Emotion regulation difficulties in the relation between stress-related insomnia symptoms and brain response to emotional faces: An fMRI study.

The aim of the current study was to investigate whether the experience of insomnia symptoms per se and symptoms of insomnia due to stress are associated with an increased brain response to the presentation of emotional faces. In addition, we also examined whether the effect of these sleep difficulties on emotional reactivity at the brain level depends on the experience of emotion regulation (ER) difficulties. The current sample consisted of 37 individuals (20 females, 17 males) selected from a larger group of 120 respondents who completed a survey about sleep problems and ER difficulties. Our results indicate that the tendency to experience stress-related insomnia symptoms but not insomnia symptoms per se modulates brain responses to emotional facial expressions, especially in areas of the parietal cortex, insula, and surrounding opercular voxels. Furthermore, difficulties in ER might play an important role, as the effect of stress-related insomnia symptoms on most of these brain regions disappears when controlling for difficulties in ER. However, an effect in the insula was maintained during the presentation of angry faces, suggesting that stress-related insomnia symptoms may increase the brain response to anger in the insula relatively independent from difficulties in ER. These findings suggest that individuals affected by stress-related insomnia symptoms show an enhanced brain response when presented with emotional stimuli (either positive or negative) in brain areas associated with hyperarousal, which could represent a possible ER deficit in these individuals. Thus, interventions that focus on targeting ER difficulties might be effective in reducing the hyperarousal state in individuals affected by stress-related insomnia symptoms.

Resting state predicts neural activity during reward-guided decision making: An fMRI study on Balloon Analogue Risk Task.

In our previous work [8], we have shown that resting state (RS) functional connectivity metrics are significantly related with behavioural performance at Balloon Analogue Risk Task (BART). In the present study we investigated the hypothesis of an association between RS metrics and neural activity evoked by BART execution. A group-level whole-brain regression was run to assess whether RS metrics predict brain activation during the BART, in a sample of 35 young healthy adults (mean age 23 ± 2 years, 25 F). Results complete the previous findings showing that RS is also significantly associated with the neural activity during BART execution. Specifically, ALFF is positively associated with the activity of both the right inferior parietal lobule and the left caudate. These new results are coherent with previous evidence indicating RS abnormalities in clinical conditions characterised by symptoms of impulse control disorders, and further suggest that RS might be a stable predictor of both behavioural indices and neural correlates of impulsivity and of reward-guided decision-making.

Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin.

BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal 'excitatory-inhibitory' metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 .

The Role of Emotion Regulation Difficulties in the Relation Between Insomnia and Depressive Symptoms.

BACKGROUND: Emotion regulation (ER) difficulties have been reported to be more severe in individuals with insomnia symptoms compared with controls, which in turn might explain the experience of depressive symptoms in these individuals. To our knowledge, no study has directly tested this hypothesis; therefore, we aimed to examine the indirect association between possible insomnia disorder and depressive symptoms through ER difficulties. METHOD: One hundred and seven individuals with possible insomnia disorder and 268 controls (based on a cutoff score on the Sleep Condition Indicator) completed measures of ER difficulties and depressive symptoms. RESULTS: As expected, individuals with possible insomnia disorder showed more severe depressive symptoms and ER difficulties compared with controls. Moreover, there was a significant indirect association between possible insomnia disorder and depressive symptoms through overall ER difficulties. CONCLUSION: ER difficulties were more severe in individuals with possible insomnia disorder and were further associated with more severe depressive symptoms. We speculate that by adding interventions aimed to develop ER abilities, Cognitive Behavioral Therapy for Insomnia (CBT-I) could become a more effective intervention for individuals with insomnia symptoms and associated emotional difficulties. LIMITATIONS: We used cross-sectional measures in our models of indirect associations.

You do not have to act to be impulsive: Brain resting-state activity predicts performance and impulsivity on the Balloon Analogue Risk Task.

OBJECTIVE: Impulsivity is a key, trait-like feature of the decision-making process. As personality traits are stable over time, we hypothesized that resting-state (RS) neural activity would predict individual impulsivity. METHODS: Thirty-five healthy individuals underwent fMRI scan during RS and subsequently performed the Balloon Analogue Risk Task (BART). In BART, impulsivity was inversely correlated to monetary earnings. A group-level whole-brain regression assessed the relationship between earnings at BART and RS evaluated by the Hurst Exponent, regional homogeneity; low frequency oscillation (LFO), (including the Amplitude of Low Frequency Fluctuations - ALFF- and the fractional Amplitude of Low Frequency Fluctuations -fALFF) and the Default Mode Network (DMN) functional connectivity. RESULTS: ALFF significantly correlates with total earnings in the ventral part of the ACC/MPFC (FWE corrected p < 0.05 (uncorrected p value <0.0005; cluster size: ≥10 voxels), while H significantly correlates with total earnings in the anterior insula and the part opercularis of the inferior frontal gyrus. CONCLUSIONS: These results suggest that impulsivity and ability to change strategies according to external cues are trait characteristics shaped in the RS's functional architecture that can be detected also when individuals are not engaged in decision-making tasks.

Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy.

Autism spectrum disorder (ASD) is a high cost neurodevelopmental condition; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies - including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown. Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites - markers of the brain's primary excitatory and inhibitory system - in both the 'typical' and autistic brain. Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design. We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the 'shift' in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group. Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.

The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD).

BACKGROUND: The potential benefits of cannabis and its major non-intoxicating component cannabidiol (CBD) are attracting attention, including as a potential treatment in neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the neural action of CBD, and its relevance to ASD, remains unclear. We and others have previously shown that response to drug challenge can be measured using functional magnetic resonance imaging (fMRI), but that pharmacological responsivity is atypical in ASD. AIMS: We hypothesized that there would be a (different) fMRI response to CBD in ASD. METHODS: To test this, task-free fMRI was acquired in 34 healthy men (half with ASD) following oral administration of 600 mg CBD or matched placebo (random order; double-blind administration). The 'fractional amplitude of low-frequency fluctuations' (fALFF) was measured across the whole brain, and, where CBD significantly altered fALFF, we tested if functional connectivity (FC) of those regions was also affected by CBD. RESULTS: CBD significantly increased fALFF in the cerebellar vermis and the right fusiform gyrus. However, post-hoc within-group analyses revealed that this effect was primarily driven by the ASD group, with no significant change in controls. Within the ASD group only, CBD also significantly altered vermal FC with several of its subcortical (striatal) and cortical targets, but did not affect fusiform FC with other regions in either group. CONCLUSION: Our results suggest that, especially in ASD, CBD alters regional fALFF and FC in/between regions consistently implicated in ASD. Future studies should examine if this affects the complex behaviours these regions modulate.

Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder.

There is increasing interest in the use of cannabis and its major non-intoxicating component cannabidiol (CBD) as a treatment for mental health and neurodevelopmental disorders, such as autism spectrum disorder (ASD). However, before launching large-scale clinical trials, a better understanding of the effects of CBD on brain would be desirable. Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). However, differences in glutamate and GABA pathways in ASD mean that the response to CBD in people with and without ASD may be not be the same. To test whether CBD 'shifts' glutamate and GABA levels; and to examine potential differences in this response in ASD, we used magnetic resonance spectroscopy (MRS) to measure glutamate (Glx = glutamate + glutamine) and GABA+ (GABA + macromolecules) levels in 34 healthy men (17 neurotypicals, 17 ASD). Data acquisition commenced 2 h (peak plasma levels) after a single oral dose of 600 mg CBD or placebo. Test sessions were at least 13 days apart. Across groups, CBD increased subcortical, but decreased cortical, Glx. Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant. Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently in ASD. Our results do not speak to the efficacy of CBD. Future studies should examine the effects of chronic administration on brain and behaviour, and whether acute brain changes predict longer-term response.

Common Sleep, Psychiatric, and Somatic Problems According to Work Schedule: an Internet Survey in an Eastern European Country.

PURPOSE: A wide range of health problems was investigated, aiming to identify the presence and severity of a set of self-reported and common sleep, psychiatric, and somatic health problems among working professionals in four different shift schedules (morning, evening, rotating, and day) in several cities in Romania. METHODS: A heterogeneous sample of 488 workers of different professions completed online a battery of tests, namely the Basic Nordic Sleep Questionnaire, the Parasomnia Questionnaire, the Epworth Sleepiness Scale, and the Patient Health Questionnaire, designed to identity symptoms of insomnia, sleepiness, snoring, parasomnia, as well as of depression, anxiety, eating, somatoform, and alcohol use disorders, respectively. The timing and the duration of the sleep, along with the presence of high blood pressure and type 2 diabetes mellitus were also inquired. The prevalence of the different health problems in relation to the type of shift schedule was evaluated with the Pearson Chi-square test. ANOVA was used to calculate the significance of the difference between the means, while associations with different health problems were estimated by binary logistic regression. RESULTS: The most common mental health problems were depression (26%), insomnia (20%), alcohol misuse (18%), and anxiety (17%). No significant differences based on the type of shift in terms of health problems were found, except for high blood pressure and symptoms of panic disorder that were more frequently reported by the workers in early morning shifts. Together with the workers in rotating shifts, they also reported increased sleepiness, poorer sleep quality, and shorter sleep duration. In contrast, the workers in evening shifts reported less severe health problems and longer sleep duration. CONCLUSIONS: Working in early morning shifts was found to be associated with poorer health outcomes, while working in rotating and early morning shifts with more severe sleep-related problems.

A blind spot on the global mental health map: a scoping review of 25 years' development of mental health care for people with severe mental illnesses in central and eastern Europe.

Just over 25 years have passed since the major sociopolitical changes in central and eastern Europe; our aim was to map and analyse the development of mental health-care practice for people with severe mental illnesses in this region since then. A scoping review was complemented by an expert survey in 24 countries. Mental health-care practice in the region differs greatly across as well as within individual countries. National policies often exist but reforms remain mostly in the realm of aspiration. Services are predominantly based in psychiatric hospitals. Decision making on resource allocation is not transparent, and full economic evaluations of complex interventions and rigorous epidemiological studies are lacking. Stigma seems to be higher than in other European countries, but consideration of human rights and user involvement are increasing. The region has seen respectable development, which happened because of grassroots initiatives supported by international organisations, rather than by systematic implementation of government policies.

Sleep quality, chronotype and social jetlag differentially associate with symptoms of attention deficit hyperactivity disorder in adults.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder which has been associated with sleep and circadian rhythm disturbances. Numerous studies have linked evening circadian typology with traits and behaviours associated with the disorder, although a precise reason for this relationship has not been clarified. The current study examines ADHD symptoms, impulsivity, cognitive failures, sleep quality and chronotype in a cohort of healthy young adults (N = 396). Results show significant, small magnitude associations between mid-point of sleep on free days, social jetlag (SJL) and ADHD symptoms and impulsivity, although not with cognitive failures. Similarly, sleep quality is also associated with ADHD symptoms and impulsivity. Group-wise approaches show that higher SJL is associated with significantly more ADHD symptoms and impulsivity, and later mid-sleep on free days is also associated with more ADHD symptoms. Stepwise multiple linear regression reveals that, when controlling for age and sex, SJL but not mid-sleep on free days is a significant predictor of ADHD symptoms and impulsivity. These results indicate that SJL may be an important factor to consider when exploring circadian rhythm associations with ADHD symptoms.

Sleep hygiene awareness: its relation to sleep quality and diurnal preference.

BACKGROUND: Sleep hygiene is a core component for psychological treatments of insomnia and essential for maintaining a satisfactory sleep. Our study aimed to measure the sleep hygiene awareness and the self-reported quality of sleep among three age groups (young adults, adults and middle-aged adults) and to determine their relation. We also measured their relation with diurnal preference. METHODS: Using an online questionnaire, we surveyed six hundred fifty two participants, recruited nationwide from the community and from the students in three main cities in Romania. RESULTS: Sleep hygiene awareness was moderate on the whole and significantly worse in young adults (compared to the other age groups) and in those complaining of poor sleep (compared to those with good sleep). Sleep quality was average and linked positively with diurnal preference (the more evening oriented, the poorer the sleep). Diurnal preference was not found to play a role regarding sleep hygiene awareness. CONCLUSIONS: Our results suggest that better sleep hygiene awareness does not necessarily guarantee better sleep quality and that it may actually be an indicator of dissatisfaction with the obtained sleep.

Assessment of SOMNOwatch plus EEG for sleep monitoring in healthy individuals.

Polysomnography (PSG) is still the standard in sleep monitoring, with several alternative solutions developed, including simplified electroencephalographic recorders such as SOMNOwatch plus EEG. In this study, we aimed to evaluate the validity of the recordings and of the analysis of the proprietary software of this solution, compared to PSG and semiautomatic scoring, respectively. From thirteen healthy adults, we recorded 27 nights simultaneously with a classical EEG amplifier (NeuroScan system) and the ambulatory SOMNOwatch plus EEG. Thereafter, we performed (semi-) automatic sleep analysis in Somnolyzer 24x7 and DOMINO Light (SOMNOwatch software). AASM scoring sensitivity of SOMNOwatch plus EEG, as revealed by Somnolyzer 24x7, was 97.79%, and specificity 87.19%. Paired T tests revealed no significant differences between the recordings of the two EEG systems, with intraclass correlation coefficients ranging from moderate to very good. When data were analyzed in DOMINO Light, sensitivity was 92.99% and specificity was 80.90%. Our data suggest that SOMNOwatch plus EEG might serve as a reliable instrument for recording sleep in healthy individuals, but its proprietary software, DOMINO Light, still seems to have weaknesses in terms of automatic sleep staging.

Sleep disturbance, circadian preference and symptoms of adult attention deficit hyperactivity disorder (ADHD).

Inattention is a core symptom of attention deficit hyperactivity disorder (ADHD) and one of the main impairments resulting from insomnia disorders. These disorders have also been reported to be linked with disturbances in circadian rhythms and with increased eveningness. To explore these associations, more than 550 adults were surveyed across Romania. Using self-reported questionnaires, the presence and severity of ADHD and insomnia symptoms were determined, together with sleep and circadian typology parameters. ADHD symptoms were more frequent and severe among younger individuals. Subjects with probable ADHD complained more frequently of sleep disturbance of the insomnia type (more than 50 %) and reported shorter sleep durations and longer sleep latencies and more frequent unwanted awakenings. Individuals likely to suffer from ADHD and/or insomnia disorder were significantly more evening oriented than controls. Inattention was associated with both insomnia and eveningness, while impulsivity was associated with poor sleep. Hyperactivity and sleep timing were associated with poor sleep only in probable insomnia group. These findings highlight the reciprocal links between ADHD symptoms, sleep and diurnal preference.