Search PubMed⌕ Search

Biomedical subjects

J M Azorin

Publications and source records attributed to J M Azorin.

At least 19 recordsLinked to original sources
PubMed2003

Proposed multidimensional structure of mania: beyond the euphoric-dysphoric dichotomy.

BACKGROUND: Although the construct of depression has been subjected to numerous factor analytic studies and phenomenological subtypes of clinical relevance have been delineated, this is not the case for mania. The few available studies have reported at least two factors, which consist of euphoric versus dysphoric-hostile subtypes. Our objective was to replicate and further enrich this literature. METHODS: In the EPIMAN French National Study we systematically evaluated 104 DSM-IV hospitalized manic patients in four university centers in different regions of France. Psychiatrists completed the Beigel-Murphy Manic State Rating Scale (MSRS), as well as the HAM-D(17), affective temperament scales, and the GAF Axis V from DSM-IV. Categorization of patients into pure versus dysphoric mania was made on the basis of clinical diagnosis, independent from psychometric measures. RESULTS: On principal component analysis of the MSRS, three factors explained the largest variance: a global manic (23.3% variance), paranoid-hostile (14.8% variance), and psychotic (9.1% variance). After varimax rotation, we obtained seven independent factors: F1 Disinhibition-instability, F2 Paranoia-hostility, F3 Deficit, F4 Grandiosity-psychosis, F5 Elation-euphoria, F6 Depression, and F7 (Hyper)sexuality. We could not demonstrate significant correlations between the individual factors and impaired functioning on GAF. However, depressive and, to some extent, cyclothymic temperaments correlated with F6 Depression. Finally, intergroup comparisons between pure versus dysphoric mania diagnosed clinically showed high levels of F3 Deficit and F5 Elation in the pure, and of F6 Depression in dysphoric, mania; F2 Paranoia-hostility did not discriminate these two clinical forms of mania. LIMITATIONS: Although the present analyses on the Beigel-Murphy represent the largest sample studied to date, they are still underpowered and do not guarantee a stable factorial structure. Our findings are cross-sectional and require prospective validation. CONCLUSIONS: Our data suggest that 'dysphoria' as used in the literature to qualify mania is insufficiently precise, and is best further specified as 'depressive' versus 'irritable.' Moreover, our data extend the rich multidimensional phenomenology of mania beyond the existing literature: we submit that disinhibition-instability (a core 'activation' component) can, on the one hand, be associated with distinct emotional presentations (euphoric, depressive, or irritable-hostile), as well as psychotic and deficit symptomatology on the other.

Adult↗
PubMed2002

Clinical issues related to depression in schizophrenia: an international survey of psychiatrists.

OBJECTIVE: Depressive symptoms in schizophrenia are associated with a substantial morbidity and mortality burden. The 'International Survey of Depression in Schizophrenia' was designed to evaluate current awareness and clinical approaches in this area. METHOD: A 48-item questionnaire was distributed to approximately 80 000 consultant psychiatrists world-wide. Responses were analysed using descriptive statistics. RESULTS: Respondents demonstrated considerable awareness of the prevalence and consequences of depression in schizophrenia. Although there was widespread adjunctive use of antidepressants, one-third of respondents indicated that they rarely or never prescribe these agents in combination with antipsychotic medication. There were considerable variations in opinions about the best approach to the treatment of depressive symptoms associated with schizophrenia. CONCLUSION: The considerable clinical burden of depressive symptomatology in schizophrenia was acknowledged by the majority of respondents to this survey. There was, however, little agreement on the best management strategy.

Adult↗
PubMed2001

Depression in schizophrenia: recognition and management in the USA.

The recognition of depression as a distinct syndrome within schizophrenia is a relatively recent development. The International Survey of Depression in Schizophrenia was designed to evaluate current clinical practice and prescribing trends in the management of the depressive component of schizophrenia. A 48-item questionnaire, comprising fixed-response questions and questions stimulated by case scenarios, was distributed to 37513 psychiatrists in the USA. A total of 43484 psychiatrists in Canada, Australia and 21 European countries also received the questionnaire. A total of 1128 US psychiatrists responded. Analysis of the data revealed that US psychiatrists identify symptoms of depression in approximately one-third of patients with schizophrenia, and largely appreciate the magnitude of the resultant burden on patients and their families. Responses to questions regarding treatment approaches and case scenarios demonstrated that the level of adjunctive prescribing of antidepressants in the USA is often higher than in other regions. Levels of awareness of depression in patients with schizophrenia and recognition of the need for effective management appear to be high among US psychiatrists. However, more than a quarter of these specialists rarely or never prescribe adjunctive antidepressant medications. Disparities in treatment approaches varying from the existing scientific evidence base underscore the need for further investigation into ways of optimizing the management of this serious coexisting condition.

Antidepressive Agents↗
PubMed2001

Toward a refined phenomenology of mania: combining clinician-assessment and self-report in the French EPIMAN study.

BACKGROUND: Because manic patients lack insight, they are generally considered unreliable observers of their own psychopathology. The present analyses sought to examine to what extent patient reports could improve formal diagnostic criteria for mania--and be validated against the Carroll-Klein (CK) psychobiological model of bipolarity. METHOD: 104 DSM-IV acutely manic (hospitalized) patients provided self-assessment on the Ahearn--Carroll scale, the Multiple Visual Analogue Scales of Bipolarity (MVAS-BP). A principal component analysis (PCA) was performed on MVAS-BP, and the data on factorial scores were then compared to dimensional scores according to the CK model and to factors on the Beigel-Murphy Manic State Rating Scale (MSRS) completed by psychiatrists. RESULTS: The PCA identified a general factor accounting for 33% of the total variance; after varimax rotation, seven independent factors emerged, essentially in coherence with the signs and symptoms of DSM-IV mania, except for the 'social disinhibition' factor, which does not figure out as a distinct criterion in DSM-IV. Strong correlations were obtained (r > or = 0.80) between the four major factors of MVAS-BP and the four dimensional categories of the CK model: 'Consummatory Reward' with F1 'Elation and Inflated Self-esteem' (r=0.93), 'Incentive Reward' with F2 'Activation' (r=0.84), 'Psychomotor Pressure' with F3 'Acceleration' (r=0.85), and 'Central Pain' with F4 'Anxiety-Depression' (r=0.84). The F2 'Activation' appeared to be strongly correlated (r > or = 0.70) to all categories of the CK model. Correlational analysis between the factor structure of MVAS-BP and the MSRS showed significant coefficients on the scores assessing the emotional factors of 'Elation' and 'Depression.' Among the MVAS-BP factors, only 'Activation' was correlated to the majority of clinician ratings as obtained by the MSRS. CONCLUSIONS: These findings provide overall construct validity to the DSM-IV criteria for mania. Self-assessment of this disorder appears feasible and potentially useful in practice; lack of insight, poor judgment, and distractibility obviously require assessment by a clinician. Although our data are correlational and require prospective validation, they nonetheless suggest that (1) activation should be raised to the status of the stem criterion for mania, (2) to specify mood as elated, depressive, anxious, or irritable, and (3) to give individual status to social disinhibition (indiscriminate gregariousness) as a core pathological behavior in mania. Combining clinician- and self-observation thus produces a more precise and complete phenomenology of mania. We finally submit that the foregoing reformulation provides a psychobiological basis to the manic construct as formulated in the Carroll-Klein model.

Bipolar Disorder↗
PubMed2001

The feasibility of self-assessment of dysphoric mania in the French national EPIMAN study.

BACKGROUND: There is presently considerable uncertainty on how to best assess mixed mania. The present contribution explores the feasibility of discriminating manic and dysphoric manic states on the basis of self-rating in the acute phase of the illness. METHODS: In the French four-site national EPIMAN study of 104 patients devoted to the clinical evaluation and subclassification of mania, we used the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self-assessment format. The study was conducted on consecutive patients hospitalized for an acute DSM-IV mania. The severity of mania was measured by the Beigel-Murphy scale (MSRS) assessed by psychiatrists. When mania abated, temperaments according to Akiskal and Mallya were administered in their French version. RESULTS: Principal component analysis revealed a general factor explaining 33% of the variance and, after rotation, seven factors defining different dimensions of the phenomenology of mania. The factorial scores, as well as the dimensional scores of the Carrol-Klein model significantly distinguished pure versus dysphoric mania made on clinical grounds. Gender seemed to influence two factors: high 'anxious-depressive' score in females (which is in line with female overrepresentation in mixed mania), vs. high score in males on the 'gregariousness' factor (which represents social disinhibition of the hyperthymic temperament known to be more prevalent in men). LIMITATION: Cross-sectional correlational study in need of longitudinal validation. CONCLUSIONS: EPIMAN data deriving from a national clinical population showed the feasiblity and face validity of self-assessment in acute mania, in particular its dysphoric subtype. Temperament in women seemed to contribute to the genesis of mixed (dysphoric) mania in accordance with Akiskal's hypothesis of opposition of temperament and polarity of bipolar episodes in mixed states. Self-assessment was capable of capturing accurately the subthreshold depressive symptomatology of mixed mania, which can be missed in hetero-evaluation by hasty clinical interview.

Acute Disease↗
PubMed2001

A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.

OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.

Adolescent↗
PubMed2000

Red blood cell triiodothyronine uptake in unipolar major depression: effect of a chronic antidepressant treatment.

The evolution of kinetic parameters (Vmax, maximal velocity, and Km, Michaelis constant) of red blood cell (RBC) triiodothyronine (L-T3) initial uptake was followed in 19 inpatients suffering from unipolar depression after 1 week (D7) and 4 weeks (D28) of a chronic administration of fluvoxamine, in relation with the clinical efficacy of the drug. In a drug-free state (DO), Vmax (in pmol/min/10(8) cells) and Km (in nM) were significantly increased in depressed patients (Vmax +/- S.D.= 1.02 +/- 0.29, p< 0.01 and Km +/- S.D.= 68.8 +/-15.4, p< 0.05; n=19) compared to healthy volunteers matched for age and sex (Vmax +/- S.D.= 0.82 +/- 0.15 and Km S.D.= 58.8 +/- 9.0; n= 19). When patients were dichotomized on the basis of their treatment response, responders had kinetic parameters significantly increased (Vmax +/-S.D.= 1.03 +/- 0.26, p< 0.01 and Km +/- S.D.= 71.7 +/- 18.7, p< 0.05, n= 10) compared to controls, whereas non-responders had not (Vmax +/- S.D.= 1.00 +/- 0.33, NS and Km +/- S.D.= 65.7 +/- 10.9, NS, n= 9). At D7, Vmax differed from the one of controls only in the responders (Vmax +/- S.D.= 1.03 +/-0.26, p< 0.01). In addition, the percentage of variation of the individual Vmax values during the first week of treatment was significantly lower in responders than in non-responders (deltaVmax(D7-D0) +/- S.D. in % = 10.7 +/- 6.0 and 22.0 +/- 11. 1, p< 0.05, respectively). At D28, kinetics of L-T3 uptake normalized only in the responders (Vmax +/- S.D.= 0.91 +/- 0.13, NS; Km+/-S.D.= 65.7 +/- 7.4, NS). The results indicate that both RBC L-T3 uptake at the pretreatment level and its change during the first week of fluvoxamine treatment were related to the further clinical response to the antidepressant. RBC L-T3 uptake seems to be a biological correlate of the depressive symptomatology since the disturbances disappear only with the clinical remission.

Adult↗
PubMed2000

Possible involvement of the dopamine D3 receptor locus in subtypes of bipolar affective disorder.

The dopamine D3 receptor gene is of potential interest in the physiopathology of affective disorder because of its expression pattern in brain structures controlling various aspects of behaviour, cognition and emotions. Moreover, it encodes for a receptor protein that is a target for psychotropic drugs, which turn out to be efficient in the treatment of this disorder. Two polymorphisms have been described at this locus (the Bal I and the Msp I Restriction Fragment Length Polymorphisms) that are useful in genetic studies. We therefore researched these polymorphisms in 60 patients suffering from bipolar affective disorder who were compared with 60 healthy volunteers. No statistical difference was observed between the whole patient sample versus the controls. However, one subgroup [homozygous for the (2-2) Bal I polymorphism] exhibits a characteristic clinical pattern consisting of: manic monopolar form of bipolar disorder, low age of onset and initiation by an acute delusional episode. A gender distribution difference for the Bal I polymorphism (chi 2 = 6.61, degrees of freedom = 1, P = 0.01) was then noted, the bipolar females being preferentially heterozygous, and the males homozygous. These results could involve the dopamine D3 receptor locus as a minor effect gene in the manic depression condition.

Adult↗
PubMed2000

Acute phase of schizophrenia: impact of atypical antipsychotics.

The acute phase of schizophrenia is characterized by the presence of positive, negative and affective symptoms. After recovery, patients still may suffer distressing residual symptoms; they also carry a high risk of relapse which may be associated with further deterioration in their condition. Prompt, early and continued treatment with an effective, well-tolerated antipsychotic agent, is therefore crucial. Typical antipsychotics are poorly tolerated, leading to lack of compliance and relapse. They also lack efficacy in controlling negative and affective symptoms. Atypical compounds such as amisulpride or risperidone are better tolerated. In addition, when compared with either haloperidol or risperidone, amisulpride has been shown to be at least as effective in controlling positive symptoms and significantly superior in alleviating negative symptoms. The onset of action of amisulpride appears more rapid than that of haloperidol. Amisulpride therefore fulfils all the requirements of a first-line agent for the treatment of the acute phase of schizophrenia.

Acute Disease↗
PubMed1999

Evidence for an increase in functional platelet 5-HT2A receptors in depressed patients using the new ligand [125I]-DOI.

Abnormalities in the serotonergic system have been implicated in the pathophysiology of depressive disorders. Human platelets possess serotonin-2A (5-HT(2A)) receptors, and previous research using LSD or ketanserin as ligands have indicated that their number is increased in depressed patients. Compared to other ligands previously used in platelet studies, DOI is highly selective for the 5-HT(2A) receptor and binds to its high-affinity state, therefore labeling only the receptors that are biologically coupled to the G-protein. We determined the density (Bmax) and the affinity (Kd) of 5-HT(2A) receptors labeled by [(125)I]-DOI in platelets from 21 untreated patients with major depression and 21 healthy volunteers. The density of the 5-HT(2A) binding sites was found to be increased in platelets from female depressed patients as compared to controls. No changes were observed in the Kd. We did not find any relationship between the binding parameters and either the severity of the depressive episode or the suicidal tendencies of the patients. Our results show that the number of coupled platelet 5-HT(2A) receptors is increased in depressed patients, indicating that platelet 5-HT(2A) receptor function is enhanced in depression.

Adult↗
PubMed1998

Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP).

BACKGROUND: This paper presents the methodology and clinical data in mid-stream from a French multi-center study (EPIDEP) in progress on a national sample of patients with DSM-IV major depressive episode (MDE). The aim of EPIDEP is to show the feasibility of validating the spectrum of soft bipolar disorders by practising clinicians. In this report, we focus on bipolar II (BP-II). METHOD: EPIDEP involves training 48 French psychiatrists in 15 sites; construction of a common protocol based on the criteria of DSM-IV and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Evaluation of Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal), family history (Research Diagnostic Criteria); and prospective follow-up. RESULTS: Results are presented on 250 (of the 537) MDE patients studied thus far during the acute phase. The rate of BP-II disorder which was 22% at initial evaluation, nearly doubled (40%) by systematic evaluation. As expected from the selection of MDE by uniform criteria, inter-group comparison between BP-II vs unipolar showed no differences on the majority of socio-demographic parameters, clinical presentation and global intensity of depression. Despite such uniformity, key characteristics significantly differentiated BP-II from unipolar: younger age at onset of first depression, higher frequency of suicidal thoughts and hypersomnia during index episode, higher scores on Hypomania Checklist and cyclothymic and irritable temperaments, and higher switching rate under current treatment. Eighty-eight percent of cases assigned to cyclothymic temperament by clinicians (with a cut-off of 10/21 items on self-rated cyclothymia) were recognized as BP-II. Evaluation of this temperament by clinician and patient correlated at a highly significant level (r=0.73; p <0.0001). Cyclothymia and hypomania were also correlated significantly (r=0.51; p < 0.001). LIMITATION: In a study conducted in diverse clinical settings, it was not possible to assure that clinicians making affective diagnoses were blind to the various temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. CONCLUSION: With a systematic search for hypomania, 40% of major depressive episodes were classified as BP-II, of which only half were known to the clinicians at study entry. Cyclothymic temperamental dysregulation emerged as a robust clinical marker of BP-II disorder. These data indicate that clinicians in diverse practice settings can be trained to recognize soft bipolarity, leading to changes in diagnostic practice at a national level.

Adult↗
PubMed1998

Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN).

BACKGROUND: This research derives from the French national multisite collaborative study on the clinical epidemiology of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along a "spectrum of mixity" extending into mixed mania with subthreshold depressive manifestations; to demonstrate the feasibility of obtaining clinically meaningful data on this entity on a national level; and to characterize the contribution of temperamental attributes and gender in its origin. METHODS: EPIMAN involves training 23 French psychiatrists in four different sites, representing four regions of France; to rigorously apply a common protocol deriving from the criteria of DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll, modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya criteria; obtaining data on comorbidity, and family history (according to Winokur's approach as incorporated into the FH-RDC); and prospective follow-up for at least 12 months. The present report concerns the clinical and temperamental features of 104 manic patients during the acute hospital phase. RESULTS: Dysphoric mania (DM defined conservatively with fullblown depressive admixtures of five or more symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence of > or = 2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts had the best positive predictive values for mixed mania. In comparison to pure mania (0-1 depressive symptoms), DM was characterized by female over-representation; lower frequency of such typical manic symptomatology as elation, grandiosity, and excessive involvement; higher prevalence of associated psychotic features; higher rate of mixed states in first episodes; and complex temperamental dysregulation along primarily depressive, but also cyclothymic, and irritable dimensions; such irritability was particularly apparent in mixed mania at the lowest threshold of depressive admixtures of two symptoms only. LIMITATION: In a study involving hospitalized affectively unstable psychotic patients, it was difficult to assure that psychiatrists making the clinical diagnoses would be blind to the temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. CONCLUSIONS: Mixed mania, defined cross-sectionally by the simultaneous presence of at least two depressive symptoms, represents a prevalent and clinically distinct form of mania. Subthreshold depressive admixtures with mania actually appear to represent the more common expression of dysphoric mania. Moreover, an irritable dimension appears to be relevant to the definition of the expression of mixed mania with the lowest threshold of depressive symptoms. Neither an extreme, nor an endstage of mania, "mixity" is best conceptualized as intrusion of mania into its "opposite" temperament - especially that defined by lifelong depressive traits - and favored by female gender. These data suggest that reversal from a temperament to an episode of "opposite" polarity represents a fundamental aspect of the dysregulation that characterizes bipolar disorder. In both men and women with hyperthymic temperament, there appears "protection" against depressive symptom formation during a manic episode which, accordingly, remains relatively "pure". Because men have higher rates of this temperament, pure mania is overrepresented in men; on the other hand, the depressive temperament in manic women seems to be a clinical marker for the well-known female tendency for depression, hence the higher prevalence of mixed mania in women.

Adult↗
PubMed1998

Increase in red blood cell triiodothyronine uptake in untreated unipolar major depressed patients compared to healthy volunteers.

1. Kinetic parameters of red blood cell (RBC) L-triiodothyronine (T3) initial uptake (Vmax, maximal velocity and Km, Michaelis constant) were determined in 34 untreated inpatients suffering from unipolar depression and in 40 healthy volunteers. 2. Both Vmax and Km were significantly increased in depressed patients as compared to controls. The alterations in kinetic parameters were not associated with the severity of depression. 3. Out of the 19 depressed patients who were submitted to TRH test, 7 of them (36%) showed a blunted TRH-induced TSH response associated with a Vmax situated outside the control mean value +/- 1 S.D. 4. The authors found a significant positive correlation between Vmax of RBC L-T3 and L-tryptophan (TRP) uptakes which is in agreement with the assumption that L-T3 and L-TRP share a common carrier system at the erythrocyte level. 5. The results indicate that the uptake of L-T3 by RBC is increased in major depression. These transport perturbations might reflect alterations in the plasmatic metabolism of L-T3. Evaluation of RBC L-T3 uptake could be useful in a best biological characterization of the depressed patients with regard to their thyroid function.

Adult↗
PubMed1997

A differential role for interleukin-6 and tumor necrosis factor-alpha in schizophrenia?

Pro-inflammatory cytokines are dysregulated in schizophrenia. To determine the nature of the so-called inflammatory syndrome in schizophrenia, we investigated the circulating levels of various cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)alpha), their natural antagonist (IL1-ra, TNF-RI, TNF-RII) and leukocyte activation markers (the soluble receptor of interleukin-2, soluble CD14 and soluble CD23) in subjects with chronic schizophrenia (n = 18) and in normal controls (n = 21). The levels of IL-1 beta and its antagonist and the levels of leukocyte activation markers were not significantly differents between patients and controls. Circulating levels of TNF alpha were significantly (p < 0.05) higher in patients than in controls and did not result from variations of its antagonist levels. The significant (p < 0.05) increase in patient IL-6 was related specifically to clinical status, i.e. illness duration. These data suggest a specific cytokine-mediated syndrome in schizophrenia. We hypothesize that TNF alpha and IL-6 reflect the genetic background of disease suceptibility.

Adolescent↗
PubMed1997

Red blood cell L-tryptophan uptake in depression. II. Effect of an antidepressant treatment.

The evolution of the kinetic parameters, maximal velocity (Vmax) and Michaelis constant (Km), of L-tryptophan (L-TRP) uptake into red blood cells (RBC) was studied in 30 depressed patients in a drug-free state (D0) and after 1 week (D7) and 4 weeks (D28) of a treatment involving a variety of antidepressant drugs, including SSRIs and tricyclics. At D0, 76% of patients exhibited abnormal values of Vmax, which were either higher (36%) or lower (40%) than the control range (control Vmax mean +/- 1 S.D.). High and low Km values were observed in parallel with high and low Vmax values. At D7, individual values of Vmax varied drastically compared to their corresponding value at D0, whatever the pretreatment value of the parameter. The magnitude of the Vmax variation during the first week of treatment was found to be significantly larger in the treatment responders than in the non-responders. At D28, Vmax values of all the responders to treatment were within the control range, whatever their pretreatment Vmax value. On the contrary, non-responders had Vmax values that were significantly lower than those of the controls. Changes in Km followed changes in Vmax during antidepressant treatment. In conclusion, normalization of L-TRP transport kinetics was concomitant with a clear alleviation of depressive symptoms, indicating that RBC L-TRP uptake is dependent on clinical state. Moreover, early reactivity of the Vmax as soon as the first week of treatment may be useful as a predictive index of clinical outcome at D28.

Adolescent↗
PubMed1997

[Cushing syndrome disclosing bronchial neuroendocrine carcinoma: value of scintigraphy with octreotide].

A 44-year-old man presenting with atypical maniac behavior and hypokaliemia was diagnosed with Cushing's syndrome and treated in emergency by bilateral adrenalectomy. Endocrine investigations were suggestive of an ectopic adrenocorticotropic (ACTH) secretion, both at baseline (mean ACTH levels = 215 pg/mL, beta-lipotropic hormone = 2329 pg/mL; molar ratio > 5) and after pharmacodynamic testing (lack of inhibition of ACTH by dexamethasone, blunted ACTH response to corticotropin releasing hormone). Ectopic ACTH secretion was investigated while pituitary ACTH secretion was suppressed by dexamethasone. A paradoxical rise of ACTH from 384 to 717 pg/mL was observed after subcutaneous administration of 500 micrograms octreotide. A right lung tumor that remained occult for 7 years was only revealed by octreotide scintigraphy, despite annual chest tomodensitometric examinations. Right inferior lung lobectomy allowed allowed for removal of a 13 mm tumor corresponding to a bronchial neuroendocrine carcinoma with positive immunostaining for ACTH. Mediastinal lymph nodes were histologically normal. Perioperative ACTH measurements, showing a more than 50% decrease from baseline at 15 minutes after tumor resection, were suggestive of complete tumor removal. This was confirmed 10 days postoperatively by undetectable ACTH levels and by a negative octreotide scintigraphy after surgery. This case report of an occult ACTH secreting bronchial neuroendocrine carcinoma illustrates the diagnostic value of octreotide scintigraphy, and the prognostic value of perioperative ACTH measurements in such cases.

ACTH Syndrome, Ectopic↗