RESUMO
BACKGROUND: Preliminary studies have shown that the addition of the partial NMDA-agonist d-cycloserine (DCS) might be promising in enhancing the results of exposure therapy in obsessive-compulsive disorder (OCD). We examined the effect of DCS addition to exposure therapy in a somewhat larger sample of OCD patients with special attention to subgroups, because of the heterogeneity of OCD. METHODS: A randomized, double-blind, placebo controlled trial was conducted in 39 patients with OCD. Patients received 6 guided exposure sessions, once a week. One hour before each session 125mg DCS or placebo was administered. RESULTS: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) declined more in the DCS group than in the placebo group, but the difference did not reach statistical significance (P=0.076, partial η2=0.13). Response percentages also did not differ between the DCS and the placebo group (37% and 15% respectively). In the 'cleaning/contamination' subgroup a significant effect was found in favour of DCS (P=0.033, partial η2=0.297). CONCLUSIONS: The results of this study did not support the application of DCS to exposure therapy in OCD. Some specific aspects need further investigation: efficacy of DCS in a larger 'cleaning/contamination' (sub-)group, DCS addition only after successful sessions, interaction with antidepressants.
Assuntos
Antidepressivos/administração & dosagem , Terapia Cognitivo-Comportamental/métodos , Ciclosserina/administração & dosagem , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Adulto , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/terapia , Terapia Assistida por Computador/métodos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Cues that are associated with the availability of food are known to trigger food anticipatory activity (FAA). This activity is expressed as increased locomotor activity and enables an animal to prepare for maximal utilization of nutritional resources. Although the exact neural network that mediates FAA is still unknown, several studies have revealed that the medial hypothalamus is involved. Interestingly, this area is responsive to the anorexigenic hormone leptin and the orexigenic hormone ghrelin that have been shown to modulate FAA. However, how FAA is regulated by neuronal activity and how leptin and ghrelin modulate this activity is still poorly understood. OBJECTIVE: We aimed to examine how the total neuronal population and individual neurons in the medial hypothalamus respond to cue-signaled food availability in awake, behaving rats. In addition, ghrelin and leptin were injected to investigate whether these hormones could have a modulatory role in the regulation of FAA. DESIGN: Using in vivo electrophysiology, neuronal activity was recorded in the medial hypothalamus in freely moving rats kept on a random feeding schedule, in which a light cue signaled upcoming food delivery. Ghrelin and leptin were administered systemically following the behavioral paradigm. RESULTS: The food-predictive cue induced FAA as well as a significant increase in neural activity on a population level. More importantly, a sub-population of medial hypothalamic neurons displayed highly correlated identical responses to both ghrelin and FAA, suggesting that these neurons are part of the network that regulates FAA. CONCLUSION: This study reveals a role for ghrelin, but not leptin, signaling within medial hypothalamus in FAA on both a population level and in single cells, identifying a subset of neurons onto which cue information and ghrelin signaling converge, possibly to drive FAA.
Assuntos
Comportamento Alimentar/fisiologia , Grelina/metabolismo , Leptina/metabolismo , Atividade Motora/fisiologia , Animais , Antecipação Psicológica/efeitos dos fármacos , Comportamento Animal , Sinais (Psicologia) , Comportamento Alimentar/efeitos dos fármacos , Grelina/farmacologia , Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leptina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Neuropeptídeo Y/metabolismo , Ratos , Ratos WistarRESUMO
In this study we tested for a protective effect of secure attachment representations in the development of posttraumatic stress disorder (PTSD). In a design with a control group, we replicated and extended a recent study that found no underrepresentation of secure attachment representations in veterans with PTSD (Nye, Katzman, Bell, Kilpatrick, Brainard, & Haaland, 2008). Furthermore, we examined the association of the Adult Attachment Interview (AAI) classification of unresolved loss or trauma and PTSD symptomatology. The Adult Attachment Interview and the Clinician Administered PTSD Scale (CAPS) were administered with 31 veterans with PTSD and 29 trauma-exposed veterans without PTSD of similar age and country of deployment. Patient and control groups did not differ in the prevalence of secure attachment representations, neither did unresolved and not unresolved subjects differ in prevalence of secure attachment representations. Unresolved state of mind with respect to deployment related trauma was found to correlate strongly with total CAPS score. This study shows no protective effect of secure attachment representations in the development of PTSD. AAI unresolved state of mind with respect to deployment related trauma and PTSD correlate strongly, due to the common core phenomenon of lack of integration.
Assuntos
Militares/psicologia , Militares/estatística & dados numéricos , Apego ao Objeto , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Adulto , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Masculino , Países Baixos , Prevalência , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto JovemRESUMO
Posttraumatic stress disorder (PTSD) is associated with alterations in corticotrophin-releasing hormone (CRH) secretion. Plasma CRH levels, which are easily acquired, might serve as a predictor of hypothalamic CRH levels. Assessment of plasma CRH, adrenocorticotrophin hormone (ACTH), and cortisol levels in 31 veterans with PTSD, 30 traumatized veterans without PTSD matched on age, year, and region of deployment (traumacontrols), and 28 age-matched healthy controls (HCs) was carried out. Plasma CRH levels were higher in PTSD patients compared to both HCs (p=0.005) and traumacontrols (p=0.007). This led to our conclusion, that elevated plasma CRH levels are specifically related to PTSD and not to exposure to traumatic stress during deployment.
Assuntos
Hormônio Liberador da Corticotropina/sangue , Transtornos de Estresse Pós-Traumáticos/sangue , Veteranos , Adulto , Feminino , Humanos , Masculino , Escalas de Graduação PsiquiátricaRESUMO
The study examined the perception of facial expressions of different emotional intensities in obsessive-compulsive disorder (OCD) subtypes. Results showed that the High Risk Assessment and Checking subtype was more sensitive in perceiving the emotions fear and happiness. This suggests that altered affective processing may underlie the clinical manifestation of OCD.
Assuntos
Emoções , Expressão Facial , Transtorno Obsessivo-Compulsivo/diagnóstico , Percepção Visual , Adulto , Medo/psicologia , Feminino , Felicidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Transtorno Obsessivo-Compulsivo/classificação , Transtorno Obsessivo-Compulsivo/psicologia , Percepção SocialRESUMO
Gamma-aminobutyric acid (GABA(A)) receptors are thought to play an important role in modulating the central nervous system in response to stress. Animal data have shown alterations in the GABA(A) receptor complex by uncontrollable stressors. SPECT imaging with benzodiazepine ligands showed lower distribution volumes of the benzodiazepine-GABA(A) receptor in the prefrontal cortex of patients with post-traumatic stress disorder (PTSD) in one, but not in another study. The objective of the present study was to assess differences in the benzodiazepine-GABA(A) receptor complex in veterans with and without PTSD using [(11)C]flumazenil and positron emission tomography (PET). Nine drug naive male Dutch veterans with deployment related PTSD and seven male Dutch veterans without PTSD were recruited, and matched for age, region and year of deployment. Each subject received a [(11)C]flumazenil PET scan and a structural magnetic resonance imaging scan. Dynamic 3D PET scans with a total duration of 60 min were acquired, and binding in template based and manually defined regions of interest (ROI) was quantified using validated plasma input and reference tissue models. In addition, parametric binding potential images were compared on a voxel-by-voxel basis using statistical parametric mapping (SPM2). ROI analyses using both template based and manual ROIs showed significantly reduced [(11)C]flumazenil binding in PTSD subjects throughout the cortex, hippocampus and thalamus. SPM analysis confirmed these results. The observed global reduction of [(11)C]flumazenil binding in patients with PTSD provides circumstantial evidence for the role of the benzodiazepine-GABA(A) receptor in the pathophysiology of PTSD and is consistent with previous animal research and clinical psychopharmacological studies.
Assuntos
Mapeamento Encefálico , Hipocampo/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de GABA-A/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Adulto , Radioisótopos de Carbono/metabolismo , Estudos de Casos e Controles , Flumazenil/metabolismo , Lateralidade Funcional/fisiologia , Moduladores GABAérgicos/metabolismo , Hipocampo/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/diagnóstico por imagem , Valores de Referência , Estatísticas não Paramétricas , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tálamo/metabolismo , Veteranos/psicologiaRESUMO
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis functioning. Arginine vasopressin (AVP), in conjunction with corticotrophin releasing hormone, has shown to be an important modulator of the HPA axis. In order to evaluate the effect of trauma and PTSD on central AVP secretion we assessed plasma AVP levels in equally trauma exposed veterans with and without PTSD and a non-traumatized healthy control group. METHODS: Assessment of plasma AVP in 29 male veterans with PTSD, 29 traumatized veterans without PTSD, matched for age, gender, year and region of deployment (trauma controls), and 26 age matched healthy controls. RESULTS: Plasma AVP levels were higher in PTSD patients compared to both healthy controls (p = 0.004) and trauma controls (p < 0.001). In PTSD patients without a comorbid MDD a significant correlation was observed between plasma AVP levels and symptoms of avoidance measured with the Clinician Administered PTSD Scale (CAPS). CONCLUSION: Elevated plasma AVP levels are specifically related to PTSD and not to exposure to traumatic stress during deployment. Our results indicate that AVP may play a role as an anxiogenic factor, but they do not support a role for AVP in the altered response to dexamethasone in PTSD.
Assuntos
Arginina Vasopressina/sangue , Transtornos de Estresse Pós-Traumáticos/sangue , Veteranos/psicologia , Adulto , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Escalas de Graduação Psiquiátrica , Psicometria , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/fisiopatologiaRESUMO
BACKGROUND: Nightmares and insomnia are experienced by 70% of patients suffering from post-traumatic stress disorder (PTSD). These sleep problems are often resistant to treatment and exert a strong negative influence on the quality of life. In the last few decades several studies have reported on the characteristics of sleep disturbances in PTSD. AIM: To provide an overview of objective features of sleep disturbances - as opposed to self-report methods - in patients with PTSD. METHOD: Articles on this topic, published in peer-reviewed journals between 1980 and the present, were retrieved from Medline and Embase, using the search terms 'PTSD', 'sleep', 'nightmares', 'insomnia', 'polysomnography'. RESULTS: Studies reported on changes in sleep efficiency, arousal regulation, motor activity during sleep, rem characteristics and delta sleep activity during sleep. Also, correlations were found between nightmares and sleep apnoea in ptsd. In some studies on sleep disturbance no objective sleep disturbances were found in PTSD patients. However, most studies on PTSD related sleep disturbances were conducted in small, heterogeneous groups, and results were therefore inconsistent. Even the results of larger and more homogeneous studies were sometimes contradictory. CONCLUSION: There is a discrepancy between the clinical importance of sleep problems in PTSD and unambiguous objective sleep disorders. Future research should try to establish objective criteria for identifying the altered sleep patterns in PTSD. These criteria should help us to understand the neurobiological mechanisms of sleep disturbances in PTSD and develop new treatment strategies.
Assuntos
Sonhos/psicologia , Transtornos do Sono-Vigília/etiologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/psicologia , Humanos , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos do Sono-Vigília/psicologia , Transtornos do Sono-Vigília/terapia , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
Findings from epidemiological, pharmacotherapeutical, genetic and neurobiological studies suggest a possible overlap in the neurobiology of generalized social anxiety disorder (gSAD) and panic disorder (PD). Previously we have found a rapid intravenous m-CPP challenge of 0.1 mg/kg to be highly sensitive and selective in the provocation of panic attacks in patients with PD. We therefore directly compared the behavioural, neuroendocrine and physiological effects of this rapid m-CPP challenge in a small sample of patients with gSAD, patients with PD and matched healthy controls. Panic attacks were significantly more provoked in patients with PD (85%), but not in patients with gSAD (14%) as compared to healthy controls (0%). Effects on the other behavioural parameters, but not on the neuroendocrine and physiological parameters, were significantly greater in patients with PD compared to patients with gSAD and controls. Our preliminary data do not support a shared neurobiology of gSAD and PD.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Hormônio do Crescimento/metabolismo , Hidrocortisona/metabolismo , Medição da Dor/efeitos dos fármacos , Transtorno de Pânico/tratamento farmacológico , Piperazinas/administração & dosagem , Agonistas do Receptor de Serotonina/administração & dosagem , Adulto , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Feminino , Humanos , Injeções Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/metabolismo , Transtorno de Pânico/fisiopatologia , Método Simples-Cego , Estatísticas não Paramétricas , Fatores de TempoRESUMO
BACKGROUND: While enhanced cortisol suppression in response to dexamethasone is one of the most consistent biological findings in posttraumatic stress disorder (PTSD), the relative contribution of trauma exposure to this finding remains unclear. METHODS: Assessment of diurnal salivary cortisol levels and 1600 h salivary cortisol before and after oral administration of 0.5mg dexamethasone in veterans with PTSD, veterans without PTSD (trauma controls) and healthy controls. Assessment of 1600 h plasma cortisol, ACTH and corticotrophin binding globulin (CBG) in response to dexamethasone in PTSD patients and trauma controls. RESULTS: Both PTSD patients and trauma controls demonstrated significantly more salivary cortisol suppression compared to healthy controls. Salivary cortisol, plasma cortisol and ACTH suppression as well as CBG levels did not differ between PTSD patients and trauma controls. PTSD patients showed a reduced awakening cortisol response (ACR) compared to healthy controls that correlated significantly with PTSD symptoms. No significant differences were observed in ACR between PTSD patients and trauma controls. CONCLUSIONS: These data suggest that enhanced cortisol suppression to dexamethasone is related to trauma exposure and not specifically to PTSD. The correlation between the ACR and PTSD severity suggests that a flattened ACR may be a result of clinical symptoms.
Assuntos
Transtorno Depressivo Maior/metabolismo , Hidrocortisona/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Estresse Psicológico/metabolismo , Veteranos/psicologia , Adaptação Fisiológica , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Análise de Variância , Área Sob a Curva , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Ritmo Circadiano , Corticosterona , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/fisiopatologia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Medicina Militar , Valores de Referência , Saliva/metabolismo , Estatísticas não Paramétricas , Estimulação Química , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Psicológico/fisiopatologia , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologiaRESUMO
Post-traumatic stress disorder (PTSD) is associated with a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA axis). In addition, there is evidence for altered glucocorticoid receptor (GR) expression and function in peripheral blood mononuclear cells. The aim of the present study was to differentiate between the effect of trauma exposure and PTSD on leukocyte GR expression and glucocorticoid immune regulation. Leukocyte GR binding characteristics and glucocorticoid sensitivity of immune activity, determined as the effect of dexamethasone (DEX) on in vitro cytokine release and T-cell proliferation, were compared between veterans with PTSD, traumatized veterans without PTSD and healthy controls. Leukocyte GR density was significantly lower in veterans with and without PTSD compared to healthy controls. DEX-induced inhibition of T-cell proliferation was significantly lower in PTSD compared to trauma and healthy controls. DEX-induced increase in lipopolysaccharide-stimulated interleukin-10 was less pronounced in traumatized veterans with and without PTSD compared to healthy controls. No group differences were observed in the effect of DEX on other cytokines or in baseline immune activity, except for lower tumor necrosis factor-alpha production in PTSD patients compared to healthy controls. The results suggest that trauma exposure is sufficient to induce changes in GR binding characteristics, whereas resistance of T-cell proliferation to DEX only occurs in PTSD. DEX resistance of in vitro immune activity was not a general phenomenon, but was restricted to specific immune functions.
Assuntos
Interleucina-10/metabolismo , Leucócitos/metabolismo , Receptores de Glucocorticoides/metabolismo , Transtornos de Estresse Pós-Traumáticos/imunologia , Estresse Psicológico/imunologia , Adulto , Análise de Variância , Proliferação de Células , Dexametasona/metabolismo , Glucocorticoides/metabolismo , Humanos , Interleucina-10/imunologia , Masculino , Valores de Referência , Estimulação Química , Transtornos de Estresse Pós-Traumáticos/metabolismo , Estresse Psicológico/metabolismo , Linfócitos T/citologia , Veteranos/psicologiaRESUMO
Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Fluvoxamina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Antidepressivos de Segunda Geração/efeitos adversos , Peso Corporal/efeitos dos fármacos , Doenças do Sistema Nervoso Central/induzido quimicamente , Fluvoxamina/efeitos adversos , Humanos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Transtornos do Sono-Vigília/tratamento farmacológicoRESUMO
Patients with schizophrenia exhibit diverse cognitive deficits, one of which is a loss of the ability to focus attention. According to the revised dopamine hypothesis of schizophrenia both an increased mesolimbic and a decreased prefrontal dopaminergic activity is suggested to be involved in schizophrenia. The current study was designed to explore the relationship between dopamine and two psychophysiological parameters of selective attention, i.e. P300 amplitude and processing negativity (PN) in healthy volunteers. In two separate experiments, with a double-blind, balanced and placebo-controlled crossover design, 18 healthy male volunteers were orally administered either 300 mg l-dopa (precursor of dopamine) or placebo (experiment I), or 1.25mg bromocriptine (D2 agonist) or placebo (experiment II). Following this treatment they were tested in an auditory, dichotic selective attention paradigm. An increase in P300 amplitude was found following deviant stimuli when compared to standard stimuli and following attended stimuli when compared to unattended stimuli, regardless of treatment. Similarly, PN was found regardless of treatment. Neither l-dopa nor bromocriptine affected task performance or the amplitudes of PN or P300. In the present study neither l-dopa nor bromocriptine affected PN, P300 amplitude or task performance in healthy controls, phenomena which are usually found to be disrupted in schizophrenia. This indicates that P300 amplitude and PN are neither affected by a global (l-dopa) increased dopaminergic activity, nor by a more selectively towards striatal areas targeted (bromocriptine) increase in dopaminergic activity.
Assuntos
Antiparkinsonianos/farmacologia , Atenção/efeitos dos fármacos , Bromocriptina/farmacologia , Agonistas de Dopamina/farmacologia , Levodopa/farmacologia , Adulto , Estudos Cross-Over , Dopamina/metabolismo , Dopamina/fisiologia , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Eletroculografia , Potenciais Evocados P300/efeitos dos fármacos , Ácido Homovanílico/sangue , Humanos , Masculino , Prolactina/sangue , Desempenho Psicomotor/efeitos dos fármacos , Psicofisiologia , Receptores de Dopamina D2/agonistasRESUMO
OBJECTIVE: To determine the 6-month prevalence of body dysmorphic disorder (BDD) in outpatient clinics of dermatology and plastic surgery in a university medical centre. DESIGN: Questionnaire study. METHOD: In the period January 2004-June 2004, the self-reported Body dysmorphic disorder questionnaire was completed by 530 and 475 new patients in the outpatient clinics of dermatology and plastic surgery, respectively. The dermatologist or plastic surgeon assessed the severity of the defect. To meet the DSM-IV criteria for BDD, the patient must have been preoccupied with treatment of all or part of their appearance, experienced obvious suffering or restriction of function with minimal or no defect present (defect score 1 or 2). RESULTS: In the outpatient clinics ofdermatology and plastic surgery 8.5% (95% CI: 6.1-10.9) and 3.2% (95% CI: 1.7-4.7) of patients screened positive for BDD, respectively. CONCLUSION: A high prevalence of BDD was found in the outpatient clinics ofdermatology and plastic surgery. Because dermatologists and plastic surgeons do not often recognise BDD, a simple screening tool is needed.
Assuntos
Dermatologia/normas , Encaminhamento e Consulta , Transtornos Somatoformes/epidemiologia , Transtornos Somatoformes/psicologia , Cirurgia Plástica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Dermatopatias/diagnóstico , Transtornos Somatoformes/diagnóstico , Cirurgia Plástica/efeitos adversos , Inquéritos e QuestionáriosRESUMO
Posttraumatic stress disorder (PTSD) is typically accompanied by acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but several studies have also used a challenge model to further assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This paper reviews common methodology and research findings on HPA function in PTSD, and discusses the pathophysiological mechanisms underlying these findings. We reviewed the literature and selected all English-language, human subject, data driven, pharmacological and non-pharmacological challenge studies pertaining to the HPA axis, and in vitro leukocyte glucocorticoid receptor studies in adult PTSD subjects. Studies using a non-pharmacological stress paradigm (cognitive stress, trauma reminders) to stimulate the HPA axis showed an exaggerated cortisol response in PTSD. The most widely used pharmacological challenge with consistent results was the low dose dexamethasone-suppression test (DST). These DST studies showed enhanced cortisol suppression in subjects with PTSD. Different hypotheses have been purported to explain the alterations in HPA axis functioning in PTSD. The results of the reviewed challenge tests, however, did not exclusively support one of the hypothesized mechanisms. Further research assessing hormones at all levels of the HPA axis at both baseline and at challenge conditions with a proper stratification of study population, will be necessary for a better understanding of stress-responsivity on the level of the HPA axis in PTSD.
Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Cognição , Hormônio Liberador da Corticotropina/administração & dosagem , Dexametasona/administração & dosagem , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , MEDLINE/estatística & dados numéricos , Testes de Função Adreno-Hipofisária , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Estresse PsicológicoRESUMO
Schizophrenic patients show a loss of sensory gating, which is reflected in a reduced P50 suppression. Because most of the symptoms in schizophrenia can be reduced by antagonists of the dopaminergic (D2) system, the loss in sensory gating might be related to an increased dopaminergic activity. Therefore, in the present study, the effects of increased dopaminergic neurotransmisson on sensory gating in healthy volunteers were investigated. In a double-blind, balanced, placebo-controlled design, healthy male volunteers were challenged in two separate studies with either 300 mg L-dopa (precursor of dopamine) or placebo (n=16) and 1.25 mg bromocriptine (D2 agonist) or placebo (n=17). Subsequently, they were tested for their sensory gating (P50 suppression). P50 suppression values in the placebo condition were comparable to those found in literature. Although both L-dopa and bromocriptine reduced P50 amplitude, they did so in an equal ratio for both the response to the conditioning (C) and the testing (T) stimuli, therefore not resulting in a reduction of the P50 suppression ratio (T/C). In the present study, neither L-dopa nor bromocriptine reduced sensory gating in healthy volunteers. This suggests that an increased dopaminergic activity in humans is not responsible for the reduction in sensory gating as seen, for example, in schizophrenia.
Assuntos
Encéfalo/efeitos dos fármacos , Bromocriptina/farmacologia , Dopaminérgicos/farmacologia , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Levodopa/farmacologia , Estimulação Acústica , Adulto , Encéfalo/fisiologia , Estudos Cross-Over , Agonistas de Dopamina/farmacologia , Método Duplo-Cego , Potenciais Evocados Auditivos/fisiologia , Ácido Homovanílico/sangue , Humanos , Masculino , Prolactina/sangue , Privação Sensorial , Fatores de TempoRESUMO
Fourteen patients with social anxiety disorder (generalized type), according to DSM-IV criteria, were treated with mirtazapine 30 mg for 12 weeks. Twelve patients completed the study. Two patients (14.3%) dropped out due to side-effects. Generally, mirtazapine was well tolerated. Five out of 12 patients (41.7%) were classified as responders, based on a Clinical Global Improvement score of 1 or 2 and a reduction of the Liebowitz Social Anxiety Scale (LSAS) of 40%. The mean total score on the LSAS, as well as the anxiety and avoidance subscores, decreased significantly. This open pilot study suggests that further investigations are warranted to prove the efficacy of mirtazapine in generalized social anxiety disorder.
Assuntos
Antidepressivos Tricíclicos/farmacologia , Mianserina/farmacologia , Transtornos Fóbicos/tratamento farmacológico , Adulto , Antidepressivos Tricíclicos/efeitos adversos , Feminino , Humanos , Masculino , Mianserina/efeitos adversos , Mianserina/análogos & derivados , Mirtazapina , Pacientes Desistentes do Tratamento , Transtornos Fóbicos/psicologia , Projetos Piloto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Accumbal dopamine (DA) is generally accepted to participate in the neural mechanisms underlying drug dependence. Recently the involvement of accumbal DA in drug-seeking behaviour has gained more experimental attention. To study an involvement of accumbal DA in drug-seeking behaviour within and between daily self-administration behaviour, changes in extracellular DA concentration in the nucleus accumbens (NAc) shell were measured during the daily dynamics of intravenous heroin and cocaine self-administration. Groups of drug naive rats were allowed to intravenously self-administer heroin (30 microg/infusion) and cocaine (30 microg/infusion) during five consecutive daily 3 h sessions. Extracellular DA concentrations in the NAc were measured before and after a single 3 h session (acute) and before and after 5 consecutive 3 h sessions (repeated). Following acute and repeated heroin and cocaine self-administration the extracellular DA concentration in the NAc shell was increased by two-fold to three-fold over baseline. These changes in DA concentrations are thought to reflect a direct effect of heroin and cocaine on DA neurotransmission in the NAC shell. Measurement of basal DA concentrations before the self-administration sessions revealed that just before the scheduled 5th self-administration session the (absolute) basal DA levels in the NAc in heroin or cocaine self-administering animals were decreased by approximately halve, as compared to drug-naive animals. It is assumed that just before a scheduled next session the (daily) desire for the drug is high. This decrease in basal DA neurotransmission in the NAc shell may, therefore, reflect an involvement of accumbal DA in drug-seeking behaviour during daily self-administration behaviour. The results demonstrate that initiation of i.v. heroin and cocaine self-administration is linked with changes in extracellular levels of DA in the NAc shell. Moreover, the present data suggest that accumbal DA might be involved in processes underlying the motivational aspects involved in daily drug-seeking behaviour, and that neuroadaptive changes in the mesolimbic DA system due to repeated drug intake lead to an tonic decrease in overall DA activity in the NAc.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Dopamina/metabolismo , Dependência de Heroína/metabolismo , Núcleo Accumbens/metabolismo , Analgésicos Opioides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Heroína/farmacologia , Masculino , Microdiálise , Ratos , Ratos Wistar , AutoadministraçãoRESUMO
The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days +/- 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.
Assuntos
Antipsicóticos/uso terapêutico , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Pirenzepina/uso terapêutico , Esquizofrenia/líquido cefalorraquidiano , Adulto , Benzodiazepinas , Humanos , Masculino , Olanzapina , Pirenzepina/análogos & derivados , Esquizofrenia/tratamento farmacológicoRESUMO
OBJECTIVE: To determine the adequacy of drug treatment for patients with obsessive compulsive disorder (OCD). DESIGN: Retrospective. METHOD: One hundred and fifty outpatients with OCD, admitted at the University Medical Centre in Utrecht, the Netherlands, were evaluated for severity as measured with the 'Yale-Brown obsessive compulsive scale' (Y-BOCS). RESULTS: At the intake, 35% of the patients used no medication, 58% used an antidepressant, less than 1% an antipsychotic and 6% a benzodiazepine. The average active dose was taken by 12% of the patients, 5% took the maximum dosage and 41% too low a dosage. Consequently, 6 out of the 10 patients used the correct medication (antidepressant) and less than 20% used a sufficiently high dosage. Of the patients, 38% had never previously taken antidepressants, 31% had previously used one antidepressant, 17% two different antidepressants and 12% at least three different antidepressants; 13% had taken the antidepressant at the highest dosage, 18% at the average active dosage and 31% at too low (thus ineffective) a dosage. This means that from a pharmacotherapeutic viewpoint not more than 1 in 8 patients had had an adequate treatment history. CONCLUSION: The results of this study show that only 1 in 8 OCD patients were treated appropriately.