Psychiatry - Research Publications

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    Altered task-related decoupling of the rostral anterior cingulate cortex in depression.
    Leonards, CA ; Harrison, BJ ; Jamieson, AJ ; Agathos, J ; Steward, T ; Davey, CG (Elsevier BV, 2024)
    Dysfunctional activity of the rostral anterior cingulate cortex (rACC) - an extensively connected hub region of the default mode network - has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression ('deactivation') - an essential feature of rACC function - during external task engagement in depression. Specifically, we aimed to explore neural patterns of functional decoupling and coupling with the rACC during its task-driven suppression. We enrolled 81 15- to 25-year-old young people with moderate-to-severe major depressive disorder (MDD) before they commenced a 12-week clinical trial that assessed the effectiveness of cognitive behavioral therapy plus either fluoxetine or placebo. Ninety-four matched healthy controls were also recruited. Participants completed a functional magnetic resonance imaging face matching task known to elicit rACC suppression. To identify brain regions associated with the rACC during its task-driven suppression, we employed a seed-based functional connectivity analysis. We found MDD participants, compared to controls, showed significantly reduced 'decoupling' of the rACC with extended task-specific regions during task performance. Specifically, less decoupling was observed in the occipital and fusiform gyrus, dorsal ACC, medial prefrontal cortex, cuneus, amygdala, thalamus, and hippocampus. Notably, impaired decoupling was apparent in participants who did not remit to treatment, but not treatment remitters. Further, we found MDD participants showed significant increased coupling with the anterior insula cortex during task engagement. Our findings indicate that aberrant task-related rACC suppression is associated with disruptions in adaptive neural communication and dynamic switching between internal and external cognitive modes that may underpin maladaptive cognitions and biased emotional processing in depression.
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    What do Australian consumers with lived experience of bipolar disorder want from early intervention services?
    Gates, J ; Bendall, S ; Tremain, H ; Shelton, C ; Hammond, D ; Macneil, C ; McGorry, P ; Berk, M ; Cotton, S ; Murray, G ; Ratheesh, A (SAGE PUBLICATIONS LTD, 2024-03)
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    An analysis of real-time suicidal ideation and its relationship with retrospective reports among young people with borderline personality disorder
    Andrewes, HE ; Cavelti, M ; Hulbert, C ; Cotton, SM ; Betts, JK ; Jackson, HJ ; McCutcheon, L ; Gleeson, J ; Davey, CG ; Chanen, AM (WILEY, 2024-02-20)
    INTRODUCTION: This study aimed to analyze the real-time variability of suicidal ideation intensity and the relationship between real-time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). METHODS: Young people (15-25-year olds) with BPD (N = 46), recruited from two government-funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. RESULTS: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real-time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. CONCLUSION: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week.
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    A longitudinal study of childhood maltreatment, subcortical development, and subcortico-cortical structural maturational coupling from early to late adolescence.
    Rakesh, D ; Elzeiny, R ; Vijayakumar, N ; Whittle, S (Cambridge University Press (CUP), 2023-12)
    BACKGROUND: Examining neurobiological mechanisms that may transmit the effects of childhood maltreatment on mental health in youth is crucial for understanding vulnerability to psychopathology. This study investigated associations between childhood maltreatment, adolescent structural brain development, and mental health trajectories into young-adulthood. METHODS: Structural magnetic resonance imaging data was acquired from 144 youth at three time points (age 12, 16, and 18 years). Childhood maltreatment was reported to occur prior to the first scan. Linear mixed models were utilized to examine the association between total childhood maltreatment, neglect, abuse and (i) amygdala and hippocampal volume development, and (ii) maturational coupling between amygdala/hippocampus volume and the thickness of prefrontal regions. We also examined whether brain development mediated the association between maltreatment and depressive and anxiety symptoms trajectories from age 12 to 28. RESULTS: Total maltreatment, and neglect, were associated with positive maturational coupling between the amygdala and caudal anterior cingulate cortex (cACC), whereby at higher and lower levels of amygdala growth, maltreatment was associated with lower and higher PFC thinning, respectively. Neglect was also associated with maturational coupling of the hippocampus with prefrontal regions. While positive amygdala-cACC maturational coupling was associated with greater increases in anxiety symptoms, it did not significantly mediate the association between maltreatment and anxiety symptom trajectories. CONCLUSION: We found maltreatment to be associated with altered patterns of coupling between subcortical and prefrontal regions during adolescence, suggesting that maltreatment is associated with the development of socio-emotional neural circuitry. The implications of these findings for mental health require further investigation.
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    Unraveling the associations between unhealthy lifestyle behaviors and mental health in the general adult Chinese population: A cross-sectional study.
    Wong, VW-H ; Yiu, EK-L ; Ng, CH ; Sarris, J ; Ho, FY-Y (Elsevier BV, 2024-03-15)
    BACKGROUND: This study examined the cumulative risk of unhealthy lifestyle behaviors and the associations between overall lifestyle and common mental disorders (CMDs), insomnia, stress, health-related quality of life (HRQOL), and functional impairment. Additionally, the treatment preferences for managing CMDs and insomnia were examined. METHODS: A survey was conducted on 1487 Chinese Hong Kong adults, assessing their lifestyle behaviors (i.e., diet and nutrition, substance use, physical activity, stress management, restorative sleep, social support, and environmental exposures), mental health-related outcomes, and treatment preferences via a vignette. RESULTS: The findings revealed significant additive relationships between the number of 'worse' lifestyle domains and the risk of all outcomes. A healthier overall lifestyle was significantly associated with reduced risks of all outcomes (AORs = 0.88 to 0.93). Having healthier practices in diet and nutrition, substance use, stress management, restorative sleep, and social support domains were significantly associated with lower risks of all outcomes (AORs = 0.93 to 0.98), except that substance use was not significantly associated with stress. Physical activity was inversely associated with only depressive symptoms (AOR = 0.98), anxiety symptoms (AOR = 0.99), and stress (AOR = 0.99). Environmental exposures were not significantly associated with functional impairment but with all other outcomes (AORs = 0.98 to 0.99). Besides, lifestyle interventions (55 %) were significantly more preferred for managing CMDs and insomnia relative to psychotherapy (35.4 %) and pharmacotherapy (9.6 %). CONCLUSIONS: Our findings underscore the importance of considering lifestyle factors when managing CMDs, insomnia, stress, HRQOL, and functional impairment, with a particular emphasis on adopting a multicomponent treatment approach.
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    A multivariate cognitive approach to predict social functioning in recent onset psychosis in response to computerized cognitive training
    Walter, N ; Wenzel, J ; Haas, SS ; Squarcina, L ; Bonivento, C ; Ruef, A ; Dwyer, D ; Lichtenstein, T ; Bastruek, O ; Stainton, A ; Antonucci, LA ; Brambilla, P ; Wood, SJ ; Upthegrove, R ; Borgwardt, S ; Lencer, R ; Meisenzahl, E ; Salokangas, RKR ; Pantelis, C ; Bertolino, A ; Koutsouleris, N ; Kambeitz, J ; Kambeitz-Ilankovic, L (PERGAMON-ELSEVIER SCIENCE LTD, 2024-01-10)
    Clinical and neuroimaging data has been increasingly used in recent years to disentangle heterogeneity of treatment response to cognitive training (CT) and predict which individuals may achieve the highest benefits. CT has small to medium effects on improving cognitive and social functioning in recent onset psychosis (ROP) patients, who show the most profound cognitive and social functioning deficits among psychiatric patients. We employed multivariate pattern analysis (MVPA) to investigate the potential of cognitive data to predict social functioning improvement in response to 10 h of CT in patients with ROP. A support vector machine (SVM) classifier was trained on the naturalistic data of the Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study sample to predict functioning in an independent sample of 70 ROP patients using baseline cognitive data. PRONIA is a part of a FP7 EU grant program that involved 7 sites across 5 European countries, designed and conducted with the main aim of identifying (bio)markers associated with an enhanced risk of developing psychosis in order to improve early detection and prognosis. Social functioning was predicted with a balanced accuracy (BAC) of 66.4% (Sensitivity 78.8%; Specificity 54.1%; PPV 60.5%; NPV 74.1%; AUC 0.64; P = 0.01). The most frequently selected cognitive features (mean feature weights > ± 0.2) included the (1) correct number of symbol matchings within the Digit Symbol Substitution Test, (2) the number of distracting stimuli leading to an error within 300 and 200 trials in the Continuous Performance Test and (3) the dynamics of verbal fluency between 15 and 30 s within the Verbal Fluency Test, phonetic part. Next, the SVM classifier generated on the PRONIA sample was applied to the intervention sample, that obtained 54 ROP patients who were randomly assigned to a social cognitive training (SCT) or treatment as usual (TAU) group and dichotomized into good (GF-S ≥ 7) and poor (GF-S < 7) functioning patients based on their level of Global Functioning-Social (GF-S) score at follow-up (FU). By applying the initial PRONIA classifier, using out-of-sample cross-validation (OOCV) to the sample of ROP patients who have undergone the CT intervention, a BAC of 59.3% (Sensitivity 70.4%; Specificity 48.1%; PPV 57.6%; NPV 61.9%; AUC 0.63) was achieved at T0 and a BAC of 64.8% (Sensitivity 66.7%; Specificity 63.0%; PPV 64.3%; NPV 65.4%; AUC 0.66) at FU. After SCT intervention, a significant improvement in predicted social functioning values was observed in the SCT compared to TAU group (P ≤0.05; ES[Cohens' d] = 0.18). Due to a small sample size and modest variance of social functioning of the intervention sample it was not feasible to predict individual response to SCT in the current study. Our findings suggest that the use of baseline cognitive data could provide a robust individual estimate of future social functioning, while prediction of individual response to SCT using cognitive data that can be generated in the routine patient care remains to be addressed in large-scale cognitive training trials.
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    Personalized and Circuit-Based Transcranial Magnetic Stimulation: Evidence, Controversies, and Opportunities.
    Cash, RFH ; Zalesky, A (Elsevier BV, 2024-03-15)
    The development of neuroimaging methodologies to map brain connectivity has transformed our understanding of psychiatric disorders, the distributed effects of brain stimulation, and how transcranial magnetic stimulation can be best employed to target and ameliorate psychiatric symptoms. In parallel, neuroimaging research has revealed that higher-order brain regions such as the prefrontal cortex, which represent the most common therapeutic brain stimulation targets for psychiatric disorders, show some of the highest levels of interindividual variation in brain connectivity. These findings provide the rationale for personalized target site selection based on person-specific brain network architecture. Recent advances have made it possible to determine reproducible personalized targets with millimeter precision in clinically tractable acquisition times. These advances enable the potential advantages of spatially personalized transcranial magnetic stimulation targeting to be evaluated and translated to basic and clinical applications. In this review, we outline the motivation for target site personalization, preliminary support (mostly in depression), convergent evidence from other brain stimulation modalities, and generalizability beyond depression and the prefrontal cortex. We end by detailing methodological recommendations, controversies, and notable alternatives. Overall, while this research area appears highly promising, the value of personalized targeting remains unclear, and dedicated large prospective randomized clinical trials using validated methodology are critical.
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    Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
    Eratne, D ; Kang, M ; Malpas, C ; Simpson-Yap, S ; Lewis, C ; Dang, C ; Grewal, J ; Coe, A ; Dobson, H ; Keem, M ; Chiu, W-H ; Kalincik, T ; Ooi, S ; Darby, D ; Brodtmann, A ; Hansson, O ; Janelidze, S ; Blennow, K ; Zetterberg, H ; Walker, A ; Dean, O ; Berk, M ; Wannan, C ; Pantelis, C ; Loi, SM ; Walterfang, M ; Berkovic, SF ; Santillo, AF ; Velakoulis, D (SAGE PUBLICATIONS LTD, 2024-01)
    OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
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    Control of Neuronal Survival and Development Using Conductive Diamond
    Falahatdoost, S ; Prawer, YDJ ; Peng, D ; Chambers, A ; Zhan, H ; Pope, L ; Stacey, A ; Ahnood, A ; Al Hashem, HN ; De Leon, SE ; Garrett, DJ ; Fox, K ; Clark, MB ; Ibbotson, MR ; Prawer, S ; Tong, W (AMER CHEMICAL SOC, 2024-01-17)
    This study demonstrates the control of neuronal survival and development using nitrogen-doped ultrananocrystalline diamond (N-UNCD). We highlight the role of N-UNCD in regulating neuronal activity via near-infrared illumination, demonstrating the generation of stable photocurrents that enhance neuronal survival and neurite outgrowth and foster a more active, synchronized neuronal network. Whole transcriptome RNA sequencing reveals that diamond substrates improve cellular-substrate interaction by upregulating extracellular matrix and gap junction-related genes. Our findings underscore the potential of conductive diamond as a robust and biocompatible platform for noninvasive and effective neural tissue engineering.
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    The Early Mid-Career Committee (EMCC) of the International Society for Bipolar Disorders: Aspirations and goals
    Huber, RS ; Douglas, KM ; Sperry, SH ; Gomes, FA ; Van Rheenen, TE ; Xu, N ; Hosang, GM (Wiley, 2022-12)
    In 2021, the International Society for Bipolar Disorders (ISBD) launched a new global initiative to support researchers and clinicians specializing in bipolar disorder who are still in the process of establishing their careers. To capture the needs of this group, an Early and Mid-Career Committee (EMCC) was formed and tasked with the development of activities and initiatives to address this objective. To this end, the committee conducted a needs assessment survey in early 2022 that was distributed and completed worldwide. This paper, authored by members of the committee, outlines the rationale, process, goals, and aspirations of the EMCC and summarizes the development of the needs survey.