Modulation of the Endocannabinoid and Oxytocinergic Systems as a Potential Treatment Approach for Social Anxiety Disorder

Santos, Rafael G. dos; Osório, Flávia de Lima; Martín‐Santos, Rocío; Zuardi, Antônio Waldo; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre de Souza

doi:10.1007/s40263-019-00669-5

Cited by 14 publications

(13 citation statements)

References 54 publications

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“…Social anxiety disorder (also known as social phobia) is characterized by a persistent fear of social situations in which the person would be exposed to possible scrutiny by others [1], with a lifetime prevalence of 2% to 7% in adults and a prevalence up to 25% in university students [2]. Individuals who have social anxiety disorder are typically hypervigilant for real or imagined feedback and more likely to rely on safety behaviors, aiming to avoid any stimuli or events that could trigger their social anxiety [3,4].…”

Section: Introductionmentioning

confidence: 99%

Virtual Reality–Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task

Hur¹,

Shin²,

Jung³

et al. 2021

JMIR Ment Health

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Background Although it has been well demonstrated that the efficacy of virtual reality therapy for social anxiety disorder is comparable to that of traditional cognitive behavioral therapy, little is known about the effect of virtual reality on pathological self-referential processes in individuals with social anxiety disorder. Objective We aimed to determine changes in self-referential processing and their neural mechanisms following virtual reality treatment. Methods We recruited participants with and without a primary diagnosis of social anxiety disorder to undergo clinical assessments (Social Phobia Scale and Post-Event Rumination Scale) and functional magnetic resonance imaging (fMRI) scans. Participants with social anxiety disorder received virtual reality–based exposure treatment for 6 sessions starting immediately after baseline testing. After the sixth session, participants with social anxiety disorder completed follow-up scans during which they were asked to judge whether a series of words (positive, negative, neutral) was relevant to them. Results Of 25 individuals with social anxiety disorder who participated in the study, 21 completed the sessions and follow-up; 22 control individuals also participated. There were no significant differences in age (P=.36), sex (P=.71), or handedness (P=.51) between the groups. Whole-brain analysis revealed that participants in the social anxiety disorder group had increased neural responses during positive self-referential processing in the medial temporal and frontal cortexes compared with those in the control group. Participants in the social anxiety disorder group also showed increased left insular activation and decreased right middle frontal gyrus activation during negative self-referential processing. After undergoing virtual reality–based therapy, overall symptoms of the participants with social anxiety disorder were reduced, and these participants exhibited greater activity in a brain regions responsible for self-referential and autobiographical memory processes while viewing positive words during postintervention fMRI scans. Interestingly, the greater the blood oxygen level dependent changes related to positive self-referential processing, the lower the tendency to ruminate on the negative events and the lower the social anxiety following the virtual reality session. Compared with that at baseline, higher activation was also found within broad somatosensory areas in individuals with social anxiety disorder during negative self-referential processing following virtual reality therapy. Conclusions These fMRI findings might reflect the enhanced physiological and cognitive processing in individuals with social anxiety disorder in response to self-referential information. They also provide neural evidence of the effect of virtual reality exposure therapy on social anxiety and self-derogation.

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Section: Introductionmentioning

confidence: 99%

Virtual Reality–Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task

Hur¹,

Shin²,

Jung³

et al. 2021

JMIR Ment Health

View full text Add to dashboard Cite

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“…Social fear makes even the simplest daily task challenging and distressful and literally disconnects individuals afflicted from others and society. Unfortunately, there are no satisfactory therapeutic options currently available (Stein and Stein, 2008;Dos Santos et al, 2019). The pathological mechanism underlying SAD is undetermined partly due to a lack of specific animal models (Toth et al, 2012.…”

Section: Introductionmentioning

confidence: 99%

Prefrontal Disinhibition in Social Fear: A Vital Action of Somatostatin Interneurons

Wang

Tian

Zeng

et al. 2020

Front. Cell. Neurosci.

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Social fear and avoidance of social partners and social situations represent the core behavioral symptom of Social Anxiety Disorder (SAD), a prevalent psychiatric disorder worldwide. The pathological mechanism of SAD remains elusive and there are no specific and satisfactory therapeutic options currently available. With the development of appropriate animal models, growing studies start to unravel neuronal circuit mechanisms underlying social fear, and underscore a fundamental role of the prefrontal cortex (PFC). Prefrontal cortical functions are implemented by a finely wired microcircuit composed of excitatory principal neurons (PNs) and diverse subtypes of inhibitory interneurons (INs). Disinhibition, defined as a break in inhibition via interactions between IN subtypes that enhances the output of excitatory PNs, has recently been discovered to serve as an efficient strategy in cortical information processing. Here, we review the rodent animal models of social fear, the prefrontal IN diversity, and their circuits with a particular emphasis on a novel disinhibitory microcircuit mediated by somatostatin-expressing INs in gating social fear behavior. The INs subtype distinct and microcircuit-based mechanism advances our understanding of the etiology of social fear and sheds light on developing future treatment of neuropsychiatric disorders associated with social fear.

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“…They are also found in glial cells as well, and to a much lesser extent, in neurons of several brain regions such as the amygdala, hippocampus, cerebral cortex, hypothalamus and cerebellum [ 83 , 84 ]. However, others reported that the comparison of CB2 with CB1 gene expression in the CNS resulted in relatively insignificant levels of CB2 receptor expression [ 85 , 86 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, impairment in social behavior may be a functional outcome both in BPD and in other psychiatric disorders (such as anxiety and schizophrenia). Given that CBD has been shown to improve social withdrawal in animal models of schizophrenia [ 152 - 153 ] and anxiety [ 85 ], the social aspects of BPD may be positively affected by CBD.…”

Section: Introductionmentioning

confidence: 99%

“…It has been recently reported that the yet unknown doses of CBD optimal for psychiatric treatment severely limit its indication, although safety has been validated. Moreover, small samples in the few published human studies on the treatment with CBD in psychiatric disorders do not yet warrant a general indication [ 85 ]. To the best of our knowledge, there is no published RCT on CBD treatment of BPD, and no established animal model for BPD.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the Endocannabinoid System in Borderline Personality Disorder: Corticolimbic and Hypothalamic Perspectives

Ferber

Hazani

Shoval

et al. 2021

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: Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships, cognitive disturbance (e.g. dissociation and suicidal thoughts) and maladaptive behaviors. BPD has a high rate of comorbidity with other mental disorders and high burden on society. In this review, we focus on two compromised brain regions in BPD – the hypothalamus and the corticolimbic system, emphasizing the involvement and potential contribution of the endocannabinoid system (ECS) to improvement in symptoms and coping. The hypothalamus-regulated endocrine axes (hypothalamic pituitary – gonadal, thyroid & adrenal) have been found to be dysregulated in BPD. There is also substantial evidence for limbic system structural and functional changes in BPD, especially in amygdala and hippocampus, including cortical regions within the corticolimbic system. Extensive expression of CB1 and CB2 receptors of the ECS has been found in limbic regions and the hypothalamus. This opens new windows of opportunity for treatment with cannabinoids such as cannabidiol (CBD) as no other pharmacological treatment has shown long-lasting improvement in the BPD population to date. This review aims to show the potential role of the ECS in BPD patients through their most affected brain regions, the hypothalamus and the corticolimbic system. The literature reviewed does not allow for general indications of treatment with CBD in BPD. However, there is enough knowledge to indicate a treatment ratio of high level of CBD to low level of THC. A randomized controlled trial investigating the efficacy of cannabinoid based treatments in BPD is warranted.

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Modulation of the Endocannabinoid and Oxytocinergic Systems as a Potential Treatment Approach for Social Anxiety Disorder

Cited by 14 publications

References 54 publications

Virtual Reality–Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task

Virtual Reality–Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task

Prefrontal Disinhibition in Social Fear: A Vital Action of Somatostatin Interneurons

Targeting the Endocannabinoid System in Borderline Personality Disorder: Corticolimbic and Hypothalamic Perspectives

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