Psychiatry - Research Publications
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ItemThe Relationship of Serum Macrophage Inhibitory Cytokine-1 Levels with Gray Matter Volumes in Community-Dwelling Older Individuals(PUBLIC LIBRARY SCIENCE, 2015-04-13)Using circulating inflammatory markers and magnetic resonance imaging (MRI), recent studies have associated inflammation with brain volumetric measures. Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) is a divergent transforming growth factor - beta (TGF-β) superfamily cytokine. To uncover the underlying mechanisms of the previous finding of a negative association between MIC-1/GDF15 serum levels and cognition, the present study aimed to examine the relationship of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a community-dwelling sample aged 70-90 years over two years (Wave 1: n = 506, Wave 2: n = 327), of which the age-related brain atrophy had been previously well defined. T1-weighted MRI scans were obtained at both waves and analyzed using the FMRIB Software Library and FreeSurfer. The results showed significantly negative associations between MIC-1/GDF15 serum levels and both subcortical and cortical GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and accumbens showed significant mediating effects on the associations between MIC-1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum levels were associated with decreases in cortical and subcortical GM volume over two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with GM volumes both cross-sectionally and longitudinally.
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ItemAssociations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study(BIOMED CENTRAL LTD, 2015-03-04)BACKGROUND: Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality. METHODS: The study included 1660 participants from the BiDirect Study (n = 840 patients with depression, n = 820 population-based controls). The psychiatric assessment was based on clinical interviews and a combination of depression scales in order to provide the classification of depression subtypes and severity. Diet quality scores, reflecting the adherence to a healthy dietary pattern, were calculated on the basis of an 18-item food frequency questionnaire. Using analysis of covariance, we calculated adjusted means of diet quality scores and tested differences between groups (adjusted for socio-demographic, lifestyle-, and health-related factors). RESULTS: We found no differences in diet quality between controls and patients with depression if depression was considered as one entity. However, we did find differences between patients with distinct subtypes of depression. Patients with melancholic depression reported the highest diet quality scores, whereas patients with atypical depression reported the lowest scores. Depression severity was not associated with diet quality. CONCLUSIONS: Previous literature has commonly treated depression as a homogeneous entity. However, subtypes of depression may be associated with diet quality in different ways. Further studies are needed to enlighten the diet-depression relationship and the role of distinct depression subtypes.
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ItemSymptom severity of depressive symptoms impacts on social cognition performance in current but not remitted major depressive disorder(FRONTIERS MEDIA SA, 2015-08-04)The aim of the present study was to investigate the social cognitive functioning of participants with depression when compared with healthy controls, and to assess the impact of symptom severity. One hundred and eight patients with depression (66 remitted and 42 current) and 52 healthy controls were assessed using the Wechsler Advanced Clinical Solutions: Social Perception Subtest, measuring facial affect recognition in isolation and in combination with prosody and body language interpretation. When healthy controls, remitted depression and currently depressed groups were compared, no associations were found on any of the social cognition subscales. Severity of depressive and anxious symptoms predicted performance on all social cognition subscales in currently depressed participants, controlling for age, gender, education and psychotropic medication. Affective depressive symptoms were inversely related to ACS Pairs and Prosody subscales, while somatic symptoms were inversely related to the ACS Affect Recognition and Total scores. There was no association between severity and the WAIS ACS in remitted depression participants. People with MDD exhibiting more severe depressive and anxious symptoms and a cluster of affective symptoms have greater difficulty undertaking complex social cognitive tasks. Given the state like nature to these deficits, these impairments may cause problems with day to day functioning and have implications in targeted therapeutic interventions.
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ItemPoor Self-Rated Health Influences Hospital Service Use in Hospitalized Inpatients With Chronic Conditions in Taiwan(LIPPINCOTT WILLIAMS & WILKINS, 2015-09)Our aim was to investigate the association between self-rated health (SRH) and use of hospital services (ie, medical outpatient department, emergency department, and general ward. admissions). Cross-sectional study data were collected from 230 consecutive patients admitted to medical departments of a 2000-bed academic medical center in Taiwan using standardized operating procedures for data collection of SRH (ie, a single-item question inquiring overall perceived health status), medical disorders, depressive symptoms, and combined service utilization over a 1-year period (ie, number of visits to outpatient department, number of visits to emergency department, and number of hospitalizations). Electronic medical records were retrieved, with self-reported external medical visits added to in-hospital frequencies of service use to provide better estimation of health service utilization. Fifty-two percent of study patients rated their health as poor or very poor. Poor SRH was associated with more visits to medical outpatient department, emergency department, and hospital admission. Multivariate logistic regression demonstrated an independent association between poor SRH and services utilization after adjustment for age, gender, hypertension, diabetes, metastatic cancer, number of chronic illness, life-threatening event, life-time suicidal ideation, and depression. SRH may be a useful research tool to model medical service use for inpatients with chronic conditions.
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ItemGraded Resistance Exercise And Type 2 Diabetes in Older adults (The GREAT2DO study): methods and baseline cohort characteristics of a randomized controlled trial(BMC, 2015-11-10)BACKGROUND: Type 2 diabetes (T2D) is projected to affect 439 million people by 2030. Medical management focuses on controlling blood glucose levels pharmacologically in a disease that is closely related to lifestyle factors such as diet and inactivity. Physical activity guidelines include aerobic exercise at intensities or volumes potentially unreachable for older adults limited by many co-morbidities. We aim to show for the first time the efficacy of a novel exercise modality, power training (high-velocity, high-intensity progressive resistance training or PRT), in older adults with T2D as a means for improving glycemic control and targeting many associated metabolic and physiological outcomes. Eligibility criteria included community-dwelling men and women previously diagnosed with T2D who met the current definition of metabolic syndrome according to the International Diabetes Federation. Participants were randomized to a fully supervised power training intervention or sham exercise control group for 12 months. Intervention group participants performed whole body machine-based power training at 80%1RM, 3 days per week. The control group undertook the same volume of non-progressive, low-intensity training. Participants were assessed at baseline, 6 months and 12 months and followed for a further 5 years, during which time participants were advised to exercise at moderate-high intensity. Glycemic control (HbA1c) and insulin resistance as measured by the homeostatic model assessment 2 (HOMA2-IR) were the primary outcomes of the trial. Outcome assessors were blinded to group assignment and participants were blinded to the investigators' hypothesis regarding the most effective intervention. RESULTS: We recruited 103 participants (48.5 % women, 71.6 ± 5.6 years). Participants had 5.1 ± 1.8 chronic diseases, had been diagnosed with T2D for 8 ± 6 years and had a body mass index (BMI) of 31.6 ± 4.0 kg/m(2). Fasting glucose and insulin were 7.3 ± 2.4 mmol/L and 10.6 ± 6.3 mU/L, respectively. HbA1c was 54 ± 12 mmol/mol. Eighty-six participants completed the 12-month assessment and follow-up is ongoing. This cohort had a lower-than-expected dropout (n = 14, 14 %) over the 12-month intervention period. CONCLUSIONS: Power training may be a feasible adjunctive therapy for improving glycemic control for the growing epidemic of T2D in older adults. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12606000436572 (24 September 2006).
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Item14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders(NATURE PORTFOLIO, 2015-07-24)Sequencing and expression analyses implicate 14-3-3ζ as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3ζ(-/-) mice in the Sv/129 background display schizophrenia-like defects. As epistatic interactions play a significant role in disease pathogenesis we generated a new congenic strain in the BALB/c background to determine the impact of genetic interactions on the 14-3-3ζ(-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3ζ(-/-) BALB/c mice identified enlarged lateral ventricles, reduced synaptic density and ectopically positioned pyramidal neurons in all subfields of the hippocampus. In contrast to our previous analyses, 14-3-3ζ(-/-) BALB/c mice lacked locomotor hyperactivity that was underscored by normal levels of the dopamine transporter (DAT) and dopamine signalling. Taken together, our results demonstrate that dysfunction of 14-3-3ζ gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3ζ-deficient BALB/c mice therefore provide a novel model to address the underlying biology of structural defects affecting the hippocampus and ventricle, and cognitive defects such as hippocampal-dependent learning and memory.
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ItemThe International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response(NATURE PUBLISHING GROUP, 2015-04-21)Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. The top association result in the meta-analysis of response represents SNPs 5′ upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.
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ItemSystematic review of the neurobiological relevance of chemokines to psychiatric disorders(FRONTIERS MEDIA SA, 2015-09-10)Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus-pituitary-adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer's disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and/or therapeutic targets in psychiatric disorders.
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ItemEpigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders(BMC, 2015-11-14)Stressor exposure during early life has the potential to increase an individual's susceptibility to a number of neuropsychiatric conditions such as mood and anxiety disorders and schizophrenia in adulthood. This occurs in part due to the dysfunctional stress axis that persists following early adversity impairing stress responsivity across life. The mechanisms underlying the prolonged nature of this vulnerability remain to be established. Alterations in the epigenetic signature of genes involved in stress responsivity may represent one of the neurobiological mechanisms. The overall aim of this review is to provide current evidence demonstrating changes in the epigenetic signature of candidate gene(s) in response to early environmental adversity. More specifically, this review analyses the epigenetic signatures of postnatal adversity such as childhood abuse or maltreatment and later-life psychopathology in human and animal models of early life stress. The results of this review shows that focus to date has been on genes involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and its correlation to subsequent neurobiology, for example, the role of glucocorticoid receptor gene. However, epigenetic changes in other candidate genes such as brain-derived neurotrophic factor (BDNF) and serotonin transporter are also implicated in early life stress (ELS) and susceptibility to adult psychiatric disorders. DNA methylation is the predominantly studied epigenetic mark followed by histone modifications specifically acetylation and methylation. Further, these epigenetic changes are cell/tissue-specific in regulating expression of genes, providing potential biomarkers for understanding the trajectory of early stress-induced susceptibility to adult psychiatric disorders.
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ItemEffects of physical exercise on central nervous system functions: a review of brain region specific adaptations.(Springer Science and Business Media LLC, 2015)Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.