Objective: The unprecedented occurrence of a global pandemic is accompanied by both physical and psychological burdens that may impair quality of life. Research relating to COVID-19 aims to determine the effects of the pandemic on vulnerable populations who are at high risk of developing negative health or psychosocial outcomes. Having an ongoing medical condition during a pandemic may lead to greater psychological distress. Increased psychological distress may be due to preventative public health measures (e.g. lockdown), having an ongoing medical condition, or a combination of these factors. Methods: This study analyses data from an online cross-sectional national survey of adults in Ireland and investigates the relationship between comorbidity and psychological distress. Those with a medical condition (n=128) were compared to a control group without a medical condition (n=128) and matched according to age, gender, annual income, education, and work status during COVID-19. Participants and data were obtained during the first public lockdown in Ireland (27.03.2020–08.06.2020). Results: Individuals with existing medical conditions reported significantly higher levels of anxiety (p<.01) and felt less gratitude (p≤.001). Exploratory analysis indicates that anxiety levels were significantly associated with illness perceptions specific to COVID-19. Post-hoc analysis reveal no significant difference between the number of comorbidities and condition type (e.g. respiratory disorders). Conclusion: This research supports individualised supports for people with ongoing medical conditions through the COVID-19 pandemic, and has implications for the consideration of follow-up care specifically for mental health. Findings may also inform future public health policies and post-vaccine support strategies for vulnerable populations.

The muscarinic-cholinergic system is involved in the pathophysiology of bipolar disorder (BD), and contributes to attention and the top-down and bottom-up cognitive and affective mechanisms of emotional processing, functionally altered in BD. Emotion processing can be assessed by the ability to inhibit a response when the content of the image is emotional. Impaired regulatory capacity of cholinergic neurotransmission conferred by reduced M2-autoreceptor availability is hypothesized to play a role in elevated salience of negative emotional distractors in euthymic BD relative to individuals with no history of mood instability. Thirty-three euthymic BD type-I (DSM-V-TR) and 50 psychiatrically-healthy controls underwent functional magnetic resonance imaging (fMRI) and an emotion-inhibition paradigm before and after intravenous cholinergic challenge using the acetylcholinesterase inhibitor, physostigmine (1 mg), or placebo. Mood, accuracy, and reaction time on either recognizing or inhibiting a response associated with an image involving emotion and regional functional activation were examined for effects of cholinergic challenge physostigmine relative to placebo, prioritizing any interaction with the diagnostic group. Analyses revealed that (1) at baseline, impaired behavioral performance was associated with lower activation in the anterior cingulate cortex in BD relative to controls during emotion processing; (2) physostigmine (vs. placebo) affected behavioral performance during the inhibition of negative emotions, without altering mood, and increased activation in the posterior cingulate cortex in BD (vs. controls); (3) In BD, lower accuracy observed during emotion inhibition of negative emotions was remediated by physostigmine and was associated with cingulate cortex overactivation. Our findings implicate abnormal regulation of cholinergic neurotransmission in the cingulate cortices in BD, which may mediate exaggerated emotional salience processing, a core feature of BD.

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Background: Graph theory applied to brain networks is an emerging approach to understand the brains' topological associations with human cognitive ability. Despite well-documented cognitive impairments in bipolar disorder (BD) and recent reports of altered anatomical network organisation, the association between connectivity and cognitive impairments in BD remains unclear. Methods: We examined the role of anatomical network connectivity derived from T1and diffusion-weighted magnetic resonance imaging in impaired cognitive performance in individuals with BD (n=32) compared to healthy controls (n=38). Fractional anisotropy-and number of streamlines-weighted anatomical brain networks were generated by mapping constrained spherical deconvolutionreconstructed white matter between 86 cortical/subcortical bilateral brain regions delineated in the individual's own coordinate space. Intelligence and executive function were investigated as distributed functions using measures of global, rich-club and interhemispheric connectivity while memory and social cognition were examined in relation to subnetwork connectivity. Results: Lower executive functioning related to higher global clustering coefficient in bipolar participants, and lower IQ performance may present with a differential relationship between global and interhemispheric efficiency in BD relative to controls. Spatial recognition memory accuracy and response times were similar between diagnostic groups and associated with basal ganglia and thalamus interconnectivity and connectivity within extended anatomical subnetworks in all participants. No anatomical subnetworks related to episodic memory, short-term memory or social cognition generally or differently in BD. Conclusions: Results demonstrate selective influence of subnetwork patterns of connectivity in underlying cognitive performance generally and abnormal global topology underlying discrete cognitive impairments in BD.

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