The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

Postural balance in patients with social anxiety disorder

Body stability is controlled by the postural system and can be affected by fear and anxiety. Few studies have addressed freezing posture in psychiatric disorders. The purpose of the present study was to assess posturographic behavior in 30 patients with social anxiety disorder (SAD) and 35 without SAD during presentation of blocks of pictures with different valences. Neutral images consisted of objects taken from a catalog of pictures, negative images were mutilation pictures and anxiogenic images were related to situations regarding SAD fears. While participants were standing on a force platform, similar to a balance, displacement of the center of pressure in the mediolateral and anteroposterior directions was measured. We found that the SAD group exhibited a lower sway area and a lower velocity of sway throughout the experiment independent of the visual stimuli, in which the phobic pictures, a stimulus associated with a defense response, were unable to evoke a significantly more rigid posture than the others. We hypothesize that patients with SAD when entering in a situation of exposure, from the moment the pictures are presented, tend to move less than controls, remaining this way until the experiment ends. This discrete body manifestation can provide additional data to the characterization of SAD and its differentiation from other anxiety disorders, especially in situations regarding facing fear.

Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

On the relationships between ultrasonic calling and anxiety-related behavior in rats

In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala.

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Psychiatric disorders and cardiac anxiety in exercising and sedentary coronary artery disease patients: a case-control study

Regular physical exercise has been shown to favorably influence mood and anxiety; however, there are few studies regarding psychiatric aspects of physically active patients with coronary artery disease (CAD). The objective of the present study was to compare the prevalence of psychiatric disorders and cardiac anxiety in sedentary and exercising CAD patients. A total sample of 119 CAD patients (74 men) were enrolled in a case-control study. The subjects were interviewed to identify psychiatric disorders and responded to the Cardiac Anxiety Questionnaire. In the exercise group (N = 60), there was a lower prevalence (45 vs 81%; P < 0.001) of at least one psychiatric diagnosis, as well as multiple comorbidities, when compared to the sedentary group (N = 59). Considering the Cardiac Anxiety Questionnaire, sedentary patients presented higher scores compared to exercisers (mean ± SEM = 55.8 ± 1.9 vs 37.3 ± 1.6; P < 0.001). In a regression model, to be attending a medically supervised exercise program presented a relevant potential for a 35% reduction in cardiac anxiety. CAD patients regularly attending an exercise program presented less current psychiatric diagnoses and multiple mental-related comorbidities and lower scores of cardiac anxiety. These salutary mental effects add to the already known health benefits of exercise for CAD patients.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.

JNK regulation of neurogenesis, neuroplasticity and anxiety-related behaviors in mice

I vår moderna värld har förekomsten av ångeststörningar drastiskt ökat, vilket påverkar välfärden i våra samhällen. Eftersom de molekylära mekanismerna bakom ångest är relativt okända, är möjligheterna till behandling av ångeststörningar begränsade. I och med utvecklingen av genetiska manipuleringmetoder och avbildningstekniker har strukturella förändringar associerade med ångeststörningar kunnat konstateras. Neuroanatomiska studier har påvisat störningar i dendritarkitektur, dendrittaggar och i neurogenesen hos vuxna individer. Särskilt neurogenesen i hippocampus anses viktig i detta sammanhang. Neurogenes i hippocampus har föreslagits spela en viktig roll i ångeststörningarnas patofysiologi och för hur vissa antidepressiva läkemedel förmedlar sin effekt. Under senare år har MAP-kinaser (MAPK) föreslagits vara involverade både i uppkomsten av affektiva störningar och i neurogenes i hippocampus. JNK är en grupp kinaser inom MAPK-familjen som aktiveras av olika externa stressfaktorer. I normala celler är aktiviteten hos JNK låg. Cell-stress ökar aktiviteten hos JNK vilket leder till bl.a. apoptos. JNK kinaser anses vara potentiella terapeutiska mål för behandling av neurodegenerativa sjukdomar men deras potential som mål för behandling av affektiva sjukdomar har tillsvidare inte utretts. Den här avhandlingen behandlar betydelsen av JNK för ångestrelaterat beteende hos möss. Med hjälp av Jnk1-knockout möss och farmakologisk inhibering av JNK-signalering, demonstreras att JNK reglerar neurogenes i hippocampus, vilket i sin tur ligger bakom mössens ångestrelaterade beteende. Jnk1-knockout möss var mindre ängsliga och uppvisade ökad neurogenes i hippcampus jämfört med kontrollmöss. Inhibering av JNK-signalering i hjärnan hos möss gjorde dem också mindre ängsliga och ökade neurogenesen i hippocampus på samma sätt som vissa antidepressiva läkemedel. Inhibering av JNK-aktivitet ledde inte bara till ökad neurogenes i hippocampus, utan främjade också mognandet av nybildade nervceller hos vuxna möss. Resultaten visar också att dendritarkitekturen och fördelningen av dendrittaggar hos CA3 neuroner i hippocampus är förändrad hos Jnk1-knockout möss. Genom screening av substratmolekyler för JNK hittades två JNKeffektormolekyler, MARCKSL1 (ett aktin-associerat protein) och MAP2 (ett mikrotubulus-associerat protein), som reglerade neuronernas sttruktur. Det här tyder på att JNK-signalering kan kontrollera ångeststörningsrelaterade förändringar hor dendriter och dendrittaggar. Sammanfattningsvis ger resultaten som presenteras i avhandlingen en ökad insikt i molekylära mekanismer som kan leda till ångeststörningsrelaterade förändringar i neurogenes och dendritstruktur. Därtill föreslås att JNKsignalbanan har potential som terapeutiskt mål för behandling av ångeststörningar.

Social physique anxiety across physical activity settings : a meta-analytical review

The purpose of this meta-analytic investigation was to review the empirical evidence specific to the effect of physical activity context on social physique anxiety (SP A). English language studies were located from computer and manual literature searches. A total of 146 initial studies were coded. Studies included in the meta-analysis presented at least one empirical effect for SPA between physical activity participants (i.e., athletes or exercisers) and non-physical activity participants. The final sample included thirteen studies, yielding 14 effect sizes, with a total sample size of 2846. Studies were coded for mean SPA between physical activity participants and non-physical activity participants. Moderator variables related to demographic and study characteristics were also coded. Using Hunter and Schmidt's (2004) protocol, statistical artifacts were corrected. Results indicate that, practically speaking, those who were physically active reported lower levels of SPA than the comparison group (dcorr = -.12; SDeorr.-=-;22). Consideration of the magnitude of the ES, the SDeorr, and confidence interval suggests that this effect is not statistically significant. While most moderator analyses reiterated this trend, some differences were worth noting. Previous research has identified SPA to be especially salient for females compared to males, however, in the current investigation, the magnitude of the ES' s comparing physical activity participants to the comparison group was similar (deorr = -.24 for females and deorr = -.23 for males). Also, the type of physical activity was investigated, and results showed that athletes reported lower levels of SP A than the comparison group (deorr = -.19, SDeorr = .08), whereas exercisers reported higher levels of SPA than the comparison group (deorr = .13, SDeorr = .22). Results demonstrate support for the dispositional nature of SP A. Consideration of practical significance suggests that those who are involved in physical activity may experience slightly lower levels of SPA than those not reporting physical activity participation. Results potentially offer support for the bi-directionality of the relationship between physical activity and SP A; however, a causality may not be inferred. More information about the type of physical activity (i.e., frequency/nature of exercise behaviour, sport classificationllevel of athletes) may help clarify the role of physical activity contexts on SPA.

Anxiety and learning / response behaviour in the context of intellectual problem solving by young children

Twenty-eight grade four students were ca.tegorized as either high or low anxious subjects as per Gillis' Child Anxiety Scale (a self-report general measure). In determining impulsivity in their response tendencies, via Kagan's Ma.tching Familiar Figures Test, a significant difference between the two groups was not found to exist. Training procedures (verbal labelling plus rehearsal strategies) were introduced in modification of their learning behaviour on a visual sequential memory task. Significantly more reflective memory recall behaviour was noted by both groups as a result. Furthermore, transfer of the reflective quality of this learning strategy produced significantly less impulsive response behaviour for high and low anxious subjects with respect to response latency and for low anxious subjects with respect to response accuracy.