Search PubMed⌕ Search

Biomedical subjects

Philip B Mitchell

Publications and source records attributed to Philip B Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2005

Executive functioning and theory of mind in euthymic bipolar disorder.

OBJECTIVES: To examine the nature of executive deficits in euthymic patients with bipolar disorder (BD). METHODS: Fifteen euthymic BD patients and 13 controls were administered a battery of executive tasks including verbal fluency, Stroop, Theory of Mind (ToM) tests and selected subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Self-report and clinician ratings of mood and social and occupational functioning were also obtained. RESULTS: There were no significant differences between BD patients and controls on the primary measures of the following executive tasks: verbal fluency, attentional set-shifting, problem solving or planning. On secondary measures of speed, BD patients were slower to complete the first trial of the Stroop task (p = 0.001). Patients with BD committed more errors across all secondary measures. Patients performed poorly when compared with controls on tests of verbal ToM (p = 0.02), and although they performed non-verbal ToM tasks at a level comparable to controls (p = 0.60), they were slower to initiate a response (p = 0.006). ToM was not significantly correlated with any measure of social and occupational functioning; however it correlated with the achievement scores of the CANTAB Stockings of Cambridge task (Pearson's r = 0.68, p < 0.01). CONCLUSIONS: Deficits found in euthymic bipolar patients suggest fronto-subcortical pathway dysfunction. This is consistent with other neuropsychological and neuroimaging research that points to a trait deficit in BD. Further investigation is necessary perhaps using more real-world tests.

Adult↗
PubMed2005

Treatment of bipolar depression: focus on pharmacologic therapies.

Recent studies have highlighted significant limitations in our capacity to effectively treat bipolar depression. This article reviews the present status of treatments for this condition, highlighting emerging new pharmacotherapies such as lamotrigine, olanzapine and quetiapine, while also addressing modern psychologic interventions such as cognitive behavioral therapy and psychoeducation. The role of older treatments such as lithium and the antidepressants is also discussed, particularly as a recent meta-analysis has thrown into question current heightened concern over antidepressant-induced mania. The advent of new pharmacologic and psychologic treatments provides optimism for improved outcomes for this highly disabling condition.

Anticonvulsants↗
PubMed2004

A Brief Measure of Worry Severity (BMWS): personality and clinical correlates of severe worriers.

This report describes the development of a brief and valid self-report measure to assess severe and dysfunctional worry (the Brief Measure of Worry Severity or BMWS). Using three independent subject groups (clinical and non-clinical), the measure was used to examine the differential severity of worry in depression and anxiety and to examine the clinical and personality correlates of severe worriers. Preliminary psychometric evaluation revealed that the BMWS possesses good construct and clinical discriminant validity. Subjects reporting greater worry severity tended to be more "introverted" and "obsessional," but less "agreeable" and "conscientious." Subjects with depression only, reported less problems with worrying compared to those with co-morbid anxiety disorders. However, among the anxiety disorders, severe and dysfunctional worry was not exclusively experienced by subjects with generalized anxiety disorder (GAD). This study suggests that pathological worry is not only relevant for patients with GAD, but may be an equally detrimental cognitive activity for patients with panic disorder and obsessive-compulsive disorder.

Adolescent↗
PubMed2004

Making new choices about antidepressants in Australia: the long view 1975-2002.

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 1975, 1980 and 1985; five in 1990; seven drugs in 1995 and 2000; and six drugs in 2001 and 2002. CONCLUSIONS: The rapid growth in antidepressant prescribing that was characteristic of the early 1990s, and reflected the emergence of new classes of agents, did not continue into the late 1990s. Selective serotonin reuptake inhibitors now dominate antidepressant prescribing in Australia.

Antidepressive Agents↗
PubMed2004

Major advances in bipolar disorder.

There have been major advances in clinical understanding and treatment of bipolar disorder over the past decade. Randomised controlled trials of pharmacological treatments and psychological interventions have shown that there are effective short-term and long-term treatments for the disorder. Despite advances in treatment, diagnosis is often delayed or mistaken, and many people who could benefit are not using the treatments available. Functional and symptomatic recovery from episodes of bipolar disorder is frequently less complete than previously considered, and disability is often profound. Although manic episodes are the distinguishing feature of bipolar disorder, it appears that depression is the predominant mood disturbance and that much of the functional impairment associated with bipolar disorder results from this. Comorbidity with anxiety disorders or substance misuse is common. Advances in genetics, brain imaging and basic pharmacology are starting to provide understanding of the complex causative processes.

Antimanic Agents↗
PubMed2004

Cognitive generation of affect in bipolar depression: an fMRI study.

Individuals with bipolar disorder manifest the full spectrum of emotions ranging from depression to mania. In attempting to understand the functional substrates of mood we attempted to identify brain regions associated with the cognitive generation of affect in bipolar depressed patients. We therefore examined ten depressed female subjects with bipolar affective disorder, and ten age-matched and sex-matched healthy comparison subjects using functional magnetic resonance imaging (fMRI) while viewing alternating blocks of captioned pictures designed to evoke negative, positive or no affective change. The activation paradigm involved the presentation of the same visual materials over three experiments alternating (experiment 1) negative and reference; (experiment 2) positive and reference and (experiment 3) positive and negative captioned pictures. The stimuli produced activation in both patients and comparison subjects in brain regions previously implicated in the generation and modulation of affect, in particular the prefrontal and anterior cingulate cortices. The activation in patients, when compared with healthy subjects, involved additional subcortical regions, in particular the amygdala, thalamus, hypothalamus and medial globus pallidus. Patients and comparison subjects displayed differential sensitivity to affective change with negative (experiment 1) and positive (experiment 2) affect induction producing converse patterns of activation. We conclude that bipolar depressed patients perhaps recruit additional subcortical limbic systems for emotional evaluation and this may reflect state-related or trait-related dysfunction. The differential patterns of activation inform us about bipolar depression and have potential diagnostic and therapeutic significance.

Adult↗
PubMed2004

Cognitive generation of affect in hypomania: an fMRI study.

OBJECTIVE: To identify the brain regions associated with the cognitive generation of affect in hypomanic bipolar patients. METHODS: The study examined 10 hypomanic female subjects with bipolar affective disorder, and 10 age- and sex-matched comparison subjects using functional magnetic resonance imaging (fMRI) while viewing alternating blocks of captioned-pictures designed to evoke negative, positive or no affective change. The activation paradigm involved the presentation of the same visual materials over three experiments alternating (a) negative and reference, (b) positive and reference and (c) positive and negative captioned-pictures. RESULTS: The stimuli produced activation in both patients and comparison subjects in brain regions previously implicated in the generation and modulation of affect, in particular the prefrontal cortex. Activation in patients involved additional subcortical regions namely the caudate and thalamus. CONCLUSIONS: This preliminary study suggests that hypomanic patients recruit additional subcortical limbic systems for emotional evaluation when advanced prefrontal cortical processing is no longer sufficient. The differential patterns of activation inform us about bipolar disorder and may have potential diagnostic and therapeutic significance.

Adult↗
PubMed2004

Bipolar depression: phenomenological overview and clinical characteristics.

OBJECTIVES: There has been increasing interest in the depressed phase of bipolar disorder (bipolar depression). This paper aims to review the clinical characteristics of bipolar depression, focusing upon its prevalence and phenomenology, related neuropsychological dysfunction, suicidal behaviour, disability and treatment responsiveness. METHODS: Studies on the prevalence of depression in bipolar disorder, the comparative phenomenology of bipolar and unipolar depression, as well as neuropsychology and brain imaging studies, are reviewed. To identify relevant papers, a literature search using MEDLINE and PubMed was undertaken. RESULTS: Depression is the predominant mood disturbance in bipolar disorder, and most frequently presents as subsyndromal, minor or dysthymic depression. Compared with major depressive disorder (unipolar depression), bipolar depression is more likely to manifest with psychosis, melancholic symptoms, psychomotor retardation (in bipolar I disorder) and 'atypical' symptoms. The few neuropsychological studies undertaken indicate greater impairment in bipolar depression. Suicide rates are high in bipolar disorder, with suicidal ideation, suicide attempts and completed suicides all occurring predominantly in the depressed phase of this condition. Furthermore, the depressed phase (even subsyndromal) appears to be the major contributant to the disability related to this condition. CONCLUSIONS: The significance of the depressed phase of bipolar disorder has been markedly underestimated. Bipolar depression accounts for most of the morbidity and mortality due to this illness. Current treatments have significant limitations.

Bipolar Disorder↗
PubMed2004

Implications of childhood trauma for depressed women: an analysis of pathways from childhood sexual abuse to deliberate self-harm and revictimization.

OBJECTIVE: Data from depressed women with and without a history of childhood sexual abuse were used to characterize clinical features that distinguished the two groups and to examine relationships of childhood sexual abuse to lifetime deliberate self-harm and recent interpersonal violence. METHOD: One hundred twenty-five women with depressive disorders were interviewed and completed self-report questionnaires. Path analysis was used to examine relationships of several childhood and personality variables with deliberate self-harm in adulthood and recent interpersonal violence. RESULTS: Women with a childhood sexual abuse history reported more childhood physical abuse, childhood emotional abuse, and parental conflict in the home, compared to women without a childhood sexual abuse history. The two groups were similar in severity of depression, but the women with a childhood sexual abuse history were more likely to have attempted suicide and/or engaged in deliberate self-harm. The women with a history of childhood sexual abuse also became depressed earlier in life, were more likely to have panic disorder, and were more likely to report a recent assault. Path analysis confirmed the contributory role of childhood sexual abuse to deliberate self-harm and the significance of childhood physical abuse for recent interpersonal violence. CONCLUSIONS: Childhood sexual abuse is an important risk factor to identify in women with depression. Depressed women with a childhood sexual abuse history constitute a subgroup of patients who may require tailored interventions to combat both depression recurrence and harmful and self-defeating coping strategies.

Adaptation, Psychological↗
PubMed2004

Therapeutic drug monitoring of non-tricyclic antidepressant drugs.

Therapeutic drug monitoring (TDM) of many of the tricyclic antidepressants (TCAs) has been demonstrated to be of clear clinical value. This article reviews studies of TDM for the selective serotonin reuptake inhibitors (SSRIs) and other non-tricyclic antidepressants such as venlafaxine, nefazodone, trazodone, mianserin and bupropion. No definitive therapeutic concentrations have been demonstrated for these agents, nor have levels indicative of toxicity been reported. The major benefit of TDM for these agents would appear to be in the assessment of the apparently treatment-refractory depressed patient, to determine whether such lack of response is related to inadequate levels that would suggest either poor compliance, ultra-rapid metabolism, or drug interactions leading to induction of metabolising enzymes. Potential future applications of TDM, in conjunction with genotyping of cytochrome P450 enzymes and pharmacogenomic evaluations, are discussed.

Antidepressive Agents, Second-Generation↗
PubMed2003

Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.

Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.

Bipolar Disorder↗
PubMed2003

Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis.

OBJECTIVE: To examine the association between trends in antidepressant prescribing and suicide rates in Australia for 1991-2000. DESIGN: Analysis of databases of suicide and rates of antidepressant prescribing according to age and sex. SETTING: Australian Bureau of Statistics data, sales data from the Australian pharmaceutical industry, prescribing data in general practice. SUBJECTS: Men and women aged 15 years and over in 10 year age groups. MAIN OUTCOME MEASURES: Trends in suicide rates and trends in antidepressant prescribing. Association measured by Spearman's rank correlations. RESULTS: While overall national rates of suicide did not fall significantly, incidence decreased in older men and women and increased in younger adults. In both men (r(s)=-0.91; P<0.01) and women (r(s)=-0.76; P<0.05) the higher the exposure to antidepressants the larger the decline in rate of suicide. CONCLUSIONS: Changes in suicide rates and exposure to antidepressants in Australia for 1991-2000 are significantly associated. This effect is most apparent in older age groups, in which rates of suicide decreased substantially in association with exposure to antidepressants. The increase in antidepressant prescribing may be a proxy marker for improved overall management of depression. If so, increased prescribing of selective serotonin reuptake inhibitors in general practice may have produced a quantifiable benefit in population mental health.

Adolescent↗
PubMed2003

Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.

BACKGROUND: Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. OBJECTIVE: To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. DESIGN: Double-blind, 8-week, randomized controlled trial. SETTING: Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86). MAIN OUTCOME MEASURE: Changes in MADRS total scores using mixed-effects model repeated-measures analyses. RESULTS: During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group (P<.001 for all). The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8. At week 8, MADRS total scores were lower than at baseline by 11.9, 15.0, and 18.5 points in the placebo, olanzapine, and olanzapine-fluoxetine groups, respectively. Remission criteria were met by 24.5% (87/355) of the placebo group, 32.8% (115/351) of the olanzapine group, and 48.8% (40/82) of the olanzapine-fluoxetine group. Treatment-emergent mania (Young Mania Rating Scale score <15 at baseline and > or =15 subsequently) did not differ among groups (placebo, 6.7% [23/345]; olanzapine, 5.7% [19/335]; and olanzapine-fluoxetine, 6.4% [5/78]). Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea. CONCLUSIONS: Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.

Adult↗
PubMed2003

Genetic refinement and physical mapping of a 2.3 Mb probable disease region associated with a bipolar affective disorder susceptibility locus on chromosome 4q35.

A susceptibility locus for bipolar affective disorder has been mapped to chromosome 4q35 in a large multigenerational pedigree. We have expanded this analysis to include 55 pedigrees (674 individuals, 214 affecteds). The evidence for linkage to 4q35 was strengthened in this larger cohort, with a maximum two-point LOD score of 3.2 for marker D4S1652. Several other markers in the region gave LOD scores greater than 1.5. Non-parametric analysis provided additional support for linkage to the 4q35 region. To further refine this region, haplotype analysis was carried out in 16 of the 55 pedigrees that showed evidence of linkage. As there is no evidence for an ancestral haplotype, nor a one-to-one correspondence between the disease and putative disease haplotype, we undertook an analysis based on pedigree-specific, identical-by-descent allele-sharing in order to define a probable disease region. This analysis indicated that the percentage sharing of alleles, identical-by-descent, in affecteds of all linked pedigrees increases from 60% at the centromeric markers to 75% for markers at the telomere. Maximal allele sharing occurred between markers D4S3051 and 4qTEL13 with this 24 cM region defining a probable disease region. We have constructed a physical map of the 4q35 interval consisting of a YAC contig and BAC clones. Based on this map the probable disease region between D4S3051 and 4qTEL13 corresponds to only 2.3 Mb. This region is very gene poor with only three known genes indicated from the YAC/BAC map. The small number of genes will facilitate systematic screening for variations associated with bipolar disorder.

Bipolar Disorder↗
PubMed2003

Severity of stressful life events in first and subsequent episodes of depression: the relevance of depressive subtype.

BACKGROUND: Recent studies have reignited debate concerning the relationship between stressful life events and depressive subtypes, particularly in relation to first versus subsequent episodes. AIMS: To investigate the relationship between stressful life events and variably defined melancholic/non-melancholic depressive subtypes, and the import of such life events to first compared with subsequent episodes across those subtypes. METHOD: Acute and chronic stressful life events were rated in 270 patients with DSM-IV Major Depressive episodes who were allocated to melancholic and non-melancholic groups separately as defined by DSM-III-R, DSM-IV, the Newcastle criteria and the CORE system. RESULTS: Severe stressful life events (both acute and chronic)-as defined by DSM-III-R axis IV-were more likely to occur prior to first rather than subsequent episodes, particularly for those with non-melancholic depression. LIMITATIONS: Dependence or independence of life events was not assessed. Genetic vulnerability to depression was not determined. Life events in first and subsequent depressive episodes were compared cross-sectionally between groups, not prospectively in the same cohort of patients. There were no differences in the number of severe life events-as defined by clinician consensus-between the first and subsequent episodes. CONCLUSIONS: These findings are consistent with other studies in suggesting an enhanced sensitisation of depressed patients to subsequent episodes of depression, but suggest that any such phenomenon is specific to non-melancholic depression, in comparison to one key previous study.

Acute Disease↗
PubMed2003

Parental care and personality in melancholic and nonmelancholic depression.

The authors hypothesized that low parental care is linked to nonmelancholic depression through depressive personality traits and personality dysfunction. This hypothesis was tested using path analysis with data provided from a sample of patients meeting DSM-IV criteria for major depression and distinguished on the basis of melancholic symptoms. The results supported their hypothesis. Lack of parental care was associated with self-critical traits, and higher levels of these traits were associated with personality dysfunction, which in turn was associated with nonmelancholic, but not melancholic, depression. Dependent traits were uniquely associated with the onset of an anxiety disorder before the first episode of depression. Researchers interested in the link between personality and depression are encouraged to focus their efforts on patients whose depressive episodes do not meet DSM-IV criteria for melancholia, and on the personality dimension of self-criticism rather than dependency.

Adult↗
PubMed2003

Pharmacotherapy to limit weight gain caused by antipsychotic use.

Obesity is a major health problem, especially in patients with severe mental illnesses. Newer atypical antipsychotics are better tolerated and have fewer extrapyramidal side effects, however, they can cause significant weight gain. This poses a considerable added burden and increases the likelihood of developing medical illnesses such as diabetes and cardiovascular disease. Obesity in patients taking antipsychotic medication can usually be avoided, if behavioural modification and pharmacological measures are implemented from the outset. Greater awareness and a willingness to address the problem are needed along with more research into the development of weight gain and its prevention. This review examines these issues with a pharmacotherapy focus.

Anti-Obesity Agents↗