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1.
Encephale ; 32(1 Pt 1): 45-59, 2006.
Article in French | MEDLINE | ID: mdl-16633290

ABSTRACT

INTRODUCTION: Although everyone working in routine mental health services recognizes the scientific and ethical importance to ensure that treatments being provided are of highest quality, there is a clear lack of consensus regarding what outcome domains to include, what measure of assessment to use and, moreover, who to question when assessing. LITERATURE FINDINGS: Since the fifties, social functioning is considered as an important dimension to take into account for treatment planning and outcome measuring. But for many years, symptoms scales have been considered as sufficient outcome measures and social functioning improvement expected on the basis of symptoms alleviation. As symptoms and social adjustment sometimes appear relatively independent, no accurate conclusion concerning the patient's social functioning can so be driven on the basis of his clinical symptoms. More attention has then been directed toward the development of instruments specifically intended to measure the extent and nature of social functioning impairments observed in most psychiatric syndromes. Many of these instruments are designed to be completed by caregivers or remain time consuming and difficult to use routinely. Presently, in clinical practice, there is a need to rely on simple and brief instruments considering patients'perspective about their social adjustment as a function of time. AIM OF THE STUDY: The aim of this study is to present a new instrument, the QFS, initially developed in order to assess social functioning in patients involved in group psychotherapy programs conducted in a specialist mental health setting, as well as its psychometric characteristics. METHODOLOGY: It was designed to be completed in less than 10 minutes and the questions are phrased in a simple and redundant way, in order to limit problems inherent to illiteracy or language comprehension. The QFS is a 16 items self-report instrument that assesses both the frequency of (8 items) and the satisfaction with (8 items) various social behaviours adopted during the 2 weeks period preceding the assessment. It yields three separate indexes of social functioning, defined a priori and labelled "frequency", "satisfaction" and "global". The higher the scores, the better the social functioning. The QFS was administered to 457 subjects, aged between 18 and 65, including 176 outpatients (99 with anxious or depressive disorders, 25 with personality disorders and 52 with psychotic disorders) and 281 healthy control subjects. RESULTS: No significant difference was found between patients and controls according to age or gender distribution. Acceptance rate was high (>95%). Moreover, the QFS was generally acceptable to the clinicians who used it. Internal consistency calculated for each index ranged from 0.65 to 0.83 (Cronbach alpha). Test-retest reliability, calculated within a 15 days time interval on a sample of 49 healthy controls, ranged from 0.69 to 0.71 (intraclass correlation coefficient). Discriminant validity was calculated on healthy controls and patients divided into sub-groups according to their diagnosis. It showed to be excellent, with significantly higher scores in control subjects than in psychiatric patients and significant differences across diagnostic categories (Kruskal-Wallis ANOVA with post-hoc tests, all p<0.05). The convergent validity of the QFS with other measures of social functioning was calculated, using the Social Adaptation Self-Evaluation Scale (SASS) and the Social Adjustment Scale Self-Report (SAS-SR). With the SASS, the convergent validity was higher among patients (Spearman rS 0.71 to 0.92, p<0.01) than controls (rS from 0.49 to 0.66, p<0.001). In healthy controls, correlation with the SAS-SR was moderate but statistically significant (rS from - 0.21 to - 0.44, p<0.05). When comparing QFS scores with self-rated symptoms severity, lower levels of social functioning were significantly associated with more severe symptoms according to the Brief Symptom Inventory (BSI: rS from - 0.38 to - 0.65, p<0.001). The QFS indexes demonstrated sensitivity to change (Wilcoxon: all p<0.05) on a sample of 27 out-patients suffering from anxious-depressive disorders questioned before and after 4 months of cognitive behavioural group therapy running on a weekly basis during 16 sessions of 2 hours each.The factorial validity of the QFS was measured through 3 separate factor analysis conducted using the data of 457 subjects. The first analysis considered only Frequency items; 7 out of 8 items had loadings above 0.5 on Factor 1 accounting for 30.7% (unrotaded) of the variance. The second analysis considered only Satisfaction items; all items had loadings above 0.6 on Factor 1 explaining 43.4% (unrotaded) of the variance. And finally, in the third factor analysis, all QFS items were included; 15 out of 16 items had loadings above 0.4 on Factor 1 accounting for 30% (unrotated) of the variance. Concerning the factorial validity of the instrument, these results suggest that all QFS items belong to the same underlying dimension. DISCUSSION: Finally, provisional norms for the QFS are provided for healthy controls, in order to characterise individual patients or patient subgroups. In conclusion, the need for assessment in clinical routine, in order to estimate different aspects of patients conditions as well as the quality of the treatment provided, has contributed to the development of a large variety of instruments measuring several domains. Concerning the level of social functioning, many instruments fail to meet chief criterion of feasibility, remaining often too complex or time onsuming. Moreover, only few of them are available in French. CONCLUSION: The QFS presented here is a brief, simple and easy to administer self-rating scale that displays satisfactory psychometric properties. It seems to be a valuable instrument for the monitoring of social functioning in psychiatric patients which, from a therapeutic point of view, may have a clear impact as it sets up expectation of change and allows both to reality test patients and therapists beliefs about the presence of progress or not and to identify if therapy is working on this specific outcome domain. Though, to date, the administration of the QFS to other populations and treatment modalities requires further investigation.


Subject(s)
Mental Disorders/psychology , Outcome Assessment, Health Care/statistics & numerical data , Personal Satisfaction , Personality Inventory/statistics & numerical data , Self-Assessment , Social Adjustment , Social Behavior , Adolescent , Adult , Anxiety Disorders/psychology , Anxiety Disorders/therapy , Cognitive Behavioral Therapy , Depressive Disorder/psychology , Depressive Disorder/therapy , Female , Humans , Male , Mental Disorders/therapy , Middle Aged , Personality Disorders/psychology , Personality Disorders/therapy , Psychiatric Department, Hospital , Psychometrics/statistics & numerical data , Psychotropic Drugs/therapeutic use , Reference Values
2.
Psiquis (Madr.) ; 25(2): 45-49, mar. 2004.
Article in Es | IBECS | ID: ibc-31866

ABSTRACT

El autor presenta un cuestionario en un formato operativo que permite evaluar la situación respecto a los Derechos Humanos en diversas instituciones o países y que se puede incorporar a los instrumentos utilizados hoy para la evaluación de la calidad de la Asistencia en Salud Mental. Consta de dos partes diferenciadas: A) Derechos que deben estar garantizados por las Legislaciones estatales y B) Exigencias sobre derechos de los pacientes en los Servicios de Salud Mental. Tales documentos están preparados para ser cotejados en ambientes distintos y evaluados separadamente. La información para el primero se obtiene de la legislación general (civil y penal) y sanitaria (Ley de Sanidad, Ley de Salud Mental) del país y de sus posibles comunidades autónomas. La información para el segundo se obtiene de los manuales de procedimiento del establecimiento en cuestión o, en su defecto, de los documentos de orden interno que regulan sus actividades (AU)


Subject(s)
Adolescent , Adult , Aged , Female , Male , Middle Aged , Child , Humans , Human Rights/trends , Human Rights/psychology , Indicators of Quality of Life , Quality of Life , Discrimination, Psychological/physiology , Prejudice , Surveys and Questionnaires , Mental Health , Mental Disorders/psychology , Legislation/organization & administration , Legislation as Topic/trends , Health Policy/legislation & jurisprudence , Intellectual Disability/diagnosis , Intellectual Disability/psychology
3.
Psiquis (Madr.) ; 25(1): 29-36, ene. 2004.
Article in Es | IBECS | ID: ibc-31545

ABSTRACT

Como la ansiedad, con la que está estrechamente emparentada, la vergüenza tiene sin duda bases biológicas precisas, aunque no bien estudiadas, cuyo desarreglo puede producir actitudes de desvergüenza. La vergüenza es específicamente humana y los biólogos desde la Antigüedad, señalaron que los animales carecen de pudor; son, de alguna manera desvergonzados. Quizás es en la sexualidad en lo que más se manifiesta la vergüenza y la necesidad de privacidad, como se observa en la necesidad de cubrir los órganos genitales y en la exigencia en todas las sociedades de privacidad para las relaciones sexuales. En ocasiones, aparecen actitudes desvergonzadas en el curso de enfermedades neuropsiquiátricas y de perversiones específicas, bajo la forma de desinhibición y exhibicionismo. La vergüenza está principalmente dirigida contra el exhibicionismo y su contrapartida la escoptofilia. El par exhibicionismo/escoptofilia domina las fantasías y el comportamiento de algunos pacientes perversos. Las actitudes desvergonzadas son características comunes a los movimientos artísticos vanguardistas, dominados por un deseo exhibicionista de "epatar a los burgueses (AU)


Subject(s)
Humans , Psychopathology , Shame , Exhibitionism/psychology , Erotica/psychology
4.
Psiquis (Madr.) ; 25(3): 122-127, 2004.
Article in Es | IBECS | ID: ibc-34948

ABSTRACT

El autor discute los objetivos docentes propuestos en distintas encuestas y reuniones de consenso acerca de los programas de formación en Psiquiatría para los futuros médicos. Propone que la enseñanza futura en España debe adaptar los programas a los objetivos docentes detectados, facilitar la autoadquisición de la información por parte de los alumnos priorizando las habilidades de comunicación y clínicas sobre los contenidos teóricos. Se debe profundizar en la enseñanza de las relaciones interpersonales a través de entrevistas con pacientes reales, entrevistas simuladas o experiencias de sensibilización grupal. La enseñanza debería realizarse en grupos pequeños y con material (historias, viñetas, vídeos) de pacientes, priorizando la enseñanza de los trastornos que se ven en Medicina General sobre los que se ven en medios hospitalarios (AU)


Subject(s)
Adult , Female , Male , Middle Aged , Humans , Teaching/methods , Teaching/standards , Teaching/organization & administration , Education/standards , Education/organization & administration , Health Education/organization & administration , Health Education/standards , Psychiatry/education , Health Programs and Plans/standards , Health Programs and Plans/organization & administration , Psychology, Medical/education , Aptitude , Interpersonal Relations , Interviews as Topic/methods , Interviews as Topic , Curriculum/standards , Problem-Based Learning/classification , Problem-Based Learning/physiology
5.
Mol Psychiatry ; 7(7): 755-67, 2002.
Article in English | MEDLINE | ID: mdl-12192620

ABSTRACT

Abnormalities in the density of neuroreceptors that regulate norepinephrine and serotonin release have been repeatedly reported in brains of suicide victims with mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G-proteins has been introduced as a suitable measure of receptor activity in postmortem human brain. The present study sought to evaluate the function of several G-protein coupled receptors in postmortem brain of suicide victims with mood disorders. Concentration-response curves of the [(35)S]GTPgammaS binding stimulation by selective agonists of alpha(2)-adrenoceptors, 5-HT(1A) serotonin, mu-opioid, GABA(B), and cholinergic muscarinic receptors were performed in frontal cortical membranes from 28 suicide victims with major depression or bipolar disorder and 28 subjects who were matched for gender, age and postmortem delay. The receptor-independent [(35)S]GTPgammaS binding stimulation by mastoparan and the G-protein density were also examined. The alpha(2A)-adrenoceptor-mediated stimulation of [(35)S]GTPgammaS binding with the agonist UK14304 displayed a 4.6-fold greater sensitivity in suicide victims than in controls, without changes in the maximal stimulation. No significant differences were found in parameters of 5-HT(1A) serotonin receptor and other receptor-mediated [(35)S]GTPgammaS binding stimulations. The receptor-independent activation of G-proteins was similar in both groups. Immunoreactive densities of G(alphai1/2)-, G(alphai3)-, G(alphao)-, and G(alphas)-proteins did not differ between suicide victims and controls. In conclusion, alpha(2A)-adrenoceptor sensitivity is increased in the frontal cortex of suicide victims with mood disorders. This receptor supersensitivity is not related to an increased amount or enhanced intrinsic activity of G-proteins. The new finding provides functional support to the involvement of alpha(2)-adrenoceptors in the pathogenesis of mood disorders.


Subject(s)
Brain/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Mood Disorders/metabolism , Receptors, Adrenergic, alpha-2/metabolism , Suicide , Adult , Aged , Female , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology , Heterotrimeric GTP-Binding Proteins/metabolism , Humans , Male , Middle Aged , Mood Disorders/diagnosis , Mood Disorders/drug therapy , Psychotropic Drugs/therapeutic use , Radioligand Assay , Receptors, Serotonin/metabolism , Receptors, Serotonin, 5-HT1 , Sulfur Radioisotopes , Tubulin/metabolism
6.
Neurosci Lett ; 304(1-2): 37-40, 2001 May 18.
Article in English | MEDLINE | ID: mdl-11335049

ABSTRACT

Increased amounts of phosphorylated neurofilaments (pNF-H and pNF-M) are found in postmortem brains of opioid addicts. Because of the potential relevance of aberrant pNF in opioid addiction (alterations of neuronal cytoskeleton and associated functions), the effects of opiate drugs on pNF-H were investigated in rat brain. Acute morphine (30 mg/kg, 2 h) induced a marked increase in the immunodensity of pNF-H in the cerebral cortex (93%). Chronic morphine (10-100 mg/kg for 5 days) followed by opiate withdrawal resulted in a time-dependent decline in pNF-H (induction of tolerance). Thus, 2 h after the last dose of morphine, the abundance of pNF-H was still increased (27%), which was followed (6-24 h) by down-regulation of pNF-H (5% increase at 6 h; 5% decrease at 12 h, and 29% decrease at 24 h). The acute (10 mg/kg for 2 h) and chronic (2 x 10 mg/kg for 14 days) treatments with naloxone, an opioid receptor antagonist, did not alter pNF-H in the cerebral cortex, suggesting that the opioid receptors (probably the mu-type) modulating the phosphorylation state of NF-H are not tonically activated by endogenous opioids. The results indicate that morphine addiction is associated with an aberrant hyperphophorylation of NF-H in the rat brain.


Subject(s)
Morphine/pharmacology , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/pharmacology , Neurofilament Proteins/drug effects , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Male , Neurofilament Proteins/metabolism , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley
7.
Brain Res ; 898(2): 224-31, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11306008

ABSTRACT

The components of cyclic AMP signaling cascade (catalytic (Calpha) subunit of cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response element binding protein (CREB)) were quantitated by Western blotting in the prefrontal cortex of depressed suicide victims (n=23) and their matched controls (n=14). There was a significant increase in the levels of CREB, both in total (tCREB; 121+/-8% (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 128+/-9%, P<0.01) forms, but not in PKA Calpha levels (109+/-9%, ns), in brains of depressed suicides compared to those in control subjects. The increases in CREB were specifically observed in antidepressant drug-free subjects (tCREB: 137+/-11%, P<0.01; pCREB: 136+/-12%, P<0.02; n=9), but not in the antidepressant-treated subjects (tCREB: 108+/-18%, ns; pCREB: 111+/-17%, ns; n=8). There were significant correlations between the levels of PKA and those of tCREB and pCREB in the prefrontal cortex of depressed suicides. These results indicate that the components of cyclic AMP signaling are upregulated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment.


Subject(s)
Brain Chemistry/physiology , Cyclic AMP/metabolism , Depression/metabolism , Prefrontal Cortex/metabolism , Signal Transduction/physiology , Suicide , Up-Regulation/physiology , Adult , Antidepressive Agents/pharmacokinetics , Biomarkers/analysis , Cyclic AMP Response Element-Binding Protein/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Depression/drug therapy , Depression/physiopathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Phosphorylation/drug effects , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology
8.
Brain Res ; 898(2): 242-55, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11306010

ABSTRACT

Interactions between brain alpha2- and beta-adrenoceptors are of interest in physiological (aging) and pathological (major depression) processes involving both receptors. In this study, total beta-adrenoceptors and beta1/2-subtypes were quantitated in postmortem human brains to investigate their relationships with alpha2A-adrenoceptors and specific G proteins during the process of aging and in brains of suicide victims. Analysis of [3H]CGP12177 binding, in the presence of CGP20712A (beta1-antagonist), indicated that the predominant beta-adrenoceptor in the frontal cortex is the beta1-subtype (65-75%). The density of total beta- (r=-0.60, n=44) or beta1-adrenoceptors (r=-0.78, n=22), but not the beta2-subtype, declined with aging (3-80 years). The density of total beta- or beta1-adrenoceptors, but not the beta2-subtype, correlated with the number of alpha2-adrenoceptors quantitated in the same brains with the agonist [3H]UK14304 (r=0.71-0.81) or the antagonist [3H]RX821002 (r=0.61-0.66). Interestingly, the ratios alpha2/beta- or alpha2/beta1-adrenoceptors did not correlate with the age of the subject at death, indicating that the proportion of alpha2/beta-adrenoceptors in brain remains rather constant during the process of aging. The density of beta-adrenoceptors correlated with the immunodensity of G(alpha)s (r=0.55) and Gbeta (r=0.61) proteins, and that of alpha2-adrenoceptors with those of G(alpha)i1/2 (r=0.88) and Gbeta (r=0.65). In brains of suicides, compared to controls, the ratio between alpha2- and beta- or beta1-adrenoceptors (alpha2-full agonist sites/beta-sites) was greater (1.3- to 2.0-fold; P<0.05). The results demonstrate a close interdependence between brain alpha2- and beta-adrenoceptors during aging, and in brains of suicides. The quantitation of the alpha2A/beta-adrenoceptor ratio could represent a relevant neurochemical index in the study of brain pathologies in which both receptors are involved.


Subject(s)
Aging/metabolism , Brain/metabolism , Depression/metabolism , GTP-Binding Proteins/metabolism , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Adrenergic, beta/metabolism , Suicide , Adolescent , Adrenergic alpha-Agonists/pharmacokinetics , Adrenergic alpha-Antagonists/pharmacokinetics , Adrenergic beta-Antagonists/pharmacokinetics , Adult , Aged , Aged, 80 and over , Brain Chemistry/physiology , Child , Child, Preschool , Depression/physiopathology , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Propanolamines/pharmacokinetics , Radioligand Assay
9.
Psiquis (Madr.) ; 21(6): 277-287, nov. 2000. tab
Article in Es | IBECS | ID: ibc-10926

ABSTRACT

En el presente trabajo se revisa, en primer lugar, la literatura sobre la eficacia global de las psicoterapias de grupo en relación con las individuales y luego se comparan los resultados de las terapias grupales duraderas con las breves y de las de diferentes orientaciones teóricas (dinámica, cognitivo-comportamental y psícoeducativa) entre sí y en pacientes con distintos diagnósticos. Algunos estudios meta-analíticos muestran un "efecto talla" ("effect size") similar al que se puede obtener en los estudios de eficacia de los psicofármacos. Hay algunos trabajos de revisión que afirman que no existen claras ventajas de unas variedades respecto de otras pero otros estudios, en cambio, privilegian ya sea las unas o las otras. Después discutimos el grado de objetividad de las investigaciones en el campo y de los instrumentos que se han utilizado con más frecuencia. Finalizamos describiendo la Batería "Bel-Air" de evaluación que utilizamos en el Departamento de Psiquiatría de la Facultad de Medicina de la Universidad de Ginebra. Consta de tres instrumentos adaptados de otros conocidos en la literatura: Una lista corta de síntomas (The Brief Symptoms Inventory, BSI), La Escala de Funcionamiento Global (GBS), El Cuestionario de Estrategias de Enfrentamiento de ("Coping index" de K. Sherrer y U. Scherrer) y El Cuestionario de Clima Grupal (adaptado de McKezie, 1990). Hemos añadido también dos instrumentos de creación propia. El cuestionario de evaluación de las relaciones con los demás (ERA, Fredenrich & Zinetti, 2000, en prensa) y el Cuestionario de Funciones sociales (QFS). Todos estos instrumentos permiten medir características comunes a grupos de muy diverso tipo en un tiempo corto. En cada grupo específico, se pueden naturalmente añadir otros instrumentos específicos para distintas patologías para otras variables. (AU)


Subject(s)
Female , Male , Humans , Psychotherapy/methods , Psychotherapy, Group/methods , Psychotherapy, Group/trends , Surveys and Questionnaires , Statistics, Nonparametric , Psychological Tests/standards , Psychological Tests/statistics & numerical data , Case-Control Studies , Health Strategies , Psychometrics/methods , Psychometrics/trends
10.
J Neurosci Res ; 61(3): 338-49, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10900081

ABSTRACT

The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.


Subject(s)
Neurofilament Proteins/metabolism , Opioid-Related Disorders/metabolism , Prefrontal Cortex/metabolism , Adult , Age Factors , Carrier Proteins/metabolism , Chronic Disease , Drug Overdose/metabolism , Electrophoresis, Polyacrylamide Gel , Glial Fibrillary Acidic Protein/metabolism , Humans , Immunoblotting , Intermediate Filament Proteins , Male , Molecular Weight , Neurofilament Proteins/chemistry , Phosphoprotein Phosphatases/metabolism , Phosphorylation , Synaptophysin/metabolism
11.
Mol Psychiatry ; 5(3): 308-15, 2000 May.
Article in English | MEDLINE | ID: mdl-10889534

ABSTRACT

Repeated opioid administration has been associated in human brain with unaltered density of mu-opioid receptors (agonist radioligand binding sites and immunodetected receptor protein). These receptors are coupled to Gi/Go-proteins, which are increased in brain of heroin addicts. To assess the activity of G-proteins and their coupling to receptors after chronic opioid abuse, [35S]GTPgammaS binding was quantified in postmortem prefrontal cortices of 15 opioid-dependent subjects and 15 matched controls. The stimulation of [35S]GTPgammaS binding by the mu-opioid receptor agonist DAMGO or the alpha2-adrenoceptor agonist UK14304 was used as a functional measure of the status of the receptor-G-protein coupling. [35S]GTPgammaS binding basal values were similar in opioid addicts (819+/-83 fmol mg-1 of protein) and controls (918+/-106 fmol mg(-1) of protein). In opioid addicts, [35S]GTPgammaS binding stimulation by DAMGO showed a maximal effect (62+/-8%) and a potency (EC50 = 1.09+/-0.26 microM) that did not differ from the maximal effect (60+/-12%) and potency (EC50 = 2.01+/-0.58 microM) in controls. In opioid addicts, [35S]GTPgammaS binding stimulation by UK14304 was not different in maximal effect (28+/-3%) from controls (32+/-8%), but the potency of the agonist was decreased (EC50 = 4.36+/-1.81 microM) when compared with controls (EC50 = 0.41+/-0.15 microM). The results provide a direct evidence of an apparent normal functional activity of brain mu-opioid receptors (Gi/Go-protein coupling) during the opioid dependence process in humans. The data also demonstrate a functional uncoupling of alpha2-adrenoceptors from G-proteins, which indicates a heterologous desensitization of these receptors. This finding could represent an adaptive mechanism against the decreased noradrenergic activity induced by the chronic presence of opioid drugs.


Subject(s)
Adrenergic alpha-2 Receptor Agonists , Brain/metabolism , Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology , GTP-Binding Proteins/metabolism , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , Opioid-Related Disorders/metabolism , Quinoxalines/pharmacology , Receptors, Opioid, mu/agonists , Adrenergic alpha-Agonists/pharmacology , Adult , Autopsy , Brain/drug effects , Brain/pathology , Brimonidine Tartrate , Humans , Male , Opioid-Related Disorders/pathology , Postmortem Changes , Reference Values , Sulfur Radioisotopes
12.
Am J Psychiatry ; 157(6): 948-55, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10831475

ABSTRACT

OBJECTIVE: Although genetic factors have been implicated in the etiology of bipolar disorder, no specific gene has been conclusively identified. Given the link between abnormalities in serotonergic neurotransmission and bipolar disorder, a candidate gene association approach was applied to study the involvement of the monoamine oxidase A (MAOA) gene, which codes for a catabolic enzyme of serotonin, in the susceptibility to bipolar disorder. METHOD: In France and Switzerland, 272 patients with bipolar disorder and 122 healthy subjects were typed for three polymorphic markers of the MAOA gene: the MAOA-CA repeat, the MAOA restriction fragment length polymorphism (RFLP), and a repeat directly adjacent to the variable number of tandem repeats (VNTR) locus. RESULTS: A significant difference in the distribution of the alleles for the MAOA-CA repeat was observed between the female bipolar patients and comparison group. CONCLUSIONS: The results obtained in the French and Swiss population confirm findings from two studies conducted in the United Kingdom.


Subject(s)
Bipolar Disorder/enzymology , Bipolar Disorder/genetics , Monoamine Oxidase/genetics , Polymorphism, Genetic , Adult , Alleles , Female , Genetic Markers , Genotype , Humans , Male , Middle Aged , Monoamine Oxidase/metabolism , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Psychiatric Status Rating Scales/statistics & numerical data , Sex Factors , Tandem Repeat Sequences
13.
Neuroimage ; 11(5 Pt 1): 458-72, 2000 May.
Article in English | MEDLINE | ID: mdl-10806032

ABSTRACT

Receptor density and ligand affinity can be assessed using positron emission tomography (PET). Biological parameters (B(max)('), k(1), k(2), k(on)/V(R), k(off)) are estimated using a compartmental model and a multi-injection protocol. Parametric imaging of the ligand-receptor model has been shown to be of special interest to study certain brain disorders. However, the low signal-to-noise ratio in kinetic curves at the pixel level hampers an adequate estimation of model parameters during the optimization procedure. For this reason, mapping requires a spatial filter, resulting in a loss of resolution. Filtering the kinetic curves in the frequency domain using the Fourier transform is not appropriate, because of difficulties in choosing a correct and efficient cutoff frequency. A wavelet-based filter is more appropriate to such tracer kinetics. The purpose of this study is to build up parametric images at the pixel level while conserving the original spatial resolution, using wavelet-based filtering. Data from [(11)C]flumazenil studies, mapping the benzodiazepine receptor density, were used. An invertible discrete wavelet transform was used to calculate the time-frequency signals of the time-concentration PET curves on a pixel-by-pixel basis. Kinetic curves observed from large regions of interest in high and low receptor-density regions were used to calibrate the threshold of wavelet coefficients. The shrunken wavelet coefficients were then transformed back to the original domain in order to obtain the filtered PET signal. Maps of all binding parameters were obtained at the pixel level with acceptable coefficients of variation of less than 30% for the B(max)(') parameter in most of the gray matter. A strong correlation between model parameter estimates using the usual regions of interest and parametric imaging was observed for all model parameters (r = 0.949 for the parameter B(max)(')). We conclude that wavelet-based filters are useful for building binding parameter maps without loss of the original spatial resolution of the PET scanner. The use of the wavelet-based filtering method can be extended far beyond the multi-injection protocol. It is likely to be also effective for other dynamic PET studies.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Models, Biological , Receptors, GABA-A/metabolism , Tomography, Emission-Computed , Computer Simulation , Flumazenil/pharmacokinetics , Fourier Analysis , GABA Modulators/pharmacokinetics , Humans , Image Processing, Computer-Assisted , Osmolar Concentration , Time Factors
14.
Int J Psychiatry Clin Pract ; 4(3): 227-32, 2000.
Article in English | MEDLINE | ID: mdl-24927458

ABSTRACT

INTRODUCTION: Two-thirds of Swiss psychiatrists are engaged, either exclusively or partially, in private practice, a proportion that is higher than in other countries. METHOD: A questionnaire survey of 1000 psychiatrists was carried out. RESULTS: Psychiatrists in private practice display a greater degree of clinical activity, mainly with individuals, than do psychiatrists employed by public institutions; and they work principally within two practice profiles, psychoanalytical and generalist, and much less in the biological profile. They show a preference for the psychological model, mostly in a psychoanalytical orientation. Psychiatrists who have a mixed privatepublic practice - more than half of them - are even more psychoanalytically oriented than psychiatrists working exclusively in private practice. They act as an interface between the public and private sectors, playing a pivotal role as guardians of psychoanalysis, proclaiming its principles to psychiatric residents. CONCLUSION: With the transformations taking place in the health care system, new care concepts are being developed, there is a wider variety of theoretical orientations, and the profession is therefore undergoing substantial changes. ( Int J Psych Clin Pract 2000; 4: 227 - 232).

15.
Med Educ ; 33(9): 639-47, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10476014

ABSTRACT

OBJECTIVES: The principal aim was to assess the psychiatric topics that doctors and students considered most important for undergraduate teaching. Differences between doctors and students, men and women, physicians/students with or without an interest in psychiatry were examined. DESIGN: A mailed questionnaire was used concerning the knowledge and skills of psychological/psychiatric medi- cine considered to be needed in medical practice. SETTING: The Medical School of the University of Geneva. SUBJECTS: Doctors and undergraduate medical students in their last 2 years of medical training. RESULTS: Both doctors and students agreed on most topics, even though the students tended to give all items a higher rating. Both groups agreed on the importance of the following main topics: the doctor-patient relationship, identification and management of the principal psychiatric disorders and their associated risks and problems of a psychosocial nature. Those doctors showing an interest in psychiatry tended to accentuate the importance attached to interpersonal skills. The male and female doctors and students expressed very similar opinions. The female doctors, however, tended to attach greater importance to relational-emotional aspects and to disorders affecting children and adolescents than did their male colleagues, which is probably a reflection of the specific role that women still play within our society. When asked to assess the current teaching they received in medical school, the students considered that certain important aspects of psychiatry were insufficiently taught. CONCLUSION: These results confirm the importance of teaching psychiatry with an emphasis on problems encountered in general practice.


Subject(s)
Education, Medical, Undergraduate , Psychiatry/education , Teaching , Attitude of Health Personnel , Female , Humans , Male , Surveys and Questionnaires , Switzerland
16.
Ann N Y Acad Sci ; 881: 392-409, 1999 Jun 21.
Article in English | MEDLINE | ID: mdl-10415944

ABSTRACT

Major depression, opioid addiction, neurodegenerative diseases, and glial tumors are associated with disturbances of imidazoline receptors (IR) in the human brain. In depression, the level of a 45-kD IR protein (putative I1-IR) is increased in the brain of suicide victims (51%) and in platelets of depressed patients (40%). The density of platelet I1-IR ([125I]-p-iodoclonidine binding) is also increased in depression (135%). The 29/30-kD IR protein (putative I2B-IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B-IR ([3H]idazoxan binding). Antidepressant drugs induce downregulation of 45-kD IR protein and I1-sites in platelets of depressed patients and upregulation of I2-sites in rat brain. The densities of I2B-IR and the related 29/30-kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I2B-IR is increased in Alzheimer's disease (63%) and decreased in Huntington's disease (56%). Brain I2B-IR is not altered in Parkinson's disease. The level of I2-IR in glial tumors is increased (two-fivefold) in parallel with the abundance of the related 29/30-kD IR protein (39%), whereas the level of 45-kD IR protein is decreased (39%). The possible functional relevance of these findings in the context of the pathogenesis of these disorders remains to be elucidated.


Subject(s)
Brain Diseases/metabolism , Brain/metabolism , Receptors, Drug/metabolism , Alcoholism/metabolism , Animals , Blood Platelets/metabolism , Brain Neoplasms/metabolism , Depressive Disorder/metabolism , Humans , Imidazoline Receptors , Neurodegenerative Diseases/metabolism , Opioid-Related Disorders/metabolism , Rats , Receptors, Drug/genetics , Suicide
17.
Schweiz Med Wochenschr ; 129(6): 225-34, 1999 Feb 13.
Article in French | MEDLINE | ID: mdl-10093881

ABSTRACT

RESEARCH QUESTIONS: Differences between male and female psychiatrists in their careers, professional and clinical activities, and clinical orientations, in general and in contrasted settings for the practice of psychiatry. METHODS: Survey by mailed questionnaire to psychiatrists working in private practice or in institutions. RESULTS: Male and female psychiatrists share some similar characteristics (age, many interests, etc.). However, female psychiatrists differ from male psychiatrists in numerous respects: more frequently engaged in private practice, shorter work-weeks, less diversification of clinical activities, more frequent reference to a psychological model. In women occupying hierarchic positions, these differences disappear, whilst they are maintained in private practice for those using the psychological model. The differences can be interpreted in part in terms of gender-specific socialization, but their origin could mainly arise from the existence of different systems of gender-based constraints in the management of professional and personal, or family, spheres. CONCLUSIONS: Adjusting the training period and working conditions in institutions could facilitate career diversification for both male and female psychiatrists.


Subject(s)
Physicians, Women/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Psychiatry , Adult , Aged , Female , Humans , Male , Middle Aged , Psychological Theory , Switzerland , Workforce
18.
J Neurochem ; 72(1): 282-91, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9886080

ABSTRACT

Suicide and depression are associated with an increased density of alpha2-adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein-coupled receptor kinases, GRKs), which work in concert with the receptors. In this study we quantitated in parallel the levels of immunolabeled alpha2A-adrenoceptors and associated regulatory proteins in brains of suicide and depressed suicide victims. Specimens of the prefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and 31 control subjects. Levels of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 were assessed by immunoblotting techniques by using specific polyclonal antisera and the immunoreactive proteins were quantitated by densitometry. Increased levels of alpha2A-adrenoceptors (31-40%), Galphai1/2 proteins (42-63%), and membrane-associated GRK 2/3 (24-32%) were found in the prefrontal cortex of suicide victims and antidepressant-free depressed suicide victims. There were significant correlations between the levels of GRK 2/3 (dependent variable) and those of alpha2A-adrenoceptors and Galphai1/2 proteins (independent variables) in the same brain samples of suicide victims (r = 0.56, p = 0.008) and depressed suicide victims (r = 0.54, p = 0.041). Antemortem antidepressant treatment was associated with a significant reduction in the levels of Galphai1/2 proteins (32%), but with modest decreases in the levels of alpha2A-adrenoceptors (6%) and GRK 2/3 (18%) in brains of depressed suicide victims. The increased levels in concert of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 in brains of depressed suicide victims support the existence of supersensitive alpha2A-adrenoceptors in subjects with major depression.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Depression/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Prefrontal Cortex/chemistry , Receptors, Adrenergic, alpha-2/metabolism , Adult , Antibodies , Brain Chemistry/physiology , Female , Guanosine Triphosphate/metabolism , Humans , Male , Middle Aged , Prefrontal Cortex/enzymology , Receptors, Adrenergic, alpha-2/immunology , Suicide , Up-Regulation/physiology
19.
Neurosci Lett ; 247(2-3): 95-8, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9655601

ABSTRACT

Imidazoline receptors (29/30- and 45-kDa proteins) were quantitated in postmortem brains of patients with Alzheimer's disease (AD) by using immunoblotting techniques and a specific antiserum. Increased levels of the 29/30-kDa protein (30%), 45-kDa protein (36%) and glial fibrillary acidic protein (88%) were found in the frontal cortex of AD patients. These findings are in line with the reported higher density of imidazoline receptors labelled by [3H]idazoxan in AD brains, suggesting that these imidazoline receptor proteins are related to the I2-imidazoline receptor located in mitochondria of glial (astrocyte) cells.


Subject(s)
Alzheimer Disease/metabolism , Frontal Lobe/chemistry , Nerve Tissue Proteins/analysis , Receptors, Adrenergic, alpha/analysis , Receptors, Drug/analysis , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Astrocytes/chemistry , Atrophy , Biomarkers/analysis , Female , Frontal Lobe/pathology , Glial Fibrillary Acidic Protein/analysis , Humans , Imidazoline Receptors , Male
20.
Biol Psychiatry ; 43(8): 616-8, 1998 Apr 15.
Article in English | MEDLINE | ID: mdl-9564448

ABSTRACT

BACKGROUND: Platelet imidazoline receptors have been shown to be up-regulated in patients with unipolar major depression. This study examines the status of imidazoline receptor proteins in platelets of euthymic bipolar patients and in brains of lithium-treated rats. METHODS: Platelets were collected from 12 bipolar patients (lithium-treated or drug-free) and brains from chronic lithium-treated rats. Imidazoline receptors were quantitated by immunoblotting, using a specific antiserum, and/or radioligand binding. RESULTS: No changes in platelet imidazoline receptors (35-kDa and 45-kDa proteins) were found. Lithium treatment did not alter brain imidazoline receptors (29/30-kDa, 45-kDa, and 66-kDa proteins or density/affinity of [3H]-idazoxan binding sites). CONCLUSIONS: Imidazoline receptor proteins are not altered in platelets of euthymic patients with bipolar affective disorder.


Subject(s)
Antimanic Agents/pharmacology , Bipolar Disorder/blood , Blood Platelets/metabolism , Brain Chemistry/drug effects , Imidazoles/blood , Lithium/pharmacology , Receptors, Drug/blood , Thymus Gland/physiology , Adult , Animals , Bipolar Disorder/psychology , Blotting, Western , Cell Membrane/drug effects , Cell Membrane/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Female , GTP-Binding Proteins/metabolism , Humans , Imidazoline Receptors , In Vitro Techniques , Male , Radioligand Assay , Rats , Rats, Sprague-Dawley
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