RESUMO
OBJECTIVES: To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. METHODS: Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. RESULTS: Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. CONCLUSION: Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.
Assuntos
Monoaminas Biogênicas/metabolismo , Climatério/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neurotransmissores/metabolismo , Transtorno de Pânico/sangue , Transtorno de Pânico/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Transtorno de Pânico/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
RATIONALE: It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. OBJECTIVES: Using a high-dose carbon dioxide (CO(2)) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO(2)-induced panic response in healthy volunteers. METHODS: Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO(2) inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO(2). RESULTS: CO(2)-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p < 0.05). In the separate-group analysis, ΔVAAS scores were positively correlated to the ratio Trp:ΣLNAA after treatment (r = 0.39; p < 0.05). CONCLUSIONS: The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects.
Assuntos
Dióxido de Carbono , Hipercapnia/psicologia , Transtorno de Pânico/prevenção & controle , Triptofano/administração & dosagem , Triptofano/deficiência , Adulto , Aminoácidos/administração & dosagem , Aminoácidos/sangue , Aminoácidos/deficiência , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipercapnia/sangue , Hipercapnia/induzido quimicamente , Masculino , Transtorno de Pânico/sangue , Transtorno de Pânico/psicologia , Testes Psicológicos , Serotonina/deficiência , Serotonina/metabolismo , Triptofano/sangueRESUMO
OBJECTIVE: There are numerous theories of panic disorder, each proposing a unique pathway of change leading to treatment success. However, little is known about whether improvements in proposed mediators are indeed associated with treatment outcomes and whether these mediators are specific to particular treatment modalities. Our purpose in this study was to analyze pathways of change in theoretically distinct interventions using longitudinal, moderated mediation analyses. METHOD: Forty-one patients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of training aimed at altering either respiration (capnometry-assisted respiratory training) or panic-related cognitions (cognitive training). Changes in respiration (PCO2, respiration rate), symptom appraisal, and a modality-nonspecific mediator (perceived control) were considered as possible mediators. RESULTS: The reductions in panic symptom severity and panic-related cognitions and the improvements in perceived control were significant and comparable in both treatment groups. Capnometry-assisted respiratory training, but not cognitive training, led to corrections from initially hypocapnic to normocapnic levels. Moderated mediation and temporal analyses suggested that in capnometry-assisted respiratory training, PCO2 unidirectionally mediated and preceded changes in symptom appraisal and perceived control and was unidirectionally associated with changes in panic symptom severity. In cognitive training, reductions in symptom appraisal were bidirectionally associated with perceived control and panic symptom severity. In addition, perceived control was bidirectionally related to panic symptom severity in both treatment conditions. CONCLUSION: The findings suggest that reductions in panic symptom severity can be achieved through different pathways, consistent with the underlying models.
Assuntos
Agorafobia/psicologia , Agorafobia/terapia , Exercícios Respiratórios , Dióxido de Carbono/sangue , Transtornos Cognitivos/psicologia , Transtornos Cognitivos/terapia , Terapia Cognitivo-Comportamental , Transtorno de Pânico/psicologia , Transtorno de Pânico/terapia , Adulto , Agorafobia/sangue , Agorafobia/diagnóstico , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Nível de Alerta , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Transtornos do Humor/terapia , Transtorno de Pânico/sangue , Transtorno de Pânico/diagnóstico , Taxa Respiratória , Adulto JovemRESUMO
OBJECTIVE: Adenosine deaminase and dipeptidyl peptidase IV are enzymes connected to T cells that play an important role in immune system functioning. In this study, in order to understand the immune processes in panic disorder, we determined the serum levels of adenosine deaminase and dipeptidyl peptidase IV in medication-free panic disorder patients and compared them to those of healthy controls. METHOD: Enzymes levels were determined in blood samples of 24 healthy controls and 33 panic disorder patients diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-IV that were medication free during the previous month and medically healthy. RESULTS: Levels of both enzymes were significantly higher in panic disorder patients than in the controls (P<0.001 for adenosine deaminase and P<0.05 for dipeptidyl peptidase IV). The levels of the enzymes did not correlate with sociodemographic variables, duration of the disorder, presence of agoraphobia, presence of stressors, number of panic attack symptoms, and Hamilton depression and anxiety rating scale scores. In addition, the 2 enzymes? levels did not correlate with each other. There was a correlation between Hamilton anxiety rating scale score and the number of panic attack symptoms (P<0.001); however, Hamilton anxiety rating scale scores were not correlated with the other variables. CONCLUSION: Our results suggest that there may be a primary or secondary impaired immune state in the course of panic disorder, as there is in many other psychiatric disorders, such as major depression. Future studies with larger samples are needed to clarify the relationship between the immune system and panic disorder.
Assuntos
Adenosina Desaminase/sangue , Dipeptidil Peptidase 4/sangue , Transtorno de Pânico/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtorno de Pânico/sangue , Transtorno de Pânico/imunologia , Escalas de Graduação Psiquiátrica , PsiconeuroimunologiaRESUMO
OBJECTIVE: Previous findings of excess brain lactate and delayed end-tidal CO(2) (pCO(2)) recovery in subjects with panic disorder during hyperventilation suggested altered acid-base regulation. Two models were posited to explain these results: 1) subjects with panic disorder demonstrate greater alkalosis to hyperventilation, implicating increased lactate as directly compensatory, or 2) subjects with panic disorder demonstrate reduced or blunted alkalosis, implicating increased lactate as overly compensatory to a normal pH response. In both models, delayed pCO(2) recovery in subjects with panic disorder could reflect slower pH normalization in the recovery phase. METHOD: Asymptomatic medicated patients with panic disorder were studied during regulated hyperventilation. Phosphorous spectroscopy was used to measure brain pH every 2 minutes. Nine subjects with panic disorder were compared to 11 healthy subjects at baseline (five scans), during regulated hyperventilation (five scans), and across recovery (10 scans). Anxiety symptoms were assessed with standard ratings. RESULTS: No subject had a panic attack before hyperventilation. Subjects with panic disorder had lower pCO(2) during hyperventilation and slower pCO(2) recovery across the posthyperventilation interval. Despite this different respiratory response in the panic disorder group, brain pH increases were not significantly greater during hyperventilation, nor was pH return to baseline slowed during posthyperventilation. A linear regression model derived from data of healthy subjects showed pH blunting in the panic disorder group. CONCLUSIONS: Although subjects with panic disorder had greater hypocapnea during hyperventilation, their observed pH response, not altered from comparison levels, implicated exaggerated buffering. It is suggested that increased lactate could account for these findings.
Assuntos
Desequilíbrio Ácido-Base/metabolismo , Encéfalo/metabolismo , Concentração de Íons de Hidrogênio , Hiperventilação/metabolismo , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/metabolismo , Alcalose/metabolismo , Dióxido de Carbono/metabolismo , Feminino , Humanos , Hiperventilação/sangue , Lactatos/sangue , Lactatos/metabolismo , Modelos Lineares , Imageamento por Ressonância Magnética/estatística & dados numéricos , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Masculino , Transtorno de Pânico/sangue , Pressão Parcial , FósforoRESUMO
BACKGROUND: Several functional imaging studies have demonstrated increases of brain activity in the temporofrontal, cingulate, and claustrum regions during a pharmacologically induced panic attack when scanning was done at a single point in time. However, no study has evaluated changes in brain activity at two time points during a panic attack. We hypothesized that in response to a single bolus injection of the panicogen cholecystokinin-4 (CCK-4) in healthy volunteers, changes in regional cerebral blood flow (rCBF) might be different if scanning were done at two different time points. METHODS: To test this hypothesis, we conducted a single-blind study, using positron emission tomography (PET). To determine the time effect of panic attack on brain activity, we performed either early scan or late scan covering the first or the second minute after CCK-4 bolus injection, respectively. The PET images were analyzed by statistical parametric mapping (SPM) followed by region of interest (ROI) analysis. RESULTS: The results showed significant differences between the early and the late scan. The early effects of CCK-4 are accompanied by increases in rCBF in the hypothalamic region, whereas the late scan showed an increase in rCBF in the claustrum-insular region. Reductions in rCBF were observed for both time groups in the medial frontal region. A separate scan for anticipatory anxiety demonstrated rCBF increases in the anterior cingulate region and decreases in the occipital regions. CONCLUSIONS: These results may support the hypothesis that changes in rCBF as a function of time during CCK-4-induced panic might correspond to a neurocircuitry involved in panic attacks.
Assuntos
Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Transtorno de Pânico/fisiopatologia , Adulto , Análise de Variância , Ansiedade/sangue , Ansiedade/diagnóstico por imagem , Ansiedade/fisiopatologia , Gânglios da Base/irrigação sanguínea , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Feminino , Hormônios/sangue , Humanos , Hipotálamo/irrigação sanguínea , Hipotálamo/diagnóstico por imagem , Hipotálamo/efeitos dos fármacos , Sistema Límbico/irrigação sanguínea , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Isótopos de Oxigênio , Transtorno de Pânico/sangue , Transtorno de Pânico/induzido quimicamente , Método Simples-Cego , Tetragastrina , Fatores de Tempo , Tomografia Computadorizada de EmissãoRESUMO
The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of pathophysiologic significance in certain patients with panic disorder. It remains to be demonstrated if the peripheral autoimmunity is representative of CNS 5-HT neuronal alterations. Replication appears warranted.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Autoanticorpos/sangue , Transtorno de Pânico/imunologia , Serotonina/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Transtorno de Pânico/sangue , Transtorno de Pânico/psicologia , Escalas de Graduação PsiquiátricaRESUMO
We have examined the responsiveness of dopamine sensitive neurones in the postpartum period in woman with a history of major depression who are at high risk of experiencing a recurrence of illness in the postpartum period. Fourteen women were assessed at 36 weeks of pregnancy and during the 3 months following delivery, using the Schedule for Affective Disorders and Schizophrenia, including its change version. They were not depressed at initial assessment. Five of the 14 women went on to experience a postpartum relapse (2 major depressive disorder, 2 generalised anxiety disorder, 1 panic disorder). On the fourth day postpartum, i.e., before relapse, the growth hormone response to the dopamine agonist apomorphine was measured as an index of the functional state of hypothalamic dopamine D2 receptors. Women who subsequently relapsed had a significantly greater growth hormone response to apomorphine than those who remained well. This was particularly marked in women with anxiety/panic. The development of increased sensitivity of hypothalamic dopamine D2 receptors in the postpartum period appears to predict the onset of depressive and anxiety disorders.