication studies are warranted, these results in schizophrenia further support the hypothesis that 5HTTLPR polymorphism is a risk factor for violent suicidal behavior.

Adult↗

A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression.

A meta-analysis was performed to compare the efficacy of tianeptine and selective serotonin reuptake inhibitors (SSRI) in the short-term treatment of depression. Consecutive selection and inclusion processes allowed five studies to be selected: two studies on tianeptine versus fluoxetine, two studies on tianeptine versus paroxetine, and one study on tianeptine versus sertraline. A total of 1348 patients were included in the five studies; 681 subjects received an SSRI and 667 tianeptine. A strict step-by-step methodology was applied in order to legitimize this meta-analysis and to interpret the results. Considering all the patients or those with a Montgomery-Asberg Depression Rating Scale (MADRS) inclusion score greater than 28, none of the assessed parameters (MADRS total score and responder rate) revealed any significant difference between the two treatment groups. Further analysis based on clinical global impression (CGI) items found no significant difference, except for CGI item 3 (therapeutic index), where a tendency (P=0.06 or 0.07 depending on the methodology) was found in favor of tianeptine. All in all, this study confirmed that tianeptine is at least as effective as SSRI, with a trend for a better acceptability profile in the treatment of depressed patients.

Antidepressive Agents, Tricyclic↗

Manic episodes: the direct cost of a three-month period following hospitalisation.

INTRODUCTION: Few data exist to estimate the burden of manic episodes on healthcare systems or the therapeutic strategies used. This study was undertaken to identify treatment strategies chosen, and to assess the "real-world" direct medical cost of treating manic episodes necessitating hospitalisation. METHOD: Case record data were reviewed during the three months following hospitalisation for a manic episode in France. Healthcare resource utilisation was assessed, direct costs calculated, and treatment strategies analysed. A total of 137 patients files (51.8% female; mean age: 35 years) were reviewed and data on 185 hospitalisations collected. RESULTS: The mean duration of hospitalisation was 47 days over the study period. The most common treatment strategy during hospitalisation was the combination of a mood stabilizer with a neuroleptic drug (64% of patients at day 30). Anticonvulsants including valproate (39%) and carbamazepine (20%) were more common than lithium (42%). Treatment received during hospitalisation was generally continued after discharge, with a trend away from neuroleptics and towards mood stabilizers. The mean direct costs incurred over the three-month study period was Euro 22297, with 98.6% of those costs due to hospitalisation. CONCLUSION: These results confirm that the costs of treating a manic episode are high, and overwhelmingly due to the cost of hospitalisation.

Adult↗

Social functioning and quality of life in the schizophrenic patient: advantages of amisulpride.

Schizophrenia is associated with significant social, psychological and occupational dysfunction. Not only is this distressing for the patients and their family and friends, but it also results in high indirect costs. Reintegration back into society, one of the most important aspects of quality life for schizophrenic patients and their physicians, must therefore take into account a patient's social functioning and employability, as well as improvement in symptoms. Although the typical antipsychotics are effective in managing the positive symptoms of schizophrenia, they may not alleviate other aspects of the disorder. They are also associated with extrapyramidal symptoms and other severe adverse events that have significant consequences for quality of life and compliance. The atypical antipsychotic, amisulpride, has an improved safety and tolerability profile and has been shown to be significantly more effective than placebo and haloperidol on a number of quality of life and social functioning scales, including the Global Assessment of Functioning, the Quality of Life Scale, the Functional Status Questionnaire and the Psychosocial Aptitude Rating Scale. In conclusion, amisulpride, in addition to its proven clinical efficacy, may help reintegration of the schizophrenic patient back into society.

Amisulpride↗

Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1.

Abuse of cannabis is frequent among the young and is suspected to precipitate schizophrenia in vulnerable subjects. Cannabinoid receptor (CB1) is particularly concentrated in dopamine-modulated areas of the nervous system. An association between an AAT polymorphism of the CB1 gene and intravenous drug abuse has been previously reported, but not with schizophrenia. In a French Caucasian population, we compared the distribution of a single-base polymorphism revealed by MspI within the first exon of the CB1 gene in patients with schizophrenia (n = 102) and ethnic- and gender-matched controls (n = 63). No significant difference was seen in the allele or genotype distribution between the whole sample of schizophrenic patients and controls. However, we found a borderline lack of allele g and a significant lack of gg genotype in the non-substance-abusing patients compared to substance-abusing patients, the latter being similar to the controls. These results are the first report of an significant association between CB1 receptor and a subtype of schizophrenia. Studies are needed to confirm and further explore the precise role of the cannabinoid system in schizophrenia.

Adult↗

[Predictive factors of response to buprenorphine in the substitutive treatment of heroin addicts. Results of a multicenter study of 73 patients].

OBJECTIVE: Buprenorphine has a partial morphine-agonist pharmacological profile. It is proposed as alternative to methadone in opiate drug addicts with greater safety of use and less cost in terms of public health. The aim of this study was to determine the clinical factors of response to this molecule. METHOD: The study was conducted in 73 patients treated for 3 months with adaptable doses. Mean dose was 8.5 mg/d (range: 3 to 16 mg/d). Response to treatment was defined as: still in the study at 3 months and absence of opiates in 75% of urinary samples over the past month. RESULTS: Forty-eight patients responded and 25 did not. The determinating clinical variables of response were: opiate drug addiction less than 10 years, high score on the Addiction Severity Index (ASI), absence of depression according to the Minnesota Multiphasic Personality Inventory (MMPI) and low rate of disinhibition on Zukerman's sensation seeking scale. Conversely, the dose of buprenorphine within the limits specified in the Marketing Authorisation did not intervene in the response. CONCLUSION: In view of its partial agonist effect, administration of buprenorphine must be reserved for patients addicted to opiates for less than 10 years, non-depressive and with low disinhibition on Zukerman's scale.

Adult↗

Substance abuse and suicidality in schizophrenia: a common risk factor linked to impulsivity.

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.

Adult↗

Is substance abuse in schizophrenia related to impulsivity, sensation seeking, or anhedonia?

OBJECTIVE: The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence. METHOD: Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview's section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. RESULTS: The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia. CONCLUSIONS: As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.

Adult↗

Histamine H2 receptor gene variants: lack of association with schizophrenia.

A role of histaminergic neuronal systems in schizophrenia was suggested by an association with several polymorphisms located in the coding region of the histamine H2-receptor (H2R) gene (Orange et al, Mol Psychiatry 1996; 1: 466-469). Using either the reference method of direct sequencing or restriction endonuclease digestion of PCR products amplified from DNA, we could not confirm the existence of these polymorphisms in 53 Swedish controls, 52 French controls and 88 French schizophrenics. In contrast, we detected a G543A transition in the coding region of the gene that was not found in the British population. This allelic variation, which was observed in 15% of the controls with no homozygotes, did not change the amino acid sequence of the receptor. We also analyzed a 1.8-kb nucleotide sequence of the promoter region in which we detected two additional polymorphisms that may modulate the expression of the H2R gene. The first one was a A-592G transition located in the minimal promoter of the gene and found in;10% of controls with no homozygotes. The second one was a G-1018A transition located in an enhancer element of the promoter and was found in;20-30% of controls (with;2-4% homozygotes). DNA analysis of the 88 French schizophrenic subjects revealed that the incidence of the three polymorphisms was not significantly different in this population. In conclusion, the present findings may suggest a surprisingly high variability of the H2R gene polymorphisms in different geographical areas but do not support an association of these allelic variations with schizophrenia.

Female↗

[Depression and manic-depressive disorders].

The two major subtypes of manic-depressive illness are bipolar disorder and recurrent major depressive disorder. Biological data strongly indicate that a significant genetic factor is involved in the development of manic-depressive illness. But, stressful life events, environmental stress and premorbid personality factors may also be involved in other important etiologic factors. Some research data indicate that cyclothymic disorder and temperamental disorders may be considered as mild forms of bipolar disorders so called "subaffective disorders". The identification of clinical or biological features reflecting the severity of the major depressive episode is very important in regard of the high potential for suicide of the illness.

Bipolar Disorder↗