Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, Jan 9, 2015
To assess the relationship between bipolar spectrum disorders, anxiety disorders, trauma, and per... more To assess the relationship between bipolar spectrum disorders, anxiety disorders, trauma, and personality function. A cohort of 37 diagnostically challenging bipolar spectrum patients, including both bipolar and personality disordered patients, were assessed using the Structured Combined Interview for DSM-IV to establish diagnosis of bipolarity and anxiety. Diagnoses were then quantitatively related to personality function, using the DSM-5 Level of Personality Function Scale, and to attachment, using the Relationship Questionnaire and Relationship Style Questionnaire. Number of comorbid anxiety disorders was significantly related to both personality and attachment, but not to bipolar status. Patients with more than one anxiety disorder were significantly more likely to have an underlying disturbance of personality. The presence of multiple anxiety disorders in bipolar spectrum patients may indicate heightened risk of an underlying personality disorder. Replication in a larger and mo...
The British journal of psychiatry : the journal of mental science, 2014
The classification of mood disorders lacks precision and consequently there has been no recent me... more The classification of mood disorders lacks precision and consequently there has been no recent meaningful advance in their treatment. By virtue of its therapeutic specificity, lithium responsivity offers an opportunity to diagnose a definitive subtype of mood disorders that may provide a platform for the development of targeted therapy.
For exposure therapy to be successful, it is essential that fear extinction learning extends beyo... more For exposure therapy to be successful, it is essential that fear extinction learning extends beyond the treatment setting. d-Cycloserine (DCS) may facilitate treatment gains by increasing generalization of extinction learning, however, its effects have not been tested in children. We examined whether DCS enhanced generalization of fear extinction learning across different stimuli and contexts among children with specific phobias. The study was a double-blind placebo-controlled randomized controlled trial among dog or spider phobic children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo (n = 17) before receiving a single prolonged exposure session to their feared stimulus. Return of fear was examined 1 week later to a different stimulus (a different dog or spider), presented in both the original treatment context and an alternate context. Avoidance and fear were measured with Behavior Approach Tests (BATs), where the child was asked to increase proximity to ...
... Gin Malhi has served on pharmaceutical advisory boards, received funding for research and bee... more ... Gin Malhi has served on pharmaceutical advisory boards, received funding for research and been in receipt of honoraria for talks at sponsored meetings involving AstraZeneca, Eli Lilly, Janssen-Cilag, Organon, Pfizer and Wyeth. ... 15 Aman MG, Arnold E, McDougle CJ et al. ...
The Australian and New Zealand journal of psychiatry, 2014
Stimulants may worsen psychotic symptoms but there is limited evidence about the impact of stimul... more Stimulants may worsen psychotic symptoms but there is limited evidence about the impact of stimulant abuse in people with schizophrenia. This study examined the prevalence and correlates of stimulant and other drug disorders in a population-based sample of people with schizophrenia, examining associations with frequent service use, physical health comorbidities and accommodation instability. New South Wales (NSW) hospital, community mental health and emergency department data were used to examine health service contact over 5 years in 13,624 people with a diagnosis of schizophrenia. Associations of stimulant disorders were examined with multinomial logistic regression, comparing people with no substance disorders to those with cannabis disorders, stimulant disorders or both. Of people with schizophrenia, 51% had substance disorders, including 14% with stimulant disorders. Stimulant disorders were more common in young adults and in urban areas, less common in migrants, and unrelated ...
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 7, 2014
Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, an... more Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asber...
The Australian and New Zealand journal of psychiatry, 2015
Stimulant abuse and dependence often complicate the care of people with psychotic disorders. This... more Stimulant abuse and dependence often complicate the care of people with psychotic disorders. This study systematically reviews the prevalence estimates reported for stimulant abuse and dependence in people with psychotic disorders, and examines personal, clinical, regional and methodological factors which explain variation in these rates. PsychINFO, EMBASE and MEDLINE (1946-2013) were searched systematically for studies reporting on stimulant drug use disorders in representative samples of people with psychotic disorders. Random effects models estimated the pooled rate of a stimulant use disorder, defined to include stimulant abuse and stimulant dependence. Study characteristics associated with heterogeneity in rates of stimulant use disorder were examined by subgroup analyses for categorical variables, by meta-regression for continuous independent variables and by multiple meta-regression. Sixty-four studies provided 68 estimates of lifetime or recent stimulant use disorders in 22,...
Objective: Bipolar disorder is a multifaceted illness and there is often a substantial delay betw... more 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.
Authors investigated the effects of current age, age at onset, and gender on the phenomenology of... more Authors investigated the effects of current age, age at onset, and gender on the phenomenology of depression. A mixed-age sample of 810 Mood Disorders Unit attendees with a diagnosis of unipolar major depressive episode at or near its nadir were interviewed by clinician-rated and self-report instruments assessing symptoms and severity of depression. Differences were found in depressive phenomenology according to current age but not age at onset, confirming previous findings. Age differences on several variables were found in women only. Subjective ratings of depression severity decreased with age, whereas objective, clinician-rated severity increased. The pattern and severity of depression change with increasing age. Longitudinal prospective studies would further elucidate this age-gender relationship. Clinicians should be aware of the decreased likelihood of older patients' reporting of depressive symptoms themselves.
Acute neural effects of antidepressant medication on emotion processing biases may provide the fo... more Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing...
The Australian and New Zealand journal of psychiatry, 2014
Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may... more Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may depend on individual differences in acute effects on neural emotion processing. The short ('S') allele of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) is associated with both negative emotion processing biases and poorer treatment outcomes. Therefore, the aim of the present study was to explore the effects of 5-HTTLPR on the impact of the SSRI escitalopram during processing of positive and negative emotional images, as well as neutral stimuli. The study employed a double-blind, randomised, placebo-controlled crossover design on 36 healthy Caucasian female participants who underwent functional magnetic resonance imaging (fMRI) scanning following placebo or escitalopram treatment, separated by a 7-day washout period. Changes in the left amygdala signal with escitalopram treatment during processing of emotional stimuli were linearly related to the 5-HTTLPR...
This MRI study examined the morphology of the olfactory sulcus, a potential marker of early neuro... more This MRI study examined the morphology of the olfactory sulcus, a potential marker of early neurodevelopment in 26 patients with bipolar I disorder and 24 matched controls. Bipolar patients had significantly shallower olfactory sulci bilaterally compared to controls, suggesting that neurodevelopmental abnormalities contribute to the neurobiology of bipolar disorder.
Anxious depression" is used variably both by researchers and clinicians to describe admixtures of... more Anxious depression" is used variably both by researchers and clinicians to describe admixtures of anxiety and depressive symptoms. The authors sought to determine the best model for conceptualizing anxious depression by studying a sample of depressed patients referred to a tertiary referral unit. Anxiety and depression were assessed using a comprehensive set of mixed symptoms that were subsequently refined to provide separate anxiety and depressive factors, and patients were trichotomized into groups of low, medium, and high anxiety on the basis of their total anxiety factor scores. Associations between the constructs of anxiety and depression in different depressive subgroups were explored, and the severity of depressive symptoms and other clinical variables across the three anxiety groupings was assessed. Depression variables were not linearly associated in a consistent pattern with anxiety-defined groups, arguing against a simple interdependence model driven by a higher-order variable such as depression severity. By contrast, the state anxiety categories were linked strongly with lifetime anxiety disorder prevalence, with some associations linear and with others evidencing a trend break association. The authors found support for a model of anxious depression, whereby anxiety both predisposes to nonmelancholic depression and contributes to its presentation by shaping its clinical features. Such a model and its definition assist in clarifying the cause of anxious depression and its treatment.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, Jan 9, 2015
To assess the relationship between bipolar spectrum disorders, anxiety disorders, trauma, and per... more To assess the relationship between bipolar spectrum disorders, anxiety disorders, trauma, and personality function. A cohort of 37 diagnostically challenging bipolar spectrum patients, including both bipolar and personality disordered patients, were assessed using the Structured Combined Interview for DSM-IV to establish diagnosis of bipolarity and anxiety. Diagnoses were then quantitatively related to personality function, using the DSM-5 Level of Personality Function Scale, and to attachment, using the Relationship Questionnaire and Relationship Style Questionnaire. Number of comorbid anxiety disorders was significantly related to both personality and attachment, but not to bipolar status. Patients with more than one anxiety disorder were significantly more likely to have an underlying disturbance of personality. The presence of multiple anxiety disorders in bipolar spectrum patients may indicate heightened risk of an underlying personality disorder. Replication in a larger and mo...
The British journal of psychiatry : the journal of mental science, 2014
The classification of mood disorders lacks precision and consequently there has been no recent me... more The classification of mood disorders lacks precision and consequently there has been no recent meaningful advance in their treatment. By virtue of its therapeutic specificity, lithium responsivity offers an opportunity to diagnose a definitive subtype of mood disorders that may provide a platform for the development of targeted therapy.
For exposure therapy to be successful, it is essential that fear extinction learning extends beyo... more For exposure therapy to be successful, it is essential that fear extinction learning extends beyond the treatment setting. d-Cycloserine (DCS) may facilitate treatment gains by increasing generalization of extinction learning, however, its effects have not been tested in children. We examined whether DCS enhanced generalization of fear extinction learning across different stimuli and contexts among children with specific phobias. The study was a double-blind placebo-controlled randomized controlled trial among dog or spider phobic children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo (n = 17) before receiving a single prolonged exposure session to their feared stimulus. Return of fear was examined 1 week later to a different stimulus (a different dog or spider), presented in both the original treatment context and an alternate context. Avoidance and fear were measured with Behavior Approach Tests (BATs), where the child was asked to increase proximity to ...
... Gin Malhi has served on pharmaceutical advisory boards, received funding for research and bee... more ... Gin Malhi has served on pharmaceutical advisory boards, received funding for research and been in receipt of honoraria for talks at sponsored meetings involving AstraZeneca, Eli Lilly, Janssen-Cilag, Organon, Pfizer and Wyeth. ... 15 Aman MG, Arnold E, McDougle CJ et al. ...
The Australian and New Zealand journal of psychiatry, 2014
Stimulants may worsen psychotic symptoms but there is limited evidence about the impact of stimul... more Stimulants may worsen psychotic symptoms but there is limited evidence about the impact of stimulant abuse in people with schizophrenia. This study examined the prevalence and correlates of stimulant and other drug disorders in a population-based sample of people with schizophrenia, examining associations with frequent service use, physical health comorbidities and accommodation instability. New South Wales (NSW) hospital, community mental health and emergency department data were used to examine health service contact over 5 years in 13,624 people with a diagnosis of schizophrenia. Associations of stimulant disorders were examined with multinomial logistic regression, comparing people with no substance disorders to those with cannabis disorders, stimulant disorders or both. Of people with schizophrenia, 51% had substance disorders, including 14% with stimulant disorders. Stimulant disorders were more common in young adults and in urban areas, less common in migrants, and unrelated ...
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 7, 2014
Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, an... more Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asber...
The Australian and New Zealand journal of psychiatry, 2015
Stimulant abuse and dependence often complicate the care of people with psychotic disorders. This... more Stimulant abuse and dependence often complicate the care of people with psychotic disorders. This study systematically reviews the prevalence estimates reported for stimulant abuse and dependence in people with psychotic disorders, and examines personal, clinical, regional and methodological factors which explain variation in these rates. PsychINFO, EMBASE and MEDLINE (1946-2013) were searched systematically for studies reporting on stimulant drug use disorders in representative samples of people with psychotic disorders. Random effects models estimated the pooled rate of a stimulant use disorder, defined to include stimulant abuse and stimulant dependence. Study characteristics associated with heterogeneity in rates of stimulant use disorder were examined by subgroup analyses for categorical variables, by meta-regression for continuous independent variables and by multiple meta-regression. Sixty-four studies provided 68 estimates of lifetime or recent stimulant use disorders in 22,...
Objective: Bipolar disorder is a multifaceted illness and there is often a substantial delay betw... more 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.
Authors investigated the effects of current age, age at onset, and gender on the phenomenology of... more Authors investigated the effects of current age, age at onset, and gender on the phenomenology of depression. A mixed-age sample of 810 Mood Disorders Unit attendees with a diagnosis of unipolar major depressive episode at or near its nadir were interviewed by clinician-rated and self-report instruments assessing symptoms and severity of depression. Differences were found in depressive phenomenology according to current age but not age at onset, confirming previous findings. Age differences on several variables were found in women only. Subjective ratings of depression severity decreased with age, whereas objective, clinician-rated severity increased. The pattern and severity of depression change with increasing age. Longitudinal prospective studies would further elucidate this age-gender relationship. Clinicians should be aware of the decreased likelihood of older patients' reporting of depressive symptoms themselves.
Acute neural effects of antidepressant medication on emotion processing biases may provide the fo... more Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing...
The Australian and New Zealand journal of psychiatry, 2014
Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may... more Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may depend on individual differences in acute effects on neural emotion processing. The short ('S') allele of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) is associated with both negative emotion processing biases and poorer treatment outcomes. Therefore, the aim of the present study was to explore the effects of 5-HTTLPR on the impact of the SSRI escitalopram during processing of positive and negative emotional images, as well as neutral stimuli. The study employed a double-blind, randomised, placebo-controlled crossover design on 36 healthy Caucasian female participants who underwent functional magnetic resonance imaging (fMRI) scanning following placebo or escitalopram treatment, separated by a 7-day washout period. Changes in the left amygdala signal with escitalopram treatment during processing of emotional stimuli were linearly related to the 5-HTTLPR...
This MRI study examined the morphology of the olfactory sulcus, a potential marker of early neuro... more This MRI study examined the morphology of the olfactory sulcus, a potential marker of early neurodevelopment in 26 patients with bipolar I disorder and 24 matched controls. Bipolar patients had significantly shallower olfactory sulci bilaterally compared to controls, suggesting that neurodevelopmental abnormalities contribute to the neurobiology of bipolar disorder.
Anxious depression" is used variably both by researchers and clinicians to describe admixtures of... more Anxious depression" is used variably both by researchers and clinicians to describe admixtures of anxiety and depressive symptoms. The authors sought to determine the best model for conceptualizing anxious depression by studying a sample of depressed patients referred to a tertiary referral unit. Anxiety and depression were assessed using a comprehensive set of mixed symptoms that were subsequently refined to provide separate anxiety and depressive factors, and patients were trichotomized into groups of low, medium, and high anxiety on the basis of their total anxiety factor scores. Associations between the constructs of anxiety and depression in different depressive subgroups were explored, and the severity of depressive symptoms and other clinical variables across the three anxiety groupings was assessed. Depression variables were not linearly associated in a consistent pattern with anxiety-defined groups, arguing against a simple interdependence model driven by a higher-order variable such as depression severity. By contrast, the state anxiety categories were linked strongly with lifetime anxiety disorder prevalence, with some associations linear and with others evidencing a trend break association. The authors found support for a model of anxious depression, whereby anxiety both predisposes to nonmelancholic depression and contributes to its presentation by shaping its clinical features. Such a model and its definition assist in clarifying the cause of anxious depression and its treatment.
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