Time to Relapse Questionnaire (TRQ): a measure of sudden relapse in substance dependence.

BACKGROUND: Relapse may occur suddenly, following a short period of craving, or after extended consideration. The time to relapse may reveal underlying mechanisms of relapse and have important implications for treatment. OBJECTIVE: The Time to Relapse Questionnaire (TRQ), a self-administered questionnaire, was designed to assess the time from the initial thought of drug use to actual use. METHODS: Psychometric properties of the TRQ were evaluated in two distinct populations (n = 183 and 194) with DSM-IV primary substance use disorders. RESULTS: Factor analysis and item refinement led to a 9-item TRQ with a three-factor solution accounting for 63% of the total variance. Three discrete types of relapse style were identified: Sudden Relapse, Short Delay Relapse, and Long Delay Relapse. The TRQ demonstrated good construct validity and adequate internal consistency for the total (alpha = .61) and individual factor (alpha = .64-.75) scores. Measures to assess convergent validity of the TRQ suggest that Sudden Relapse may not reflect more generalized deficits of inhibitory control. CONCLUSIONS AND SIGNIFICANCE: The TRQ may provide a useful self-report measure to discriminate between addicted patients who relapse without forewarning compared to those with a period of delay. Clinical interventions may be targeted towards different relapse styles.

Which depressive symptoms remain after response to cognitive therapy of depression and predict relapse and recurrence?

BACKGROUND: Major Depressive Disorder (MDD) is highly prevalent, severely debilitating, and often recurrent. Greater residual depressive symptoms after acute phase treatment predict greater relapse and recurrence. It is unknown, however, which specific depressive symptoms remain and are most predictive. METHOD: The current study examined (a) which specific residual symptoms remained after effective treatment with acute phase cognitive therapy (A-CT) for recurrent depression and (b) if any of those specific residual symptoms were risk factors for relapse and recurrence over a 2-year follow-up. RESULTS: After completing 20 sessions of A-CT, a substantial proportion of adult responders continued to endorse somatic anxiety (42%), psychological anxiety (37%), middle insomnia (36%), depressed mood (29%), loss of libido (29%), late insomnia (24%), anergia (21%), guilt feelings (18%), early insomnia (17%), and anhedonia (14%), as defined by the 17-item Hamilton Rating Scale for Depression (HRSD). Decreased agitation, increased psychological anxiety, increased loss of appetite, increased loss of libido, and increased hypochondriasis were all risk factors for relapse and recurrence over a 2-year follow-up (all p<.05), after stratifying on number of previous episodes and controlling for age at onset and whether A-CT responders received continuation phase CT instead of assessment only control. LIMITATIONS: These findings are based on a limited sample size (n=84), which was modestly restricted in terms of gender, ethnicity, region, and mean education level. CONCLUSIONS: These results confirm that residual symptoms are common after A-CT. We hypothesize that treatments, intervention modules, or durations that effect and/or target specific residual symptoms may further reduce depression relapse and recurrence.

Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness.

BACKGROUND: Long-term ingestion of alcohol produces marked alterations in hypothalamic-pituitary-adrenal axis activity. The authors engaged in a series of studies to determine the distinct role of the hypothalamus and the pituitary and adrenal glands in the disturbances observed in abstinent alcohol-dependent subjects. In this first of a two-part study, the authors report on (1) the basal secretory profile of corticotropin and cortisol from 2000 to 0800 hrs, (2) adrenocortical sensitivity in both the presence and absence of endogenous pituitary activation, and (3) pituitary glucocorticoid sensitivity to dexamethasone. METHODS: Eleven male, 4 to 6 weeks abstinent, alcohol-only-dependent subjects and 10 age-matched male healthy controls were studied. Basal circulating concentrations of corticotropin and cortisol were obtained from 2000 to 0800 hr. A submaximal dose of cosyntropin (0.01 microg/kg), a corticotropin analogue was then administered to assess adrenocortical sensitivity. In a separate session, cosyntropin was administered following high-dose dexamethasone (8 mg iv) to assess adrenocortical sensitivity in the relative absence of endogenous corticotropin. In addition, the corticotropin response to dexamethasone was measured to determine pituitary glucocorticoid responsiveness. RESULTS: Cortisol, but not corticotropin, pulse amplitude (p < 0.05) and mean concentration (p= 0.05) was significantly lower in alcohol-dependent subjects compared with controls. The cortisol response to cosyntropin was lower in alcohol-dependent subjects following endogenous corticotropin suppression by high-dose dexamethasone (p <0.04) but not without dexamethasone pretreatment. Mean corticotropin (p <0.004) and cortisol (p <0.05) concentrations in response to dexamethasone were attenuated in the patients compared to controls. Basal concentrations of 11-deoxycortisol, the precursor to cortisol, were also decreased in alcohol-dependent subjects (p <0.05). CONCLUSION: Attenuated basal and stimulated adrenocortical concentrations in abstinent alcohol-dependent men are coupled with a nonhomeostatic increase in pituitary glucocorticoid inhibition. A decrease in stress-axis responsivity in alcohol dependence may have implications for treatment outcome.

Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 2: response to ovine corticotropin-releasing factor and naloxone.

BACKGROUND: Pituitary and adrenal responsiveness is suppressed in abstinent alcohol-dependent individuals. To clarify the specific organizational disruption in hypothalamic-pituitary-adrenal functioning during early abstinence, the authors separately assessed each level of the stress-response axis. In this second of a two-part study, ovine corticotropin-releasing factor (oCRH) was used to stimulate the pituitary corticotrophs, and naloxone was used to activate the axis at the hypothalamic level. In addition, pulsatile characteristics of corticotropin and cortisol were assessed over a 12-hr period (0800 to 2000 hr). METHODS: Eleven abstinent alcohol-dependent men and 10 healthy comparison participants were assessed. All participants were between the ages of 30 and 50 years, and alcohol-dependent patients were abstinent from 4 to 6 weeks. Basal concentrations of corticotropin and cortisol were obtained every 10 min from 0800 to 2000 hr and subjected to pulsatile analysis. Plasma corticotropin and cortisol concentrations were then obtained every 5 to 10 min after low-dose, intravenously administered doses of oCRH (0.4 microg/kg) or naloxone (0.125 mg/kg). Medications were administered at 2000 hr and the two challenge studies were separated by 48 hr. RESULTS: Pulsatile analysis revealed that the mean corticotropin amplitude was increased in alcohol-dependent patients relative to controls (p <0.05). Other pulsatile characteristics of corticotropin and all cortisol pulsatile measures were not significantly different between the two groups. The integrated cortisol response to oCRH was significantly lower in alcohol-dependent patients compared with controls (p <0.01), but the integrated corticotropin response was not significantly different. In contrast, neither the corticotropin nor the cortisol response to naloxone was significantly different between groups. CONCLUSIONS: Adrenocorticoid hyposensitivity persists after oCRH infusion for at least 1 month after cessation of drinking, whereas hyporesponsiveness of the pituitary corticotrophs to CRH seems to resolve with continued abstinence. The authors suggest that adrenocortical hyporesponsiveness during prolonged abstinence may impact relapse risk.

Increased salivary cortisol concentrations during chronic alcohol intoxication in a naturalistic clinical sample of men.

BACKGROUND: Cortisol, the primary glucocorticoid in humans, is intimately involved in the regulation of such varied and critical biological processes as emotion, cognition, reward, immune functioning, and energy utilization. A persistent increase in cortisol concentration as a result of chronic intoxication could therefore result in alcohol-related disorders such as sleep disruption, cognitive deficits, diabetes, and mood disturbances. Although moderate levels of acute alcohol ingestion are reported to produce an increase in cortisol levels, it is uncertain whether cortisol remains persistently increased during long-term chronic intoxication. METHODS: Salivary cortisol and breath alcohol concentrations (BAC) were obtained on 73 subjects with primary alcohol dependence on initial presentation for treatment and 22 alcohol-dependent subjects participating in a residential treatment program. RESULTS: Both intoxicated alcohol-dependent subjects (n = 38) and nonintoxicated subjects in acute alcohol withdrawal (n = 30) demonstrated significantly increased salivary cortisol concentrations compared with abstinent subjects (n = 27; p < 0.001). Nonintoxicated subjects in acute withdrawal demonstrated significantly increased salivary cortisol concentrations compared with highly intoxicated subjects (BAC >100 mg/dl) but were similar to subjects with lower levels of intoxication (BAC, 10-100 mg/dl). CONCLUSIONS: Chronic alcohol-dependent subjects experience continuously increased concentrations of cortisol during both intoxication and withdrawal. Increased levels of cortisol during chronic intoxication seem to progressively increase with the onset of withdrawal. This suggests a daily cycle of hypercortisolemia during the active drinking phase, with further increases on the cessation of drinking and the emergence of withdrawal symptoms. Persistently increased levels of cortisol may extract a costly allostatic load, resulting in significant central nervous system and peripheral organ morbidity.