Anxiety disorders, including Panic Disorder, and alcohol problems co-occur at greater rates than chance in the general population. It has also been suggested that alcohol is used to cope with anxiety symptoms, such as trait anxiety. While pregnancy may be a protective period against Panic Disorder and panic symptoms, trait anxiety remains relatively stable during pregnancy. The purpose of the present study was to examine differences in rates of current Panic Disorder, panic attacks, and trait anxiety in pregnant and non-pregnant women receiving care at an urban OB/GYN clinic. The study also examined correlates and differences in alcohol use and at-risk drinking among these women. In addition, the study assessed whether meeting diagnostic criteria for Panic Disorder, having had a recent panic attack, and trait anxiety influence alcohol use and at risk drinking among women, and whether pregnancy status moderates these associations. Participants included pregnant (N = 412) and non-pregnant (N = 139) women receiving care at VCU Health Systems' OB/GYN clinics. As predicted, pregnant women were less likely than non-pregnant women to have current Panic Disorder and/or a recent panic attack. There were no differences in trait anxiety levels between pregnant and non pregnant women, and women with Panic Disorder and/or a recent panic attack had higher trait anxiety compared to women without Panic Disorder and/or a recent panic attack, regardless of pregnancy status. After controlling for demographics, Panic Disorder and higher trait anxiety were significant predictors of greater amounts of alcohol consumption in pregnant and non-pregnant women. In addition, non-pregnant women with high trait anxiety consumed greater amounts of alcohol than pregnant women with high trait anxiety. Furthermore, race and panic attacks were both predictors of being at-risk for problematic drinking. Overall, current study findings support the need to examine Panic Disorder, panic attacks, and trait anxiety, as potential risk factors for alcohol use among pregnant and non-pregnant women in the community. Study findings have important implications for assessment and treatment of panic, anxiety, and alcohol use.

[pt] Este estudo investiga o papel do hipocampo no comportamento de defesa condicionado e incondicionado examinando o efeito de lesões eletrolíticas pré-treino no hipocampo dorsal e ventral de ratos expostos a dois tipos de estímulos aversivos: estimulação elétrica da matéria cinzenta periaquedutal dorsal e choque nas patas. A lesão na parte dorsal e ventral diminuiu significativamente o comportamento defensivo condicionado. No comportamento defensivo incondicionado, a lesão ventral alterou significativamente o congelamento pré-fuga e a fuga. Os resultados sugerem um papel específico da parte dorsal e ventral do hipocampo na modulação de defesa através da utilização do modelo animal de ataque de pânico e TAG. / [en] This study investigates the role of the hippocampus in both unconditioned and conditioned defense behavior by examining the effects of pre-training electrolytic lesions to the dorsal and ventral hippocampus in male rats exposed to two types of threat stimuli: electrical stimulation of the DPAG and footshock. Our results indicate that ventral and dorsal lesions significantly attenuated conditioned defensive behavior. During unconditioned trials, ventral hippocampal lesion altered threshold needed for escape and pre-escape freezing. These results suggest a specific role of the ventral and dorsal hippocampus in modulating GAD and panic-attack like behaviors in certain animal model of defense.

[pt] A matéria cinzenta periaquedutal dorsal (MCPD) é associada com comportamento defensivo e ataques de pânico em humanos. Estimulações elétricas da MCPD induzem a um repertório de defesa: o congelamento pré fuga, reação de fuga e congelamento pós fuga. Evidências já apresentadas suportam a hipótese que enquanto o congelamento pré fuga seria um modelo de ataque de pânico o congelamento pós fuga seria um modelo de transtorno de pânico. Os resultados no experimento 1 indicaram que as duas linhagens de animais selecionadas para alto (Carioca alto congelamento) e baixo (Carioca baixo congelamento) congelamento em resposta ao contexto associado com choque nas patas, demonstraram que embora a ansiedade antecipatória possa exercer um efeito inibitório na expressão do congelamento pré fuga e na reação de fuga, pode por sua vez facilitar o congelamento pós fuga. No experimento 2, o efeito de lesões eletrolíticas no Córtex Cingulado Anterior Rostral não alteraram o congelamento pré fuga e a reação de fuga, porém as mesmas exercem um efeito inibitório no congelamento pós fuga demonstrando que os tipos de congelamento no medo incondicionado são mediados por circuitarias de defesa independentes. No experimento 3, o efeito de lesões eletrolíticas no Córtex Cingulado Anterior Rostral (CCAr) aumentou a sensibilidade a dor (comportamento recuperativo) de animais submetidos ao teste de formalina no paradigma de analgesia condicionada demonstrando a importância do CCAr na modulação da circuitaria de dor. / [en] The dorsal portion of the periaqueductal Gray (DPAG) is notably associated with defensive behavior and panic attacks in humans. Electrical stimulation of the DPAG induces a repertoire of defense: dPAG-evoked freezing, escape reaction and dPAG post-stimulation freezing. Past evidence support the hypothesis that whereas dPAG-evoked freezing would serve as model of panic attack, the dPAG post-stimulation freezing appears to be a model of panic disorder. The experiment 1 used two lines of animals selectively bred for high (Carioca High-Freezing) and low (Carioca Low-Freezing) freezing in response to contextual cues associated with footshock. The results suggest that although anticipatory anxiety might exert an inhibitory effect on the dPAG-evoked freezing and escape reaction, it might also facilitate the dPAG post-stimulation freezing. The experiment 2 studied the effect of electrolytic lesions on rostral anterior cingulated cortex (rACC). The results of electrolytic lesions on rACC suggest that although rACC lesions did not change the dPAG-evoked freezing and escape threshold, it might exert an inhibitory effect on the dPAG post-stimulation freezing, reinforcing the hypothesis that dPAG-evoked freezing and dPAG post- stimulation freezing are modulated by two independent circuitry of defense. The experiment 3 studied pain sensibility of rACC lesioned animals submitted to formalin test on conditioned analgesia paradigm. The results suggest that rACC lesions might exert an inhibitory effect on conditioned analgesia and consequently exacerbates recuperative behavior. The results also support the hypothesis of the rule of rACC on pain modulation.

[pt] Este estudo investiga o envolvimento do córtex pré-frontal medial ventral nos comportamentos de defesa inatos e aprendidos em paradigmas de condicionamento de medo e estimulação elétrica intracraniana em ratos. A lesão cortical aumentou significativamente o comportamento defensivo condicionado. No comportamento defensivo incondicionado, a lesão cortical diminuiu significativamente o congelamento pós-fuga dos animais. Os resultados replicam os dados da literatura científica a respeito do papel do córtex infralímbico como uma estrutura inibitória do estímulo condicionado em um circuito amidaloide de medo condicionado, e indicam uma participação do córtex pré-frontal na modulação dos comportamentos de defesa originários da estimulação da MCPd, em especial a sustentação do congelamento motor pós fuga. / [en] This study investigates the role of the prefrontal cortex in the innate and conditioned defensive behaviors in rats during classical conditioning and intracranial electrical stimulation procedurals. It was found that the cortical lesion augmented the conditioned freezing behavior to contextual fear cues. On the other hand, the lesions impaired the motor freezing presented after the escaping provoked by dPAG stimulation. These results replicate the findings from the literature about a prefrontal cortex role as an inhibitory structure in the aversive classic conditioning circuitry, as well as presenting a role for it in modulating freezing behavior in a panic circuitry involving the dPAG, especially regarding its function as a possible short term memory device for innate fear expression.

[pt] A matéria cinzenta periaquedutal dorsal (MCPD) é associada com comportamento defensivo e ataques de pânico em humanos. Estimulações elétricas ou farmacológicas da MCPD induzem a reações aversivas de corrida e pulo em ratos. Os resultados no experimento 1 indicaram que animais submetidos a um contexto previamente associado com choques nas patas, obtiveram um comportamento defensivo de congelamento robusto e tiveram menores reações defensivas de corridas e pulos através da microinjeção de de 0.3 µl N-metil-D- aspartato (NMDA; 15.0 mg/kg), quando comparado com o grupo controle que não foi exposto ao procedimento de medo ao contexto. No experimento 2, o efeito de injeções de pentilenotetrazol (PTZ; 15.0 mg/kg i.p.) em ratos microinjetados com NMDA nas reações de corridas e pulos foi investigado. Os resultados mostraram que o PTZ (1ml/100gr) foi capaz de minimizar as reações aversivas de corridas e pulos induzidas pela microinjeção de NMDA na MCPD. Esses resultados sugerem que a ativação de mecanismos cerebrais que permeiam a ansiedade produzem um efeito inibitório em ataques de pânico. / [en] The dorsal portion of the periaqueductal gray (DPAG) is notably associated with defensive behavior and panic attacks in humans. Electrical or pharmacological stimulation of the DPAG induces aversive reactions such as running and jumping in rats. Our results indicate that animals exposed to contextual cues, that were previously associated with electrical footshocks, engaged in robust defensive freezing behavior and were less likely to display running and jumping defensive reactions by microinjection of 0.3 µl N-methyl-D-aspartate (NMDA; 15.0 mg/kg) into DPAG when compared with control animals that were not exposed to the context fear conditioning procedure. Furthermore the effect of pentylenotetrazole injections (PTZ; 15.0 mg/kg i.p.) in microinjected NMDA rats in aversive reactions of running and jumping was investigated. The result showed that PTZ dose (1ml/100gr) was capable to minimize the aversive reactions of running and jumping induced by microinjection of NMDA into DPAG. These results suggest that activation of the brain mechanisms that underlie anxiety produces an inhibitory effect on panic attacks.

Les patients psychosomatiques et ceux souffrant d’attaque de panique, ont de manifestations corporelles et de plus ils présentent une intense souffrance psychique. L’association libre se trouve interférée à cause de vécus traumatiques durant la période précoce de la constitution psychique.Phase 1A rétrospectiveLe groupe contrôle a été sélectionné à partir de 417 patients asthmatiques en cabinets extérieurs de la Division de Pneumologie de l’Hôpital des Cliniques « J. de San Martín ». A pu être établi l’association entre type d’asthme et type d’accomplissement (X2=53.42 significatif à 1 %). Pour tous les types d’asthme la probabilité la plus faible de s’améliorer correspondait aux patients discontinuant ≥ 3 jours et modifiant les doses de leur médicament. Les patients accomplissant correctement leur traitement ont 87% de probabilité d’améliorer leur trouble.Phase 1B Prospective. Patients asthmatiques en groupe de parole.Phase prospective. 33 patients asthmatiques sévères et presque fatals ont été évalués cliniquement sur un an dans un programme qui incluait le groupe de parole. Au début du groupe thérapeutique tous les patients présentaient un mauvais niveau d’observance du traitement. A la fin de l’année la proportion de patients n’accomplissant pas correctement leur traitement est descendue à 10%. L’asthme nocturne s’est vu associé aux variables de compliance et statistiquement significatif (p<0.001). L’association directe entre amélioration du spiromètre et des variables de compliance est significative (p<0.001).Phase II prospective. Patients asthmatiques en groupe Photolangage®.Dans cette phase j’ai incorporé une technique de médiation par des photos dans des groupes (dans l´Institute d´ Investigations Médicales Prof. A. Lanari) pour favoriser l’association libre, la croissance du préconscient et la symbolisation. L’approche psychologique en groupe Photolangage® pour un traitement intégral de patients asthmatiques est une variable capable d’influencer favorablement l’évolution et le pronostique de la maladie. Les patients n’ont pas eu recours aux services d’urgence ni à des hospitalisations. La souffrance psychique du patient psychosomatique est archaïque. Ils ont subi les effets d’une contenance maternelle brusquement changeante. Ils ont pu construire une identité plus autonome et dépasser les batailles de l’ambivalence.Phase III prospective. Patients atteints de crise de panique en groupePhotolangage®L’approche psychologique en groupes Photolangage® pour un traitement intégral de patients aux crises de panique a favorisée l’évolution et le pronostique de la maladie.Ces patients ont subi des châtiments, humiliations, et douleurs psychiques alors que l’appareil psychique était déjà formé et avait atteint un certain niveau de symbolisation. Ils ont pu construire un plus grand nombre de représentations préconscientes et bloquer, dépasser ou amoindrir le quantum d’angoisse insupportable. Ils ont pu établir la différence entre une situation particulière à caractéristiques mortifères et les autres, entre l’avant et le maintenant.Le groupe de Photolangage® établi la distance nécessaire pour créer les liaisons et représentations préconscientes qui favorisent la capacité de penser facilitant les processus de transcription à deux niveaux simultanés celui du groupe et celui de l’individu. Ce travail permet rencontrer le sens fondateur du symptôme. Ils ont pu construire une plus grande autonomie et ont accédé à certains niveaux d’altérité par des identifications vitales et un degré d’idéalisation possible. / Psychosomatic patients and those suffering from panic disorder have a history of medical treatments for their body ailments and they have also an intense psychological distress. This research is divided in three phases:Phase 1A retrospectiveA control group was selected from 417 asthmatic patients of the Hospital de Clinicas J. de San Martin (Buenos Aires, Argentine). It was established an association between asthma degree and type of compliance (X 2 = 53.42 significant at 1%). It was found that in all kinds of asthma, lower probability of improvement corresponds to patients who discontinued ≥ 3 days and/or or changed the dose of medication. Patients with good compliance have 87% of chance to improve and those with poor compliance only 38%.Prospective Phase 1B asthmatic word groups33 patients were evaluated with severe and almost fatal asthma for 1 year in a program that included word group. At the beginning of the therapeutic word group all patients had a bad compliance. At the end of the year, the proportion of patients who did not fulfil their treatment correctly was 10%. Nocturnal asthma is associated with compliance variables and is statistically significant (p <0.001).The direct association between improvement in spirometer and compliance variables is significant (p <0.001).Phase II prospective asthmatics patients in Photolanguage® groups.Psychological approach in Photolanguage® groups for asthma treatment is a variable able to influence favourably the evolution and prognosis of these patients as it improves compliance and favours free association, expanding preconscious and symbolization.Also they could turn a more complex psychic apparatus, and showed no emergencies or hospitalizations. The psychosomatic patient's psychic suffering began in archaic time and his mother´s continence was abruptly changing. Patients could built a more autonomous identity after many ambivalence battles.Phase III prospective. Patients with panic attack in Photolanguage® groups.The psychological approach to patients with panic disorder in Photolanguage® groups is a useful tool for the evolution and better prognosis, in addition to the necessary pharmacological indications. These patients have a history of punishment, humiliation and psychic pain, which occurred when their psychic apparatus had some level of symbolization. They showed no subsequent panic attacks without medication, unbearable anguish decreased. They could differentiate characteristics about deadly situations from those that are not and also between time before and now. A Photolanguage® group creates the necessary distance needed to create links favouring preconscious thinking ability and transcription processes. Psychic work isdone simultaneously over the group level and over their effects on the individual level.Number of preconscious representations increased, patients could build autonomy and certain otherness levels, with vital and possible identifications. Photolanguage ®produces personal work awareness (foundation sense) allowing each think and connect with their own history.

Background. Previous studies of the dimensional structure of panic attack symptoms have mostly identified a respiratory and a vestibular/mixed somatic dimension. Evidence for additional dimensions such as a cardiac dimension and the allocation of several of the panic attack symptom criteria is less consistent. Clarifying the dimensional structure of the panic attack symptoms should help to specify the relationship of potential risk factors like anxiety sensitivity and fear of suffocation to the experience of panic attacks and the development of panic disorder. Method. In an outpatient multicentre study 350 panic patients with agoraphobia rated the intensity of each of the ten DSM-IV bodily symptoms during a typical panic attack. The factor structure of these data was investigated with nonlinear confirmatory factor analysis (CFA). The identified bodily symptom dimensions were related to panic cognitions, anxiety sensitivity and fear of suffocation by means of nonlinear structural equation modelling (SEM). Results. CFA indicated a respiratory, a vestibular/mixed somatic and a cardiac dimension of the bodily symptom criteria. These three factors were differentially associated with specific panic cognitions, different anxiety sensitivity facets and suffocation fear. Conclusions. Taking into account the dimensional structure of panic attack symptoms may help to increase the specificity of the associations between the experience of panic attack symptoms and various panic related constructs.

Text in Afrikaans / In this study the researcher explored and described the use of Gestalt play therapy with specific focus on self-support with the child in middle childhood years. A literature study was undertaken to examine the concepts of child, Gestalt play therapy, self-support and the play therapy process. This literature study forms the theoretical frame in which this study was done. After the completion of the literature study, the empirical study was conducted. The researcher made use of unstructured interviews within a intrinsic single case study in order to compile research data. During the empirical study ten therapy sessions were conducted with the participant which was explored within the framework of qualitative research methodology. The researcher was able to use ample Gestalt play therapy concepts and principles during the description of the case study in order to explore self-support within the child during middle childhood. These concepts and principles will be discussed in depth within this study. / Social Work / M.Diac. (Spelterapie-rigting)

Background. Previous research suggests that individuals experiencing DSM-IV panic attacks (PA) are at increased risk for various forms of psychopathology, including anxiety, depressive and substance use disorders. However, little is known regarding whether the sole occurrence of fearful spells (FS-only; distressing spells of anxiety with less than four panic symptoms and/or lacking crescendo in symptom onset) similarly elevates the risk for subsequent psychopathology and could therefore be promising to identify high-risk groups for targeted preventive interventions. Thus, the current dissertation thesis aims to examine (a) whether FS-only predict incident mental disorders in addition to full-blown PA and whether their associations with subsequent psychopathology differ from those obtained for PA, (b) whether FS-only, PA, and panic disorder (PD) share similar etiologies, (c) which characteristics of initial FS/PA and other risk factors predict a progression to more severe panic pathology and other mental disorders, and (d) whether help-seeking/potential treatment in individuals with panic alters the risk for subsequent psychopathology. Methods. A representative community sample of adolescents and young adults (N=3021, aged 14-24 at baseline) was prospectively followed up in up to three assessment waves over a time period of up to 10 years. FS-only, PA, PD, and other mental disorders were assessed at each assessment wave using the DSM-IV-M-CIDI. Additional modules/questionnaires were used to assess characteristics of initial FS/PA (T1/T2), potential risk factors, and help-seeking/potential treatment. Logistic regressions were applied to test associations (Odds Ratios, OR) of FS-only and PA at baseline with incident mental disorders at follow-up as well as respective interactive effects with help-seeking at baseline. Associations (Hazard Ratios, HR) of putative risk factors with the onset of panic pathology (FS-only, PA, and PD) or the onset of subsequent anxiety/depressive vs. substance use disorders in those with panic pathology (aggregated data across assessment waves) were estimated with Cox regressions. Multinomial logistic regressions were used to test associations of initial FS/PA characteristics (aggregated from T1 and T2) with PA and PD (lifetime incidences aggregated across assessment waves). Results. FS-only at baseline predicted incident anxiety and depressive disorders at follow-up (OR 1.59-4.36), while PA at baseline predicted incident anxiety, depressive, and substance use disorders at follow-up (OR 2.08-8.75; reference group: No FS/PA). Merely any anxiety disorder (OR=3.26) and alcohol abuse/dependence (OR=2.26) were significantly more strongly associated with PA than with FS-only. Female sex, parental anxiety disorders, parental depressive disorders, behavioral inhibition, harm avoidance, lower coping efficacy, and parental rejection predicted FS-only, PA, and PD (HR 1.2-3.0), whereas the associations with other risk factors partially differed for FS-only, PA, and PD and tended to be more pronounced for PA and PD than for FS-only. Alcohol consumption, use of drugs/medication, and physical illness as perceived reasons for the initial FS/PA were associated with the occurrence of full-blown PA (without PD, OR 2.46-5.44), while feelings of anxiety/depression and having always been anxious/nervous as perceived reasons for the initial FS/PA, appraising the initial FS/PA as terrible and long-term irritating/burdensome, subsequent feelings of depression, avoidance of situations/places, and consumption of medication, alcohol, or drugs were associated with the development of PD (OR 2.64-4.15). A longer duration until “feeling okay again” was associated with both PA and PD (OR 1.29-1.63 per category). Moreover, partially different risk constellations in subjects with panic pathology (FS/PA/PD) predicted the onset of subsequent anxiety/depressive vs. substance use disorders. Panic pathology (FS/PA) and help-seeking/potential treatment at baseline interacted on predicting incident PD (OR=0.09) and depression (OR=0.22) at follow-up in a way that panic pathology only predicted these disorders in individuals not seeking help at baseline. Conclusions. Findings suggest that individuals with FS-only are at similar risk of developing subsequent psychopathology compared to individuals with full-blown PA. Specific initial FS/PA characteristics and additional risk factors may be used to identify sub-groups of individuals with panic pathology, which are at particular risk of progressing to more severe panic pathology or other mental disorders and might therefore profit from supplemental outcome-related preventive interventions in addition to panic-specific treatment. Future research may replicate the current findings and test the efficacy of targeted preventive interventions in panickers at elevated risk for PD and other forms of psychopathology. / Theoretischer Hintergrund. Auf Grundlage früherer Forschungsbefunde ist anzunehmen, dass Personen mit DSM-IV-Panikattacken (PA) ein erhöhtes Risiko für zahlreiche psychische Störungen, einschließlich Angst-, depressiver und Substanzstörungen, aufweisen. Unklar ist jedoch, ob das alleinige Auftreten von Fearful Spells (FS-only, Angstanfälle mit weniger als vier Paniksymptomen und/oder fehlendem Crescendo in der Symptomentwicklung) das Risiko für Psychopathologie in ähnlicher Weise erhöht und hilfreich sein könnte, um Hochrisikogruppen für Präventivinterventionen zu identifizieren. Innerhalb der vorliegenden Dissertation wird daher untersucht, (a) ob FS-only zusätzlich zu PA inzidente psychische Störungen vorhersagen und ob sich Unterschiede in den Assoziationen von FS-only vs. PA mit nachfolgender Psychopathologie ergeben, (b) ob FS-only, PA und Panikstörung (PS) ähnliche Ätiologien teilen, (c) welche Merkmale initialer FS/PA und welche anderen Risikofaktoren die Entwicklung schwerer Panikpathologie und weiterer psychischer Störungen vorhersagen und (d) ob Hilfesuchverhalten/potenzielle Behandlung bei Personen mit Panik das Risiko für nachfolgende Psychopathologie verändert. Methodik. Eine repräsentative Bevölkerungsstichprobe Jugendlicher und junger Erwachsener (N=3021, 14-24 Jahre zur Baseline-Erhebung) wurde in bis zu drei Erhebungswellen über einen Zeitraum von bis zu 10 Jahren untersucht. FS-only, PA, PS und andere psychische Störungen wurden zu jeder Erhebungswelle mithilfe des DSM-IV-M-CIDI erfasst. Merkmale initialer FS/PA (T1/T2), mögliche Risikofaktoren sowie Hilfesuchverhalten/potenzielle Behandlung wurden mit weiteren Modulen und Fragebögen erhoben. Mithilfe logistischer Regressionen wurden Assoziationen (Odds Ratios, OR) von FS-only und PA zu Baseline mit inzidenten psychischen Störungen zum Follow-Up sowie diesbezügliche Interaktionen mit Hilfesuchverhalten zu Baseline getestet. Zusammenhänge zwischen möglichen Risikofaktoren und dem Auftreten von Panikpathologie (FS-only, PA und PS) bzw. nachfolgender Angst-/depressiver und Substanzstörungen bei Personen mit Panikpathologie (Verwendung von über die Erhebungswellen hinweg aggregierter Daten) wurden mithilfe von Cox-Regressionen geschätzt. Multinomiale logistische Regressionen wurden genutzt, um Assoziationen von Merkmalen initialer FS/PA (aggregiert über T1 und T2) mit PA und PS (über die Erhebungswellen hinweg aggregierte Lebenszeitinzidenzen) zu erfassen. Ergebnisse. FS-only zu Baseline sagten inzidente Angst- und depressive Störungen zum Follow-Up vorher (OR 1.59-4.36), wohingegen PA zu Baseline inzidente Angst-, depressive und Substanzstörungen zum Follow-Up vorhersagten (OR 2.08-8.75; Referenzkategorie: Keine FS/PA). Lediglich irgendeine Angststörung (OR=3.26) und Alkoholmissbrauch/-abhängigkeit (OR=2.26) waren signifikant stärker mit PA als mit FS-only assoziiert. Weibliches Geschlecht, elterliche Angst- und depressive Störungen, Verhaltenshemmung, Schadensvermeidung, geringere Coping-Erwartung und elterliche Zurückweisung sagten FS-only, PA und PS vorher (HR 1.2-3.0), während sich teils unterschiedliche Assoziationen anderer Risikofaktoren mit FS-only, PA und PS ergaben, die tendenziell stärker für PA und PS als für FS-only waren. Alkoholkonsum, Drogen-/Medikamentengebrauch und körperliche Erkrankungen als wahrgenommene Gründe für die initiale FS/PA waren mit dem Auftreten vollständiger PA assoziiert (ohne PS; OR 2.46-5.44), während Gefühle von Angst/Depression und die Einschätzung schon immer ängstlich/nervös gewesen zu sein als wahrgenommene Gründe für die initiale FS/PA, die Bewertung der initialen FS/PA als schrecklich und langfristig verunsichernd/belastend, nachfolgende Gefühle von Niedergeschlagenheit, Vermeidung von Situationen/Orten und Konsum von Medikamenten, Alkohol oder Drogen mit der Entwicklung von PS assoziiert waren (OR 2.64-4.15). Eine längere Dauer bis sich die betroffene Person wieder vollständig in Ordnung fühlte war sowohl mit PA als auch mit PS assoziiert (OR 1.29-1.63 pro Kategorie). Weiterhin sagten teils unterschiedliche Risikokonstellationen bei Personen mit Panikpathologie (FS/PA/PS) die nachfolgende Entstehung von Angst-/depressiven und Substanzstörungen vorher. Panikpathologie (FS/PA) und Hilfesuchverhalten/potenzielle Behandlung zu Baseline interagierten bei der Vorhersage von inzidenter PS (OR=0.09) und Depression (OR=0.22) zum Follow-Up; d.h. das Vorhandensein von Panikpathologie sagte diese Störungen nur bei Personen ohne, nicht aber bei Personen mit Hilfesuchverhalten zu Baseline vorher. Schlussfolgerungen. Die vorliegenden Ergebnisse implizieren, dass Personen mit FS-only im Vergleich zu Personen mit vollständigen PA ein ähnliches Risiko für die Entwicklung nachfolgender Psychopathologie aufweisen. Spezifische Merkmale initialer FS/PA und zusätzliche Risikofaktoren könnten zur Identifikation von Sub-Gruppen von Personen mit Panik genutzt werden, die sich durch ein besonderes Risiko für schwergradige Panikpathologie und andere psychische Störungen auszeichnen und demzufolge von Outcome-bezogenen Präventionen (ergänzend zu Panik-spezifischer Intervention) profitieren könnten. Zukünftige Studien sollten die vorliegenden Befunde replizieren und die Effektivität gezielter Präventivinterventionen bei Personen mit erhöhtem Risiko für PS und andere psychische Störungen testen.

Há estudos que mostraram que o ácido N-metil-D-aspártico (NMDA), microinjetado nas estruturas do teto mesencefálico (corpos quadrigêmeos) de ratos evoca comportamentos defensivos do tipo pânico que podem ser seguidos por uma resposta antinociceptiva. Tem sido sugerido que respostas defensivas relacionadas ao medo organizadas por neurônios do tronco cerebral podem ser moduladas por projeções ascendentes mediadas pelo neurotransmissor 5-hidroxitriptamina (5-HT) do núcleo dorsal da rafe (NDR), e fenômenos antinociceptivos induzidos pelo medo inato podem ser organizados por vias serotoninérgicas descendentes também originadas no NDR. Os neurônios do NDR que originam tais conexões, por sua vez, podem ser moduladas por monoaminas que recrutam receptores 5-HT2A localizados no NDR. Não obstante, háuma escassez de estudos mostrando o papel dos receptores 5-HT2A do NDR na modulação do comportamento do tipo pânico e da antinocicepção induzida pelo medo inato organizados nos colículos superiores e inferiores. O objetivo deste estudo foi investigar a participação dos receptores 5-HT2A do NDR na modulação do comportamento de defesa organizado pelos corpos quadrigêmeos e da antinocicepção induzida pelo medo evocados por microinjeções de NMDA nos corpos quadrigêmeos. No experimento I, os animais receberam microinjeção de veículo (NaCl 0,9% / 0,2?L) ou 6, 9 e 12 nmol NMDA no CI. No experimento II, foi realizado o pré-tratamento do NDR com microinjeções de veículo ou o antagonista seletivo do receptor 5HT2A (R-96544) nas concentrações de 5, 10 e 15 nM. Dez minutos depois, o NMDA na dose mais efetiva (12 nmol) foi injetado no CI. Em ambos os experimentos, as respostas defensivas foram analisadas quantitativamente durante 10 min e, em seguida, as latências de retirada de cauda foram medidas a intervalos de 10 min durante 70 min. No experimento III, os animais receberam microinjeção de salina fisiológica ou NMDA (6, 9 e 12 nmol) nas cpSC. No experimento IV, a dose mais efetiva de NMDA (12 nmol) ou veículo foi precedida por microinjeções de veículo ou antagonista seletivo do receptor 5HT2A (R- 96544) em diferentes concentrações, 0.5, 5 e 10 nM. Ambos os efeitos pró-eversivos e antinociceptivos provocados pelas injecções intra-cpCS de NMDA foram atenuados pelo pré-tratamento do NDR com R-96544. No experimento V, a análise morfológica mostrou que os receptores 5-HT2A estão presentes nos interneurônios GABAérgicos do NDR. Em conjunto, esses achados sugerem que o bloqueio dos receptores 5-HT2A no NDR é capaz de atenuar tanto o comportamento defensivo do tipo pânico quanto a antinocicepção induzida pelo medo organizada pelos corpos quadrigêmeos. / There are studies that suggest that N-methyl-D-aspartic acid (NMDA) microinjected into the midbrain tectum structures, such corpora quadrigemina, of rats evokes panic-like defensive behaviours that can be followed by an antinociceptive response. It has been suggested that fear-related defensive responses organised by brainstem neurons can be modulated by ascending projections mediated by the neurotransmitter 5-hydroxytryptamine (5-HT) of the dorsal raphe nucleus (DRN), and phenomena of innate fear-induced antinociception can be organised by descending serotonergic pathways also originating from the DRN. The DRN neurons that give rise to such connections, in turn, can be moduled by monoamines that recruit 5-HT2A receptors located in the DRN. Nevertheless, there is a shortage of studies showing the role of DRN 5-HT2A receptors in the modulation of panic-like behaviour and innate fearinduced antinociception organised by superior and inferior colliculi. The purpose of this study was to investigate the participation of DRN 5-HT2A receptors in the modulation of panic-like behaviour and antinociception evoked by corpora quadrigemina injections of NMDA. In experiment I, the animals received microinjection of vehicle (0.9%NaCl/0.2?L) or 6, 9 and 12 nmol NMDA into the IC. In experiment II, it was performed the pretreatment of DRN with microinjections of vehicle or the 5HT2A receptor selective antagonist (R-96544) in a concentration of 5, 10 and 15 nM. Ten minutes later, NMDA at the most effective dose (12nmol) was injected in the IC. In both experiments, the defensive responses were quantitatively analysed for 10 min and then the tail-flick withdrawal latencies were measured at 10 min-intervals for 70 min. In experiment III, the animals received microinjection of physiological saline or NMDA (6, 9 and 12 nmol) into the deep layers of SC (dlSC). In experiment IV, the most effective dose of NMDA (12 nmol) or vehicle was preceded by microinjections of vehicle or 5HT2A receptor selective antagonist (R-96544) at different concentrations (0.5, 5, and 10 nM). Both proaversive and antinociceptive effects elicited by intra-dlSC injections of NMDA were attenuated by the pretreatment of the DRN with R-96544. In experiment V, the morphological analysis showed that 5-HT2A receptors are present in GABAergic interneurons in the DRN. Taken together, these findings suggest that the blockade of DRN 5-HT2A receptors decreased both panic attack-like defensive behaviour and fear- induced antinociception organised by the corpora quadrigemina neurons.