Task-Related Deactivation and Functional Connectivity of the Subgenual Cingulate Cortex in Major Depressive Disorder

Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. Methods: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. Conclusion: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive–attentional processes

Functional brain imaging studies of youth depression: A systematic review

AbstractBackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression

The experience of young people receiving cognitive behavioural therapy for major depression : A qualitative study

Aim Major depressive disorder (MDD) has far reaching impacts for young people, their families and society. Cognitive behavioural therapy (CBT) is one of the first-line treatments for young people experiencing MDD; however, there is limited research examining how young people with MDD experience CBT. The aim of this study was to explore their experience and their views of this intervention. Methods We employed a qualitative research design, with semi-structured interviews and thematic analysis. Eight participants aged between 17 and 24 years who received CBT for MDD in a randomized controlled trial were recruited. Results Five themes were identified: the importance of relationship with clinician; the range of useful components within CBT; the ability for CBT to accommodate different techniques and presenting issues; the importance of checking in with clients during the process of therapy; and the impacts of MDD on therapy. Conclusions The findings highlight the importance of clinicians having a youth friendly and collaborative approach that allows a modular delivery of a range of CBT techniques to suit the client's presenting issue and formulation. There is a need to continually check how young people are responding to interventions, and to be aware of potential cognitive deficits and adjust therapy accordingly. This is a small study that provides insight into how young people with MDD experience CBT and avenues to explore for tailoring provision of CBT to enhance the therapeutic experience for this population

Referral in a routine Italian optometric examination: towards an evidence-based model.

Italian optometrists refract patients and prescribe optical appliances. The routine optometric examination that is currently conducted in Italy, however, does not include a comprehensive ocular health assessment. Like many other countries, in Italy ophthalmologists are solely responsible for the diagnosis and treatment of ocular pathologies, yet, the care an optometrist provides must be done with the aim of promoting the general and ocular health of patients seen in practice. Such scope has to be pursued using a close collaboration with ophthalmologists, ultimately facilitating the earliest medical diagnosis and minimisation of visual impairment. Referral represents the basis of optometrist-ophthalmologist collaboration, yet, no guidance is available to Italian optometrists indicating when referral is warranted. The purpose of this study was to identify the circumstances deserving a referral in a routine Italian optometric examination in adults, ultimately constituting preliminary evidence-based indications of a referral model oriented to enhance the ocular and general health of patients. A literature review was conducted on Pubmed and the Cochrane Library, mainly targeting high quality secondary literature such as systematic reviews, meta-analysis and clinical guidelines. Several reasons for referral were identified. Further, while a wide range of anomalies of the visual system are likely to be discovered by the Italian optometric examination, up to 20% of patients could suffer an underlying condition undetected by the current assessment. This results in the need to refer seemingly healthy patients if they have not attended routine ophthalmological examinations within optimal time frames. In Italy, and countries with similar settings, the referral is an essential instrument that optometrists must largely use to ensure early diagnosis of ocular conditions by ophthalmologists and minimisation of avoidable visual impairment

Neural mediators of subjective and autonomic responding during threat learning and regulation

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined the neural mediators of trial-by-trial skin conductance responses (SCR), and subjective reports of anxious arousal and valence in participants (n = 27; 17 females) performing a threat reversal task during ultra-high field functional magnetic resonance imaging. This allowed us to identify brain mediators during initial threat learning and subsequent threat reversal. Significant neural mediators of anxious arousal during threat learning included the dorsal anterior cingulate, anterior insula cortex (AIC), and ventromedial prefrontal cortex (vmPFC), subcortical regions including the amygdala, ventral striatum, caudate and putamen, and brain-stem regions including the pons and midbrain. By comparison, autonomic changes (SCR) were mediated by a subset of regions embedded within this broader circuitry that included the caudate, putamen and thalamus, and two distinct clusters within the vmPFC. The neural mediators of subjective negative valence showed prominent effects in posterior cortical regions and, with the exception of the AIC, did not overlap with threat learning task effects. During threat reversal, positive mediators of both subjective anxious arousal and valence mapped to the default mode network; this included the vmPFC, posterior cingulate, temporoparietal junction, and angular gyrus. Decreased SCR during threat reversal was positively mediated by regions including the mid cingulate, AIC, two sub-regions of vmPFC, the thalamus, and the hippocampus. Our findings add novel evidence to support distinct underlying neural processes facilitating autonomic and subjective responding during threat learning and threat reversal. The results suggest that the brain systems engaged in threat learning mostly capture the subjective (anxious arousal) nature of the learning process, and that appropriate responding during threat reversal is facilitated by participants engaging self- and valence-based processes. Autonomic changes (SCR) appear to involve distinct facilitatory and regulatory contributions of vmPFC sub-regions

Clergy work-related satisfactions in parochial ministry: the influence of personality and churchmanship

The aim of this study was to test several hypotheses that clergy work-related satisfaction could be better explained by a multidimensional rather than a unidimensional model. A sample of 1071 male stipendiary parochial clergy in the Church of England completed the Clergy Role Inventory, together with the short-form Revised Eysenck Personality Questionnaire. Factor analysis of the Clergy Role Inventory identified five separate clergy roles: Religious Instruction, Administration, Statutory Duties (conducting marriages and funerals), Pastoral Care, and Role Extension (including extra-parochial activities). Respondents also provided an indication of their predispositions on the catholic-evangelical and liberal-conservative dimensions. The significant associations of the satisfactions derived from each of the roles with the demographic, personality, and churchmanship variables were numerous, varied, and, with few exceptions, small in magnitude. Separate hierarchical regressions for each of the five roles indicated that the proportion of total variance explained by churchmanship was, in general, at least as great as that explained by personality, and was greater for three roles: Religious Instruction, Statutory Duties, and Role Extension. It was concluded that clergy satisfactions derived from different roles are not uniform and that churchmanship is at least as important as personality in accounting for clergy work satisfaction

Synthesis and Antiviral Activity of Fatty Acyl Conjugates of Remdesivir Against Severe Acute Respiratory Syndrome Coronavirus 2 and Ebola Virus

We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3′ position. Monofatty acyl conjugates, 3′-O-tetradecanoyl (4a) (IC50(VeroE6) = 2.3 μM; IC50(Calu3) = 0.24 μM), 3′-O-4-oxatetradodecanoyl (4b) (IC50(VeroE6) = 2.0 μM; IC50(Calu3) = 0.18 μM), and 3′-O-(12-ethylthiododecanoyl) (4e) (IC50(VeroE6) = 2.4 μM; IC50(Calu3) = 0.25 μM) derivatives exhibited less activity than RDV (IC50(VeroE6) = 0.85 μM; IC50(Calu3) = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b, 3e, and 4b, were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c, respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria.

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of $\textit{Synechocystis }$ sp. PCC 7002 and $\textit{Synechocystis }$ sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that $\textit{Synechocystis }$ sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.T.L. was supported by BBSRC Research Grant BB/J016985/1 to C.W.M. D.J.L-S. was supported by the Environmental Services Association Education Trust. L.L.B was supported by a BBSRC Doctoral Training Grant (BB/F017464/1)

Online and social networking interventions for the treatment of depression in young people: a systematic review

BACKGROUND: Major depression accounts for the greatest burden of all diseases globally. The peak onset of depression occurs between adolescence and young adulthood, and for many individuals, depression displays a relapse-remitting and increasingly severe course. Given this, the development of cost-effective, acceptable, and population-focused interventions for depression is critical. A number of online interventions (both prevention and acute phase) have been tested in young people with promising results. As these interventions differ in content, clinician input, and modality, it is important to identify key features (or unhelpful functions) associated with treatment outcomes. OBJECTIVE: A systematic review of the research literature was undertaken. The review was designed to focus on two aspects of online intervention: (1) standard approaches evaluating online intervention content in randomized controlled designs (Section 1), and (2) second-generation online interventions and services using social networking (eg, social networking sites and online support groups) in any type of research design (Section 2). METHODS: Two specific literature searches were undertaken. There was no date range specified. The Section 1 search, which focused on randomized controlled trials, included only young people (12-25 years) and yielded 101 study abstracts, of which 15 met the review inclusion criteria. The Section 2 search, which included all study design types and was not restricted in terms of age, yielded 358 abstracts, of which 22 studies met the inclusion criteria. Information about the studies and their findings were extracted and tabulated for review. RESULTS: The 15 studies identified in Section 1 described 10 trials testing eight different online interventions, all of which were based on a cognitive behavioral framework. All but one of the eight identified studies reported positive results; however, only five of the 15 studies used blinded interviewer administered outcomes with most trials using self-report data. Studies varied significantly in presentation of intervention content, treatment dose, and dropout. Only two studies included moderator or clinician input. Results for Section 2 were less consistent. None of the Section 2 studies reported controlled or randomized designs. With the exception of four studies, all included participants were younger than 25 years of age. Eight of the 16 social networking studies reported positive results for depression-related outcomes. The remaining studies were either mixed or negative. Findings for online support groups tended to be more positive; however, noteworthy risks were identified. CONCLUSIONS: Online interventions with a broad cognitive behavioral focus appear to be promising in reducing depression symptomology in young people. Further research is required into the effectiveness of online interventions delivering cognitive behavioral subcomponents, such as problem-solving therapy. Evidence for the use of social networking is less compelling, although limited by a lack of well-designed studies and social networking interventions. A range of future social networking therapeutic opportunities are highlighted