Orygen Research Center

Parkville, Australia

Orygen Research Center

Parkville, Australia
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Berk M.,Deakin University | Berk M.,University of Melbourne | Berk M.,Orygen Research Center | Berk M.,Florey Institute of Neuroscience and Mental Health | And 6 more authors.
Trends in Pharmacological Sciences | Year: 2013

N-Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimer's and Parkinson's diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate. © 2013 Elsevier Ltd. All rights reserved.

Bora E.,University of Melbourne | Fornito A.,University of Melbourne | Yucel M.,University of Melbourne | Yucel M.,Orygen Research Center | Pantelis C.,University of Melbourne
Psychological Medicine | Year: 2012

Background Recent evidence from genetic and familial studies revitalized the debate concerning the validity of the distinction between schizophrenia and bipolar disorder. Comparing brain imaging findings is an important avenue to examine similarities and differences and, therefore, the validity of the distinction between these conditions. However, in contrast to bipolar disorder, most patient samples in studies of schizophrenia are predominantly male. This a limiting factor for comparing schizophrenia and bipolar disorder since male gender is associated with more severe neurodevelopmental abnormalities, negative symptoms and cognitive deficits in schizophrenia.Method We used a coordinate-based meta-analysis technique to compare grey matter (GM) abnormalities in male-dominated schizophrenia, gender-balanced schizophrenia and bipolar disorder samples based on published voxel-based morphometry (VBM) studies. In total, 72 English-language, peer reviewed articles published prior to January 2011 were included. All reports used VBM for comparing schizophrenia or bipolar disorder with controls and reported whole-brain analyses in standard stereotactic space.Results GM reductions were more extensive in male-dominated schizophrenia compared to gender-balanced bipolar disorder and schizophrenia. In gender-balanced samples, GM reductions were less severe. Compared to controls, GM reductions were restricted to dorsal anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex in schizophrenia and ACC and bilateral fronto-insular cortex in bipolar disorder.Conclusions When gender is controlled, GM abnormalities in bipolar disorder and schizophrenia are mostly restricted to regions that have a role in emotional and cognitive aspects of salience respectively. Dorsomedial and dorsolateral prefrontal cortex were the only regions that showed greater GM reductions in schizophrenia compared to bipolar disorder. © 2011 Cambridge University Press.

Harvey C.,University of Melbourne | Harvey C.,North Western Mental Health | Killackey E.,University of Melbourne | Killackey E.,Orygen Research Center | And 3 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2012

Objective: Access to adequate housing consistent with personal preferences and needs is a human right and supports recovery from psychosis. This study aimed to: (1) describe people with psychosis living in different housing types, and their preferences and needs; (2) explore selected demographic and social inclusion correlates in relation to housing; and (3) compare two subgroups participants living in supported group accommodation and supported housing on key demographic, functional, clinical and social inclusion variables. Method: Current housing, preferences, needs and assistance, and housing-related social inclusion variables were assessed in a two-phase prevalence survey conducted within seven catchment areas across five Australian states. Two supported housing models were compared: supported group accommodation and supported housing (rental accommodation with in-reach support). Descriptive statistics were used. Results: Of the total participants (n = 1825), one half were living in public or private rented housing (48.6%) and 22.7% were waiting for public housing. Despite being the preferred form of housing, only 13.1% were living in their own home. One in 20 participants (5.2%) was currently homeless; 12.8% had been homeless in the previous 12 months. Residents of supported group accommodation felt safer in their locality than those in supported housing, but experienced less privacy and choice. Conclusions: Although fewer participants were homeless compared with the first Australian survey of psychosis, the proportion remains high. Housing difficulties are experienced by people with psychoses living in various accommodation and concern housing adequacy and safety as well as autonomy and choice. Access to public housing is restricted compared with the identified need. Since residents of supported group accommodation felt safer in their locality than those in supported housing, but experienced less privacy and choice, each supported housing model may offer different advantages to people with psychosis, and contribute to services that support and maintain recovery. © The Royal Australian and New Zealand College of Psychiatrists 2012.

Aggarwal S.,Orygen Research Center | Angus B.,Orygen Research Center
Australasian Psychiatry | Year: 2015

Objective: The diagnosis of children with autism spectrum disorders (ASDs) is sometimes delayed until adolescence. This study tries to identify the symptoms in clients that initiated a referral to an autism team of an early intervention service providing psychiatric care for young people between the ages of 15 and 25 and who subsequently receive a new diagnosis of autism. Methods: Thirty-one ASD assessments were carried out during a period of 3 years in an early intervention service in Australia. An attempt to identify the common presenting symptoms and trends in the referrals for ASD assessment within the service was made. Results: Most common presentation of adolescents getting referred for ASD assessment was with depressive symptoms followed by mixed anxiety and depression and primary psychotic symptoms. There was a significant gender difference, with a higher number of males getting referred for ASD assessment. Conclusion: ASDs can go undetected during childhood and these clients can sometimes present during adolescence to mental health services for a psychiatric comorbidity. Regular training opportunities for clinicians dealing with them could improve the chances of ASDs being picked up during their episode of care at an early intervention service, thus optimizing their management. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Hayley A.C.,Deakin University | Hayley A.C.,Institute for Breathing and Sleep | Williams L.J.,Deakin University | Venugopal K.,Deakin University | And 7 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2015

Objective: To determine the association between insomnia, obstructive sleep apnoea (OSA), and comorbid insomnia- OSA and depression, while controlling for relevant lifestyle and health factors, among a large population-based sample of US adults. Method: We examined a sample of 11,329 adults (≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2005-2008. Insomnia was classified via a combination of self-reported positive physician diagnosis and high-frequency 'trouble falling asleep', 'waking during the night', 'waking too early', and 'feeling unrested during the day'. OSA was classified as a combination of a positive response to a physician-diagnosed condition, in addition to a high frequency of self-reported nocturnal 'snoring', 'snorting/stopping breathing' and 'feeling overly sleepy during the day'. Comorbid insomnia-OSA was further assessed by combining a positive response to either insomnia (all), or sleep apnoea (all), as classified above. Depressive symptomology was assessed by the Patient Health Questionnaire-9 (PHQ-9), with scores of >9 used to indicate depression. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disorders and depression were attained from logistic regression modelling adjusted for sex, age, poverty level, smoking status and body mass index (BMI). Results: Those who reported insomnia, OSA or comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%, 27.1%, respectively), and consistently reported poorer physical health outcomes than those who did not report sleep disorders. After adjusting for sex, age, poverty level, smoking status and BMI (kg/m2), insomnia (OR 6.57, 95% CI 3.89-11.11), OSA (OR 5.14, 95% CI 3.14-8.41) and comorbid insomnia-OSA (OR 6.67, 95% CI 4.44-10.00) were associated with an increased likelihood of reporting depression. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Pasco J.A.,Deakin University | Pasco J.A.,University of Melbourne | Williams L.J.,University of Melbourne | Jacka F.N.,Deakin University | And 7 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2013

Objective: To examine the cross-sectional association between overweight and obesity and positive and negative affect. Method: Participants included 273 women, aged 29-84 years, who were enrolled in the Geelong Osteoporosis Study (GOS). Weight and height were measured and overweight and obesity determined from body mass index (BMI; kg/m2) according to WHO criteria. Medical history and lifestyle exposures were assessed by questionnaire. Positive and negative affect scores were derived using the validated 20-item Positive and Negative Affect Schedule (PANAS) and categorised into tertiles. Results: A pattern of greater negative affect scores was observed for increasing levels of BMI. Setting normal weight as the referent category, the odds for having a negative affect score in the highest tertile were sequentially increased for women who were overweight (OR = 1.31, 95% CI: 0.72-2.40) and obese (OR = 1.95, 95% CI: 1.02-3.73). The association between obesity and increased negative affect was diminished by adjusting for physical illness (adjusted OR = 1.76, 95% CI: 0.91-3.42). These associations were not substantially influenced by positive affect score or other exposures. No association was detected between BMI categories and positive affect scores. Conclusions: We report data suggesting that obesity is associated with greater negative affect scores, reflecting emotions such as distress, anger, disgust, fear and shame, and that this association is attenuated by physical illness. Further investigations are now warranted to explore possible mechanistic interplay between pathological, neurobiological and psychosocial factors. © TheRoyal Australian and New Zealand College of Psychiatrists 2013.

Parker G.,University of New South Wales | Parker G.,Hospital Road | Fletcher K.,University of New South Wales | Fletcher K.,Hospital Road | And 5 more authors.
Psychiatry Research | Year: 2013

While psychotherapies are of established value, they may, as active treatments, risk adverse outcomes. As there is no validated measure of potentially negative psychotherapeutic ingredients, we sought to develop such a measure for use in psychotherapy evaluation studies. Based on a review of the literature, a 103-item experiential measure was derived. Psychometric properties and scale score correlates were examined in a sample of more than 700 respondents. Principal component analyses revealed a five factor solution, explaining 53.4% of the variance; namely 'Negative Therapist', 'Pre-occupying Therapy', 'Beneficial Therapy', 'Idealization of Therapist' and 'Passive Therapist' constructs. Derived factors had high internal consistency, and scale scores were correlated with a number of clinically relevant demographic and treatment characteristics. An independent study established high test-retest reliability for the measure. Assessment of any adverse effects of psychotherapy is of clinical and research significance. We report the development of a measure that should allow the impact of such effects to be quantified in treatment studies, and especially in apportioning the contribution of such non-specific therapeutic effects. © 2012 Elsevier Ireland Ltd.

Kulkarni J.,Monash University | Gurvich C.,Monash University | Lee S.J.,Monash University | Gilbert H.,Monash University | And 8 more authors.
Psychoneuroendocrinology | Year: 2010

Estrogen treatment may enhance the recovery of schizophrenia in women. However, adverse effects on uterine and breast tissue and other physical side effects may limit the long-term therapeutic use of estrogen. Raloxifene hydrochloride is a selective estrogen receptor modulator that acts as an estrogen antagonist in breast tissue and may have agonistic actions in the brain, potentially offering mental health benefits with few estrogenic side effects. To provide an indication of the potential therapeutic dose for raloxifene hydrochloride in postmenopausal women with schizophrenia, this study pools data from an ongoing randomized controlled trial of adjunctive 120. mg/day oral raloxifene hydrochloride (n= 13) versus oral placebo (n= 13), with data from a previous pilot study administering 60. mg/day raloxifene hydrochloride (n= 9). Analysis of variance found significant interaction effects for total (p=01) and general (p=02) Positive and Negative Syndrome Scale (PANSS) symptomatology. Participants randomized to receive 120. mg/day raloxifene hydrochloride experienced a significantly more rapid recovery of total and general psychotic symptoms compared to both 60. mg/day raloxifene hydrochloride and placebo. The demonstrated benefit of adjunctive treatment with 120mg/day raloxifene hydrochloride offers support for the potential role of this selective estrogen receptor modulator in treating postmenopausal women with schizophrenia. © 2010 Elsevier Ltd.

Bora E.,University of Melbourne | Yucel M.,University of Melbourne | Yucel M.,Orygen Research Center | Pantelis C.,University of Melbourne | And 3 more authors.
Acta Psychiatrica Scandinavica | Year: 2011

Objective: The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls. Method: Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls. Results: Individuals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains. Conclusion: Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness. © 2010 John Wiley & Sons A/S.

Malhi G.S.,Royal North Shore Hospital | Malhi G.S.,University of Sydney | Bargh D.M.,Royal North Shore Hospital | Bargh D.M.,University of Sydney | And 8 more authors.
Bipolar Disorders | Year: 2014

Objective: Bipolar disorder is a multifaceted illness and there is often a substantial delay between the first onset of symptoms and diagnosis. Early detection has the potential to curtail illness progression and disorder-associated burden but it requires a clear understanding of the initial bipolar prodrome. This article summarizes the phenomenology of bipolar disorder with an emphasis on the initial prodrome, the evolution of the illness, and the implications for prevention and early intervention. Methods: A literature review was undertaken using Medline, Web of Science, and a hand search of relevant literature using keywords (e.g., phenomenology, initial or early symptoms, risk factors, and predictors/prediction). Findings from the literature were reviewed and synthesized and have been put into a clinical context. Results: Bipolar disorder is a recurrent, persistent, and disabling illness that typically develops in adolescence or early adulthood. The literature search yielded 28 articles, in which mood lability, nonspecific, non-mood symptoms, and cyclothymic temperament were the most cited prodromal features. Conclusions: A small number of key prospective studies have provided evidence in support of an initial bipolar prodrome; however, methodological differences across studies have prohibited its clear delineation. It is, therefore, not currently possible to anticipate those who will develop bipolar disorder solely on the basis of early phenomenology. Accurate characterization of the bipolar disorder prodrome through high-quality, prospective research studies with adequate control groups will ultimately facilitate prompt and accurate diagnosis. © 2013 John Wiley & Sons A/S.

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