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.

Anxiety and joint hypermobility association: a systematic review

BACKGROUND: Anxiety disorders are often associated with several non-psychiatric medical conditions. Among the clinical conditions found in association with anxiety stands out the joint hypermobility (JH). OBJECTIVES: To carry out a systematic review of the clinical association between anxiety disorders and JH. METHOD: A survey was conducted in MEDLINE, PsychINFO, LILACS e SciELO databases up to December 2011. We searched for articles using the keywords 'anxiety', 'joint' and 'hypermobility' and Boolean operators. The review included articles describing empirical studies on the association between JH and anxiety. The reference lists of selected articles were systematically hand-searched for other publications relevant to the review. RESULTS: Seventeen articles were included in the analysis and classified to better extract data. We found heterogeneity between the studies relate to the methodology used. Most of the studies found an association between anxiety features and JH. Panic disorder/agoraphobia was the anxiety disorder associated with JH in several studies. Etiological explanation of the relationship between anxiety and JH is still controversial. CONCLUSION: Future research in large samples from the community and clinical setting and longitudinal studies of the association between anxiety and HA and the underlying biological mechanisms involved in this association are welcome.

Social anxiety and negative early life events in university students

INTRODUCTION: There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. METHODS: In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. RESULTS: Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). CONCLUSION: University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

Outlining new frontiers for the comprehension of obsessive-compulsive disorder: a review of its relationship with fear and anxiety

Anxiety is an important component of the psychopathology of the obsessive-compulsive disorder (OCD). So far, most interventions that have proven to be effective for treating OCD are similar to those developed for other anxiety disorders. However, neurobiological studies of OCD came to conclusions that are not always compatible with those previously associated with other anxiety disorders. OBJECTIVES: The aim of this study is to review the degree of overlap between OCD and other anxiety disorders phenomenology and pathophysiology to support the rationale that guides research in this field. RESULTS: Clues about the neurocircuits involved in the manifestation of anxiety disorders have been obtained through the study of animal anxiety models, and structural and functional neuroimaging in humans. These investigations suggest that in OCD, in addition to dysfunction in cortico-striatal pathways, the functioning of an alternative neurocircuitry, which involves amygdalo-cortical interactions and participates in fear conditioning and extinction processes, may be impaired. CONCLUSION: It is likely that anxiety is a relevant dimension of OCD that impacts on other features of this disorder. Therefore, future studies may benefit from the investigation of the expression of fear and anxiety by OCD patients according to their type of obsessions and compulsions, age of OCD onset, comorbidities, and patterns of treatment response.

Prevalence of anxiety, depression and quality of life in HTLV-1 infected patients

The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. Objective: The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. Material and Methods: This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame’s Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. Results: The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. Conclusion: A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients.

Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis

Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis.

Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence

Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system