Endophenotyping social cognition in the broader autism phenotype.

Relatives of individuals with autism spectrum disorder (ASD) may display milder social traits of the broader autism phenotype (BAP) providing potential endophenotypic markers of genetic risk for ASD. We performed a case-control comparison to quantify social cognition and pragmatic language difficulties in the BAP (n = 25 cases; n = 33 controls) using the Faux Pas test (FPT) and the Goldman-Eisler Cartoon task. Using deep phenotyping we then examined patterns of inheritance of social cognition in two large multiplex families and the spectrum of performance in 32 additional families (159 members; n = 51 ASD, n = 87 BAP, n = 21 unaffected). BAP individuals showed significantly poorer FPT performance and reduced verbal fluency with the absence of a compression effect in social discourse compared to controls. In multiplex families, we observed reduced FPT performance in 89% of autistic family members, 63% of BAP relatives and 50% of unaffected relatives. Across all affected families, there was a graded spectrum of difficulties, with ASD individuals showing the most severe FPT difficulties, followed by the BAP and unaffected relatives compared to community controls. We conclude that relatives of probands show an inherited pattern of graded difficulties in social cognition with atypical faux pas detection in social discourse providing a novel candidate endophenotype for ASD.

Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype.

Families comprising many individuals with Autism Spectrum Disorders (ASD) may carry a dominant predisposing mutation. We implemented rigorous phenotyping of the "Broader Autism Phenotype" (BAP) in large multiplex ASD families using a novel endophenotype approach for the identification and characterisation of distinct BAP endophenotypes. We evaluated ASD/BAP features using standardised tests and a semi-structured interview to assess social, intellectual, executive and adaptive functioning in 110 individuals, including two large multiplex families (Family A: 30; Family B: 35) and an independent sample of small families (n = 45). Our protocol identified four distinct psychological endophenotypes of the BAP that were evident across these independent samples, and showed high sensitivity (97%) and specificity (82%) for individuals classified with the BAP. Patterns of inheritance of identified endophenotypes varied between the two large multiplex families, supporting their utility for identifying genes in ASD.

A systematic review and meta-analysis of psychological functioning in chronic tinnitus.

Chronic tinnitus, the phenomenon of a chronic ringing in the ears or head, has a significant negative impact on an individual's health and wellbeing. Despite this, there is no cure or consensus regarding factors maintaining ongoing awareness of the sensation in this population, or the severity of its impact. We aimed to comprehensively and systematically review behavioural studies investigating the psychological functioning of adults with chronic tinnitus. We identified 64 papers meeting our search criteria for inclusion, which are reviewed with regard to psychological factors involved with the presence of chronic tinnitus, and those relating to its severity. The majority of studies assessed the presence and impact of chronic tinnitus with regard to emotional wellbeing (n=59), with a more recent interest in cognitive functioning (n=16). A subset of 36 studies was included in meta-analyses investigating the relationships between emotional wellbeing and the presence and impact of chronic tinnitus using random-effects models. Our findings indicate the presence of chronic tinnitus may be associated with reduced cognitive functioning, particularly attention, and with reduced emotional wellbeing, particularly anxiety and depression. We also found consistent evidence indicating severity of chronic tinnitus is associated with a broad range of psychological features, primarily symptoms of depression and anxiety. We recommend investigating the complexity of the relationships between emotional wellbeing, cognitive functioning, and chronic tinnitus using a range of methodologies to further elucidate the role of psychological functioning in chronic tinnitus.

Identification of a Neurocognitive Mechanism Underpinning Awareness of Chronic Tinnitus.

Tinnitus (ringing in the ears) is a common auditory sensation that can become a chronic debilitating health condition with pervasive effects on health and wellbeing, substantive economic burden, and no known cure. Here we investigate if impaired functioning of the cognitive control network that directs attentional focus is a mechanism erroneously maintaining the tinnitus sensation. Fifteen people with chronic tinnitus and 15 healthy controls matched for age and gender from the community performed a cognitively demanding task known to activate the cognitive control network in this functional magnetic resonance imaging study. We identify attenuated activation of a core node of the cognitive control network (the right middle frontal gyrus), and altered baseline connectivity between this node and nodes of the salience and autobiographical memory networks. Our findings indicate that in addition to auditory dysfunction, altered interactions between non-auditory neurocognitive networks maintain chronic tinnitus awareness, revealing new avenues for the identification of effective treatments.

Cognitive Mechanisms in Chronic Tinnitus: Psychological Markers of a Failure to Switch Attention.

The cognitive mechanisms underpinning chronic tinnitus (CT; phantom auditory perceptions) are underexplored but may reflect a failure to switch attention away from a tinnitus sound. Here, we investigated a range of components that influence the ability to switch attention, including cognitive control, inhibition, working memory and mood, on the presence and severity of CT. Our participants with tinnitus showed significant impairments in cognitive control and inhibition as well as lower levels of emotional well-being, compared to healthy-hearing participants. Moreover, the subjective cognitive complaints of tinnitus participants correlated with their emotional well-being whereas complaints in healthy participants correlated with objective cognitive functioning. Combined, cognitive control and depressive symptoms correctly classified 67% of participants. These results demonstrate the core role of cognition in CT. They also provide the foundations for a neurocognitive account of the maintenance of tinnitus, involving impaired interactions between the neurocognitive networks underpinning attention-switching and mood.

Psychological mediators of chronic tinnitus: The critical role of depression.

BACKGROUND: Maintenance of chronic tinnitus has been proposed to result from a vicious cycle of hypervigilance occurring when a phantom sound is associated with anxiety and limbic system overactivity. Depression, obsessive-compulsiveness, illness attitudes and coping strategies are known to impact tinnitus, but their relationship with the vicious cycle is unknown. As such, we aimed to identify psychological mediators of the vicious cycle. We also examined the relationship between coping strategies and any identified mediators to facilitate the translation of our research to treatment settings. METHODS: We comprehensively assessed a heterogeneous community sample of 81 people with chronic tinnitus who completed measures assessing their tinnitus and psychological wellbeing. Specifically, we examined the mediating role of depressive symptoms, illness attitudes, and obsessive-compulsiveness in the vicious cycle. RESULTS: While the predicted relationship between tinnitus handicap and anxiety was observed, this was fully mediated by depressive symptoms. In addition, we identified avoidant behaviours and self-blame as maladaptive coping strategies in people with chronic tinnitus and depressive symptoms, identifying potential new treatment targets. LIMITATIONS: This work requires replication in a clinical cohort of people with chronic tinnitus, and further investigations of the role of coping strategies. CONCLUSIONS: These results extend our understanding of the complex role of psychology in the experience of tinnitus, highlighting the importance of depressive symptoms that may be underpinned by functional disruption of specific neurocognitive networks. We have also identified depressive symptoms and maladaptive coping strategies as new treatment targets to improve the health wellbeing of people with chronic tinnitus.