Human Anxiety Research Articles

Lines of doubt, fear and tenderness in the work of José Luis Cuevas and Tommi Parrish

ABSTRACT How is it that within the graphic tradition particular images, often composed of only lines and washes on paper, can convey complex states of being and speak to questions of existence? For the philosopher Søren Kierkegaard (1813–55) to exist is to face uncertainties and commit oneself passionately to a way of life, which emerges only through the acting-out of that commitment. This paper considers the work of two very different artists and aims to illuminate the common philosophical ground and expose significant differences. José Luis Cuevas was a Mexican self-taught artist who made drawings of human suffering. He began drawing fallible images of humanity at a very young age after a prolonged illness. He worked in opposition to established works of art in his home country. Tommi Parrish is a contemporary Australian transgender comic book artist whose work often traverses gaps in human understanding, sexuality, identity and anxiety to convey tenderness and humour. The work of Tommi is noteworthy in terms of how sequenced imagery builds on often wordless tension between awkward individuals and the situation they find themselves in. I seek to reveal an alternative narrative layer for each artist by considering gestures within their work.

Effects of ecgonine methyl ester on cognition in scopolamine-impaired and aged rats.

Searches for antidotes to cocaine, and for cognition enhancers potentially applicable to Alzheimer's disease, have revealed a novel regulatory site on nicotinic acetylcholine receptors. In the presence of an agonist, inhibitors binding to this site changed the ion channel equilibrium from the open-channel form towards the closed form. Other, related, molecules could bind to the site without changing the equilibrium. These latter compounds were predicted to displace the inhibitors without affecting receptor function per se. These compounds alleviated the inhibition. One of them is ecgonine methyl ester (EME), which is generally described as inactive, but this work suggested a beneficial effect on cognition. This in vivo study tested for cognitive enhancement by EME in scopolamine-impaired, and aged, rats. Memory was the primary endpoint, but thigmotaxis became an important secondary endpoint in the light of observations made during the study. Impaired cognition was pharmacologically induced by scopolamine in young rats, and spontaneously present in aged rats. Learning ability before and after administration of EME was tested in Morris water maze protocols. Concentrations of EME in the brain and plasma were analyzed by gas chromatography-mass spectrometry. A single dose of EME reversed scopolamine impairment, indicating involvement of acetylcholine receptors. Longer-term treatment improved cognition in aged rats, with enhanced rates of learning in the absence of an exogenous cognition-impairing compound. Impairment returned with a new challenge; the improvement could be re-established with continued dosing. EME also reversed thigmotaxis seen in aged rats; thigmotaxis is believed to indicate anxiety. The concentrations of EME in the brain proved adequate drug exposure. Since other investigators have shown cognition impairment caused by cocaine in aged rats, this work shows that cocaine and EME have opposite effects in Morris water maze models. EME might induce cognitive enhancement and relief of anxiety in cocaine-impaired humans, and in other cognitive disorders.

Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4–5- month-old) and old (11–13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4–6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.

Transcranial Direct Current Stimulation in Patients with Anxiety: Current Perspectives.

Anxiety is one of the most prevalent and debilitating psychiatric conditions worldwide. Pharmaco- and psycho-therapies have been employed in the treatment of human anxiety to date. Yet, either alone or in combination, unsatisfactory patient outcomes are prevalent, resulting in a considerable number of people whose symptoms fail to respond to conventional therapies with symptoms remaining after intervention. The demand for new therapies has given birth to several noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) has arisen as a promising tool and has been proven to be safe and well tolerated for the treatment of many diseases, including chronic pain, depression, and anxiety. Here, reports of the use of tDCS in anxiety disorders in human patients were reviewed and summarized. A literature search was conducted in mid-2019, to identify clinical studies that evaluated the use of tDCS for the treatment of anxiety behavior. The PubMed, Web of Science, and Scielo and PsycInfo databases were explored using the following descriptors: “anxiety”, “anxious behavior”, “tDCS”, and “transcranial direct current stimulation”. Among the selected articles, considerable variability in the type of tDCS treatment applied in interventions was observed. Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combination with others.

CITIZENSHIP IN THE CONDITIONS OF SOCIAL TRANSFORMATIONS IN SOCIETY

The article analyzes the theoretical aspects of the manifestation of the psychological phenomenon of anxiety. The concept is defined: anxiety, fear and peculiarities of anxiety as a personal property. It has been found that anxiety has also been studied at different levels, such as: the normal (optimal) level of anxiety that is perceived as necessary for effective adaptation, the level of adaptive anxietyand excessively high levels that are perceived as a non-adaptive response . Anxiety, anxiety, fear, panic, horror are phenomena that are often present in our mental lives. They can be different in intensity, duration, structure from mild short-term anxiety to paralyzing horror, forming a diverse range of experiences that accompany a variety of life events: illness, conflict, unpleasant and unexpected events. The scientific tradition of analyzing human anxiety mainly captures the following basic approaches: typical mental state as a response to probable threats; a special mental state that most often manifests itself in crisis or extreme conditions; the specific property of the person; multifaceted emotional experience of predominantly negative orientation; the realization of fear and the like. It is established that the problem of anxiety is a well-developed scientific topic in works related to the study of individual-typological characteristics of a person. It is concluded that among many forms of verbal regulation and self-programming, scientists call self-satisfaction, autonomy, dedication, self-help, self-realization, self-realization . It is revealed that the results of the ascertainment experiment state that the high level of personal anxiety in early adolescence is largely caused by personality, adaptation and motivational factors, which indicates the need to find ways, forms and methods of specially organized corrective action for preventive action in order to correct the high level of personality anxiety of young men. Key words: anxiety, anxiety, personality, emotional state, fear, cognition, emotions, phenomenon. Accepted: 30.11.2019 Reviewed: 09.12 .2019 Published: 19.12 .2019 DOI: http://doi.org/10.31108/3.2019.3.4.4 * * * * * Download/read PDF

Differential Effects of Serotonin Transporter Genotype on Anxiety-Like Behavior and Cognitive Judgment Bias in Mice.

In humans, the short allele of a common polymorphism in the serotonin transporter (5-HTT) gene is associated with a higher risk to develop depression and anxiety disorders. Furthermore, individuals carrying this allele are characterized by negative judgment biases, as they tend to interpret ambiguous information in a more pessimistic way. 5-HTT knockout mice, lacking the 5-HTT gene either homo- or heterozygously, provide a widely used model organism for the study of symptoms related to human anxiety disorders. In the present study, we aimed to prove the anxiety-like phenotype of the 5-HTT mouse model, and to investigate whether 5-HTT genotype also causes differences in judgment bias. While our results confirm that homozygous 5-HTT knockout mice display highest levels of anxiety-like behavior, it was decreased in heterozygous mice. Against our expectations, we did not detect differences in the animals’ judgment bias. These results indicate that at least in mice the association between 5-HTT genotype and judgment bias is not straightforward and that other factors, including multiple genes as well as environmental influences, are implicated in the modulation of judgment biases. More research is needed to gain further insights into their function as potential endophenotypes for psychopathology.

The bradykinin system in stress and anxiety in humans and mice

Pharmacological research in mice and human genetic analyses suggest that the kallikrein-kinin system (KKS) may regulate anxiety. We examined the role of the KKS in anxiety and stress in both species. In human genetic association analysis, variants in genes for the bradykinin precursor (KNG1) and the bradykinin receptors (BDKRB1 and BDKRB2) were associated with anxiety disorders (p < 0.05). In mice, however, neither acute nor chronic stress affected B1 receptor gene or protein expression, and B1 receptor antagonists had no effect on anxiety tests measuring approach-avoidance conflict. We thus focused on the B2 receptor and found that mice injected with the B2 antagonist WIN 64338 had lowered levels of a physiological anxiety measure, the stress-induced hyperthermia (SIH), vs controls. In the brown adipose tissue, a major thermoregulator, WIN 64338 increased expression of the mitochondrial regulator Pgc1a and the bradykinin precursor gene Kng2 was upregulated after cold stress. Our data suggests that the bradykinin system modulates a variety of stress responses through B2 receptor-mediated effects, but systemic antagonists of the B2 receptor were not anxiolytic in mice. Genetic variants in the bradykinin receptor genes may predispose to anxiety disorders in humans by affecting their function.

Vagus nerve stimulation produces immediate dose-dependent anxiolytic effect in rats

BackgroundChronic vagus nerve stimulation (VNS) attenuates anxiety in rats and humans. However, it is unclear whether VNS can promote acute anxiolytic effects. Here we examined short-term anxiolytic effects of VNS using single or multiple trains in rats submitted to a battery of tests. MethodsThree groups of rats were implanted with VNS cuffs and tested for anxiety using the elevated plus maze (EPM), novelty suppressed feeding (NSF), and acoustic startle response (ASR), after receiving either one or five VNS trains (0.4 mA/30 Hz/30‑sec), or sham stimulation. ResultsBoth single and multiple VNS trains reduced state anxiety as measured using the EPM, but only multiple trains reduced anxiety in the EPM and NSF. VNS did not decrease arousal as measured using the ASR. LimitationsThe anxiolytic effects of VNS may be differently influenced by test order or prior-exposure to stress. VNS did not affect startle responses in naïve rats but the present findings do not determine whether VNS would affect startle responses that are potentiated by fear or anxiety. ConclusionA single VNS train can produce an anxiolytic-like effect in the EPM minutes later, an effect that is not observed in the NSF. Delivering 5 VNS trains restores the immediate effects across tests of anxiety, indicating that more trains produce a more robust anxiolytic effect. The lack of effects on ASR suggests that VNS affects state anxiety but not baseline arousal in naïve rats. We suggest that the anxiolytic effect of VNS can increase tolerability and reduce dropout in exposure-based therapies.

A Microglia Sublineage Protects from Sex-Linked Anxiety Symptoms and Obsessive Compulsion

Aberrant microglia activity is associated with many neurological and psychiatric disorders, yet our knowledgeabout the pathological mechanisms is incomplete. Here, we describe a genetically defined microgliasublineage in mice which has the ability to suppress obsessive compulsion and anxiety symptoms. These microglia derive from precursors expressing the transcription factor Hoxb8. Selective ablation of Hoxb8-lineage microglia or the Hoxb8 gene revealed that dysfunction in this cell type causes severe over-grooming and anxiety-like behavior andstress responses. Moreover, we show that the severity of the pathology is set by female sex hormones. Together, our findings reveal that different microglia lineages have distinct functions. In addition, our data suggest a mechanistic link between biological sex and genetics, two major risk factors for developing anxiety and related disorders in humans.

Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior.

Stressful life events are major environmental risk factors for anxiety disorders, although not all individuals exposed to stress develop clinical anxiety. The molecular mechanisms underlying the influence of environmental effects on anxiety are largely unknown. To identify biological pathways mediating stress-related anxiety and resilience to it, we used the chronic social defeat stress (CSDS) paradigm in male mice of two inbred strains, C57BL/6NCrl (B6) and DBA/2NCrl (D2), that differ in their susceptibility to stress. Using a multi-omics approach, we identified differential mRNA, miRNA and protein expression changes in the bed nucleus of the stria terminalis (BNST) and blood cells after chronic stress. Integrative gene set enrichment analysis revealed enrichment of mitochondrial-related genes in the BNST and blood of stressed mice. To translate these results to human anxiety, we investigated blood gene expression changes associated with exposure-induced panic attacks. Remarkably, we found reduced expression of mitochondrial-related genes in D2 stress-susceptible mice and in exposure-induced panic attacks in humans, but increased expression of these genes in B6 stress-susceptible mice. Moreover, stress-susceptible vs. stress-resilient B6 mice displayed more mitochondrial cross-sections in the post-synaptic compartment after CSDS. Our findings demonstrate mitochondrial-related alterations in gene expression as an evolutionarily conserved response in stress-related behaviors and validate the use of cross-species approaches in investigating the biological mechanisms underlying anxiety disorders.

White matter correlates of contextual pavlovian fear extinction and the role of anxiety in healthy humans

Pavlovian contextual fear extinction is viewed as an important mechanism for behavioral adaptation in everyday life, including challenging situations of stress and anxiety. It has frequently been shown to relate to the function of brain areas like the hippocampus and medial prefrontal cortex (mPFC), while the role of structural properties, like white matter tracts in these regions, has been less studied. We employed diffusion tensor imaging to determine structural white matter connectivity (cingulum and uncinate fasciculus) correlates of contextual pavlovian fear extinction indicators measured through functional magnetic resonance imaging, skin conductance responses (SCRs) and self-reports of valence, arousal and contingency in 93 healthy individuals. Higher fractional anisotropy values in the hippocampal cingulum were significantly related to higher SCRs during extinction of contextual conditioned responses (explained variance: 11.2%) as an indicator of extinction deficits on the level of physiological arousal. However, FA was neither related to any of the other fear extinction measures, nor did we find associations with functional extinction responses in the hippocampus or mPFC. Trait anxiety was a significant moderator of the SCR-hippocampal cingulum association (explained variance: 32.09%). The data add evidence for a critical role of the hippocampal formation in contextual pavlovian extinction, and, together with the strong effect of trait anxiety, may have implications for the development of anxiety disorders where contextual extinction learning deficits are observed.

Blockade of the cholecystokinin CCK-2 receptor prevents the normalization of anxiety levels in the rat

Cholecystokinin (CCK), through the CCK-2 receptor, exerts complex effects on anxiety. While CCK agonists are panicogenic, CCK-2 antagonists fail to alleviate human anxiety. Preclinical studies with CCK-2 antagonists are also inconsistent because their anxiolytic effects largely depend on the behavioral paradigm and antecedent stress. The controversy might be accounted by the neuromodulatory role for CCK in anxiety which is ill-defined. If this is its actual role, blocking CCK-2 will have carry-over effects on the anxiety baseline over time. To test this hypothesis, the consequences of acute administration of the CCK-2 antagonist Ly225.910 (0.1 mg Kg−1) was evaluated in the temporal expression of aversion toward exploration-conflicting tasks. Ly225.910 effects were evaluated in rats exposed to the elevated plus-maze (EPM) twice, an approach-avoidance anxiety-like test. While LY225.910-treated rats had less anxiety than vehicle-treated rats, the difference was reversed during the EPM retest 24 h later without drug. Moreover, Ly225.910 effects in stress-induced cognitive impairment was measured giving the novel-object discrimination (NOD) test to rats not habituated to the exploration apparatus to elicit neophobia. After a first encounter with objects (“old”), Ly225.910-treated rats did not recognize the “novel” object introduced 6 h later. Ly225.910-exposed rats did not discriminate the new location of the “novel object” when it was repositioned in the arena 24 h later. Ly225.910-treated rats also failed to explore objects. In line with its neuromodulatory role, aversive carry-over effects of Ly225.910 suggest that CCK-2 activation by endogenous CCK, rather than triggering anxiety, may return the anxiety state to its normal level.

Reconstruction and Analysis of Gene Networks of Human Neurotransmitter Systems Reveal Genes with Contentious Manifestation for Anxiety, Depression, and Intellectual Disabilities.

Background: The study of the biological basis of anxiety, depression, and intellectual disabilities in humans is one of the most actual problems of modern neurophysiology. Of particular interest is the study of complex interactions between molecular genetic factors, electrophysiological properties of the nervous system, and the behavioral characteristics of people. The neurobiological understanding of neuropsychiatric disorders requires not only the identification of genes that play a role in the molecular mechanisms of the occurrence and course of diseases, but also the understanding of complex interactions that occur between these genes. A systematic study of such interactions obviously contributes to the development of new methods of diagnosis, prevention, and treatment of disorders, as the orientation to allele variants of individual loci is not reliable enough, because the literature describes a number of genes, the same alleles of which can be associated with different, sometimes extremely different variants of phenotypic traits, depending on the genetic background, of their carriers, habitat, and other factors. Results: In our study, we have reconstructed a series of gene networks (in the form of protein–protein interactions networks, as well as networks of transcription regulation) to build a model of the influence of complex interactions of environmental factors and genetic risk factors for intellectual disability, depression, and other disorders in human behavior. Conclusion: A list of candidate genes whose expression is presumably associated with environmental factors and has potentially contentious manifestation for behavioral and neurological traits is identified for further experimental verification.

Effect of low dose vitamin C on public speaking stress during group presentation

Vitamin C ascorbic acid is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. The purpose of this study is to investigate the effect of vitamin C on decreasing the level of public speaking stress in term of heart rate, blood pressure and stress assessment. A purposive sample of (45) were included in this randomized placebo-placebo trial study, that was conducted at Faculty of nursing / university of Kufa. Public speaking stress was determined by a questionnaire scale developed from (public speaking anxiety scale). Study group included volunteer students who took a dose of 500 mg a day of vitamin C for one week before a group presentation, while the placebo group is given a placebo before one week of before a group presentation. The result indicated that the blood pressure (systolic and diastolic) before presentation between the two groups ( student group and placebo) was not significantly different. In relation to heart rate, a significant decrease (p< 0.05) was recorded in student group as compared to placebo. The student group has recorded significant difference in many items of stress assessment when comparing to placebo (e.g. increase of heart rate, dry mouth, GIT cramps and anxiety due to fear from failure). The assessment of presentation stress between the two groups (student group and placebo) was determined by means of scores. The results revealed that there is a significant difference (P< 0.05) in presentation stress between student group and placebo group. It was concluded that student group which took 500 mg vitamin C for one week express less presentation stress. The most stress signs that has been improved by vitamin C intake are: increase of heart rate, dry mouth, GIT cramps and anxiety due to fear from failure.

New Frontiers in Anxiety Research: The Translational Potential of the Bed Nucleus of the Stria Terminalis.

After decades of being overshadowed by the amygdala, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Converging research indicates that the amygdala and BNST play complementary but distinct functional roles during threat processing, with the BNST specializing in the detection of a potential threat to maintain hypervigilance and anxiety, while the amygdala responds to the perceived presence of an aversive stimulus (i.e., fear). Therefore, given that human anxiety is largely driven by future-oriented hypothetical threats that may never occur, studies involving the BNST stand at the forefront of essential future research with the potential to bring about profound insights for understanding and treating anxiety disorders. In this article, we present a narrative review on the BNST, summarizing its roles in anxiety and the stress response and highlighting the most recent advances in the clinical realm. Furthermore, we discuss oversights in the current state of anxiety research and identify avenues for future exploration.

Cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion.

Few studies have used matched affective paradigms to compare humans and non-human primates. In monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. Given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. A total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesus monkeys (Macaca mulatta) completed matched behavioral paradigms. Four monkeys received bilateral excitotoxic amygdala lesions and four served as unoperated controls. Compared to healthy youth, anxious youth exhibited increased pupillary constriction in response to emotional and non-emotional distractors (F(1,48) = 6.28, P=0.02, η2p= 0.12). Pupillary response was associated significantly with anxiety symptoms severity (F(1,48) = 5.59, P=0.02, η2p= 0.10). As hypothesized, lesioned monkeys exhibited the opposite pattern i.e. decreased pupillary constriction in response to distractors, compared to unoperated control monkeys (F(1,32) = 24.22, P<0.001, η2= 0.33). Amygdala lesioned monkeys and youth with anxiety disorders show opposite patterns of pupil constriction in the context of an affective distractor task. Such findings suggest the presence of altered amygdala circuitry functioning in anxiety. Future lesion and human neuroimaging work might examine the way in which specific amygdala sub-nuclei and downstream circuits mediate these effects.

Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences.

Animal models of anxiety disorders are important for elucidating neurobiological defense mechanisms. However, animal models are limited when it comes to understanding the more complex processes of anxiety that are unique to humans (e.g., worry) and to screen new treatments. In this review, we outline how the Experimental Psychopathology approach, based on experimental models of anxiety in healthy subjects, can mitigate these limitations and complement research in animals. Experimental psychopathology can bridge basic research in animals and clinical studies, as well as guide and constrain hypotheses about the nature of psychopathology, treatment mechanisms, and treatment targets. This review begins with a brief review of the strengths and limitations of animal models before discussing the need for human models of anxiety, which are especially necessary to probe higher-order cognitive processes. This can be accomplished by combining anxiety-induction procedures with tasks that probe clinically relevant processes to identify neurocircuits that are potentially altered by anxiety. The review then discusses the validity of experimental psychopathology and introduces a methodological approach consisting of five steps: (1) select anxiety-relevant cognitive or behavioral operations and associated tasks, (2) identify the underlying neurocircuits supporting these operations in healthy controls, 3) examine the impact of experimental anxiety on the targeted operations in healthy controls, (4) utilize findings from step 3 to generate hypotheses about neurocircuit dysfunction in anxious patients, and 5) evaluate treatment mechanisms and screen novel treatments. This is followed by two concrete illustrations of this approach and suggestions for future studies.

First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog

There is a well-established relationship between joint hypermobility and anxiety in humans, that has not previously been investigated in other species. A population of 5575 assistance dogs were scored for both hip hypermobility and 13 behaviour characteristics using previously validated methods. Our results suggest a positive association between hip joint hypermobility and emotional arousal in domestic dogs, which parallel results found in people.

Leptin, Anxiety Symptoms, and Hypothalamic-Pituitary-Adrenal Axis Activity among Drug-Free, Female Suicide Attempters

Background: Dysregulation of leptin secretion and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the pathophysiology of suicide. Preclinical and clinical studies have shown interactions between the HPA axis and leptin. There is also evidence for a negative relationship between leptin and anxiety in humans. However, these possible associations have not been studied in individuals with attempted suicide. Objectives: To examine the relationship between leptin, HPA axis activity, and anxiety in individuals with a recent suicide attempt. Method: Sixty-nine individuals with a recent suicide attempt (n = 37 females; n = 32 males) were recruited and subjected to the Dexamethasone Suppression Test (DST), lumbar puncture, and evaluation with the Comprehensive Psychopathological Rating Scale from which the Brief Scale for Anxiety (BSA) was derived. Leptin was analyzed in cerebrospinal fluid (CSF) and cortisol in serum. Leptin was corrected for body mass index (BMI) by dividing CSF-leptin by BMI (CSF-leptin/BMI). Due to gender-related differences in leptin secretion and HPA axis activity, calculations were made for males and females separately. Results: Significant differences were only found among females; CSF-leptin/BMI levels correlated significantly and negatively with BSA (p < 0.05), pre-DST cortisol, and post-DST serum cortisol at 8 a.m. and 3 p.m. (all p < 0.05). Furthermore, CSF-leptin/BMI was significantly lower in nonsuppressors of dexamethasone as compared to suppressors (p < 0.05). Conclusions: These findings suggest that in females with a recent suicide attempt, low CSF leptin may be related to symptoms of anxiety and a hyperactive HPA axis.

Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening

Functional coupling between the basolateral amygdala (BLA) and areas of the dorsal prefrontal cortex (dPFC) have been implicated in the generation of negative affective states under stressful conditions; however, the synaptic and molecular mechanisms by which stress increases BLA-dPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here we show that BLA-dPFC functional connectivity is enhanced under conditions of potential threat and correlates with trait anxiety in humans and that acute stress exposure increases anxiety-like behavior and synaptic strength within a reciprocal BLA-dPFC-BLA subcircuit in mice. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-dPFC synapses and the collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and dPFC and the translation of environmental stress to affective pathology.