Psychiatry - Research Publications
Now showing items 1-12 of 527
Microstructural correlates of 23Na relaxation in human brain at 7 Tesla.
23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue.
Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis
Background. There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.Method. The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1464923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.Results. The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18-64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.D.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.D.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.Conclusions. Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.
Mental Health Professional Online Development (MHPOD): a web-based training tool for the non-government community mental health workforce
Purpose of this paper is to evaluate the usefulness and relevance of the Mental Health Professional Online Development (MHPOD) training package in further developing the skills in mental health and recovery-informed practice of the Australian non-government community mental health workforce.
The neural cascade of olfactory processing: A combined fMRI-EEG study
Olfaction is dependent on respiration for the delivery of odorants to the nasal cavity. Taking advantage of the time-locked nature of inspiration and olfactory processing, electroencephalogram dipole modeling (EEG/DT) has previously been used to identify a cascade of inspiration-triggered neural activity moving from primary limbic olfactory regions to frontal cortical areas during odor perception. In this study, we leverage the spatial resolution of functional magnetic resonance imaging (fMRI) alongside the temporal resolution of EEG to replicate and extend these findings. Brain activation identified by both modalities converged within association regions of the orbitofrontal cortex that were activated from approximately 150-300 ms after inspiration onset. EEG/DT was additionally sensitive to more transient activity in primary olfactory regions, including the parahippocampal gyrus and amygdala, occurring approximately 50 ms post-inspiration. These results provide a partial validation of the spatial profile of the olfactory cascade identified by EEG source modeling, and inform novel future directions in the investigation of human olfaction.
Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths
BACKGROUND: Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy.METHODS: High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping.RESULTS: Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy.CONCLUSIONS: Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with psychopathy.
Functional brain imaging studies of youth depression: A systematic review
Background: There 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.Methods: A 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 19-25 years of age, respectively.Results: Twenty-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.Conclusions: Youth 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.
Does motion-related brain functional connectivity reflect both artifacts and genuine neural activity?
Imaging research on functional connectivity is uniquely contributing to characterize the functional organization of the human brain. Functional connectivity measurements, however, may be significantly influenced by head motion that occurs during image acquisition. The identification of how motion influences such measurements is therefore highly relevant to the interpretation of a study's results. We have mapped the effect of head motion on functional connectivity in six different populations representing a wide range of potential influences of motion on functional connectivity. Group-level voxel-wise maps of the correlation between a summary head motion measurement and functional connectivity degree were estimated in 80 young adults, 71 children, 53 older adults, 20 patients with Down syndrome, 24 with Prader-Willi syndrome and 20 with Williams syndrome. In highly compliant young adults, motion correlated with functional connectivity measurements showing a system-specific anatomy involving the sensorimotor cortex, visual areas and default mode network. Further characterization was strongly indicative of these changes expressing genuine neural activity related to motion, as opposed to pure motion artifact. In the populations with larger head motion, results were more indicative of widespread artifacts, but showing notably distinct spatial distribution patterns. Group-level regression of motion effects was efficient in removing both generalized changes and changes putatively related to neural activity. Overall, this study endorses a relatively simple approach for mapping distinct effects of head motion on functional connectivity. Importantly, our findings support the intriguing hypothesis that a component of motion-related changes may reflect system-specific neural activity.
A systematic review of diffusion weighted MRI studies of white matter microstructure in adolescent substance users
Recent studies using diffusion weighted magnetic resonance imaging (DW-MRI) have provided evidence of abnormal white matter microstructure in adults with substance use disorders (SUDs). While there is a growing body of research using DW-MRI to examine the impact of heavy substance use during adolescence, this literature has not been systematically reviewed. Online databases were searched for DW-MRI studies of adolescent substance users, and 10 studies fulfilled the inclusion and exclusion criteria. We identified consistent evidence for abnormal white matter microstructure in neocortical association pathways as well as in projection and thalamic pathways. Dose-dependent relationships between DW-MRI measures and patterns of substance use were also observed. The consistency of these findings with DW-MRI research in adults suggests that white matter microstructure is impacted in the early stages of heavy substance use. However, given the largely cross-sectional nature of the available data, important questions remain regarding the extent to which white matter abnormalities are a consequence of adolescent exposure to alcohol and other drugs of abuse or reflect pre-existing differences that increase risk for SUDs.
S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: Efficacy and effects of histamine and carnitine as moderators of response
Objective: To assess the antidepressant efficacy of S-adenosyl methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response.Methods: We examined a subsample (n=144) from one site of a two site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600-3200 mg/daily), escitalopram (10-20 mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response).Results: On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 (p=0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo (d=0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17 >= 50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D <= 7) were 34% for SAMe (p=0.003), 23% for escitalopram (p=0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment.Limitations: While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups clue to site differences) must be taken into consideration.Conclusions: These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
Cognitive impairment in euthymic major depressive disorder: a meta-analysis
(CAMBRIDGE UNIV PRESS, 2013-10-27)
Background. There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients.Method. Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined.Results. Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions.Conclusions. Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.