Peter R. Joyce

Eating disorders and antecedent anxiety disorders: a controlled study

We compared the prevalence and age of onset of adult and childhood anxiety disorders relative to the primary diagnosis in 68 women with anorexia nervosa (AN), 116 women with bulimia nervosa (BN), 56 women with major depression with no eating disorder (MD) and 98 randomly selected controls (RC) in order to determine whether antecedent anxiety disorders are plausible risk factors for AN and BN. Comorbid anxiety disorders were common in all three clinical groups (AN, 60%; BN, 57%; MD, 48%). In 90% of AN women, 94% of BN women and 71 % of MD women, anxiety disorders preceded the current primary condition (P=0.01), although panic disorder tended to develop after the onset of AN, BN or MD. In multivariate logistic regressions, the odds ratios (ORs) for overanxious disorder (OR=13.4) and obsessive‐compulsive disorder (OR=11.8) were significantly elevated for AN. The ORs for overanxious disorder and social phobia were significantly elevated for BN (OROAD,=4.9; ORSP=15.5) and MD (OROAD,=6.1; ORSP=6.4). These data suggest that certain anxiety disorders are non‐specific risk factors for later affective and eating disorders, and others may represent more specific antecedent risk factors.

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 (χ2 = 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).

Temperament, character and suicide attempts in anorexia nervosa, bulimia nervosa and major depression

Bulik CM, Sullivan PF, Joyce PR. Temperament, character and suicide attempts in anorexia nervosa, bulimia nervosa and major depression. Acta Psychiatr Scand 1999: 100: 27–32.

Unemployment and serious suicide attempts

BACKGROUNDnThis study used a case-control design to examine the association between unemployment and risk of medically serious suicide attempt.nnnMETHODnA sample of 302 individuals who made serious suicide attempts was contrasted with 1028 randomly selected community control subjects.nnnRESULTSnIndividuals who made serious suicide attempts reported higher rates of current unemployment (OR = 4.2) than control subjects. This association was similar for males and females. However, even before adjustment for confounding factors it was evident that exposure to unemployment made only a small contribution to suicide attempt risk. The population attributable risk for exposure to unemployment was 7.3%. After adjustment for antecedent childhood, family and educational factors the association between unemployment and risk of serious suicide attempt was reduced but remained significant (OR = 2.1), suggesting that common antecedent factors made a large contribution to risks of both unemployment and serious suicide attempt. When both antecedent family and childhood factors, and psychiatric morbidity were taken into account, unemployment was not significantly related to risks of serious suicide attempt.nnnCONCLUSIONnThe results of this study provide support for the contention that much of the association between unemployment and suicidal behaviour is non-causal, and reflects common or correlated factors that contribute to risks of both unemployment and suicidal behaviour. Any remaining association between unemployment and suicide attempt risk appears to arise from the correlation that exists between unemployment and psychiatric disorder.

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.

Bipolar II disorder: personality and outcome in two clinical samples

OBJECTIVEnTo compare the personality traits and disorders of patients with bipolar II disorder and major depression and to examine the impact on treatment outcome of a bipolar II diagnosis.nnnMETHODnPatients from two clinical trials, a depressive sample (n = 195, 10% bipolar II) and a bulimic sample (n = 135, 16% bipolar II), were assessed for personality traits using DSM-IV criteria. Patients were randomised to treatments (fluoxetine or nortriptyline for depressive sample; cognitive behaviour therapy for bulimic sample) and followed for 3 years (depressive sample) or 5 years (bulimic sample) to assess the impact on outcome of a bipolar II diagnosis.nnnRESULTSnBipolar II patients were assessed as having more borderline, histrionic and schizotypal personality traits than patients with major depression. A baseline bipolar II diagnosis did not impact negatively on treatment outcome, and less than 5% of bipolar II patients developed bipolar I disorder during follow up.nnnCONCLUSIONSnThe low rate of conversion of bipolar II to bipolar I disorder and the lack of adverse impact of the diagnosis on outcome, questions the need for antimanic or mood stabiliser medication in most bipolar II patients.

Towards an understanding of defense style in terms of temperament and character

The aim was to investigate the relationships between a model of personality based on the concept of defense mechanisms, as articulated by Vaillant, with the psychobiological model of personality, as developed by Cloninger. A total of 128 adults from 11 family pedigrees with at least two alcohol‐dependent members completed the self‐report Defense Style Questionnaire and the Temperament and Character Inventory. Immature defenses were largely explained by low character scores, while neurotic defenses were part temperament and part character. Cluster A, B and C defenses were related to low reward dependence, high novelty‐seeking and high harm avoidance respectively. In a regression analysis, cluster B and C defenses were more related to low character scores than to temperament but, for cluster A defenses, temperament and character both contributed. The results suggest that it is possible to integrate an ego defense model of personality with a psychobiological model of personality, thereby enriching both approaches.

The hypothalamic-pituitary-thyroid axis in major depression

We investigated the capacity of several thyroid‐axis measures to distinguish between depressed and control subjects and determined whether these variables were related to antidepressant treatment response. We studied 105 subjects who fulfilled the DSM‐III‐R criteria for a current major depressive episode and 41 volunteers with no current mental disorder. The following thyroid‐axis variables were measured: difference between T4 levels at 09.00 hours and 13.00 hours; baseline TSH; maximal TSH response to 400 μg TRH (Δmax TSH); and presence of a blunted Δmax TSH. The T4 difference variable alone distinguished between depressed and control subjects. In multivariate analyses, T4 difference and Δmax TSH were independently related to antidepressant‐treatment outcome, and predicted a modest proportion (14%) of the variance in outcome. The relationship between these two variables and treatment outcome was particularly strong in depressed male subjects who were receiving desipramine, for whom they accounted for 36% of the variance in treatment outcome. The T4 difference variable both distinguished between depressed and control subjects and was related to treatment outcome. Although this finding requires replication, it is consistent with other reports of the usefulness of thyroid‐axis indices measured at different times of day in depressed patients.

Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response

Objective: To evaluate the CORE measure of melancholia, against the DSM-IV construct of melancholia. To evaluate the validity of both the CORE and DSM-IV constructs of melancholia against psychosocial risk factors, anxiety and personality disorder comorbidity, neuroendocrine markers and differential antidepressant response to fluoxetine and nortriptyline. Method: One hundred and ninety-five outpatients with major depression were evaluated for melancholia with both the DSM-IV criteria and the CORE evaluation. Both constructs were evaluated for validity against psychosocial risk factors, comorbidity, biological markers and differential antidepressant response. Results: The CORE measure has satisfactory interrater reliability when used dimensionally, but has unacceptably low agreement for making a categorical diagnosis of melancholia. There is remarkably poor agreement (kappa = 0.11) between the CORE and DSM-IV criteria for melancholia. Neither the DSM-IV nor CORE criteria for melancholia identified subgroups of patients with better childhood environments or less anxiety or personality disorder comorbidity. The CORE criteria for melancholia, but not DSM-IV, identified patients with neuroendocrine disturbance. CORE scores also were associated with differential responses to fluoxetine and nortriptyline, but not in anticipated directions. Thus, high CORE scores were associated with a higher recovery rate with fluoxetine than nortriptyline. Conclusion: While the episode specifier of melancholia should be retained in diagnostic systems, the DSM-IV criteria were not validated against any of the variables examined in this study. The CORE construct of melancholia, was validated against neuroendocrine measures, and was associated with a differential antidepressant response. However, the limits imposed by interrater reliability, suggest the CORE measure should be used dimensionally and not to make a categorical diagnosis of melancholia.

Endocrine and behavioral responses to methylphenidate in normal subjects

Methylphenidate (0.3 mg/kg) was administered intravenously to 20 normal subjects. Behavioral responses varied considerably among individuals. Both cortisol and growth hormone showed significant increases (p less than 0.001). The adrenocorticotrophic hormone (ACTH) response seemed insufficient to explain the increase in cortisol. For men only, the increase in cortisol correlated positively with the increase in epinephrine (r = 0.77, p less than 0.05) and correlated negatively with baseline cortisol (r = -0.70, p less than 0.05), with increase in growth hormone (r = -0.70, p less than 0.05), and with the increase in energy (r = -0.83, p less than 0.01). The growth hormone response varied between the sexes, and for men, the growth hormone correlated with both an increase in energy (r = 0.70, p less than 0.05) and friendliness (r = 0.68, p less than 0.05). For all subjects, baseline heart rate correlated with the increase in energy (r = -0.69, p less than 0.002). In a separate study, six male subjects received, on different occasions, saline and a lower dose of methylphenidate. Together, these studies show that the increases in cortisol, growth hormone, and epinephrine, and the decrease in prolactin are dose-dependent.