Anthony Harris | The University of Sydney (original) (raw)

Papers by Anthony Harris

Psychiatric Rehabilitation Journal, 2022

OBJECTIVE There is growing interest in using mobile health (mHealth) devices to monitor physiolog... more OBJECTIVE There is growing interest in using mobile health (mHealth) devices to monitor physiological stress associated with mental deterioration. Research is currently examining whether physiological information returned to individuals with serious mental illness (SMI) and their clinicians enhances early intervention. The aim of this study was to explore patient and clinician-related acceptability of an mHealth device to monitor stress for SMI. METHOD Individuals with SMI and their clinicians at a community youth mental health service were shown how an mHealth device could be used to monitor stress. Focus groups and interviews regarding the acceptability of the mHealth device were then conducted with participants (N = 22). Content was transcribed and analyzed using an inductive thematic analysis focusing on perceptions of potential benefit, barriers and facilitators of uptake. RESULTS Six themes were identified. Individuals with SMI and clinicians identified two themes related to benefits of the mHealth device: (a) self-monitoring improves symptom insight and (b) clinician monitoring as a benefit to treatment. They identified one barrier theme: (c) privacy and data misuse concerns. They also identified three facilitators of uptake: (d) ease of use, (e) engaging design and (f) procedural guidelines. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The perceived benefits of passive physiological monitoring afforded by an mHealth device come with concerns regarding its privacy and the potential for ambiguity in the patient-clinician relationship. Results suggest the importance of codesign to ensure that it is secure, easy to use and engaging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

SPIE Proceedings, 2007

We describe a new framework for measuring cortical thickness from MR human brain images. This inv... more We describe a new framework for measuring cortical thickness from MR human brain images. This involves the integration of a method of tissue classification with one to estimate thickness in 3D. We have determined an additional boundary detection step to facilitate this. The classification stage utlizes the Expectation Maximisation (EM) algorithm to classify voxels associated with the tissue types that

Neurocase, 2014

The diagnostic boundary between schizophrenia and bipolar disorder can be unclear, particularly w... more The diagnostic boundary between schizophrenia and bipolar disorder can be unclear, particularly with early onset. We assessed if emotion brain circuits differentiate psychosis versus mania symptoms in a series of six early onset patients. Symptoms were dissociated by direction, awareness condition, and brain regions. Greater psychosis symptoms were correlated with greater prefrontal, anterior cingulate, amygdala, and fusiform face area activation during masked fear processing. By contrast, greater mania symptoms were correlated with less amygdala activation during unmasked fear and happy processing. This suggests emotion dysfunction in schizophrenia versus bipolar disorder may arise from partially distinct neural mechanisms of susceptibility.

Australian & New Zealand Journal of Psychiatry

Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotro... more Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n= 65) and non-melancholic depression (n= 59).

Schizophrenia Research, 2010

work integration of people with severe mental illnesscould optimism in this context be linked to ... more work integration of people with severe mental illnesscould optimism in this context be linked to feelings of self-efficacy? The purpose of this study was therefore to increase our understanding of correlates of optimism in people with severe mental illness in two samples: individuals with recent onset of psychosis, and individuals engaged in a vocational rehabilitation service. Methods: Study 1: This sample consisted of 150 individuals with early psychosis, with a mean age of 25 (SD = 6.4), 61% (N = 92) male and 60% (N = 88) Caucasian. Study 2: This sample consists of a total of 254 individuals taking part in a study on predictors of work outcomes in Prevocational Programs in Montreal (Quebec, Canada). The average age was 38 (S.D. = 8.7), with 53% (N = 135) of the sample being female. Results: Study 1: Optimism was correlated with conscientiousness, neuroticism and extraversion. As expected, optimism was also correlated with self-esteem, the positive, negative and total scores on the SERS-SF(Lecomte et al., 2006). In terms of symptoms, optimism was indeed negatively correlated with depression, anxiety and suicidality, measured on the BPRS but not with psychotic symptoms, either positive or negative. Insight was also negatively correlated with optimism. Regarding relational variables, significant links were found between optimism and all but the relationship as secondary peer attachment scales on the ASQ, as well as the development of friendships and of having leisure activities as measured by the CASIG. Finally, the alliance, assessed with the WAI was significantly linked with optimism as well. The Stepwise linear regression shows that 53% (adjusted R 2 = 52.8) of the variance on the optimism score can be explained by a model including: self-esteem (total score, B = 0.46), capacity for leisure activities (B = 0.16), confidence in others (B = 0.19), low depression (B =-0.16), and low insight (B =-0.14). Study 2: The correlation matrix revealed significant links between optimism and all of the measured concepts (selfefficacy, symptoms, self-esteem and social support). The Stepwise linear regression revealed that 43% (adjusted R2 = 42.7) of the variance is explained by a model including self-esteem total score (B = 0.29), depression (B =-0.33), and reflected self-esteem (B = 0.16)-a social support scale. Discussion: Our results support those of other studies with 'normal' populations suggesting links between optimism and self-esteem and depression. However, optimism after a recent psychotic episode is also linked to abilities to have a network and to perceptions regarding social or familial network. Similarly, individuals trying to integrate the workplace will be more positive about the outcome of their efforts if they also believe they are esteemed by others. Limitations and implications for treatment will be presented.

Early Intervention in Psychiatry, 2009

Aim: This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychologi... more Aim: This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychological variables are most closely associated with functional status around the time of diagnosis of first-episode psychosis. This was with a view to determining factors that should be the focus of intervention in these early stages of illness. Methods: The Western Sydney First Episode Psychosis Project collected data on young persons (aged 13-25) with newly diagnosed psychosis (n = 92). Psychosocial functional status was measured using the Role Functioning Scale (RFS). Multiple regression analyses were carried out to identify predictors of RFS score from a wide range of predictor variables. Results: Psychiatric variables accounted for the most variance in RFS score. Positive and Negative Syndrome Scale (PANSS) Negative subscale and Young Mania Rating Scale score were found to be significant individual predictors, with variables from the other domains failing to contribute to the overall model. In separate models, demographic/ premorbid and neuropsychological factors weakly related to functional status. Conclusions: Psychiatric factors were the main influence on psychosocial functioning in first-episode psychosis at baseline. Evidence suggests the relationships between symptoms, cognition and demographics with function might change over time, depending on the stage of illness being examined.

Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have b... more Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have been found in delusional people. Delusions are also effectively modified by cognitive behavioural therapy (CBT). We sought to examine whether CBT reduces delusional conviction by changing such general reasoning anomalies. Sixteen patients commenced an 8-11 week CBT programme that targeted their delusions. Probabilistic reasoning, attributional biases, and ToM were assessed pre- and post-treatment. Delusional conviction, preoccupation, and distress were rated at each session. Pretreatment task performances were compared to norms. Repeated measures analyses compared pre- and posttreatment task performances and ratings of delusions. Correlational analyses were used to identify factors associated with reduced delusional conviction. At baseline, 11 patients showed some form of abnormal probabilistic reasoning, 13 excessive attributional biases, and 13 defective ToM compared to norms. Fourteen patients completed the CBT programme and showed significant reductions in delusional conviction and preoccupation. Despite some inconsistent evidence of improvement in verbal ToM tasks, reasoning styles in these 14 patients were largely unchanged by CBT. Reasoning anomalies associated with delusions in this sample mark a vulnerability that persists and is independent of the effectiveness of CBT.

Acta Neuropsychiatrica, 2006

Australian and New Zealand Journal of Psychiatry, 2012

Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor... more Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n = 65) and non-melancholic depression (n = 59). A mediation approach ((G × G) × E mediation model) was employed to confirm the indirect effects of ELS on the relationship between 5-HTTPLR × BDNF polymorphism combinations and depression subtype. A series of binary logistic regressions were then conducted to determine whether genotype, ELS, and their interaction were able to predict depression subtype. Key findings indicated that BDNF and 5-HTT polymorphisms in combination with ELS contributed to the development of non-melancholic depression. An interaction between BDNF and ELS increased the risk of non-melancholia by 3.327, whereas the interaction between 5-HTT and ELS increased risk by 2.406. The results support a role for genetic factors in the development of non-melancholia. The lack of findings in melancholia indicates that other mechanisms may underlie the subtype. Alternatively, null findings may reflect a Type II error associated with a small sample size. Future studies should consider further examination of differential gene-environment interactions for melancholia versus non-melancholia.

Journal of Affective Disorders, 2015

The prevalence of depression and anxiety symptoms and their comorbidity varies between males and ... more The prevalence of depression and anxiety symptoms and their comorbidity varies between males and females for reasons still unknown. This study aims to test whether differences between males and females in self-reported symptoms and their covariation are caused by variations in the magnitude of genetic and environmental factors. 750 monozygotic and dizygotic healthy twin pairs (18-60 years; M=39.77 years) participated in the TWIN-E project. Univariate and multivariate genetic modelling was undertaken using the Depression Anxiety Stress Scale (DASS-42). Additive genetics and unique environment contributed to self-reported depression (heritability, h(2): 34%), anxiety (h(2): 30%) and stress (h(2): 34%) scores in univariate models, and to the common latent factor (h(2): 39%) in the multivariate model. No sex differences in magnitude of estimates for DASS-42 scores were found in the univariate model. However when considering correlated depression and anxiety symptomatology only shared genetic factors between depression and anxiety contributed to depression scores in males, but both specific and shared genetic factors contributed to depression scores in females. The results are limited to the sample of healthy, community, adult, same sex twin pairs who participated in the study. Differences in males and females in genetic aetiology of self-reported dimensions of depression are only apparent when taking into consideration the covariation with self-reported anxiety. This difference is highlighted by the finding that both common and specific genetic factors contribute to self-reported depression in females but not males. This novel finding may help explain the increased incidence of depression symptoms in females.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 20, 2015

In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingul... more In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established ...

Neuropsychopharmacology, 2015

Although the cost of poor treatment outcomes of depression is staggering we do not yet have clini... more Although the cost of poor treatment outcomes of depression is staggering we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in MDD and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with major depressive disorder (MDD) in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. 80 MDD outpatients were scanned pre-treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by >=50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (cohen's d effect size.63 to.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward "normalization" post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity which progressed to hypo-reactivity rather than normalization post-treatment and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general versus differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin-norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.Neuropsychopharmacology accepted article preview online, 31 March 2015. doi:10.1038/npp.2015.89.

Neuropsychiatric disease and treatment, 2015

To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable palipe... more To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18...

Frontiers in psychology, 2014

Major depressive disorder (MDD) is associated with increased heart rate and reductions in its var... more Major depressive disorder (MDD) is associated with increased heart rate and reductions in its variability (heart rate variability, HRV) - markers of future morbidity and mortality - yet prior studies have reported contradictory effects. We hypothesized that increases in heart rate and reductions in HRV would be more robust in melancholia relative to controls, than in patients with non-melancholia. A total of 72 patients with a primary diagnosis of MDD (age M: 36.26, SE: 1.34; 42 females) and 94 controls (age M: 35.69, SE: 1.16; 52 females) were included in this study. Heart rate and measures of its variability (HRV) were calculated from two 2-min electrocardiogram recordings during resting state. Propensity score matching controlled imbalance on potential confounds between patients with melancholia (n = 40) and non-melancholia (n = 32) including age, gender, disorder severity, and comorbid anxiety disorders. MDD patients with melancholia displayed significantly increased heart rate ...

International Journal of Neuroscience, 1998

Journal of Affective Disorders, 2015

This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and ps... more This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. Patients with melancholic features (n=339; 33.7%) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. Due to the cross-sectional nature of this study, causal pathways cannot be concluded. Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one׳s emotions. This distinctly poorer capacity for social skills remained post-treatment. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment.

Schizophrenia Research, 2014

Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia an... more Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n = 34, mean age = 14.11, 53% female) and healthy controls (HC, n = 42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness.

Schizophrenia Research, 2014

Objective: Patients with chronic schizophrenia are characterized by deficits in identifying facia... more Objective: Patients with chronic schizophrenia are characterized by deficits in identifying facial expressions of emotion, and these deficits relate to impaired social and occupational function. It is not yet known if these deficits are trait-like and present at the onset of psychosis, preceding a subsequent diagnosis of schizophrenia. Our objective was to systematically review and analyze the extant literature to assess if there is a consistent profile of emotion identification problems in early-onset and first-episode psychosis. Methods: We conducted a systematic review and meta-analysis of 12 peer-reviewed studies of facial emotion identification in early-onset and first-episode psychosis, published between 1980 and March 2013. We examined the average mean difference between patients and controls on measures of facial emotion identification. Results: Findings suggest that patients with early-onset and first-episode psychosis have impairment in identifying facial expressions of biologically salient emotion. Across the 12 studies, the onset of psychosis was distinguished by a generalized effect of significantly poorer accuracy for identifying facial expressions of emotion than healthy controls, and this difference had a substantial effect size (d = −0.88, N = 378, 95% CI = −1.42 to −0.32). Within this general effect some emotions were also harder for patients to identify than others, with the magnitude of impairment found to be (i) large for disgust, fear and surprise, and (ii) medium for sadness, and happiness. No between groups mean differences were found for anger or neutral facial expressions. Conclusions: Deficits in facial emotion identification are evident at first onset of a psychotic episode. The findings suggest that, over and above a generalized deficit in identifying facial emotion, patients may find some emotions harder to identifying than others. This reflects findings with chronic schizophrenia populations and suggests that emotion identification impairment represents a trait susceptibility marker, rather than a sequeale of illness. They signal the urgent need to treat emotion identification deficits at the onset of illness, which could improve functional outcomes.

Psychiatry Research, 2014

Schizophrenia is characterized by deficits in face and facial emotion processing. This is the fir... more Schizophrenia is characterized by deficits in face and facial emotion processing. This is the first study using event-related potentials (ERPs) to investigate the corresponding neural activation in first onset psychosis. ERPs for 108 first onset psychosis participants and 108 matched healthy controls were recorded while they viewed facial expressions. Group differences on general (neutral) face processing and emotional valence were examined under both unmasked (conscious) and backward-masked (nonconscious implicit) conditions over frontal and temporo-occipital regions. Clinical significance was assessed by comparing diagnoses and correlating ERPs with symptoms. During general face processing, patients showed reduced activation within 70 ms and exaggerated later processing from 160 ms over the frontal region, with a negative shift in voltage over left temporal and occipital regions across the time course. In addition, from 70 ms onwards, patients showed a positive shift in voltage for disgust whereas controls showed a negative shift in voltage for fear and anger (both compared to happy) over temporo-occipital regions. Effects were related to disorganization and depression symptoms and (preliminarily) were apparent across psychotic diagnoses. These results suggest that first onset psychosis is characterized by general as well as emotion-specific face processing impairments from the earliest, automatic processing period.

Psychiatric Rehabilitation Journal, 2022

OBJECTIVE There is growing interest in using mobile health (mHealth) devices to monitor physiolog... more OBJECTIVE There is growing interest in using mobile health (mHealth) devices to monitor physiological stress associated with mental deterioration. Research is currently examining whether physiological information returned to individuals with serious mental illness (SMI) and their clinicians enhances early intervention. The aim of this study was to explore patient and clinician-related acceptability of an mHealth device to monitor stress for SMI. METHOD Individuals with SMI and their clinicians at a community youth mental health service were shown how an mHealth device could be used to monitor stress. Focus groups and interviews regarding the acceptability of the mHealth device were then conducted with participants (N = 22). Content was transcribed and analyzed using an inductive thematic analysis focusing on perceptions of potential benefit, barriers and facilitators of uptake. RESULTS Six themes were identified. Individuals with SMI and clinicians identified two themes related to benefits of the mHealth device: (a) self-monitoring improves symptom insight and (b) clinician monitoring as a benefit to treatment. They identified one barrier theme: (c) privacy and data misuse concerns. They also identified three facilitators of uptake: (d) ease of use, (e) engaging design and (f) procedural guidelines. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The perceived benefits of passive physiological monitoring afforded by an mHealth device come with concerns regarding its privacy and the potential for ambiguity in the patient-clinician relationship. Results suggest the importance of codesign to ensure that it is secure, easy to use and engaging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

SPIE Proceedings, 2007

We describe a new framework for measuring cortical thickness from MR human brain images. This inv... more We describe a new framework for measuring cortical thickness from MR human brain images. This involves the integration of a method of tissue classification with one to estimate thickness in 3D. We have determined an additional boundary detection step to facilitate this. The classification stage utlizes the Expectation Maximisation (EM) algorithm to classify voxels associated with the tissue types that

Neurocase, 2014

The diagnostic boundary between schizophrenia and bipolar disorder can be unclear, particularly w... more The diagnostic boundary between schizophrenia and bipolar disorder can be unclear, particularly with early onset. We assessed if emotion brain circuits differentiate psychosis versus mania symptoms in a series of six early onset patients. Symptoms were dissociated by direction, awareness condition, and brain regions. Greater psychosis symptoms were correlated with greater prefrontal, anterior cingulate, amygdala, and fusiform face area activation during masked fear processing. By contrast, greater mania symptoms were correlated with less amygdala activation during unmasked fear and happy processing. This suggests emotion dysfunction in schizophrenia versus bipolar disorder may arise from partially distinct neural mechanisms of susceptibility.

Australian & New Zealand Journal of Psychiatry

Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotro... more Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n= 65) and non-melancholic depression (n= 59).

Schizophrenia Research, 2010

work integration of people with severe mental illnesscould optimism in this context be linked to ... more work integration of people with severe mental illnesscould optimism in this context be linked to feelings of self-efficacy? The purpose of this study was therefore to increase our understanding of correlates of optimism in people with severe mental illness in two samples: individuals with recent onset of psychosis, and individuals engaged in a vocational rehabilitation service. Methods: Study 1: This sample consisted of 150 individuals with early psychosis, with a mean age of 25 (SD = 6.4), 61% (N = 92) male and 60% (N = 88) Caucasian. Study 2: This sample consists of a total of 254 individuals taking part in a study on predictors of work outcomes in Prevocational Programs in Montreal (Quebec, Canada). The average age was 38 (S.D. = 8.7), with 53% (N = 135) of the sample being female. Results: Study 1: Optimism was correlated with conscientiousness, neuroticism and extraversion. As expected, optimism was also correlated with self-esteem, the positive, negative and total scores on the SERS-SF(Lecomte et al., 2006). In terms of symptoms, optimism was indeed negatively correlated with depression, anxiety and suicidality, measured on the BPRS but not with psychotic symptoms, either positive or negative. Insight was also negatively correlated with optimism. Regarding relational variables, significant links were found between optimism and all but the relationship as secondary peer attachment scales on the ASQ, as well as the development of friendships and of having leisure activities as measured by the CASIG. Finally, the alliance, assessed with the WAI was significantly linked with optimism as well. The Stepwise linear regression shows that 53% (adjusted R 2 = 52.8) of the variance on the optimism score can be explained by a model including: self-esteem (total score, B = 0.46), capacity for leisure activities (B = 0.16), confidence in others (B = 0.19), low depression (B =-0.16), and low insight (B =-0.14). Study 2: The correlation matrix revealed significant links between optimism and all of the measured concepts (selfefficacy, symptoms, self-esteem and social support). The Stepwise linear regression revealed that 43% (adjusted R2 = 42.7) of the variance is explained by a model including self-esteem total score (B = 0.29), depression (B =-0.33), and reflected self-esteem (B = 0.16)-a social support scale. Discussion: Our results support those of other studies with 'normal' populations suggesting links between optimism and self-esteem and depression. However, optimism after a recent psychotic episode is also linked to abilities to have a network and to perceptions regarding social or familial network. Similarly, individuals trying to integrate the workplace will be more positive about the outcome of their efforts if they also believe they are esteemed by others. Limitations and implications for treatment will be presented.

Early Intervention in Psychiatry, 2009

Aim: This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychologi... more Aim: This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychological variables are most closely associated with functional status around the time of diagnosis of first-episode psychosis. This was with a view to determining factors that should be the focus of intervention in these early stages of illness. Methods: The Western Sydney First Episode Psychosis Project collected data on young persons (aged 13-25) with newly diagnosed psychosis (n = 92). Psychosocial functional status was measured using the Role Functioning Scale (RFS). Multiple regression analyses were carried out to identify predictors of RFS score from a wide range of predictor variables. Results: Psychiatric variables accounted for the most variance in RFS score. Positive and Negative Syndrome Scale (PANSS) Negative subscale and Young Mania Rating Scale score were found to be significant individual predictors, with variables from the other domains failing to contribute to the overall model. In separate models, demographic/ premorbid and neuropsychological factors weakly related to functional status. Conclusions: Psychiatric factors were the main influence on psychosocial functioning in first-episode psychosis at baseline. Evidence suggests the relationships between symptoms, cognition and demographics with function might change over time, depending on the stage of illness being examined.

Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have b... more Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have been found in delusional people. Delusions are also effectively modified by cognitive behavioural therapy (CBT). We sought to examine whether CBT reduces delusional conviction by changing such general reasoning anomalies. Sixteen patients commenced an 8-11 week CBT programme that targeted their delusions. Probabilistic reasoning, attributional biases, and ToM were assessed pre- and post-treatment. Delusional conviction, preoccupation, and distress were rated at each session. Pretreatment task performances were compared to norms. Repeated measures analyses compared pre- and posttreatment task performances and ratings of delusions. Correlational analyses were used to identify factors associated with reduced delusional conviction. At baseline, 11 patients showed some form of abnormal probabilistic reasoning, 13 excessive attributional biases, and 13 defective ToM compared to norms. Fourteen patients completed the CBT programme and showed significant reductions in delusional conviction and preoccupation. Despite some inconsistent evidence of improvement in verbal ToM tasks, reasoning styles in these 14 patients were largely unchanged by CBT. Reasoning anomalies associated with delusions in this sample mark a vulnerability that persists and is independent of the effectiveness of CBT.

Acta Neuropsychiatrica, 2006

Australian and New Zealand Journal of Psychiatry, 2012

Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor... more Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n = 65) and non-melancholic depression (n = 59). A mediation approach ((G × G) × E mediation model) was employed to confirm the indirect effects of ELS on the relationship between 5-HTTPLR × BDNF polymorphism combinations and depression subtype. A series of binary logistic regressions were then conducted to determine whether genotype, ELS, and their interaction were able to predict depression subtype. Key findings indicated that BDNF and 5-HTT polymorphisms in combination with ELS contributed to the development of non-melancholic depression. An interaction between BDNF and ELS increased the risk of non-melancholia by 3.327, whereas the interaction between 5-HTT and ELS increased risk by 2.406. The results support a role for genetic factors in the development of non-melancholia. The lack of findings in melancholia indicates that other mechanisms may underlie the subtype. Alternatively, null findings may reflect a Type II error associated with a small sample size. Future studies should consider further examination of differential gene-environment interactions for melancholia versus non-melancholia.

Journal of Affective Disorders, 2015

The prevalence of depression and anxiety symptoms and their comorbidity varies between males and ... more The prevalence of depression and anxiety symptoms and their comorbidity varies between males and females for reasons still unknown. This study aims to test whether differences between males and females in self-reported symptoms and their covariation are caused by variations in the magnitude of genetic and environmental factors. 750 monozygotic and dizygotic healthy twin pairs (18-60 years; M=39.77 years) participated in the TWIN-E project. Univariate and multivariate genetic modelling was undertaken using the Depression Anxiety Stress Scale (DASS-42). Additive genetics and unique environment contributed to self-reported depression (heritability, h(2): 34%), anxiety (h(2): 30%) and stress (h(2): 34%) scores in univariate models, and to the common latent factor (h(2): 39%) in the multivariate model. No sex differences in magnitude of estimates for DASS-42 scores were found in the univariate model. However when considering correlated depression and anxiety symptomatology only shared genetic factors between depression and anxiety contributed to depression scores in males, but both specific and shared genetic factors contributed to depression scores in females. The results are limited to the sample of healthy, community, adult, same sex twin pairs who participated in the study. Differences in males and females in genetic aetiology of self-reported dimensions of depression are only apparent when taking into consideration the covariation with self-reported anxiety. This difference is highlighted by the finding that both common and specific genetic factors contribute to self-reported depression in females but not males. This novel finding may help explain the increased incidence of depression symptoms in females.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 20, 2015

In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingul... more In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established ...

Neuropsychopharmacology, 2015

Although the cost of poor treatment outcomes of depression is staggering we do not yet have clini... more Although the cost of poor treatment outcomes of depression is staggering we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in MDD and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with major depressive disorder (MDD) in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. 80 MDD outpatients were scanned pre-treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by >=50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (cohen's d effect size.63 to.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward "normalization" post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity which progressed to hypo-reactivity rather than normalization post-treatment and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general versus differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin-norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.Neuropsychopharmacology accepted article preview online, 31 March 2015. doi:10.1038/npp.2015.89.

Neuropsychiatric disease and treatment, 2015

To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable palipe... more To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18...

Frontiers in psychology, 2014

Major depressive disorder (MDD) is associated with increased heart rate and reductions in its var... more Major depressive disorder (MDD) is associated with increased heart rate and reductions in its variability (heart rate variability, HRV) - markers of future morbidity and mortality - yet prior studies have reported contradictory effects. We hypothesized that increases in heart rate and reductions in HRV would be more robust in melancholia relative to controls, than in patients with non-melancholia. A total of 72 patients with a primary diagnosis of MDD (age M: 36.26, SE: 1.34; 42 females) and 94 controls (age M: 35.69, SE: 1.16; 52 females) were included in this study. Heart rate and measures of its variability (HRV) were calculated from two 2-min electrocardiogram recordings during resting state. Propensity score matching controlled imbalance on potential confounds between patients with melancholia (n = 40) and non-melancholia (n = 32) including age, gender, disorder severity, and comorbid anxiety disorders. MDD patients with melancholia displayed significantly increased heart rate ...

International Journal of Neuroscience, 1998

Journal of Affective Disorders, 2015

This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and ps... more This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. Patients with melancholic features (n=339; 33.7%) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. Due to the cross-sectional nature of this study, causal pathways cannot be concluded. Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one׳s emotions. This distinctly poorer capacity for social skills remained post-treatment. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment.

Schizophrenia Research, 2014

Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia an... more Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n = 34, mean age = 14.11, 53% female) and healthy controls (HC, n = 42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness.

Schizophrenia Research, 2014

Objective: Patients with chronic schizophrenia are characterized by deficits in identifying facia... more Objective: Patients with chronic schizophrenia are characterized by deficits in identifying facial expressions of emotion, and these deficits relate to impaired social and occupational function. It is not yet known if these deficits are trait-like and present at the onset of psychosis, preceding a subsequent diagnosis of schizophrenia. Our objective was to systematically review and analyze the extant literature to assess if there is a consistent profile of emotion identification problems in early-onset and first-episode psychosis. Methods: We conducted a systematic review and meta-analysis of 12 peer-reviewed studies of facial emotion identification in early-onset and first-episode psychosis, published between 1980 and March 2013. We examined the average mean difference between patients and controls on measures of facial emotion identification. Results: Findings suggest that patients with early-onset and first-episode psychosis have impairment in identifying facial expressions of biologically salient emotion. Across the 12 studies, the onset of psychosis was distinguished by a generalized effect of significantly poorer accuracy for identifying facial expressions of emotion than healthy controls, and this difference had a substantial effect size (d = −0.88, N = 378, 95% CI = −1.42 to −0.32). Within this general effect some emotions were also harder for patients to identify than others, with the magnitude of impairment found to be (i) large for disgust, fear and surprise, and (ii) medium for sadness, and happiness. No between groups mean differences were found for anger or neutral facial expressions. Conclusions: Deficits in facial emotion identification are evident at first onset of a psychotic episode. The findings suggest that, over and above a generalized deficit in identifying facial emotion, patients may find some emotions harder to identifying than others. This reflects findings with chronic schizophrenia populations and suggests that emotion identification impairment represents a trait susceptibility marker, rather than a sequeale of illness. They signal the urgent need to treat emotion identification deficits at the onset of illness, which could improve functional outcomes.

Psychiatry Research, 2014

Schizophrenia is characterized by deficits in face and facial emotion processing. This is the fir... more Schizophrenia is characterized by deficits in face and facial emotion processing. This is the first study using event-related potentials (ERPs) to investigate the corresponding neural activation in first onset psychosis. ERPs for 108 first onset psychosis participants and 108 matched healthy controls were recorded while they viewed facial expressions. Group differences on general (neutral) face processing and emotional valence were examined under both unmasked (conscious) and backward-masked (nonconscious implicit) conditions over frontal and temporo-occipital regions. Clinical significance was assessed by comparing diagnoses and correlating ERPs with symptoms. During general face processing, patients showed reduced activation within 70 ms and exaggerated later processing from 160 ms over the frontal region, with a negative shift in voltage over left temporal and occipital regions across the time course. In addition, from 70 ms onwards, patients showed a positive shift in voltage for disgust whereas controls showed a negative shift in voltage for fear and anger (both compared to happy) over temporo-occipital regions. Effects were related to disorganization and depression symptoms and (preliminarily) were apparent across psychotic diagnoses. These results suggest that first onset psychosis is characterized by general as well as emotion-specific face processing impairments from the earliest, automatic processing period.

American Journal of Psychiatry, 2004

There has been consistent evidence for a lower incidence and milder course of schizophrenia in wo... more There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia.

Schizophrenia Research, 2010

work integration of people with severe mental illnesscould optimism in this context be linked to ... more work integration of people with severe mental illnesscould optimism in this context be linked to feelings of self-efficacy? The purpose of this study was therefore to increase our understanding of correlates of optimism in people with severe mental illness in two samples: individuals with recent onset of psychosis, and individuals engaged in a vocational rehabilitation service. Methods: Study 1: This sample consisted of 150 individuals with early psychosis, with a mean age of 25 (SD = 6.4), 61% (N = 92) male and 60% (N = 88) Caucasian. Study 2: This sample consists of a total of 254 individuals taking part in a study on predictors of work outcomes in Prevocational Programs in Montreal (Quebec, Canada). The average age was 38 (S.D. = 8.7), with 53% (N = 135) of the sample being female. Results: Study 1: Optimism was correlated with conscientiousness, neuroticism and extraversion. As expected, optimism was also correlated with self-esteem, the positive, negative and total scores on the SERS-SF (Lecomte et al., 2006). In terms of symptoms, optimism was indeed negatively correlated with depression, anxiety and suicidality, measured on the BPRS but not with psychotic symptoms, either positive or negative. Insight was also negatively correlated with optimism. Regarding relational variables, significant links were found between optimism and all but the relationship as secondary peer attachment scales on the ASQ, as well as the development of friendships and of having leisure activities as measured by the CASIG. Finally, the alliance, assessed with the WAI was significantly linked with optimism as well. The Stepwise linear regression shows that 53% (adjusted R 2 = 52.8) of the variance on the optimism score can be explained by a model including: self-esteem (total score, B = 0.46), capacity for leisure activities (B = 0.16), confidence in others (B = 0.19), low depression (B = -0.16), and low insight (B = -0.14). Study 2: The correlation matrix revealed significant links between optimism and all of the measured concepts (selfefficacy, symptoms, self-esteem and social support). The Stepwise linear regression revealed that 43% (adjusted R2 = 42.7) of the variance is explained by a model including self-esteem total score (B = 0.29), depression (B = -0.33), and reflected self-esteem (B = 0.16) -a social support scale. Discussion: Our results support those of other studies with 'normal' populations suggesting links between optimism and self-esteem and depression. However, optimism after a recent psychotic episode is also linked to abilities to have a network and to perceptions regarding social or familial network. Similarly, individuals trying to integrate the workplace will be more positive about the outcome of their efforts if they also believe they are esteemed by others. Limitations and implications for treatment will be presented.