Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p. 149-167.

his study compared auditory behavioral and physiological measures among three subject groups: 1) Normal control subjects, 2) subjects who were on a prescribed SSRI for depression, and 3) subjects who were prescribed an SSRI for depression, but were not medicated at the time of testing. Test measures included: Standard audiological tests (audiometry and tympanometry), electrophysiological procedures for analysis of auditory- evoked brainstem and late responses, and standardized behavioral speech tests (SCAN-A, SSI, and the low predictability sentence list of the R-SPIN). Analysis of results indicated a statistically significant increase of group mean amplitude of the ABR peak V, from 15dBnSL to 55dBnSL, in the non-medicated group compared to controls. Also, the non-medicated group scored significantly less favorably than controls on the most challenging listening condition (-20 MCR) of the SSI, in the left ear. Although other test measures indicated consistent differences between these two groups, they were not, however, significant.

The purpose of this study was to investigate the relationship between selective serotonin reuptake inhibitor (SSRI) medication on auditory skills in clinically depressed subjects. Experimental subjects prescribed an SSRI were tested in a medicated and an unmedicated condition, and the test results were compared. Furthermore, the experimental group was compared with a control group consisting of normal subjects. Test measures included pure tone audiometry, tympanometry, acoustic reflex thresholds, and auditory electrophysiologic measures such as auditory brainstem and auditory late responses. An assessment scale for depression (Beck Depression Inventory-II) was also used. Results indicated statistically significant differences for the BDI-II between the control and experimental groups for both conditions. Electrophysiologic measures indicated a significantly shorter latency for auditory late potential P1 at 55 dBnSL, and a significantly larger amplitude at 45 dBnSL for the N1/P2 component for the unmedicated group. Although the other measures showed trends, they did not reach significance.

This study examined the relationship between selective serotonin reuptake inhibitor (SSRI) medication and auditory measures in clinically depressed women. Experimental subjects were tested in both a medicated and unmedicated condition. Experimental subjects were compared to a normal control group; additionally intrasubject comparison was made within the experimental group. Test measures included: audiometry, tympanometry, otoacoustic emissions, uncomfortable loudness level, masking level difference, SCAN-A, Synthetic Sentence Identification (SSI), and the low predictability section of the Revised Speech in noise (RSPIN). The unmedicated group scored significantly less favorably than the control group on the following tests; SCAN-A (composite, filtered words, and auditory figure ground), R-SPIN (0MCR condition in both the right and left ears). Additionally, the unmedicated group scored significantly less favorably than the medicated group on the SSI (-20MCR condition right ear only) and of the R-SPIN (0MCR condition right ear only). Other test measures indicated consistent trends but did reach significance.

A patogenia da hiponatremia decorrente do uso da Fluoxetina em pacientes idosos não está bem definida. Este achado tem sido atribuído a uma secreção inapropriada do Hormônio Antidiurétido (HAD), embora ainda não tenha sido evidenciado um aumento dos níveis plasmático deste hormônio nestes pacientes. Desta forma, este trabalho visa investigar o efeito da Fluoxetina sobre o rim e mais especificamente se ela teria um efeito direto sobre o Ducto Coletor Medular Interno (DCMI) de ratos normais: 1) Estudos in vivo- 10 ratos foram suplementados com aplicações intraperitoniais diárias de 10mg/kg de Fluoxetina. Após 10 dias os animais foram sacrificados e o sangue e os rins foram coletados para posterior análise. 2) Estudos in vitro- a) estudos com a técnica de Imunoblotting para avaliar a expressão da proteína da Aquaporina 2 (AQP2) em ratos suplementados e em suspensão de túbulos de DCMI de 10 ratos normais incubados com 10-7M de Fluoxetina por 30 min. b) estudos com microperfusão de segmentos isolados do nefron- a permeabilidade osmótica à água (Pf, mm./sec) foi determinada em DCMI perfundidos de ratos normais(n=6) com a técnica standart, na presença de10-7M de Fluoxetina. Resultados: 1) Os estudos in vivo mostraram que o peso caiu de 179±1,28g para 158±1,15g (p<0,0001), o Na plasmático caiu de 139,3±0,78mEq/l para 134,9±0,5mEq/l (p<0,0001) e não houve alterações do K e do HAD plasmáticos. 2) Os estudos in vitro-a) a análise densitométrica dos ensaios com imunoblotting mostraram um aumento da expressão da proteína da AQP2 de 40%, ambos, em ratos suplementados (cont-99,6± 5,2 vs Fx 145,6±16,9, p< 0,05) e em frações de membrana da suspensão de túbulos incubados com Fluoxetina (cont-100,0±3,5.vs 143,0±2,0, p<0,01). b) A Fluoxetina aumentou a Pf nos DCMI, na ausência de HAD de 7,24±2,07 para Fx- 15,77±3,25 (p<0,01). Em resumo, nossos dados revelaram que a Fluoxetina determinou uma diminuição do peso corporal e do nível plasmático de Na sem alterar os níveis plasmáticos de K e HAD e ocasionou um aumento da expressão da proteína da AQP2 e um aumento da permeabilidade à água nos DCMI, levando-nos à conclusão de que o efeito direto da Fluoxetina no DCMI, aumentando a reabsorção de água, pode ser responsável pela hiponatremia encontrada nos pacientes idosos com depressão que fazem uso desta droga. / The pathogenesis of the hyponatremia after Fluoxetine(Fx) supply in elderly is not well understood. This event has been attributed to an inappropriate antidiuretic hormone secretion although the vasopressin enhanced plasma level has not been demonstrated yet in these pacients. Thus, this experiment was designed to investigate the effect of Fx on the kidney and more specifically if it would have a direct effect in the inner medullary collecting duct (IMCD) from normal rats: 1) in vivo study- 10 rats were supplied daily with i.p. injections of Fx 10 mg/kg. After five days, the rats were sacrificed and blood and kidneys were collected. 2) in vitro studya) Immunobloting studies for AQP2 protein expression, in IMCD from supplied rats and in IMCD tubules suspension from 10 normal rats incubated with mm./sec) Fx. by 30 min. b) Microperfusion studies- the osmotic water permeability (Pf, mm./sec) was determined in normal rats IMCD(n=6) isolated and perfused by the standart methods.Fx (10-7M) was added to the bath fluid. Results: In vivo study showed that the weight decreased from 179±1.28g to 158±1.5g(p<0.0001); the Na+ plasma level decreased from 139.3±0.78mEq/l to 134.9±0.5mEq/l(p<0.0001), the K+ and the ADH plasma level remained unchanged. In vitro study- a) the densitometric analysis of the immunobloting essays showed an increase in AQP2 protein abundance of about about 40%, both, in supplied rats (cont-99.6± 5.2 vs Fx 145.6±16.9, p< 0.05), and in membrane fraction extracted from IMCD tubule suspension incubated with Fx ( cont-100.0±3.5.vs 143.0±2.0,p<0.01). b) Fx increased the Pf in IMCD in absence of vasopressin from the control period- 7.24±2.07 to Fx- 15.77±3.25 (p<0.01). In summary, our data revealed that, after Fx, weight, and plasma Na+ level decreased, the plasma K+ and ADH levels remained unchanged, whereas the AQP2 protein abundance and the water absorption in IMCD increased, leading us to conclude that the direct effect of Fx in the IMCD, could account for the hyponatremia produced by this drug in depressed elderly.

INTRODUÇÃO: Apesar dos Inibidores Seletivos da Recaptura da Serotonina (ISRSs) serem a primeira escolha no tratamento do Transtorno de Estresse Pós-Traumático (TEPT) seu mecanismo de ação não é completamente compreendido. Possivelmente, um aumento na resiliência ao estresse esteja envolvido. Como a serotonina (5HT) ajuda a mediar as respostas ao estresse em outros transtornos ansiosos, o paradigma de Depleção de Triptofano Aguda (DTa) foi usado para diminuir a 5HT central em Pacientes com TEPT remitido com ISRSs. MÉTODOS: Dez pacientes com TEPT (diagnosticados pela Mini Entrevista Neuropsiquiátrica Internacional) que tiveram resposta completa com um ISRS (Escala de Impressões Clínicas Globais de Melhora 1-2 por pelo menos 3 meses) foram selecionados para o experimento. Os pacientes foram testados em duas ocasiões diferentes separadas por uma semana nas quais os pacientes receberam uma mistura contendo grandes aminoácidos neutros ou com (Depleção de Triptofano Falsa [DTf]; dia controle) ou sem triptofano (dia DTa). Auto relatos de ansiedade e humor, bem como medidas cardiovasculares, foram obtidos ao longo dos testes. Cinco horas e meia após a ingestão da mistura os pacientes foram re-expostos aos seus traumas através do procedimento de imaginação guiada de Pitman. RESLTADOS: Esses procedimentos provocaram elevados escores nas medidas avaliadas em ambos os dias, com respostas significativamente mais intensas no dia DTa conforme avaliado pelas Escalas Visuais Analógicas (DTa 47,57 [21,75] -v- DTf 20,71 [18,4]; p=0,001), Escala de Trauma de Davidson (29,4 [12,7] -v- 15,7 [7,79]; p=0,001), Inventário de Ansiedade de Spielberger versão Estado (28,9 [11,03] -v- 18,5 [10,13]; p=0,066, e Perfis de Estados de Humor (p<0,001). CONCLUSÕES: Esses dados são os primeiros a demonstrar que a depleção de 5HT piora as respostas subjetivas a re-experimentação de memórias traumáticas no TEPT e sugere que o aumento na função da 5HT induzida por ISRSs diminui os sintomas de TEPT, especialmente sob provocação, i.e. 5HT ajuda a mediar a resiliência ao estresse. Além de fornecer insights sobre o como os ISRSs funcionam no TEPT, esses dados também oferecem uma abordagem de potenciais novos tratamentos para esse transtorno / INTRODUCTION: Although Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line Posttraumatic Stress Disorder (PTSD) treatments their mechanism of action is unclear, but possibly improvement of stress resilience is involved. As serotonin (5HT) helps regulate stress responses in other anxiety disorders, the acute tryptophan depletion (aTD) technique was used to lower brain 5HT in SSRSs-remitted PTSD patients. METHODS: Ten patients with PTSD (Mini-International Neuropsychiatric Interview diagnosed) who had made a full recovery on SSRIs (Clinical Global Impressions Improvement Scale 1-2 for at least 3 months) were enrolled in the experiment. Patients were tested on 2 separate occasions a week apart - each session they received a drink containing large neutral amino acids either with (Sham Depletion [SD]; control day) or no tryptophan (aTD day). Self reports of anxiety and mood, as well as cardiovascular measures, were obtained throughout the tests. At 5.5 hours after the drink subjects were reexposed to their trauma using a modification of Pitmans imagery guided method. RESULTS: These procedures provoked elevated ratings on both days, with significantly more marked responses on the aTD day according to Visual Analogue Scales (aTD 47.57 [21.75] -v- SD 20.71 [18.4]; p=0.006), Davidson Trauma Scale (29.4 [12.7] -v- 15.7 [7.79]; p=0.001), Spielberger State Anxiety Inventory (28.9 [11.03] -v- 18.5 [10.13]; p=0.066, and Profile of Mood States (p<0.001). CONCLUSIONS: These data are the first to show that 5HT depletion worsens the subjective responses to reliving traumatic memories in PTSD and suggest that that SSRI-induced increases in 5HT function restrains PTSD symptoms, especially under provocation, i.e. 5HT helps mediate resilience to stress. As well as giving insights into how SSRIs work in PTSD, these data may also offer a translational approach to potential new treatments for this disorder

INTRODUÇÃO: Apesar dos Inibidores Seletivos da Recaptura da Serotonina (ISRSs) serem a primeira escolha no tratamento do Transtorno de Estresse Pós-Traumático (TEPT) seu mecanismo de ação não é completamente compreendido. Possivelmente, um aumento na resiliência ao estresse esteja envolvido. Como a serotonina (5HT) ajuda a mediar as respostas ao estresse em outros transtornos ansiosos, o paradigma de Depleção de Triptofano Aguda (DTa) foi usado para diminuir a 5HT central em Pacientes com TEPT remitido com ISRSs. MÉTODOS: Dez pacientes com TEPT (diagnosticados pela Mini Entrevista Neuropsiquiátrica Internacional) que tiveram resposta completa com um ISRS (Escala de Impressões Clínicas Globais de Melhora 1-2 por pelo menos 3 meses) foram selecionados para o experimento. Os pacientes foram testados em duas ocasiões diferentes separadas por uma semana nas quais os pacientes receberam uma mistura contendo grandes aminoácidos neutros ou com (Depleção de Triptofano Falsa [DTf]; dia controle) ou sem triptofano (dia DTa). Auto relatos de ansiedade e humor, bem como medidas cardiovasculares, foram obtidos ao longo dos testes. Cinco horas e meia após a ingestão da mistura os pacientes foram re-expostos aos seus traumas através do procedimento de imaginação guiada de Pitman. RESLTADOS: Esses procedimentos provocaram elevados escores nas medidas avaliadas em ambos os dias, com respostas significativamente mais intensas no dia DTa conforme avaliado pelas Escalas Visuais Analógicas (DTa 47,57 [21,75] -v- DTf 20,71 [18,4]; p=0,001), Escala de Trauma de Davidson (29,4 [12,7] -v- 15,7 [7,79]; p=0,001), Inventário de Ansiedade de Spielberger versão Estado (28,9 [11,03] -v- 18,5 [10,13]; p=0,066, e Perfis de Estados de Humor (p<0,001). CONCLUSÕES: Esses dados são os primeiros a demonstrar que a depleção de 5HT piora as respostas subjetivas a re-experimentação de memórias traumáticas no TEPT e sugere que o aumento na função da 5HT induzida por ISRSs diminui os sintomas de TEPT, especialmente sob provocação, i.e. 5HT ajuda a mediar a resiliência ao estresse. Além de fornecer insights sobre o como os ISRSs funcionam no TEPT, esses dados também oferecem uma abordagem de potenciais novos tratamentos para esse transtorno / INTRODUCTION: Although Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line Posttraumatic Stress Disorder (PTSD) treatments their mechanism of action is unclear, but possibly improvement of stress resilience is involved. As serotonin (5HT) helps regulate stress responses in other anxiety disorders, the acute tryptophan depletion (aTD) technique was used to lower brain 5HT in SSRSs-remitted PTSD patients. METHODS: Ten patients with PTSD (Mini-International Neuropsychiatric Interview diagnosed) who had made a full recovery on SSRIs (Clinical Global Impressions Improvement Scale 1-2 for at least 3 months) were enrolled in the experiment. Patients were tested on 2 separate occasions a week apart - each session they received a drink containing large neutral amino acids either with (Sham Depletion [SD]; control day) or no tryptophan (aTD day). Self reports of anxiety and mood, as well as cardiovascular measures, were obtained throughout the tests. At 5.5 hours after the drink subjects were reexposed to their trauma using a modification of Pitmans imagery guided method. RESULTS: These procedures provoked elevated ratings on both days, with significantly more marked responses on the aTD day according to Visual Analogue Scales (aTD 47.57 [21.75] -v- SD 20.71 [18.4]; p=0.006), Davidson Trauma Scale (29.4 [12.7] -v- 15.7 [7.79]; p=0.001), Spielberger State Anxiety Inventory (28.9 [11.03] -v- 18.5 [10.13]; p=0.066, and Profile of Mood States (p<0.001). CONCLUSIONS: These data are the first to show that 5HT depletion worsens the subjective responses to reliving traumatic memories in PTSD and suggest that that SSRI-induced increases in 5HT function restrains PTSD symptoms, especially under provocation, i.e. 5HT helps mediate resilience to stress. As well as giving insights into how SSRIs work in PTSD, these data may also offer a translational approach to potential new treatments for this disorder