Psychiatry - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 2846
-
ItemNeuroimaging Insights: Kava's (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder.(MDPI AG, 2023-10-28)Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.
-
ItemCumulative trauma load and timing of trauma prior to military deployment differentially influences inhibitory control processing across deployment(NATURE PORTFOLIO, 2023-12-05)Military personnel experience high trauma load that can change brain circuitry leading to impaired inhibitory control and posttraumatic stress disorder (PTSD). Inhibitory control processing may be particularly vulnerable to developmental and interpersonal trauma. This study examines the differential role of cumulative pre-deployment trauma and timing of trauma on inhibitory control using the Go/NoGo paradigm in a military population. The Go/NoGo paradigm was administered to 166 predominately male army combat personnel at pre- and post-deployment. Linear mixed models analyze cumulative trauma, trauma onset, and post-deployment PTSD symptoms on NoGo-N2 and NoGo-P3 amplitude and latency across deployment. Here we report, NoGo-N2 amplitude increases and NoGo-P3 amplitude and latency decreases in those with high prior interpersonal trauma across deployment. Increases in NoGo-P3 amplitude following adolescent-onset trauma and NoGo-P3 latency following childhood-onset and adolescent-onset trauma are seen across deployment. Arousal symptoms positively correlated with conflict monitoring. Our findings support the cumulative trauma load and sensitive period of trauma exposure models for inhibitory control processing in a military population. High cumulative interpersonal trauma impacts conflict monitoring and response suppression and increases PTSD symptoms whereas developmental trauma differentially impacts response suppression. This research highlights the need for tailored strategies for strengthening inhibitory control, and that consider timing and type of trauma in military personnel.
-
ItemMulti-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.(Springer Science and Business Media LLC, 2024-01-11)Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
-
ItemMajor depressive disorder associated alterations in the effective connectivity of the face processing network: a systematic review(SPRINGERNATURE, 2024-01-25)Major depressive disorder (MDD) is marked by altered processing of emotional stimuli, including facial expressions. Recent neuroimaging research has attempted to investigate how these stimuli alter the directional interactions between brain regions in those with MDD; however, methodological heterogeneity has made identifying consistent effects difficult. To address this, we systematically examined studies investigating MDD-associated differences present in effective connectivity during the processing of emotional facial expressions. We searched five databases: PsycINFO, EMBASE, PubMed, Scopus, and Web of Science, using a preregistered protocol (registration number: CRD42021271586). Of the 510 unique studies screened, 17 met our inclusion criteria. These studies identified that compared with healthy controls, participants with MDD demonstrated (1) reduced connectivity from the dorsolateral prefrontal cortex to the amygdala during the processing of negatively valenced expressions, and (2) increased inhibitory connectivity from the ventromedial prefrontal cortex to amygdala during the processing of happy facial expressions. Most studies investigating the amygdala and anterior cingulate cortex noted differences in their connectivity; however, the precise nature of these differences was inconsistent between studies. As such, commonalities observed across neuroimaging modalities warrant careful investigation to determine the specificity of these effects to particular subregions and emotional expressions. Future research examining longitudinal connectivity changes associated with treatment response may provide important insights into mechanisms underpinning therapeutic interventions, thus enabling more targeted treatment strategies.
-
ItemExtreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies(SPRINGERNATURE, 2023-12-02)There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/- 2.6 standard deviations from the mean were considered extreme deviations from the norm. We found that no more than 6.4% of psychosis patients had extreme deviations in a single brain region (regional overlap) demonstrating a high degree of heterogeneity. Mann-Whitney U tests were run on z-scores for each region and significantly lower z-scores were observed in FEP patients in the frontal, temporal, parietal and occipital lobes. Finally, linear mixed-effects modelling showed that negative deviations in cortical thickness in parietal and temporal regions at baseline are related to more severe negative symptoms over the medium-term. This study shows that even at the early stage of symptom onset normative modelling provides a framework to identify individualised cortical markers which can be used for early personalised intervention and stratification.
-
ItemMetergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen(SPRINGER, 2023-12)Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders.
-
ItemSmartphone-delivered multicomponent lifestyle medicine intervention for improving mental health in a nonclinical population: a randomized controlled trial.(Frontiers Media SA, 2023)OBJECTIVE: To prevent the exacerbation of mental health burdens, a growing body of research has recommended a balanced approach that emphasizes both the delivery of mental health treatments to individuals with common mental disorders (CMDs) and the strengthening of protective factors for CMDs among nonclinical populations. This randomized controlled trial (RCT) evaluated the efficacy of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, for improving mental health among a nonclinical population of Chinese adults. METHODS: A total of 106 participants with Patient Health Questionnaire-9 total score < 10 and Generalized Anxiety Disorder 7-Item Scale <8 were randomly assigned to either the Lifestyle Hub intervention group (LH, n = 53) or the waitlist control group (WL, n = 53). Lifestyle Hub is an 8-week smartphone-delivered multicomponent LM intervention developed based on the transtheoretical model. The intervention components included lifestyle psychoeducation, physical activity, diet and nutrition, stress management, sleep management, and motivation and goal-setting techniques. Assessments were conducted at baseline, immediate post-intervention, and 1-month follow-up (LH only). RESULTS: The linear mixed effect model based on the intention-to-treat principle indicated that Lifestyle Hub significantly improved overall mental health, depressive symptoms, anxiety symptoms, stress, insomnia severity, overall health-promoting behaviors, dietary quality, and stress management compared to the WL group at immediate post-intervention (d = 0.13-0.56). No significant between-group differences were observed in terms of functional impairment, health-related quality of life, health responsibility, physical activity level, spiritual growth, and interpersonal relations. The intervention gains in the LH group were maintained at 1-month follow-up. The LH participants indicated that Lifestyle Hub was an acceptable intervention for improving mental health, although a significantly higher level of study attrition was observed in the LH group (20.8%) relative to the WL group (5.7%). CONCLUSION: Lifestyle Hub may serve as an efficacious and acceptable intervention for improving mental health in nonclinical adult populations. To extend the benefits of LM interventions at the population level, future studies are warranted to examine a stepped-care approach to delivering LM interventions.Trial registration: This randomized controlled trial was pre-registered with ClinicalTrials.gov (NCT04295369).
-
ItemExploring individual fixel-based white matter abnormalities in epilepsy(OXFORD UNIV PRESS, 2023-12-28)Diffusion MRI has provided insight into the widespread structural connectivity changes that characterize epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies to date have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical value, they should be able to detect white matter microstructural changes in individual patients. In this study, we apply an individualized approach to a technique known as fixel-based analysis, to examine fibre-tract-specific abnormalities in individuals with epilepsy. We explore the potential clinical value of this individualized fixel-based approach in epilepsy patients with differing syndromic diagnoses. Diffusion MRI data from 90 neurologically healthy control participants and 10 patients with epilepsy (temporal lobe epilepsy, progressive myoclonus epilepsy, and Dravet Syndrome, malformations of cortical development) were included in this study. Measures of fibre density and cross-section were extracted for all participants across brain white matter fixels, and mean values were computed within select tracts-of-interest. Scanner harmonized and normalized data were then used to compute Z-scores for individual patients with epilepsy. White matter abnormalities were observed in distinct patterns in individual patients with epilepsy, both at the tract and fixel level. For patients with specific epilepsy syndromes, the detected white matter abnormalities were in line with expected syndrome-specific clinical phenotypes. In patients with lesional epilepsies (e.g. hippocampal sclerosis, periventricular nodular heterotopia, and bottom-of-sulcus dysplasia), white matter abnormalities were spatially concordant with lesion location. This proof-of-principle study demonstrates the clinical potential of translating advanced diffusion MRI methodology to individual-patient-level use in epilepsy. This technique could be useful both in aiding diagnosis of specific epilepsy syndromes, and in localizing structural abnormalities, and is readily amenable to other neurological disorders. We have included code and data for this study so that individualized white matter changes can be explored robustly in larger cohorts in future work.
-
ItemNo Preview AvailableAltered task-related decoupling of the rostral anterior cingulate cortex in depression.(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.
-
ItemNo Preview AvailableWhat do Australian consumers with lived experience of bipolar disorder want from early intervention services?(SAGE PUBLICATIONS LTD, 2024-03)