Psychiatry - Research Publications

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    Secure attachment primes reduce fear consolidation
    Toumbelekis, M ; Liddell, BJ ; Bryant, RA (WILEY, 2021-05-05)
    BACKGROUND: Recent studies have found that attachment security primes can inhibit fear acquisition. This current study aimed to examine whether a brief imaginal prime of one's attachment figure could impact on fear consolidation. METHODS: A total of 75 participants underwent fear conditioning on Day 1 and fear recall was tested on Day 2. Immediately following conditioning, half the participants were instructed to imagine an attachment figure while the other half imagined a nonattachment positive situation. Fear-potentiated startle and subjective expectancy of shock ratings were used as the measures of fear learning across trials. RESULTS: The attachment group showed significantly lower levels of fear recall on Day 2 at both physiological and subjective levels. Furthermore, this effect was moderated by attachment anxiety, such that it was greatest for individuals who were securely attached. CONCLUSIONS: These findings suggest that attachment relationships are protective during the consolidation of fear memories, and may have implications for how social attachments may impact how anxiety disorders can develop.
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    Investigating neural circuits of emotion regulation to distinguish euthymic patients with bipolar disorder and major depressive disorder.
    Rai, S ; Griffiths, K ; Breukelaar, IA ; Barreiros, AR ; Chen, W ; Boyce, P ; Hazell, P ; Foster, S ; Malhi, GS ; Bryant, RA ; Harris, AWF ; Korgaonkar, MS (Wiley, 2021-05)
    BACKGROUND: Up to 40% of patients with bipolar disorder (BD) are initially diagnosed as having major depressive disorder (MDD), and emotional lability is a key aspect of both sets of mood disorders. However, it remains unknown whether differences in the regulation of emotions through cognitive reappraisal may serve to distinguish BD and MDD. Therefore, we examined this question in euthymic BD and MDD patients. METHODS: Thirty-eight euthymic BD, 33 euthymic MDD and 37 healthy control (HC) participants, matched for age, gender and depression severity, engaged in an emotion regulation (ER) cognitive reappraisal task during an fMRI scan were examined. Participants either reappraised (Think condition) or passively watched negative (Watch condition) or neutral (Neutral condition) pictures and rated their affect. Activation and connectivity analyses were used to examine group differences in reappraisal (Think vs Watch) and reactivity (Watch vs Neutral) conditions in ER-specific neural circuits. RESULTS: Irrespective of group, participants rated most negatively the images during the Watch condition relative to Think and Neutral conditions, and more negatively to Think relative to Neutral. Notably, BD participants exhibited reduced subgenual anterior cingulate activation (sgACC) relative to MDD during reappraisal, but exhibited greater sgACC activation relative to MDD during reactivity, whereas MDD participants elicited greater activation in right amygdala relative to BD during reactivity. We found no group differences in task-related connectivity. CONCLUSIONS: Euthymic BD and MDD patients engage differential brain regions to process and regulate emotional information. These differences could serve to distinguish the clinical groups and provide novel insights into the underlying pathophysiology of BD.
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    Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
    Blokland, GAM ; Grove, J ; Chen, C-Y ; Cotsapas, C ; Tobet, S ; Handa, R ; St Clair, D ; Lencz, T ; Mowry, BJ ; Periyasamy, S ; Cairns, MJ ; Tooney, PA ; Wu, JQ ; Kelly, B ; Kirov, G ; Sullivan, PF ; Corvin, A ; Riley, BP ; Esko, T ; Milani, L ; Jonsson, EG ; Palotie, A ; Ehrenreich, H ; Begemann, M ; Steixner-Kumar, A ; Sham, PC ; Iwata, N ; Weinberger, DR ; Gejman, P ; Sanders, AR ; Buxbaum, JD ; Rujescu, D ; Giegling, I ; Konte, B ; Hartmann, AM ; Bramon, E ; Murray, RM ; Pato, MT ; Lee, J ; Melle, I ; Molden, E ; Ophoff, RA ; McQuillin, A ; Bass, NJ ; Adolfsson, R ; Malhotra, AK ; Martin, NG ; Fullerton, JM ; Mitchell, PB ; Schofield, PR ; Forstner, AJ ; Degenhardt, F ; Schaupp, S ; Comes, AL ; Kogevinas, M ; Guzman-Parra, J ; Reif, A ; Streit, F ; Sirignano, L ; Cichon, S ; Grigoroiu-Serbanescu, M ; Hauser, J ; Lissowska, J ; Mayoral, F ; Muller-Myhsok, B ; Schulze, TG ; Nothen, MM ; Rietschel, M ; Kelsoe, J ; Leboyer, M ; Jamain, S ; Etain, B ; Bellivier, F ; Vincent, JB ; Alda, M ; O'Donovan, C ; Cervantes, P ; Biernacka, JM ; Frye, M ; McElroy, SL ; Scott, LJ ; Stahl, EA ; Landen, M ; Hamshere, ML ; Smeland, OB ; Djurovic, S ; Vaaler, AE ; Andreassen, OA ; Baune, BT ; Air, T ; Preisig, M ; Uher, R ; Levinson, DF ; Weissman, MM ; Potash, JB ; Shi, J ; Knowles, JA ; Perlis, RH ; Lucae, S ; Boomsma, D ; Penninx, BWJH ; Hottenga, J-J ; de Geus, EJC ; Willemsen, G ; Milaneschi, Y ; Tiemeier, H ; Grabe, HJ ; Teumer, A ; Van der Auwera, S ; Volker, U ; Hamilton, SP ; Magnusson, PKE ; Viktorin, A ; Mehta, D ; Mullins, N ; Adams, MJ ; Breen, G ; McIntosh, AM ; Lewis, CM ; Hougaard, DM ; Nordentoft, M ; Mors, O ; Mortensen, PB ; Werge, T ; Als, TD ; Borglum, AD ; Petryshen, TL ; Smoller, JW ; Goldstein, JM (ELSEVIER SCIENCE INC, 2021-11-29)
    BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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    Methodological implications of sample size and extinction gradient on the robustness of fear conditioning across different analytic strategies.
    Ney, LJ ; Laing, PAF ; Steward, T ; Zuj, DV ; Dymond, S ; Harrison, B ; Graham, B ; Felmingham, KL ; Andreatta, M (Public Library of Science (PLoS), 2022)
    Fear conditioning paradigms are critical to understanding anxiety-related disorders, but studies use an inconsistent array of methods to quantify the same underlying learning process. We previously demonstrated that selection of trials from different stages of experimental phases and inconsistent use of average compared to trial-by-trial analysis can deliver significantly divergent outcomes, regardless of whether the data is analysed with extinction as a single effect, as a learning process over the course of the experiment, or in relation to acquisition learning. Since small sample sizes are attributed as sources of poor replicability in psychological science, in this study we aimed to investigate if changes in sample size influences the divergences that occur when different kinds of fear conditioning analyses are used. We analysed a large data set of fear acquisition and extinction learning (N = 379), measured via skin conductance responses (SCRs), which was resampled with replacement to create a wide range of bootstrapped databases (N = 30, N = 60, N = 120, N = 180, N = 240, N = 360, N = 480, N = 600, N = 720, N = 840, N = 960, N = 1080, N = 1200, N = 1500, N = 1750, N = 2000) and tested whether use of different analyses continued to produce deviating outcomes. We found that sample size did not significantly influence the effects of inconsistent analytic strategy when no group-level effect was included but found strategy-dependent effects when group-level effects were simulated. These findings suggest that confounds incurred by inconsistent analyses remain stable in the face of sample size variation, but only under specific circumstances with overall robustness strongly hinging on the relationship between experimental design and choice of analyses. This supports the view that such variations reflect a more fundamental confound in psychological science-the measurement of a single process by multiple methods.
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    Prevalence of gambling problems, help-seeking, and relationships with trauma in veterans.
    Metcalf, O ; Lawrence-Wood, E ; Baur, J ; Van Hooff, M ; Forbes, D ; O'Donnell, M ; Sadler, N ; Hodson, S ; Benassi, H ; Varker, T ; Battersby, M ; McFarlane, AC ; Cowlishaw, S ; Osório, FL (Public Library of Science (PLoS), 2022)
    BACKGROUND AND AIMS: Veterans who have recently left the military (i.e., transitioned) may be vulnerable to the development of psychiatric disorders, but little is known about gambling problems in this population. This study investigated the prevalence and risk factors of gambling problems, help-seeking amongst veterans with gambling problems, and relationships with trauma and posttraumatic psychopathology. METHODS: Cross-sectional self-report survey data from 3,511 Australian Defence Force members who left the military within the past five years. Surveys included measures of gambling problems (PGSI); depressive symptoms (PHQ-9); posttraumatic stress disorder (PCL-5); help-seeking behaviours; military and non-military-related trauma. RESULTS: Prevalence rates for problem gambling (PGSI ≥ 5) were 4.6%, while an additional 8.8% were classified in terms of at-risk gambling (PGSI = 1-4). Time since leaving the military was not associated with gambling problems. Only 2.1% of veterans with problem gambling reported help-seeking for their gambling. While trauma exposure, depression, and Posttraumatic Stress Disorder (PTSD) were all related to gambling problems at the bivariate level, only arousal and dysphoric-related affect were uniquely associated with gambling problems when adjusting for covariates. DISCUSSION: Gambling problems may be under-recognised relative to other psychiatric issues. Posttraumatic mental health problems, rather than trauma exposure per se, may explain the relationship between trauma and gambling problems. CONCLUSIONS: Some veterans are in a period of vulnerability during transition out of military service, and harms associated with gambling problems may be exacerbated during this period.
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    Relationship between the Bolsa Família national cash transfer programme and suicide incidence in Brazil: A quasi-experimental study.
    Machado, DB ; Williamson, E ; Pescarini, JM ; Alves, FJO ; Castro-de-Araujo, LFS ; Ichihara, MY ; Rodrigues, LC ; Araya, R ; Patel, V ; Barreto, ML ; Wang, Y-P (Public Library of Science (PLoS), 2022-05)
    BACKGROUND: Socioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world's largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population. METHODS AND FINDINGS: We used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the "Bolsa Família" programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma. CONCLUSIONS: We observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic.
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    Emerging experience with selected new categories in the ICD-11: complex PTSD, prolonged grief disorder, gaming disorder, and compulsive sexual behaviour disorder.
    Reed, GM ; First, MB ; Billieux, J ; Cloitre, M ; Briken, P ; Achab, S ; Brewin, CR ; King, DL ; Kraus, SW ; Bryant, RA (Wiley, 2022-06)
    Among the important changes in the ICD-11 is the addition of 21 new mental disorders. New categories are typically proposed to: a) improve the usefulness of morbidity statistics; b) facilitate recognition of a clinically important but poorly classified mental disorder in order to provide appropriate management; and c) stimulate research into more effective treatments. Given the major implications for the field and for World Health Organization (WHO) member states, it is important to examine the impact of these new categories during the early phase of the ICD-11 implementation. This paper focuses on four disorders: complex post-traumatic stress disorder, prolonged grief disorder, gaming disorder, and compulsive sexual behaviour disorder. These categories were selected because they have been the focus of considerable activity and/or controversy and because their inclusion in the ICD-11 represents a different decision than was made for the DSM-5. The lead authors invited experts on each of these disorders to provide insight into why it was considered important to add it to the ICD-11, implications for care of not having that diagnostic category, important controversies about adding the disorder, and a review of the evidence generated and other developments related to the category since the WHO signaled its intention to include it in the ICD-11. Each of the four diagnostic categories appears to describe a population with clinically important and distinctive features that had previously gone unrecognized as well as specific treatment needs that would otherwise likely go unmet. The introduction of these categories in the ICD-11 has been followed by a substantial expansion of research in each area, which has generally supported their validity and utility, and by a significant increase in the availability of appropriate services.
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    Trajectories of depressive symptoms in older adults and associated health outcomes
    Agustini, B ; Lotfaliany, M ; Mohebbi, M ; Woods, RL ; McNeil, JJ ; Nelson, MR ; Shah, RC ; Murray, AM ; Reid, CM ; Tonkin, A ; Ryan, J ; Williams, LJ ; Forbes, MP ; Berk, M (Springer Science and Business Media LLC, 2022-04-01)
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    A critical review of mechanisms of adaptation to trauma: Implications for early interventions for posttraumatic stress disorder.
    Bryant, RA (Elsevier BV, 2021-04)
    Although many attempts have been made to limit development of posttraumatic stress disorder (PTSD) by early intervention after trauma exposure, these attempts have achieved only modest success. This review critiques the biological and cognitive strategies used for early intervention and outlines the extent to which they have prevented PTSD. The major predictors of PTSD are reviewed, with an emphasis on potential mechanisms that may underpin the transition from acute stress reaction to development of PTSD. This review highlights that there is a wide range of biological and cognitive factors that have been shown to predict PTSD. Despite this, the major attempts at early intervention have focused on strategies that attempt to augment extinction processes or alter appraisals in the acute period. The documented predictors of PTSD indicate that a broader range of potential strategies could be explored to limit PTSD. The evidence that people follow different trajectories of stress response following trauma and there is a wide array of acute predictors of PTSD indicates that a flexible and tailored approach needs to be investigated to evaluate more effective early intervention strategies.