Individual differences in striatal and amygdala response to emotional faces are related to symptom severity in social anxiety disorder

Crane, Natania A.; Chang, Fini; Kinney, Kerry L.; Klumpp, Heide

doi:10.1016/j.nicl.2021.102615

Cited by 13 publications

(10 citation statements)

References 62 publications

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“…This was not completely unexpected, given that we previously found no effect of age in males during the CS (Dulka et al, 2020). It has been suggested that a more appropriate time point to assess trace fear recall is SFP time point because this is when the animal should have learned to expect a shock and, thus, is a conditional response to the auditory cue (Gilmartin et al, 2012). During the SFP time point, 22-mo males froze less than 15-mo males (P = 0.02) and tended to freeze less than 3-mo males (P = 0.065).…”

Section: Resultssupporting

confidence: 52%

Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex

Dulka

Trask

Helmstetter

2021

Front. Aging Neurosci.

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Aging is marked by an accumulation of damaged and modified brain proteins, and the ubiquitin-proteasome system (UPS) is important for cellular protein degradation. Recent work has established a critical role for the UPS in memory and synaptic plasticity, but the role of the UPS in age-related cognitive decline remains poorly understood. We trained young, middle-aged, and aged male and female rats using trace fear conditioning (TFC) to investigate the effects of age and sex on memory. We then measured markers of UPS-related protein degradation (phosphorylation of the Rpt6 proteasome regulatory subunit and K48-linked polyubiquitination) using western blots. We found that aged males, but not aged females, showed behavioral deficits at memory retrieval. Aged males also displayed reduced phosphorylation of the Rpt6 proteasome subunit and accumulation of K48 in the basolateral amygdala, while aged females displayed a similar pattern in the medial prefrontal cortex. These findings suggest that markers of UPS function are differentially affected by age and sex in a brain region-dependent manner. Together these results provide an important step toward understanding the UPS and circuit-level differences in aging males and females.

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Section: Resultssupporting

confidence: 52%

Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex

Dulka

Trask

Helmstetter

2021

Front. Aging Neurosci.

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“…However, these early FC changes were not associated with symptom changes at either early/during treatment or post-treatment, suggesting that other neural processes that are not captured by resting state measures may be more closely related to symptom change. For example, other studies have shown SAD symptoms were associated with brain activity in fear, reward, attention, or executive control circuitry (Crane, Chang, Kinney, & Klumpp, 2021; Mizzi, Pedersen, Lorenzetti, Heinrichs, & Labuschagne, 2021). Further studies could assess other downstream processes by evaluating pre- to post-treatment fMRI scan, which may be more closely related to symptom change.…”

Section: Discussionmentioning

confidence: 99%

Resting state connectivity predictors of symptom change during gaze-contingent music reward therapy of social anxiety disorder

Lee

Lazarov

Dolan³

et al. 2022

Psychol. Med.

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Background Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT). Methods Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2–3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2–3), and post-treatment. Results SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2–3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2–3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval. Conclusion We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

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“…Amygdala dysfunction is closely related to the occurrence of psychiatric diseases such as anxiety disorder [25][26][27][28]. Considerable evidence from animal models and humans has consistently shown the hyperactivation of amygdala neurons in response to stress exposure [29,30].…”

Section: Stress and Brainmentioning

confidence: 99%

Connectivity and functional characterization of the mouse contralateral projecting neurons in basolateral amygdala

Zou¹,

Shang²,

Liu³

et al. 2022

Stress and Brain

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Amygdala is widely known as a critical neural hub for modulating negative emotions such as fear and anxiety. Recent studies have shown that the basolateral amygdala (BLA) has reciprocal innervation, which plays an important role in regulating social interaction and associative memory. However, the connectivity pattern and functional role of the contralateral projecting BLA neurons in stress-related anxiety are not fully understood. Here, using the virus tracing strategy, we first characterized the connectivity pattern of the contralateral projecting neurons in BLA. Then, we examined the effect of stress on the functional changes of those specific neuronal populations using a mouse model of inescapable footshock stress. The results showed that the fibers of the contralateral projecting BLA neurons labeled by enhanced green fluorescent protein (EGFP) have no collateral projections to the ipsilateral or contralateral hippocampus. Interestingly, they have some collateral projections to the ipsilateral medial prefrontal cortex. Behavioral results showed that footshock stress increases the anxiety-like behavior in mice; however, the excitatory synaptic transmission and intrinsic excitability of the contralateral projecting BLA neurons measured by whole-cell patch clamp recording did not change after stress exposure. In conclusion, our results indicate that contralateral projecting BLA neurons may not contribute to footshock stress-related anxiety-like behavior.

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Individual differences in striatal and amygdala response to emotional faces are related to symptom severity in social anxiety disorder

Cited by 13 publications

References 62 publications

Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex

Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex

Resting state connectivity predictors of symptom change during gaze-contingent music reward therapy of social anxiety disorder

Connectivity and functional characterization of the mouse contralateral projecting neurons in basolateral amygdala

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