Pub Date : 2002-03-01DOI: 10.1017/S1461145701002681
E. S. Hansen, S. Hasselbalch, I. Law, T. Bolwig
Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.
{"title":"The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study.","authors":"E. S. Hansen, S. Hasselbalch, I. Law, T. Bolwig","doi":"10.1017/S1461145701002681","DOIUrl":"https://doi.org/10.1017/S1461145701002681","url":null,"abstract":"Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"82 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130303841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-01DOI: 10.1017/S1461145701002759
A. Halaris, He Zhu, Jeffery Ali, A. Nasrallah, C. Lindsay De Vane, J. Piletz
An elevation of I1 (imidazoline-1)-binding sites on platelets may be a state marker for depression. Herein, platelet I1 sites were compared in two groups of unipolar depressed patients given different regimens of bupropion treatment: Regimen 1 (n = 13 titrated up to 300 mg/d by week 4 and held constant until week 6); Regimen 2 (n = 15 titrated up to 300 mg/d by week 2, to 450 mg/d by week 6, and held constant until week 8). Platelet I1 sites were quantified by p-[125I]iodoclonidine binding (0.5-15 nM) and displaced by moxonidine under a saturating concentration of norepinephrine to mask alpha2-adrenoceptors. I1 B max values were confirmed to be high at pretreatment in depressed patients (n = 28) compared to healthy control subjects (n = 18; p = 0.02). Highest B max values at pretreatment were found in patients who responded worst to treatment. More than two-thirds of patients recovered from depression (69 and 80% in Regimens 1 and 2, respectively) after treatment. Dose and/or time of exposure to bupropion were relevant variables since (1). only Regimen 2 led to platelet I1 down-regulation and (2). the extent of down-regulation correlated with plasma concentrations of bupropion. The data suggest a dissociation exists between I1 down-regulation and therapeutic response, or else platelet I1 down-regulation lags behind clinical antidepressant response before becoming measurable.
{"title":"Down-regulation of platelet imidazoline-1-binding sites after bupropion treatment.","authors":"A. Halaris, He Zhu, Jeffery Ali, A. Nasrallah, C. Lindsay De Vane, J. Piletz","doi":"10.1017/S1461145701002759","DOIUrl":"https://doi.org/10.1017/S1461145701002759","url":null,"abstract":"An elevation of I1 (imidazoline-1)-binding sites on platelets may be a state marker for depression. Herein, platelet I1 sites were compared in two groups of unipolar depressed patients given different regimens of bupropion treatment: Regimen 1 (n = 13 titrated up to 300 mg/d by week 4 and held constant until week 6); Regimen 2 (n = 15 titrated up to 300 mg/d by week 2, to 450 mg/d by week 6, and held constant until week 8). Platelet I1 sites were quantified by p-[125I]iodoclonidine binding (0.5-15 nM) and displaced by moxonidine under a saturating concentration of norepinephrine to mask alpha2-adrenoceptors. I1 B max values were confirmed to be high at pretreatment in depressed patients (n = 28) compared to healthy control subjects (n = 18; p = 0.02). Highest B max values at pretreatment were found in patients who responded worst to treatment. More than two-thirds of patients recovered from depression (69 and 80% in Regimens 1 and 2, respectively) after treatment. Dose and/or time of exposure to bupropion were relevant variables since (1). only Regimen 2 led to platelet I1 down-regulation and (2). the extent of down-regulation correlated with plasma concentrations of bupropion. The data suggest a dissociation exists between I1 down-regulation and therapeutic response, or else platelet I1 down-regulation lags behind clinical antidepressant response before becoming measurable.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122125978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002620
M. Raja, A. Azzoni
The growing use of atypical antipsychotics has led to a decrease of acute dystonic reactions (ADR). To evaluate the prevalence of ADR, we recorded all ADR occurring in a population of patients consecutively admitted to a psychiatric intensive care unit. Among 1337 cases treated with antipsychotics, we observed 41 cases (3.1%) affected by ADR. At discharge, mean chlorpromazine-equivalent daily dose was 465.8 (+/-421.5) mg, while 39 cases (3.0%), all treated with typical neuroleptics, received anticholinergics. During hospitalization, 15 cases received quetiapine, 19 sertindole, 95 olanzapine, 142 clozapine, 495 risperidone and 561 typical neuroleptics. Four ADR occurred among the cases treated with risperidone monotherapy, and 4 occurred in risperidone-treated patients after emergency parenteral treatment with typical neuroleptics. In these last 4 cases, temporal relationship suggested that typical neuroleptics had caused ADR. One ADR occurred in a patient treated with olanzapine and 1 ADR in a patient treated with quetiapine. Among cases assuming typical neuroleptics, 32 ADR occurred. The difference between typical and atypical neuroleptics is highly significant (chi2 = 27.756; d.f. = 1; p = 0.000). Atypical antipsychotics carry a minimal risk of ADR.
{"title":"Novel antipsychotics and acute dystonic reactions.","authors":"M. Raja, A. Azzoni","doi":"10.1017/S1461145701002620","DOIUrl":"https://doi.org/10.1017/S1461145701002620","url":null,"abstract":"The growing use of atypical antipsychotics has led to a decrease of acute dystonic reactions (ADR). To evaluate the prevalence of ADR, we recorded all ADR occurring in a population of patients consecutively admitted to a psychiatric intensive care unit. Among 1337 cases treated with antipsychotics, we observed 41 cases (3.1%) affected by ADR. At discharge, mean chlorpromazine-equivalent daily dose was 465.8 (+/-421.5) mg, while 39 cases (3.0%), all treated with typical neuroleptics, received anticholinergics. During hospitalization, 15 cases received quetiapine, 19 sertindole, 95 olanzapine, 142 clozapine, 495 risperidone and 561 typical neuroleptics. Four ADR occurred among the cases treated with risperidone monotherapy, and 4 occurred in risperidone-treated patients after emergency parenteral treatment with typical neuroleptics. In these last 4 cases, temporal relationship suggested that typical neuroleptics had caused ADR. One ADR occurred in a patient treated with olanzapine and 1 ADR in a patient treated with quetiapine. Among cases assuming typical neuroleptics, 32 ADR occurred. The difference between typical and atypical neuroleptics is highly significant (chi2 = 27.756; d.f. = 1; p = 0.000). Atypical antipsychotics carry a minimal risk of ADR.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125786024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002632
G. Bagdy, Márton Gráf, Z. Anheuer, Edit A. Modos, S. Kantor
The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0.2 mg/kg, i.p. In contrast, the selective 5-HT1A receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants. Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.
{"title":"Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.","authors":"G. Bagdy, Márton Gráf, Z. Anheuer, Edit A. Modos, S. Kantor","doi":"10.1017/S1461145701002632","DOIUrl":"https://doi.org/10.1017/S1461145701002632","url":null,"abstract":"The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0.2 mg/kg, i.p. In contrast, the selective 5-HT1A receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants. Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"128 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128296754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002565
P. Bech
When attempting to demonstrate a purely antidepressive effect of new antidepressants the HAMD depression factor has been found adequate in placebo-controlled trials. When attempting to demonstrate an early onset of action of amitriptyline the HAMD item of depressed mood has previously been found sufficient, using effect size as outcome statistic. Therefore, the HAMD depression factor as well as the HAMD item of depressed mood have been used separately in this meta-analysis to evaluate the pure antidepressive effect and early onset of action of mirtazapine when compared to placebo or amitriptyline. The results showed that in all placebo-controlled trials mirtazapine obtained an effect size of 0.42 on the HAMD depression factor subscale and 0.49 on the full HAMD. In the trials in which mirtazapine was compared to amitriptyline the effect sizes for the HAMD depression factor subscale were 0.40 and 0.57, respectively. This difference was not statistically significant. An early onset of action was found for the HAMD item of depressed mood as well as the total HAMD both for mirtazapine and amitriptyline when compared to placebo. As early as after 1 wk of therapy both drugs were significantly better than placebo. In conclusion, a purely antidepressive effect of mirtazapine has been demonstrated concerning both improvement after the acute therapy of major depression and early onset of action.
{"title":"Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression.","authors":"P. Bech","doi":"10.1017/S1461145701002565","DOIUrl":"https://doi.org/10.1017/S1461145701002565","url":null,"abstract":"When attempting to demonstrate a purely antidepressive effect of new antidepressants the HAMD depression factor has been found adequate in placebo-controlled trials. When attempting to demonstrate an early onset of action of amitriptyline the HAMD item of depressed mood has previously been found sufficient, using effect size as outcome statistic. Therefore, the HAMD depression factor as well as the HAMD item of depressed mood have been used separately in this meta-analysis to evaluate the pure antidepressive effect and early onset of action of mirtazapine when compared to placebo or amitriptyline. The results showed that in all placebo-controlled trials mirtazapine obtained an effect size of 0.42 on the HAMD depression factor subscale and 0.49 on the full HAMD. In the trials in which mirtazapine was compared to amitriptyline the effect sizes for the HAMD depression factor subscale were 0.40 and 0.57, respectively. This difference was not statistically significant. An early onset of action was found for the HAMD item of depressed mood as well as the total HAMD both for mirtazapine and amitriptyline when compared to placebo. As early as after 1 wk of therapy both drugs were significantly better than placebo. In conclusion, a purely antidepressive effect of mirtazapine has been demonstrated concerning both improvement after the acute therapy of major depression and early onset of action.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"84 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128367771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002590
D. Javitt, D. Javitt, D. Javitt, G. Silipo, A. Cienfuegos, A. Shelley, Nigel Bark, Mohan Park, J-P Lindenmayer, Ray Suckow, S. Zukin
Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.
{"title":"Adjunctive high-dose glycine in the treatment of schizophrenia.","authors":"D. Javitt, D. Javitt, D. Javitt, G. Silipo, A. Cienfuegos, A. Shelley, Nigel Bark, Mohan Park, J-P Lindenmayer, Ray Suckow, S. Zukin","doi":"10.1017/S1461145701002590","DOIUrl":"https://doi.org/10.1017/S1461145701002590","url":null,"abstract":"Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134063554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002644
A. Neumeister, A. Konstantinidis, N. Praschak-Rieder, Matthaeus Willeit, E. Hilger, J. Stastny, S. Kasper
Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD. The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy.
{"title":"Monoaminergic function in the pathogenesis of seasonal affective disorder.","authors":"A. Neumeister, A. Konstantinidis, N. Praschak-Rieder, Matthaeus Willeit, E. Hilger, J. Stastny, S. Kasper","doi":"10.1017/S1461145701002644","DOIUrl":"https://doi.org/10.1017/S1461145701002644","url":null,"abstract":"Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD. The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133247782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002619
Monique S. Gevaerd, E. Miyoshi, Rodolfo Silveira, N. Canteras, Reinaldo N. Takahashi, C. D. Cunha
The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.
{"title":"L-Dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats.","authors":"Monique S. Gevaerd, E. Miyoshi, Rodolfo Silveira, N. Canteras, Reinaldo N. Takahashi, C. D. Cunha","doi":"10.1017/S1461145701002619","DOIUrl":"https://doi.org/10.1017/S1461145701002619","url":null,"abstract":"The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131228919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002668
P. Brambilla, F. Barale, J. Soares
The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.
{"title":"Perspectives on the use of anticonvulsants in the treatment of bipolar disorder.","authors":"P. Brambilla, F. Barale, J. Soares","doi":"10.1017/S1461145701002668","DOIUrl":"https://doi.org/10.1017/S1461145701002668","url":null,"abstract":"The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134541147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002577
S. File, E. Fluck, A. Leahy
In a double-blind, placebo-controlled study, we examined the effects of nicotine (2 mg administered by inhalator) on the cognitive performance of male and female non-smoking students and on mood changes following a moderately stressful task. The groups were matched for age and IQ, and did not differ in pre-test measures of anxiety, depression, extroversion and neuroticism or in their weekly alcohol or daily caffeine intake. Nicotine did not change performance in tests of attention and memory. Exposure to moderate stress significantly increased ratings of anxiety, discontent and aggression and nicotine blocked these mood changes in females, but enhanced them in males. This suggests that young women may start regular smoking as a form of stress self-medication, which implies that preventative and smoking cessation programmes would be more successful in women if they addressed issues of stress and anxiety, which may be core factors underlying initiation and maintenance of regular smoking.
{"title":"Nicotine has calming effects on stress-induced mood changes in females, but enhances aggressive mood in males.","authors":"S. File, E. Fluck, A. Leahy","doi":"10.1017/S1461145701002577","DOIUrl":"https://doi.org/10.1017/S1461145701002577","url":null,"abstract":"In a double-blind, placebo-controlled study, we examined the effects of nicotine (2 mg administered by inhalator) on the cognitive performance of male and female non-smoking students and on mood changes following a moderately stressful task. The groups were matched for age and IQ, and did not differ in pre-test measures of anxiety, depression, extroversion and neuroticism or in their weekly alcohol or daily caffeine intake. Nicotine did not change performance in tests of attention and memory. Exposure to moderate stress significantly increased ratings of anxiety, discontent and aggression and nicotine blocked these mood changes in females, but enhanced them in males. This suggests that young women may start regular smoking as a form of stress self-medication, which implies that preventative and smoking cessation programmes would be more successful in women if they addressed issues of stress and anxiety, which may be core factors underlying initiation and maintenance of regular smoking.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125975940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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