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Biomedical subjects

Philip Mitchell

Publications and source records attributed to Philip Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans.

Previous research has shown that D-cycloserine (DCS) facilitates extinction of Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The aim of this study was to test the effect of DCS on extinction of fear conditioning in humans. In three experiments, 238 participants were given either DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a differential shock conditioning paradigm. Clear extinction and recovery (return of fear) effects were observed on both skin conductance and self-reported shock expectancy measures in three studies. DCS had no influence on these effects. The same pattern was observed when the analysis was restricted to aware participants or to good conditioners, when fear-relevant cues (pictures of snakes) were used as the conditioned stimuli, or when analysis was restricted to heightened snake-fearful participants. These results suggest that DCS may not enhance the extinction, or prevent the recovery, of learned fear in a differential Pavlovian conditioning paradigm in humans. Further experimental research is needed to better understand the mechanisms underlying the therapeutic effects of DCS.

Adult↗
PubMed2006

A randomized controlled trial of the effect of D-cycloserine on exposure therapy for spider fear.

Previous research [Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, et al. Augmentation of exposure therapy for social anxiety disorder with D-cycloserine. Archives of General Psychiatry 2006;63:298-304; Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, et al. Cognitive enhancers as adjuncts to psychotherapy: use of d-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry 2004;61:1136-44] suggests that d-cycloserine (DCS) facilitates the reduction of clinical fear in humans. We used a well established intervention to evaluate the effectiveness of administering DCS as an adjunct to exposure therapy in a heightened, but sub-clinical, fear population. Over two studies, 100 spider-fearful participants were allocated to DCS or placebo before treatment and were assessed at pre-, immediate post-, and 3.5 weeks post-treatment. Significant treatment effects and return of fear was observed at follow-up, particularly in non-treatment contexts; however, both studies failed to demonstrate any enhancing effects of DCS (50 or 500 mg). DCS did not enhance the reduction of spider fears or the generalisation of treatment of a single session of exposure-based therapy. These results suggest that DCS may not enhance loss of non-clinical levels of fear in human populations.

Adolescent↗
PubMed2005

Vascular risk and low serum B12 predict white matter lesions in patients with major depression.

BACKGROUND: While patients with depression have been shown to have a greater incidence of vascular risk factors and structural brain changes, any association with dietary co-factors is unclear. METHODS: Forty-seven patients with major depression (mean age = 52.8 years, SD = 12.6) and 21 healthy volunteers (mean age = 54.7 years, SD = 9.1) underwent high-resolution magnetic resonance imaging scanning. T2-weighted films were scored for deep white matter (DWM), periventricular (PV), and subcortical (SC) hyperintensities. RESULTS: There was no difference in lesion severity between patients and control subjects. After controlling for age, vitamin B12 levels were predictive of DWM lesions in patients. DWM and SC lesions were associated with histories of hypertension and diabetes. LIMITATIONS: A relatively small sample of patients were recruited from specialist services and the findings may not represent those observed in larger or community-based cohorts. CONCLUSIONS: In patients with major depression, vitamin B12 levels and histories of hypertension and/or diabetes are predictive of white matter lesions.

Adult↗
PubMed2005

Great expectations: factors influencing patient expectations and doctors recommendations at a Mood Disorders Unit.

BACKGROUND: Literature about expectations and management of depression within community samples reflects attitudes of people who have generally not received treatment. We examined the factors influencing treatment expectations and psychiatrists' treatment recommendations for patients referred to a mood disorders unit with identified episodes of major depression. METHODS: Prior to attending a mood disorders unit, 182 men and women who met DSM-III-R or DSM-IV criteria for current major depression provided data on sociodemographic details, history of medical and psychiatric illness and expectations of treatment. Psychiatrists' treatment recommendations to the referring clinician were assessed to determine whether the patients' initial expectations were met. RESULTS: Data analyses revealed three factors relating to patients' expectations: "enhanced coping", "providing fresh ideas for the referring doctor" and "providing fresh ideas to self". Patients' expectations were influenced by sociodemographic and illness-related characteristics. In particular, young female patients typically expected to receive strategies to enhance coping, while those with lifetime anxiety expected less active involvement on their part. Some clinicians' recommendations were dependent upon depression type and patient factors. Women and those with a history of anxiety disorders received more education and recommendations for relationship counselling and support groups. LIMITATIONS: The study design did not allow determination of the impact of patients' expectations on the psychiatrists' recommendations. CONCLUSIONS: Individual and illness characteristics are important predictors of treatment expectations prior to specialist care. It appears that doctors take these factors into account with implications for patients' satisfaction with the type of care recommended.

Adaptation, Psychological↗
PubMed2005

Mechanical characteristics of the bone-graft-cement interface after impaction allografting.

Impaction allografting is an attractive procedure for the treatment of failed total hip replacements. The graft-cement-host bone interface after impaction allografting has not been characterized, although it is a potential site of subsidence for this type of revision total hip reconstruction. In six human cadaveric femurs, the cancellous bone was removed proximally and local diaphyseal lytic defects were simulated. After the impaction grafting procedure, the specimens were sectioned in 6 mm transverse sections and push-out tests were performed. From the adjacent sections the percentage cement contact of the PMMA cement with the endosteal bone surface was determined. The host bone interface mechanical properties varied significantly along the femur largely due to different interface morphologies. The apparent host bone interface shear strength was highest around the lesser trochanter and lowest around the tip of the stem. A significant positive correlation was found between the percentage cement contact and the apparent host bone interface shear strength (r2 = 0.52). The sections failed in 69% of the cases through a pure host bone interface failure without cement or allograft failure, 19% failed with local cement failure, and 12% with a local allograft failure. The apparent host bone interface strength was on average 89% lower than values reported for primary total hip replacements and were similar to cemented revisions proximally and lower distally. This study showed that cement penetration to the endosteal surface enhanced the host bone-graft interface.

Biomechanical Phenomena↗
PubMed2005

Considerations in the management of bipolar disorder in women.

OBJECTIVE: Recent research has emphasized important gender differences in the epidemiology, course, comorbidity and treatment of bipolar disorder. This article aims to provide an overview of these important findings in order to assist the clinician in treating women with bipolar disorder. Complex issues regarding the treatment of bipolar disorder during pregnancy and the post-partum period are discussed. METHOD: A literature review was undertaken using Medline (1966-current), PsychInfo and PubMed databases. Search terms used were gender, sex, women, bipolar disorder, suicide, epidemiology, rapid cycling, mixed episode, treatment, mood stabilizers, antidepressants, antipsychotics, pregnancy, post-partum, menopause, lactation and breast-feeding. RESULTS: The lifetime prevalence of bipolar I disorder is equal in men and women; however, bipolar II appears to be more common in women. Gender differences have been reported in the phenomenology, course and outcome of this condition. Some comorbid disorders, such as thyroid disease and anxiety disorders have more relevance to women. Increasingly, sex differences in the pharmacokinetics and pharmacodynamics of medications used in bipolar disorder are being reported. CONCLUSIONS: There is increasing evidence for gender differences in a number of clinical features of bipolar disorder that have relevance to management. Although more studies are needed, it is important for clinicians to be aware of these issues to optimize treatment of women with this condition.

Antidepressive Agents↗
PubMed2005

Self-harming in depressed patients: pattern analysis.

OBJECTIVE: As deliberate self-harm (DSH) is a common concomitant of depressive disorders, we undertook a study examining the relevance of possible determinants and correlates of DSH. METHOD: Three separate samples of depressed outpatients were studied to determine consistency of identified factors across samples, with principal analyses involving gender, age and diagnosis-matched DSH and non-DSH subjects. RESULTS: Across the samples, some 20% of subjects admitted to episodes of DSH. Women reported higher rates and there was a consistent trend for higher rates in bipolar patients. Univariate analyses examined the relevance of several sociodemographic variables, illicit drug and alcohol use, past deprivational and abusive experiences, past suicidal attempts and disordered personality functioning. Multivariate analyses consistently identified previous suicide attempts and high 'acting out' behaviours across the three samples, suggesting the relevance of an externalizing response to stress and poor impulse control. CONCLUSIONS: Results assist the identification and management of depressed patients who are at greater risk of DSH behaviours.

Adult↗
PubMed2005

Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation.

In an open study, four subjects with a stable deficit syndrome of schizophrenia received high frequency repetitive transcranial magnetic stimulation (15 Hz at 90% of motor threshold, 1800 pulses each session, daily for 20 sessions over 4 weeks) over the left dorsolateral prefrontal cortex. Subjects showed a significant reduction in negative symptoms and improvement in function, with no change in positive symptoms. This improvement was maintained at the 1 month follow up. Repetitive transcranial magnetic stimulation as a treatment of the deficit syndrome of schizophrenia is feasible, safe and may be beneficial. A systematic study in randomized control trials would be appropriate.

Adult↗
PubMed2005

Age and gender in the phenomenology of depression.

OBJECTIVE: Authors investigated the effects of current age, age at onset, and gender on the phenomenology of depression. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2005

Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression.

BACKGROUND: Hippocampal volume reduction has been reported inconsistently in people with major depression. AIMS: To evaluate the interrelationships between hippocampal volumes, memory and key clinical, vascular and genetic risk factors. METHOD: Totals of 66 people with depression and 20 control participants underwent magnetic resonance imaging and clinical assessment. Measures of depression severity, psychomotor retardation, verbal and visual memory and vascular and specific genetic risk factors were collected. RESULTS: Reduced hippocampal volumes occurred in older people with depression, those with both early-onset and late-onset disorders and those with the melancholic subtype. Reduced hippocampal volumes were associated with deficits in visual and verbal memory performance. CONCLUSIONS: Although reduced hippocampal volumes are most pronounced in late-onset depression, older people with early-onset disorders also display volume changes and memory loss. No clear vascular or genetic risk factors explain these findings. Hippocampal volume changes may explain how depression emerges as a risk factor to dementia.

Adult↗
PubMed2005

Atypical depression: Australian and US studies in accord.

PURPOSE OF REVIEW: A 2004 review of 'atypical depression' in Current Opinion in Psychiatry could be read as more reifying the Columbian and DSM-IV concept rather than considering an alternative model that has been supported by independent studies undertaken in Australia and North America. Additional analyses of the Australian data set are reported to examine inter-study agreement further and to consider the implications. RECENT FINDINGS: Both studies recruited patients meeting criteria for a major depressive episode, and then contrasted patients meeting or not meeting DSM-IV criteria for definite atypical depression. In both studies, those with atypical depression were comparable in terms of female preponderance, age, age at first episode and depression severity, but developed earlier and more persistent episodes, showed a slight female preponderance, and were more likely to meet criteria for panic disorder, social phobia and hypochondriasis, and of avoidant and dependent personality styles. In both, there was a lack of evidence suggesting that atypical depression differs in severity, in being clearly less likely to have certain 'endogeneity' symptoms, or in being more likely to be associated with bipolar disorder, while neither the centrality of mood reactivity nor interdependence of symptoms could be demonstrated. SUMMARY: Findings from both studies challenge the view that atypical depression is an entity and the current model of its constituent features. Both found support for primacy of personality style (rather than mood reactivity) and for certain expressions of anxiety. Both effectively argue for and assist shaping of a revisionist model for conceptualizing atypical depression as a syndrome or spectrum disorder.

Journal Article↗
PubMed2004

A randomized controlled study of cognitive behavior therapy and behavioral family therapy for anorexia nervosa patients.

Very few studies have examined the role of cognitive behavior therapy (CBT) in the outpatient treatment of anorexia nervosa. This study used a randomized, controlled design to evaluate a 12-month, manual based program of CBT, with behavioral family therapy as the comparison group. Twenty-five adolescents and young adults with anorexia nervosa, currently living with their families, were recruited into the study with both treatment groups receiving 21-25 sessions of therapy. Outcome measures included nutritional status, eating behaviors, mood, self-esteem, and family communication. Sixty percent of the total sample and 72% of treatment completers had "good" outcome (defined as maintaining weight within 10% of average body weight and regular menstrual cycles) at post-treatment and at six months follow-up. No significant differences between treatment groups were found and the majority of patients did not reach symptomatic recovery. While limited by the small sample size, the findings compliment and extend previous research.

Journal Article↗
PubMed2004

Length of therapy with selective serotonin reuptake inhibitors and tricyclic antidepressants in Australia.

OBJECTIVE: To investigate the proportion of patients starting on either selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) who continued treatment for a period consistent with recommended guidelines for major depression, that is at least 6 months. METHOD: Cohort study using a national dispensing claims database involving patients eligible for social security entitlements in Australia. Two 'new user' cohorts were established of patients who were supplied a prescription for either an SSRI (6026) or a TCA (4158) in the first week of April 2000 and who had not received a prescription for any antidepressant in the preceding three months. The main outcome measure was the proportion of patients who were still having any SSRI or TCA prescription, respectively, dispensed between 6 and 8 months after initiation. Additionally, for patients starting on either a leading SSRI (sertraline) or TCA (dothiepin), the proportions of those that remained on these drugs or had changed to other antidepressants were determined. The dispensing data are not linked to reason for prescribing in the national dataset. RESULTS: 2267 SSRI 'new users' (38%) were still receiving SSRIs 6-8 months later, compared with 1269 (31%) of the 4158 TCA 'new users' (p < 0.001). The difference between the groups occurred early, by the 2-4 month time interval. 1038 (41%) of patients starting on the individual SSRI and 385 (38%) of patients starting on the individual TCA were receiving some type of antidepressant therapy at 6-8 months, with no significant difference (p = 0.6) in the proportions that had changed to another antidepressant. CONCLUSIONS: In 2000, only 40% of patients started on an antidepressant continued to be prescribed some antidepressant therapy 6-8 months later. Patients were more likely to continue on SSRIs as a class than on TCAs and the difference in continuation between these two classes occurred within the first 2 months of therapy. However, patients starting on an individual SSRI or TCA were equally likely to change to another antidepressant.

Antidepressive Agents, Tricyclic↗
PubMed2004

Verrucous carcinoma of the esophagus eluding multiple sets of endoscopic biopsies and endoscopic ultrasound: a case report and review of the literature.

A 56-year-old woman was noted to have a 5 cm to 6 cm long, irregular narrowing of the distal esophagus on an upper gastrointestinal series. Initial endoscopy revealed a polypoid mass in the distal esophagus and concurrent endoscopic ultrasound revealed changes typical of inflammation but no evidence of an obvious neoplastic process. Repeated biopsies revealed only inflammation with no evidence of malignancy. Only after prolonged acid suppression did biopsies reveal verrucous carcinoma of the esophagus. The patient underwent a trans-hiatal esophagectomy and has remained well with no evidence of progression since. Verrucous carcinoma is a rare variant of squamous cell carcinoma, taking on a papillary or warty appearance grossly. Histological diagnosis may be difficult because this tumour typically shows no high-grade dysplasia. Therefore, diagnosis can be challenging, often requiring multiple sets of endoscopic biopsies due to the overlying hyperkeratotic layer. Of the 20 cases that have been reported, this is the second to provide an endosonographic description and the first to describe a change in endoscopic appearance with acid suppression.

Biopsy↗
PubMed2003

Distinguishing early and late onset non-melancholic unipolar depression.

AIM: We seek to determine whether unipolar non-melancholic major depression commencing early in life has a differing clinical picture, and whether it may have differing determinants. METHODS: We study a sample of such patients, comparing those with depression onset in their first 25 years against residual subjects, matching exactly by sex and controlling for age. RESULTS: There were no differences in current depression severity. Despite early onset subjects having a distinctly younger current mean age, they had a lifetime pattern of both greater depression chronicity and disability, and judged themselves as less likely to have benefited from any antidepressant medication or psychotherapy. 'Phenotypically' early onset subjects did not differ in terms of 'depressive' symptoms, but were distinguished by a greater irritability, which we interpret as reflecting a temperament dimension influencing symptom expression. Multivariate analyses indicated that the clinical pattern in those with an early onset was distinguished by more evident irritability and anxiety, that there was a distinct familial contribution to early onset depression, that its forerunners were an early personality style of behavioural inhibition or shyness, and that they were more likely to use alcohol and illicit drugs. CONCLUSIONS: While early onset unipolar depression is unlikely to be a pure depressive 'type', it may well be that certain familial temperament characteristics lead to an early onset of depression marked by irritability, a process that invokes a spectrum disorder concept linking temperament style and the depressive manifestations. Early onset depression is indicative of a poor prognosis, both in terms of response to interventions and in regard to chronicity and disability.

Adult↗
PubMed2003

Prevalence and correlates of DSM-IV major depression in an Australian national survey.

BACKGROUND: Community surveys have reported prevalence of depressive disorders in adult populations since the 1970s. Until recently, no epidemiological studies of the same magnitude have been conducted to provide a profile of the adult population in Australia. This study examines the current (30-day) prevalence and correlates of major depression in the adult Australian population using data from the National Survey of Mental Health and Well-being, and compares the results with other national studies. METHODS: Data were derived from a national sample of 10,641 people 18-75+ years of age surveyed using the computerised version of the Composite International Diagnostic Interview Version 2.1. RESULTS: The overall weighted prevalence of current (30-day) major depression was 3.2% with the highest rate (5.2%) being found in females in mid life. This rate is between those of the USA National Comorbidity Survey and the Epidemiological Catchment Area study, and similar to the British Psychiatric Morbidity Survey. The strongest correlates for reported current major depression include being unemployed, smoking, having a medical condition, followed by being in mid life, previously married, and female. Living with a partner and drinking 1 to 2 glasses of alcohol per day were least correlated. Some correlates of major depression relate to social disadvantage and lifestyle issues. LIMITATIONS: The study design does not allow definition of direction of causality. CONCLUSION: Lowering the prevalence rate of major depression will require close attention to public health approaches to address the relationships between smoking, social isolation, poor health, mood and physical well-being. The best focus for this approach may be primary care settings.

Adolescent↗
PubMed2003

Heterogeneity of admission history among patients with bipolar disorder.

BACKGROUND: Patients on a first admission for bipolar disorder often have a history of other psychiatric diagnoses for previous admissions. AIMS: The current study examines the time course and diagnoses of psychiatric admissions prior and subsequent to a first hospitalisation for a diagnosis of bipolar disorder. METHOD: The prior admission histories (over the period 1965-1989) of 1167 patients who had been hospitalised in state mental health facilities with their first admission with diagnosis of bipolar disorder between 1983 and 1989 were examined. RESULTS: A total of 542 (46.4%) patients had at least one previous hospitalisation with a psychiatric diagnosis other than bipolar disorder. Two prominent groups emerged; one group which had primarily a history of prior admissions with diagnoses of depression over 1-3 years, and a second which mainly had previous admissions for schizophrenia, over a period longer than for those with a primarily depressive history. The group with a history of schizophrenia was significantly younger and had a greater number of admissions prior to the first bipolar disorder diagnosis than the depression group. LIMITATIONS: This was a record-based study which did not examine cases which were not hospitalised. CONCLUSIONS: There appeared to be three distinct patterns of prior presentations in those patients admitted with a diagnosis of bipolar disorder.

Adult↗