Psychiatry - Research Publications

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http://hdl.handle.net/11343/232

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Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?

Russell, SE ; Wrobel, AL ; Ashton, MM ; Turner, A ; Mohebbi, M ; Berk, M ; Cotton, S ; Dodd, S ; Ng, CH ; Malhi, GS ; Dean, OM (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2023-08)

OBJECTIVE: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. METHODS: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (＋4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. RESULTS: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. CONCLUSION: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
Genetic and Epigenetic Regulation in Lingo-1: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia

Andrews, JL ; Zalesky, A ; Nair, S ; Sullivan, RP ; Green, MJ ; Pantelis, C ; Newell, KA ; Fernandez, F (MDPI, 2023-11)

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3'-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016-1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology.
Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study

Ravanfar, P ; Syeda, WT ; Rushmore, RJ ; Moffat, B ; Lyall, AE ; Merritt, AH ; Devenyi, GA ; Chakravarty, MM ; Desmond, P ; Cropley, VL ; Makris, N ; Shenton, ME ; Bush, AI ; Velakoulis, D ; Pantelis, C ; Walterfang, M (AMER SOC NEURORADIOLOGY, 2023-06-22)

BACKGROUND AND PURPOSE: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls. MATERIALS AND METHODS: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses. RESULTS: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity. CONCLUSIONS: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.
Investigation of brain iron in anorexia nervosa, a quantitative susceptibility mapping study

Ravanfar, P ; Rushmore, RJ ; Lyall, AEE ; Cropley, V ; Makris, N ; Desmond, P ; Velakoulis, D ; Shenton, MEE ; Bush, AII ; Rossell, SLL ; Pantelis, C ; Syeda, WTT ; Phillipou, A (BMC, 2023-08-21)

BACKGROUND: Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN. METHODS: In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values. RESULTS: Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group. CONCLUSIONS: This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation.
The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder

Schwartz, OS ; Amminger, P ; Baune, BT ; Bedi, G ; Berk, M ; Cotton, SM ; Daglas-Georgiou, R ; Glozier, N ; Harrison, B ; Hermens, DF ; Jennings, E ; Lagopoulos, J ; Loo, C ; Mallawaarachchi, S ; Martin, D ; Phelan, B ; Read, N ; Rodgers, A ; Schmaal, L ; Somogyi, AA ; Thurston, L ; Weller, A ; Davey, CG (BMC, 2023-10-24)

BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .
The Longitudinal Association Between Posttraumatic Stress Disorder, Emotion Dysregulation, and Postmigration Stressors Among Refugees

Specker, P ; Liddell, BJ ; O'Donnell, M ; Bryant, RA ; Mau, V ; McMahon, T ; Byrow, Y ; Nickerson, A (SAGE PUBLICATIONS INC, 2023-04-21)

Although emotion dysregulation has been robustly associated with posttraumatic stress disorder (PTSD), there is relatively little understanding of this process in refugees. Specifically, longitudinal methodology has not been used to examine the relationship between emotion dysregulation and PTSD among refugees. In this study, we investigated the temporal relationship between emotion dysregulation, postmigration stressors, and PTSD clusters (reexperiencing, avoidance, negative alterations in mood and cognition [NAMC], and hyperarousal) from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders among a community sample of refugees ( N = 1,081) over a 2-year period. Random intercept cross-lagged panel analysis found that emotion dysregulation was antecedent to within-persons increases in reexperiencing and NAMC symptoms over time and bidirectionally associated with hyperarousal and postmigration stressors. In addition, postmigration stressors were antecedent to within-persons increases in reexperiencing, avoidance, and NAMC and bidirectionally associated with hyperarousal symptoms. Findings provide novel evidence in support of postmigration stressors and emotion dysregulation as mechanisms maintaining PTSD and highlight the potential utility of tailoring interventions to address these factors.
The mental health effects of changing from insecure to secure visas for refugees

Nickerson, A ; Byrow, Y ; O'Donnell, M ; Bryant, RA ; Mau, V ; Mcmahon, T ; Hoffman, J ; Mastrogiovanni, N ; Specker, P ; Liddell, BJ (SAGE PUBLICATIONS LTD, 2023-11)

OBJECTIVE: In response to growing numbers of refugees worldwide, host governments are increasingly implementing temporary protection policies; however, little is known regarding the mental health impact of these policies. This online longitudinal study investigated whether refugees who transitioned from low visa security (e.g. short-term transient visas) to medium (e.g. temporary protection visas) or high visa (e.g. permanent visas) security showed changes in depression symptoms, social difficulties and immigration-related fears. METHODS: Participants were 1,201 refugees and asylum-seekers from Arabic, Farsi, Tamil or English-speaking backgrounds. Study variables were measured prior to and after change in visa status (6 months apart). RESULTS: Refugees who transitioned from low to medium security visas showed reduced immigration-related fear (B = -0.09, 95% confidence interval = -0.29 to -0.06), but no change in depression symptoms or social difficulties compared to those who retained low visa security. Refugees who transitioned from low to high security visas showed reduced depression symptoms (B = -0.02, 95% confidence interval = -0.04 to -0.01), social difficulties (B = -0.04, 95% confidence interval = -0.05 to -0.01) and immigration-related fear (B = -0.03, 95% confidence interval = -0.06 to -0.01) compared to those who retained low visa security. CONCLUSION: Findings indicate that the increased security afforded by temporary protection policies (vs short-term transient visas) did not translate into improved mental health and social outcomes for refugees. In contrast, permanent protection was associated with significant improvements in psychological and social functioning. These results have important policy implications for countries who have committed to protect and facilitate improved mental health among refugees.
Association between mental health workforce supply and clusters of high and low rates of youth suicide: An Australian study using suicide mortality data from 2016 to 2020

Hill, N ; Bouras, H ; Too, L ; Perry, Y ; Lin, A ; Weiss, D (SAGE PUBLICATIONS LTD, 2023-11)

OBJECTIVE: To examine the association between mental health workforce supply and spatial clusters of high versus low incidence of youth suicide. METHODS: A cross-sectional analysis of spatial suicide clusters in young Australians (aged 10-25) from 2016 to 2020 was conducted using the scan statistic and suicide data from the National Coronial Information System. Mental health workforce was extracted from the 2020 National Health Workforce Dataset by local government areas. The Geographic Index of Relative Supply was used to estimate low and moderate-to-high mental health workforce supply for clusters characterised by a high and low incidence of suicide (termed suicide hotspots and coldspots, respectively). Univariate and multivariate logistic regression was used to determine the association between suicide clusters and a range of sociodemographic characteristics including mental health workforce supply. RESULTS: Eight suicide hotspots and two suicide coldspots were identified. The multivariate analysis showed low mental health workforce supply was associated with increased odds of being involved in a suicide hotspot (adjusted odds ratio = 8.29; 95% confidence interval = 5.20-13.60), followed by residential remoteness (adjusted odds ratio = 2.85; 95% confidence interval = 1.68-4.89), and illicit drug consumption (adjusted odds ratio = 1.97; 1.24-3.11). Both coldspot clusters occurred in areas with moderate-to-high mental health workforce supply. CONCLUSION: Findings highlight the potential risk and protective roles that mental health workforce supply may play in the spatial distributions of youth suicide clusters. These findings have important implications for the provision of postvention and the prevention of suicide clusters.
Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety

Moller, C ; Badcock, PB ; Hetrick, SE ; Rice, S ; Berk, M ; Witt, K ; Chanen, AM ; Dean, OM ; Gao, C ; Cotton, SM ; Davey, CG (SAGE PUBLICATIONS LTD, 2023-08)

OBJECTIVE: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. METHODS: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15-25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. RESULTS: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. CONCLUSIONS: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.
Fair funding for mental health research

Yung, AR ; Milicevic, M ; Berk, M (SAGE PUBLICATIONS LTD, 2023-08)

Psychiatry - Research Publications

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