Delayed fear extinction in individuals with insomnia disorder.

Study Objectives: Insomnia increases the risk for anxiety disorders that are also associated with fear-extinction deficits. We compared activation of fear and extinction networks between insomnia disorder (ID) without comorbidity and good sleepers (GS). Methods: Twenty-three ID participants age- and sex-matched to 23 GS participants completed 14 days of actigraphy and diaries, three nights of ambulatory polysomnography and a 2-day fear conditioning and extinction paradigm. Fear conditioning and extinction learning occurred on the first day, followed 24 hours later by extinction recall. Blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) signal and skin conductance responses (SCR) were recorded. Nineteen participants per group produced usable fMRI data. Beta weights from areas where activation differed between groups were regressed against sleep and psychophysiological measures. SCR was compared between groups at various stages of the paradigm. Results: During fear conditioning, both ID (N = 19) and GS (N = 19) activated fear-related structures. Across extinction learning, ID (N = 19) demonstrated little change, whereas GS (N = 16) activated both fear and extinction-related areas, including the hippocampus, insula, dorsal anterior cingulate (dACC), and ventromedial prefrontal (vmPFC) cortices. During extinction recall, while GS (N = 17) demonstrated limited activation, ID (N = 16) activated regions similar to those previously activated in GS (vmPFC, dACC, insula). Sleep quality was predictive of activations seen at various stages of the paradigm. SCR data suggested ID were more physiologically reactive than GS. Conclusions: Across extinction learning, GS but not ID activated both fear and extinction-related networks. At extinction recall, ID engaged similar regions whereas GS no longer did so. Individuals with ID may show a delayed acquisition of fear extinction memories.

Effects of post-exposure naps on exposure therapy for social anxiety.

Exposure therapy for social anxiety disorder (SAD) utilizes fear extinction, a memory process enhanced by sleep. We investigated whether naps following exposure sessions might improve symptoms and biomarkers in response to social stress in adults undergoing 5-week exposure-based group SAD therapy. Thirty-two participants aged 18-39 (18 females) with SAD were randomized. Before and after treatment, participants completed the Liebowitz Social Anxiety Scale (LSAS) and underwent a Trier Social Stress Test with psychophysiological monitoring (mpTSST) that included skin conductance (SCL), electromyographic (EMG) and electrocardiographic recording, and an auditory startle procedure while anticipating the social stressor. At sessions 3 and 4, exposure was followed by either a 120-min polysomnographically monitored sleep opportunity (Nap, N = 17) or wakefulness (Wake, N = 15). Primary hypotheses about SAD symptom change (LSAS) and EMG blink-startle response failed to differ with naps, despite significant symptom improvement (LSAS) with therapy. Some secondary biomarkers, however, provided preliminary support for enhanced extinction learning with naps, with trend-level Time (pre-, post-treatment) × Arm interactions and significant reduction from pre- to post treatment in the Nap arm alone for mpTSST SCL and salivary cortisol rise. Because of the small sample size and limited sleep duration, additional well-powered studies with more robust sleep interventions are indicated.

Resting state functional connectivity in primary insomnia, generalized anxiety disorder and controls.

Sleep abnormalities are extremely common in anxiety disorders and may contribute to their development and persistence. Their shared pathophysiological mechanisms could thus serve as biomarkers or targets for novel therapeutics. Individuals with Primary Insomnia were age- and sex-matched to controls and to persons with Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and actigraphy. All participants completed state-anxiety and neuroticism inventories. Whole-brain connectivity of 6 fear- and extinction-related seeds were compared between the 3 groups using ANOVA. The only significant between-group main effect was seen for connectivity between the left amygdala seed and a bilateral cluster in the rostral anterior cingulate cortex. The latter is believed to exert top-down control over amygdala activity and their interaction may thus constitute an emotion regulatory circuit. This connectivity was significantly greatest in controls while Primary Insomnia was intermediate between that of controls and Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean connectivity decreased with poorer sleep. Across all 3 groups, connectivity decreased with greater neuroticism and pre-scan anxiety. Decreased top-down control of the amygdala may increase risk of developing an anxiety disorder with preexisting Primary Insomnia.