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Biomedical subjects

P R Joyce

Publications and source records attributed to P R Joyce.

At least 19 recordsLinked to original sources

Brain function and personality in normal males: a SPECT study using statistical parametric mapping.

Understanding the differences between individuals' personality types at a functional brain level is now possible due to recent developments in both functional brain imaging and personality models. The psychobiological model for temperament and character offers one approach to exploring personality. This study uses SPECT imaging to investigate brain function in relationship to the personality traits in the Temperament and Character Index. A general linear model approach was implemented at a voxel-by-voxel level, using quartile groupings for the personality predictors. t contrasts were used to investigate significant clusters of activation or deactivation. The results show a number of significant relationships between personality traits and regional cerebral blood flow, which show distinct nonlinear trends. All seven of the Cloninger personality traits were significantly related to regional cerebral blood flow. The results suggest that differences in brain function in some regions may reflect differences in personality traits.

Adult↗

Thyroid indices and treatment outcome in bulimia nervosa.

OBJECTIVE: This study examined the thyroxine (T4) and free T4 (FT4) status of women with bulimia nervosa and its value as a predictor of outcome. METHOD: A total of 135 women with bulimia nervosa underwent 12-weeks cognitive behavioral therapy treatment. Prior to and at 3-year follow-up patients completed psychiatric assessments and serumT4 and FT4 were measured. RESULTS: At 3-year follow-up, 71% had no eating disorder and 29% met criteria for any eating disorder diagnosis. Mean T4 and FT4 concentrations were within normal ranges. Pre-treatment T4 and FT4 concentrations were inversely associated with food restriction and purging frequency, respectively. Compared with women with no eating disorder, those with any eating disorder at follow-up had lower pretreatment T4 concentrations. When pre-treatment food restriction, oral contraceptive use and binge frequency where controlled for, low T4 concentration was the only predictor of eating disorder diagnosis at follow-up. CONCLUSION: Low T4 concentrations at pretreatment may be a predictor of poor outcome in bulimia nervosa.

Adolescent↗

A differential response to nortriptyline and fluoxetine in melancholic depression: the importance of age and gender.

OBJECTIVE: To consider the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine in melancholic depression. METHOD: Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender. RESULTS: Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age 18-24 years, especially women, had a markedly superior response to fluoxetine. CONCLUSION: Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.

Adolescent↗

Schizophrenia and bipolar affective disorder: perspectives for the development of therapeutics.

Schizophrenia and bipolar disorder remain two of the most severe and difficult to treat psychotic disorders hampered by our poor understanding of their pathologies. The development of typical antipsychotic drugs opened an avenue of investigation through the dopamine D2 receptor in schizophrenia. With the reintroduction of the atypical antipsychotic clozapine came the development of a new generation of atypical agents and hypotheses challenging the centrality of this receptor in explaining antipsychotic effects. Evaluation of these competing theories does not provide sufficient evidence to displace the importance of the dopamine D2 receptor in antipsychotic efficacy, but does raise limitations of it as an explanatory hypothesis. Further, the treatment of other symptom domains in schizophrenia remains relatively neglected and open for the development of novel therapies. Similar to schizophrenia, bipolar disorder presents a diversity of clinical states but unlike schizophrenia, its mainstay of treatment, lithium, has not had a clear receptor target impeding understanding of the disorder's pathology and treatment. This has pushed investigation into other domains emphasising a number of intracellular signalling pathways and glial-neuronal interactions. The heavy genetic loading of bipolar disorder has allowed linkage analyses to identify a number of putative regions, however, the diversity of phenotypes complicates such studies. Polymorphisms of candidate genes have yielded potential leads such as dopamine beta hydroxylase in mood disorder and the serotonin transporter for treatment response. It is anticipated that combiningthe above approaches may hold promise for the development of more effective treatments.

Antipsychotic Agents↗

A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression.

The multi-drug resistance gene ABCB1 (or MDR1) encodes a P-glycoprotein (P-gp) that regulates passage of many substances across the blood-brain barrier. The antidepressant amitriptyline and its metabolites (including nortriptyline) are substrates for P-gp, and in mice lacking P-gp, penetration of amitriptyline, but not fluoxetine, into the brain is enhanced. We reasoned that polymorphic variation of P-gp may contribute to differing responses of patients to antidepressant drugs. A single nucleotide polymorphism (SNP) of ABCB1 (3435C>T) was recently correlated with expression levels and in vivo function of P-gp. We examined this SNP in patients with major depression enrolled in a randomized antidepressant treatment trial of nortriptyline and fluoxetine, and observed a significant association between nortriptyline-induced postural hypotension and 3435C>T (chi(2) = 6.78, df = 2, P = 0.034). Our results suggest that homozygosity for 3435T alleles of ABCB1 is a risk factor for occurrence of nortriptyline-induced postural hypotension (OR = 1.37, P = 0.042, 95% CI 1.01-1.86).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Changes in cue reactivity following treatment for bulimia nervosa.

OBJECTIVE: To examine changes in cue reactivity following cognitive-behavior therapy (CBT) for bulimia nervosa and to evaluate whether changes are associated with treatment modality or treatment outcome. METHOD: Subjects were 135 women (17-45 years old) with a current, primary diagnosis of bulimia nervosa. They were participants in a randomized clinical trial examining the additive efficacy of exposure and nonexposure-based behavior therapy to a core of CBT. Physiological, self-report, and behavioral measures of cue reactivity to individualized high-risk binge foods were obtained at pretreatment and posttreatment. Primary, secondary, and tertiary outcome measures are reported for posttreatment. RESULTS: Bulimic patients experienced significant changes in cue reactivity following treatment. With the exception of salivary reactivity, patients experienced less reactivity at posttreatment. Changes in cue reactivity were not related to treatment modality, but were related to positive treatment outcome for self-report measures of cue reactivity. DISCUSSION: Favorable treatment outcome among bulimic women is associated with low cue reactivity on self-report measures at posttreatment.

Adolescent↗

Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine.

RATIONALE: Subjects with depression may exhibit activation of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the response of basal hormone levels to antidepressant therapy. OBJECTIVES: To determine whether treatment of depression with standard antidepressant medications resulted in reductions in basal activity of afternoon cortisol, ACTH and AVP. A secondary aim was to examine whether there was any difference in hormonal response between an SSRI (fluoxetine) and a tricyclic antidepressant (nortriptyline). METHODS: Forty-three subjects with a DSM-IV diagnosis of depression (Hamilton score 18.9+/-0.6 at baseline) had five basal venous blood samples drawn at 15-min intervals between 1400 and 1500 hours for cortisol, ACTH and AVP, before and 6 weeks after randomisation to treatment with fluoxetine (n=27) or nortriptyline (n=16). RESULTS: Both medications resulted in a similar improvement in depression as determined by Hamilton score. In the group as a whole, ACTH levels showed a significant decrease over the 6 weeks (4.1+/-0.4 pmol/l at baseline versus 3.3+/-0.3 at 6 weeks, P<0.05), while cortisol and AVP levels were unchanged. Further analysis revealed that the fall in plasma ACTH occurred predominantly in the subgroup treated with fluoxetine (drug x time interaction by ANOVA, P=0.035). There was a significant relationship between cortisol and ACTH at baseline (r=0.48, P=0.002), that weakened considerably after treatment (r=0.22, P=0.16). The subgroup with baseline hypercortisolemia [mean cortisol >276 nmol/l (10 microg/dl), n=18] demonstrated a reduction in both cortisol and ACTH following treatment, but also showed a loss of the relationship between the two. CONCLUSIONS: It is postulated that the initial recovery of the HPA axis during the treatment of depression with fluoxetine is mediated via restoration of glucocorticoid negative feedback on ACTH levels.

Adolescent↗

Comparison between noradrenergic and serotonergic medications using the social adjustment scale: is drive enhancement necessary for recovery of social functioning?

The Social Adjustment Scale (SAS) was used to assess social functioning sequentially over 13 weeks in a group of 188 depressed outpatients randomized to either the noradrenergic antidepressant, nortriptyline, or the selective serotonin reuptake inhibitor, fluoxetine. Over the period of 13 weeks, there were no differences in total SAS scores between the nortriptyline and the fluoxetine group. In comparing the SAS subscale scores, which may measure different areas of motivation and behaviour (drive), there were differences between the two groups in only two subscales. At 13 weeks, the group randomized to fluoxetine were more impaired in marital role (p = 0.026) whereas, at 6 weeks, the group randomized to nortriptyline were more impaired in friction scores (p = 0.012). These results do not support the concept of specific augmentation of drive-related behaviour by noradrenergic medication. This challenges the earlier findings relating to drive enhancement and social adjustment using such medication.

Adrenergic Agents↗

The contribution of temperament, childhood neglect, and abuse to the development of personality dysfunction: a comparison of three models.

We examined the contribution of temperament, childhood neglect, and abuse to the development of personality dysfunction as postulated in three different but correlated models of personality: the psychobiological, Vaillant's psychoanalytic, and DSM psychopathology models. Character, defense style, and personality disorder symptomatology (the dependent variables), and temperament, childhood neglect, and abuse (the independent variables) were assessed in 168 depressed outpatients. High harm avoidance (temperament) tended to be the strongest and most consistent risk factor across the three models. Deficient parental care predicted personality dysfunction, however low care was not consistently predictive across all three models. Emotional/psychological abuse and actual physical abuse were risk factors for increasing personality disorder symptomatology only. Childhood sexual abuse was not as predictive of personality dysfunction as might be expected, thereby raising questions as to the importance placed on child sexual abuse as a general risk factor for personality psychopathology.

Adult↗

Changes on the stroop test following treatment: relation to word type, treatment condition, and treatment outcome among women with bulimia nervosa.

OBJECTIVE: To examine changes in speed of information processing on a modification of the Stroop color-naming task following cognitive-behavior therapy (CBT) and to evaluate whether changes are associated with word type, treatment condition, or treatment response. METHOD: Subjects were 98 women aged between 17 and 45 years with a current primary diagnosis of bulimia nervosa who were participating in a randomized clinical trial evaluating CBT. Data were available on all relevant variables for 98 women. Speed of information processing was assessed at pretreatment and posttreatment using a modification of the Stroop color-naming paradigm. RESULTS: Significant main effects were found for the factors time (pretreatment vs. posttreatment) and word type (food/body words vs. color words, food/body words vs. control words). Predicted interactions between time and word type were not identified. DISCUSSION: Changes in information processing speed over treatment were not specifically associated with word type, treatment condition, or treatment response. Consequently, the utility of the modified Stroop paradigm as a measure of change over time for bulimia nervosa is questioned.

Adolescent↗

Menstrual cycle irregularity in bulimia nervosa. Associated factors and changes with treatment.

OBJECTIVES: This study determined the clinical and nutritional variables associated with menstrual disturbance in women with bulimia nervosa (BN). METHODS: Eighty-two women with DSM-IV BN underwent psychiatric, nutritional and menstrual related assessments prior to an outpatient treatment programme and at 12 months follow-up. RESULTS: Forty-five percent reported a current irregular menstrual cycle. A high frequency of vomiting, low thyroxine concentrations and low dietary fat intake were independently associated with irregular menses at pretreatment. At 12 months follow-up, 30.5% reported irregular menstrual cycles. A greater difference between past maximum and minimum body weight, smoking and depression were associated with menstrual irregularity at 12 months follow-up. Of those with irregular menstrual cycles at pretreatment, 56.8% became regular at 12 months follow-up. CONCLUSION: Menstrual irregularity in BN is associated with indices of nutritional restriction that are not reflected by low body weight or energy intake. Depression, cigarette smoking and fluctuations in body weight may act as metabolic stresses that contribute to the perpetuation of menstrual disturbances.

Adolescent↗

Gender differences in the presentation of depressed outpatients: a comparison of descriptive variables.

BACKGROUND: Gender differences in the clinical manifestation of depression and related variables were examined in 170 depressed outpatients. METHOD: Age of onset of depression, chronicity, recurrence, subtype of depression, self-harm history and prior treatment history were assessed with structured clinical interviews. Depression symptom profile, family psychiatric history and social, occupational and interpersonal functioning were assessed with self-report and clinician ratings. RESULTS: Overall, males and females were remarkably similar. Significant findings were that depressed females reported significantly more appetite increase, weight gain and carbohydrate craving, and in general, expressed their depression in a more emotional manner, than depressed males. CONCLUSION: Psychosocial and biological explanations for these results are explored. LIMITATIONS: Descriptive study and multiple testing

Adult↗

Predictors of rapid and sustained response to cognitive-behavioral therapy for bulimia nervosa.

OBJECTIVE: To examine characteristics of individuals who show a rapid and sustained response to cognitive-behavioral therapy (CBT) for bulimia nervosa (BN). METHOD: As part of a randomized clinical trial designed to dismantle CBT for BN, we compared 19 individuals who exhibited complete abstinence from binging and purging after only eight sessions of CBT and maintained abstinence throughout the duration of treatment and the 1-year follow-up interval, to 79 individuals who had a more variable response to treatment. Demographics, baseline clinical characteristics, lifetime comorbidity, and personality disorder symptoms and profiles from the Temperament and Character Inventory were examined. RESULTS: In univariate analyses, frequency of binging and purging at baseline, low scores on the Eating Disorders Inventory (EDI) Bulimia subscale, lower harm avoidance, and higher self-directedness were associated with rapid response. In multiple regression analyses, frequency of binging at baseline (OR = 0.87; 95% CI 0.77-0.98) and self-directedness (OR = 1.12; 95% CI 1.04-1.21) independently predicted rapid and sustained treatment response. CONCLUSION: Frequency of binging and the character quality of self-directedness may be useful predictors of those individuals who are likely to respond positively to a brief course of CBT for BN.

Adolescent↗

Gender differences in the rate of comorbid axis I disorders in depressed outpatients.

We examined gender differences in comorbid Axis I disorders in 236 outpatients with major depression. Axis I comorbidity, age of onset of depression and comorbid disorder were assessed with the SCID-P. Depression severity was assessed with the HAM-17. The results indicated that males had a higher rate of comorbid substance abuse/dependence, while females had a higher rate of comorbid bulimia nervosa. These results are consistent with previous research, with the marked exception that females did not have higher rates of anxiety disorders in general, and in particular, panic disorder, simple and social phobia, obsessive-compulsive disorder and agoraphobia. It is concluded that the female predominance in anxiety disorders found in general population studies may be due to comorbidity with depression.

Adult↗

Body weight in bulimia nervosa.

OBJECTIVES: The objectives of this study were to determine: 1) factors associated with body mass index (BMI) in women with bulimia nervosa prior to treatment; 2) changes in BMI during cognitive behavioral therapy (CBT) for bulimia nervosa; and 3) predictors of weight change during CBT treatment. METHODS: Participants were 94 women with DSM-III-R bulimia nervosa enrolled in a randomized clinical trial of CBT. Eating disorder symptomatology, past and current psychopathology, and BMI were measured prior to treatment and after twelve weeks of treatment. RESULTS: A significantly lower BMI prior to treatment was independently associated with a history of anorexia nervosa, substance use, cigarette smoking, and a high frequency of vomiting. Reductions in binge eating, purging, and food restriction after treatment did not result in significant changes in BMI. Increasing age, higher maximum lifetime body weight, and a high frequency of binge eating at baseline predicted weight gain during treatment. Weight loss during treatment was predicted by a high frequency of vomiting, and elevated levels of body dissatisfaction prior to treatment. DISCUSSION: Patients hesitant to engage in treatment for fear of weight gain upon cessation of their bulimic behaviors should be reassured that CBT is not usually accompanied by substantial weight gain. Identification of women at risk of significant weight gain or loss during CBT may enable therapists to focus on its aspects that help to prevent excessive body weight changes.

Adolescent↗

Visceral protein and hematological status of women with bulimia nervosa and depressed controls.

Serum visceral protein and hematological indices and their behavioral and clinical correlates were determined in women with bulimia nervosa and depressed controls. One hundred and fifty-two women who met DSM-IV criteria for bulimia nervosa and 68 women with DSM-IV major depression completed a structured clinical interview and had blood samples drawn prior to admission to outpatient treatment programs. Albumin and prealbumin concentrations were lower in the depressed women, possibly due to recent weight loss. Elevated transferrin values suggested mild iron deficiency in nearly one-fifth of women with bulimia nervosa. Of women with bulimia nervosa, the 10.7% who had hemoglobin and 5.1% who had vitamin B12 levels below the normal range were not distinguishable on measures of body mass index, binge eating, vomiting, or restriction frequency. The 4.3% with low prealbumin levels experienced significantly more episodes of binge eating and vomiting in the prior fortnight than those with normal values. Frequency of vomiting was also inversely associated with albumin concentration. Hamilton Depression Rating Scale scores were inversely and linearly related to serum vitamin B12. Lower B12 levels in those with alcohol abuse/dependence did not explain the association between B12 and HDRS scores. No hematological indices were related to body mass index, binge eating or restriction frequency, or restriction intensity. In summary, women with bulimia nervosa do not appear to be at greater risk of visceral protein or hematological abnormalities than psychiatric controls. It is suggested that a high frequency of vomiting and alcohol abuse/dependence, increases the risk of subclinical malnutrition in women with bulimia nervosa, and that poor vitamin B12 nutriture may interfere with the functioning of the serotonergic or catecholaminergic systems and contribute to depressive symptoms in bulimia nervosa.

Adolescent↗