[Clinical research in psychiatry: what role for nurses?].
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Clinical Trials as Topic↗
Biomedical subjects
M F Poirier
Publications and source records attributed to M F Poirier.
Effects of lithium on saccadic eye movements in healthy subjects in a ten-day double-blind placebo-controlled cross-over pilot study.
INTRODUCTION: Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. METHODS: A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. RESULTS: There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. CONCLUSION: The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.
Adult↗
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↗
Double-blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers.
OBJECTIVE: The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. METHODS: In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. RESULTS: There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). CONCLUSION: Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions.
Adult↗
Disorganization syndrome is correlated to working memory deficits in unmedicated schizophrenic patients with recent onset schizophrenia.
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Adult↗
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↗
[Schizophrenia and drug abuse: genetic aspects].
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Brain↗
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↗
Impairment of predictive saccades in schizophrenia.
Using infrared oculography, we compared saccades toward predictable and pseudo-random visual targets in 19 neuroleptic-free patients with schizophrenia (including 13 neuroleptic-naïve patients) and in 29 age- and gender-matched healthy volunteers. Externally driven saccades were not different between patients and controls, whether or not the target was predictable. Anticipated saccades were specifically less accurate in the patients compared to the controls. The difference between primary gain of anticipated and non-anticipated saccades was markedly higher in the patients compared to controls (p=0.003). These results point to a deficit in the early step of internally driven oculomotor planning in schizophrenia.
Adult↗
Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.
1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.
Adolescent↗
Genetic vulnerability to drug abuse.
Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.
Female↗
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↗
Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia.
Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.
Adult↗
The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine.
BACKGROUND: Changes in serotonin (5-HT)2 receptor densities were reported in depression by postmortem studies and following treatment with tricyclic antidepressants in animal studies. Here, 5-HT2 receptors were studied in vivo in depressed patients. METHODS: Cortical 5-HT2 receptors were investigated prospectively using positron-emission tomography and [18F]-setoperone in 7 depressed patients, before and after at least 3 weeks of clomipramine (CMI), 150 mg daily. They were compared to 7 age-matched controls. RESULTS: There was no significant difference between the untreated patients and the controls, except in the frontal region, where the [18F]-setoperone specific binding was slightly lower in patients. After CMI treatment, depression scores significantly improved and [18F]-setoperone specific binding decreased in cortical regions, suggesting receptor occupancy and/or receptor regulation, by CMI; however, no clinical score correlated with the 5-HT2 receptor measurements either in the untreated or in the treated conditions. CONCLUSIONS: These data substantiate the view that tricyclic antidepressants such as clomipramine significantly interact with cortical 5-HT2 serotoninergic receptors in actual therapeutic situations.
Adult↗
Obsessive-compulsive disorder: evaluation of clinical and biological circadian parameters during fluoxetine treatment.
RATIONALE: Many biological abnormalities have been found in obsessive-compulsive disorder (OCD). The circadian rhythm investigations of different clinical and biological parameters may provide a comparison with depression. Fluoxetine is one of the efficient drugs in alleviating symptoms of OCD. The effect of fluoxetine can highlight some clues to the neurotransmitter alterations in the disorder. OBJECTIVE: The present study investigated clinical and biological circadian modifications in OCD patients during a fluoxetine treatment. METHODS: Daily clinical symptoms, and circadian rhythms of axillary temperature, plasma cortisol and plasma melatonin were assessed in eight patients suffering from OCD. These parameters were compared in the same patients, before and after an 8-week fluoxetine treatment period. RESULTS: A therapeutic effect of fluoxetine was obtained. No significant differences were observed either in daily clinical variations or in biological circadian rhythms measured before and after treatment. CONCLUSION: The therapeutic efficacy of fluoxetine was not related to the biological parameters assessed.
Adult↗
Impairment of consciously controlled use of memory in schizophrenia.
Recent studies of memory in schizophrenia have shown that explicit but not implicit memory performance is impaired. The hypothesis that schizophrenia is associated with a failure of consciously but not unconsciously (automatic) controlled influence of memory on performance was tested using a procedure providing uncontaminated estimates of consciously controlled and automatic memory processes (i.e., the process-dissociation procedure in a stem completion task). Performance of 35 patients with schizophrenia was compared with that of 35 normal participants. Consciously controlled use but not automatic influences of memory was significantly lower in patients with schizophrenia than in controls. Consciously controlled use of memory was negatively and significantly correlated with positive symptoms of schizophrenia. Schizophrenia differentially affects 2 types of memory processes: It impairs consciously controlled use of memory but spares automatic influences. Positive symptoms could reflect the lack of control from higher level conscious processes.
Adult↗