Papers by Philip Mitchell
Psychological Medicine, 2020
BackgroundBipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal... more BackgroundBipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.MethodNeuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.ResultsCompared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independen...
Bipolar Disorders, 2020
Introduction of lithium carbonate to treat manic excitement in 1949 by John Cade in Melbourne ope... more Introduction of lithium carbonate to treat manic excitement in 1949 by John Cade in Melbourne opened a new, revolutionary era in psychiatry with the first clinically effective pharmacological treatment for a major psychiatric disorder. By 1960, there followed explosive discovery and development of at least one of every class of psychotropic medicines currently available.1 Further development of lithium as a safe and effective treatment for bipolar disorder (BD), both for acute mania and reduction of risk of recurrences of mania and bipolar depression was led by Mogens Schou in Denmark, following the initial report of long-term protective effects by Cade.
Medical Journal of Australia, 2004
Medical Journal of Australia, 2006
• General practitioners have a key role in managing patients with bipolar disorder, a condition w... more • General practitioners have a key role in managing patients with bipolar disorder, a condition which affects at least one in 200 Australians each year and is the sixth leading cause of disability in the population.
Medical Journal of Australia, 2010
Medical Journal of Australia, 2010
Medical Journal of Australia, 2004
Objective: To examine trends in types of antidepressant medications prescribed in Australia betwe... more Objective: To examine trends in types of antidepressant medications prescribed in Australia between 1975 and 2002. Design: Sales data from the Australian pharmaceutical industry were used to examine trends in overall antidepressant prescribing and changes in the types of antidepressants prescribed between 1975 and 2002. Main outcome measures: Antidepressant sales were expressed as defined daily doses (DDDs) per 1000 people per day, using the estimated Australian population for each year obtained from the Australian Bureau of Statistics. Results: Average annual growth in the sales of antidepressants was 1.1% per year from 1975 to 1990, after which growth rose steeply to reach 29% in 1995. By 2002 the rate of growth had slowed to 6.6%. Eighty per cent of total sales were accounted for by four drugs in
Medical Journal of Australia, 1995
Medical Journal of Australia, 1997
Medical Journal of Australia, 1999
Medical Journal of Australia, 1999
John Cade and the discovery of lithium treatment for manic depressive illness P ew people in Aust... more John Cade and the discovery of lithium treatment for manic depressive illness P ew people in Australia, including many medical practitioners, would have heard of John Cade, and fewer still would list him among the most famous Australians of this century. But this quiet and unassuming man, ever curious about the world, was responsible for the discovery of lithium's role in manic depressive illness. In an article in the MJA in 1949 entitled Lithium salts in the treatment ofpsychotic excitement, he described the successful treatment of the first 10 patients with this medication. 1 When Cade began his trials with lithium (Box), there was no effective method available of calming patients with mania. The severity and disturbance of mania made it perhaps the most difficult of acute conditions in clinical psychiatric prac
Death studies
Death of a relative or friend is a potentially disruptive event in the lives of adolescents. To p... more Death of a relative or friend is a potentially disruptive event in the lives of adolescents. To provide targeted help, it is crucial to understand their grief and mental health experiences. Thematic analysis of 39 semistructured telephone interviews yielded two themes: Grieving apart together and Personal growth. High self-reliance and selective sharing were common. Feelings of guilt and "why" questions seemed more pronounced among the suicide bereaved. There was strong evidence of personal growth, increased maturity, and capacity to deal with personal mental health/suicidality. Despite its devastating effects, experiencing a death can be a catalyst for positive mental health.
Death studies, Jan 2, 2018
Despite the potentially devastating effects of a death on the lives of adolescents, little is kno... more Despite the potentially devastating effects of a death on the lives of adolescents, little is known about their help-seeking experiences. We interviewed by telephone 39 bereaved adolescents on their help-seeking experiences. Thematic analysis resulted in three themes: Formal support, Informal support and School-related support. Participants provided a critical appraisal of positive and negative experiences, and noted barriers and facilitators for help-seeking. As adolescents bereaved through suicide may receive less social support, professional help is a much-needed auxiliary. Parental encouragement is important in accessing adequate professional help.
Crisis, 2018
Many of the bereaved through suicide are interested in participating in postvention studies. Howe... more Many of the bereaved through suicide are interested in participating in postvention studies. However, there is a contradiction between the positive experiences of research participation and concerns raised by ethical boards. To review studies on the experience of research participation by those bereaved through suicide, including initial contact with the study and its short- and long-term impacts. Systematic searches in Embase, Medline, PsycINFO, as well as Google Scholar identified 12 papers reporting on 11 studies. The majority (73-100%) of study participants evaluated participation positively, and would recommend it to others (90-100%), as it was related to altruism, social support, and personal growth. A minority experienced participation as negative (2-10%) or upsetting (5-22%) due to feelings of guilt or painful memories. However, having a painful experience does not preclude seeing it as helpful. Most studies concerned face-to-face psychological autopsy studies, and only two ...
NeuroImage. Clinical, 2018
Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocir... more Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which structural changes disrupt the superimposed brain dynamics, leading to the emotional lability that is characteristic of BD. Average controllability is a concept from network control theory that extends structural connectivity data to estimate the manner in which local neuronal fluctuations spread from a node or subnetwork to alter the state of the rest of the brain. We used this theory to ask whether structural connectivity deficits previously observed in HR individuals ( = 84, mean age 22.4), patients with BD ( = 38, mean age 23.9), and age- and gender-matched controls ( = 96, mean age 22.6) translate to differences in the ability of brain systems to be manipulated between states. Localized im...
Journal of affective disorders, 2018
To develop an empirically derived, reliable and valid measure of grief in adolescents, aged 12-18... more To develop an empirically derived, reliable and valid measure of grief in adolescents, aged 12-18 years old. An online survey comprising 59 items derived from a qualitative study of 39 bereaved adolescents, the Hogan Inventory of Bereavement Children and Adolescents (HIB), the Depression, Anxiety and Stress Scales (DASS-21), the Multidimensional Scale of Perceived Social Support (MSPSS), and a series of death- and mental health-related questions, targeted adolescents bereaved when aged 12-18 years, with 176 adolescents (80.6% girls) completing the survey. Factor Analysis of the 59-items resulted in a final solution, the Adolescent Grief Inventory (AGI) comprised of 40 items and 6 factors: Sadness, Self-blame, Anxiety and Self-harm, Shock, Anger and Betrayal, and Sense of Peace, with indices of good fit (RMSEA = 0.057, CFI = 0.952, TLI = 0.948). There was strong evidence of convergent (HIB) and divergent (MSPSS) validity. Adolescents bereaved by suicide scored higher on Self-blame, A...
Molecular psychiatry, Jan 2, 2018
The notion that specific cognitive and emotional processes arise from functionally distinct brain... more The notion that specific cognitive and emotional processes arise from functionally distinct brain regions has lately shifted toward a connectivity-based approach that emphasizes the role of network-mediated integration across regions. The clinical neurosciences have likewise shifted from a predominantly lesion-based approach to a connectomic paradigm-framing disorders as diverse as stroke, schizophrenia (SCZ), and dementia as "dysconnection syndromes". Here we position bipolar disorder (BD) within this paradigm. We first summarise the disruptions in structural, functional and effective connectivity that have been documented in BD. Not surprisingly, these disturbances show a preferential impact on circuits that support emotional processes, cognitive control and executive functions. Those at high risk (HR) for BD also show patterns of connectivity that differ from both matched control populations and those with BD, and which may thus speak to neurobiological markers of both ...
Australian prescriber, 2017
Australian suicide rates are increasing. GPs have a key role in the early detection and managemen... more Australian suicide rates are increasing. GPs have a key role in the early detection and management of suicidality and the treatment of commonly associated mood disorders and substance misuse. Drugs are indicated for moderate to severe depression. They can also be considered for patients who have been unable to access, do not want or have not responded to psychological treatments. Selective serotonin reuptake inhibitors are less toxic than serotonin noradrenaline reuptake inhibitors. Tricyclic antidepressants are the most dangerous in overdose. Mood stabilising drugs can be prescribed, but in large quantities they are dangerous in overdose. In depressed adolescents psychological therapies are first-line treatments. When drugs are indicated, in older people selective serotonin reuptake inhibitors are generally well tolerated, but paroxetine and fluoxetine are best avoided. Suicide prevention is most likely to be effective if a combination of evidenced-based strategies are used both at the individual and population levels. 1,4 One of the strongest evidence-based strategies for suicide prevention is the education of primary care clinicians. 10 In Australia, GPs are the most frequent providers of mental health care and many patients who attempt suicide visit their GP in the preceding months. 11 This makes GPs well placed to help reduce the rate of suicide. Doctors should remember that a therapeutic relationship can be protective. 12-14 The approach to the suicidal patient Most suicidal patients will be distressed and many will feel stigmatised and ashamed. Clinicians should offer comfort, reassurance and hope, and avoid judgement. 15 When a patient admits to suicidal thoughts or behaviour, understanding their predicament begins with an exploration of these phenomena (Box 1). This includes the nature of the thoughts or behaviours, any plans, previous suicide attempts and access to means of harm, for example firearms, poisons, and medicines that are dangerous in overdose such as quetiapine, opioids and tricyclic antidepressants. The clinician should then review the circumstances that might be contributing to the patient's suicidality (Box 2). Management plans should be negotiated with the patient. In most cases family, friends or other psychosocial supports should be involved. 15 A key element of any management plan will be to consider the least restrictive environment for safely starting treatment. Most patients can be managed
Molecular psychiatry, Jan 31, 2018
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biolo... more Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by l...
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Papers by Philip Mitchell