Changes in cocaine consumption are associated with fluctuations in self-reported impulsivity and gambling decision-making.

BACKGROUND: In cross-sectional studies, cocaine users generally display elevated levels of self-reported and cognitive impulsivity. To what extent these impairments are stable v. variable markers of cocaine use disorder, and, thus, are pre-existing or drug-induced, has not yet been systematically investigated. METHOD: We conducted a longitudinal study with cocaine users who changed or maintained their consumption intensity, measuring self-reported impulsivity with the Barratt Impulsiveness Scale (BIS-11), and cognitive impulsivity with the Rapid Visual Processing task (RVP), Iowa Gambling task (IGT), and Delay Discounting task (DD) at baseline and at 1-year follow-up. We assessed 48 psychostimulant-naive controls and 19 cocaine users with decreased, 19 users with increased, and 19 users with unchanged cocaine intake after 1 year as confirmed by hair analysis. RESULTS: Results of linear multilevel modelling showed significant group × time interactions for the BIS-11 total score and the IGT total card ratio. Increasers showed a trend for elevated scores, whereas decreasers exhibited reduced self-reported impulsivity scores within 1 year. Surprisingly, increasers' IGT performance was improved after 1 year, whereas decreasers' performance deteriorated. By contrast, neither RVP response bias B" nor DD total score showed substantial group × time interactions. Importantly, BIS-11 and DD revealed strong test-retest reliabilities. CONCLUSION: Self-reported impulsivity (BIS-11) and decision-making impulsivity (IGT) covary with changing cocaine use, whereas response bias and delay discounting remain largely unaffected. Thus, self-reported impulsivity and gambling decision-making were strongly state-dependent in a stimulant-using population and may be suitable to monitor treatment success, whereas delay of gratification was confirmed as a potential endophenotype of stimulant addiction.

Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity.

The definitions of bipolar-I (BP-I) and bipolar-II (BP-II) disorders are currently under revision by the APA and by the WHO. We provide evidence of a revised set of criteria for bipolar disorders and major depressive disorder (MDD) which could serve to strengthen the construct and predictive validity of both disorders and enable more incisive studies of treatments and courses of both disorders. In the diagnostic Bridge Study of 5,635 patients with major depressive episodes from 18 countries (Europe, North Africa, Near East and Far East) leading psychiatrists in each country assessed a pre-specified group of symptoms, illness course, family history and duration of episodes; these data allowed tests of several definitions of bipolarity. The primary revised specifier diagnosis of BP-I disorder included manic episodes based on an additional category A criterion (increased activity/energy) and did not apply any exclusion criteria. The revised BP-II disorders included hypomanic episodes of 1-3 days. Family history and illness course validators (history of mania/hypomania among first degree relatives, 2 or more lifetime episodes and first symptoms having occurred before age 30) discriminated clearly between patients with bipolar-I or bipolar-II disorders meeting bipolarity specifier criteria and those with MDD. Specifier definitions provided better discrimination between MDD and the two bipolar subgroups. Patterns of concurrent comorbidities also differed significantly between patients meeting criteria for MDD compared with those meeting bipolar specifier criteria. Comorbidity patterns differed between bipolar-I and bipolar-II patients. This study provides evidence for the validity of modified (specifier) BP-I and BP-II definitions that incorporate illness course and family history which reduce ambiguities of major depressive episodes between bipolar-I and bipolar-II disorders and MDD.

The role played by depression associated with somatic symptomatology in accounting for the gender difference in the prevalence of depression.

PURPOSE: A variety of studies suggest the existence of a distinct phenotype of somatic depression, i.e., depression accompanied by significant somatic symptomatology. Previous research suggests that the gender difference in the prevalence of depression is primarily due to a difference in somatic depression. The aim of this study was to compare the gender difference in the prevalence of somatic depression and of depression not accompanied by significant somatic symptomatology (labelled "pure" depression) in two representative samples, the National Comorbidity Survey-Replication (NCS-R) and the Zurich Study. METHOD: The gender difference in lifetime somatic depression was compared to that of pure depression based on analyses weighted back to the general population in two representative samples. The NCS-R analyses involved a narrow definition of somatic depression with items from the DSM criteria for depression--appetite, sleep, and fatigue. The analysis of the Zurich study added headaches, body image issues, and breathing difficulties to the criteria and comparison to atypical depression. RESULTS: In both samples, the gender difference in depressive prevalence was due to a large difference in somatic depression with other phenotypes showing little or no gender difference. The gender differences were found to be due to the somatic symptoms rather than the number of symptoms and were much larger for somatic than for atypical depression. CONCLUSION: The gender difference in the prevalence of depression results from the higher prevalence among women of a specific phenotype, somatic depression.

Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes.

To assess the clinical validity of individual DSM-IV criteria for hypomania. In an international sample of 5,635 patients with major depressive episodes (Bridge Study), DSM-IV criteria for hypomania (stem questions, number and quality of symptoms, duration and exclusion criteria) were systematically assessed and their validity analysed on the basis of clinical data including family history, course, and other clinical characteristics. Three stem questions for hypomania, irritability, elevated mood and the added question of increased activity, showed comparable validity. The results support the current DSM-IV requirement for a higher symptom threshold (4 of 7 hypomanic symptoms) in cases of irritable mood. Longer durations of hypomanic episodes were associated with higher scores on all validators. The results did not support the DSM-IV durational requirements for hypomanic episodes (4 days) and manic episodes (7 days). Brief hypomanic episodes of 1, 2 or 3 days were valid and would meet validity criteria for inclusion. The three exclusion criteria in DSM-IV (hypomania due to the use of antidepressants or of other substances, or to other medical conditions) were found to exclude patients with bipolar depression and should therefore not be retained. These results support several revisions of the DSM-IV concept of hypomanic episodes: specifically, the inclusion of increased activity as a gate question, the inclusion of 1 or 2 to 3-day episodes and the elimination of all exclusion criteria.

Subjective distress predicts treatment seeking for depression, bipolar, anxiety, panic, neurasthenia and insomnia severity spectra.

OBJECTIVE: To examine correlates of mental health treatment seeking such as gender, diagnosis, impairment, distress and mastery. METHOD: Longitudinal epidemiological data from the Zurich Study of common psychiatric syndromes, including unipolar and bipolar depression, panic, anxiety, neurasthenia and insomnia, were utilized. In longitudinal Generalized Estimating Equations, treatment seeking was regressed on measures of subjective distress and impairment, childhood family problems, mastery and number of comorbid diagnoses. RESULTS: Approximately half of all treated participants across all six syndromes suffered from subthreshold disorders. Meeting full or subthreshold diagnostic criteria was associated with treatment seeking for insomnia. Being female was associated with treatment seeking for depression. The only variable highly and consistently associated with treatment seeking, across all syndromes, was subjective distress. Treated participants reported high levels of distress, work and social impairment in both diagnostic and subthreshold groups. CONCLUSION: Subjective distress may be a better indicator of treatment seeking than symptom count.

Parsing the clinical phenotype of depression: the need to integrate brief depressive episodes.

OBJECTIVE: To expand the concept of recurrent brief depression (RBD) to brief depression (BD) and to test its clinical relevance. METHOD: Subjects (N = 591) were studied prospectively six times from ages 20/21 to 40/41 years. RBD was defined according to DSM-IV as episodes under 2 weeks with about monthly recurrence and work impairment. BD embraces RBD and brief depressive episodes with a frequency of 1-11 per year. RESULTS: Pure BD and pure major depressive episodes (MDE) did not differ in treatment rates, family history of mood and anxiety disorders or comorbidity with bipolar spectrum and anxiety disorders but they differed in work impairment, suicide attempt rates and distress self-ratings. The combination of BD + MDE identified a very severe group of MDE, comparable with combined depression (MDE + RBD) and double depression (MDE + dysthymia). CONCLUSION: Our data argue for the use of BD as a diagnostic specifier for severe MDE. RBD remains an important independent subgroup.

Melancholia and atypical depression in the Zurich study: epidemiology, clinical characteristics, course, comorbidity and personality.

OBJECTIVE: A comparison of psychiatric, psychological and somatic characteristics in specified subgroups of major depressive episodes (MDE). METHOD: In a stratified community sample of young adults investigated prospectively from age 20/21 to 40/41, we defined four MDE subgroups: i) DSM-IV melancholia or atypical depression (the 'combined group'), ii) pure melancholia, iii) pure atypical depression, and iv) unspecified MDE. RESULTS: The cumulative incidence rates of the four groups were 4.1%, 7.1%, 3.5% and 8.2% respectively. Women were over-represented in the combined and atypically depressed group. In 56 of 117 (47.9%) cases, melancholia was longitudinally associated with atypical MDE (n = 84) (OR = 11.9). CONCLUSION: Melancholic MDE was more severe than atypical MDE although the two groups shared many characteristics. The longitudinal overlap of melancholia with atypical depression in almost half of all cases calls for comparative analyses of combined, pure and unspecified MDE.

Asthma and body weight change: a 20-year prospective community study of young adults.

OBJECTIVE: There is increasing evidence for an association between asthma and body weight change. The objectives of these analyses were to examine the temporal relationships of this association and to explore the role of childhood depression as an explanatory factor. METHODS: Data were derived from six subsequent semistructured interviews on health habits and health conditions from a single-age community study of 591 young adults followed up between ages 20 and 40 years. RESULTS: Cross-sectionally (over the whole study period), asthma was significantly associated with obesity (odds ratio=3.9 [95% confidence interval 1.2, 12.2]). Multivariate longitudinal analyses revealed that asthma was associated with increased later weight gain and later obesity among women after controlling for potentially confounding variables, whereas weight gain and obesity were not associated with later asthma. A secondary analysis showed that depressive symptoms during childhood were associated with adult obesity and asthma, partially explaining the asthma-obesity comorbidity. CONCLUSION: This study encourages further research on mechanisms underlying the asthma-obesity comorbidity, particularly on shared psychosocial factors operating during critical periods in childhood and adolescence that may influence the development and persistence of both obesity and asthma during adulthood.

Depressive symptoms during childhood and adult obesity: the Zurich Cohort Study.

Depression and obesity have become major health problems with increasing prevalence. Given the limited effectiveness of treatment for weight problems, the identification of novel, potentially modifiable risk factors may provide insights on new preventive approaches to obesity. The purpose of this study was to test the hypothesis that depressive symptoms during childhood are associated with weight gain and obesity during young adulthood. Participants were from a prospective community-based cohort study of young adults (N=591) followed between ages 19 and 40 years. The sample was stratified to increase the probability of somatic and psychological syndromes. Information was derived from six subsequent semistructured diagnostic interviews conducted by professionals over 20 years. The outcome measures were body mass index (BMI) and obesity (BMI>30). Among women, depressive symptoms before age 17 years were associated with increased weight gain (4.8 vs 2.6% BMI increase per 10 years) representing greater risk for adult obesity (hazard ratio=11.52, P<0.05). Among men, only after controlling for confounders, depressive symptoms before age 17 years were associated with increased weight gain (6.6 vs 5.2% BMI increase per 10 years) in adulthood but not with occurrence of obesity. These associations between childhood depressive symptoms and adult body weight were adjusted for baseline body weight, a family history of weight problems, levels of physical activity, consumption of alcohol and nicotine, and demographic variables. As the magnitude of the associations was high, and depression during childhood is a prevalent and treatable condition, this finding may have important clinical implications for the prevention and treatment of obesity. Whether the results of this study are limited to populations with elevated levels of psychopathology remains to be tested.

The associations between psychopathology and being overweight: a 20-year prospective study.

BACKGROUND: Psychiatric disorders and being overweight are major health problems with increasing prevalence. The purpose of this study was to test the hypothesis that being overweight is associated with a range of psychiatric conditions including minor and atypical depressive disorders, binge eating, and aggression. METHOD: Prospective community-based cohort study of young adults (n = 591) followed between ages 19 and 40. Information derived from six subsequent semi-structured diagnostic interviews conducted by professionals over twenty years. Outcomes were being overweight [body-mass index (BMI)> 25] and average yearly weight change between ages 20 and 40 (BMI slope). RESULTS: 18.9 % of the participants were classified as being overweight. Being overweight turned out to be a stable trait: 77.7% of subjects were assigned to the same weight class at each interview. Atypical depression and binge eating were positively associated with both, increased weight gain and being overweight, while psychiatric conditions associated with aggressive behaviors (aggressive personality traits, sociopathy) were positively associated with being overweight, but were not related to the rate of weight change. Generalized anxiety disorder was negatively associated with overweight. These results persisted after controlling for substance use, levels of physical activity, demographic variables and family history of weight problems. CONCLUSIONS: This study shows relatively strong associations between eating-related and aggressive psychopathology and being overweight. Given the high prevalence rates of these conditions, this study encourages further research on the causality of psychopathology-overweight associations that might provide insight on novel preventive approaches for major health problems.

The Zurich Study: participation patterns and Symptom Checklist 90-R scores in six interviews, 1979-99.

OBJECTIVE: The Zurich study is a longitudinal study in psychiatric epidemiology that started in the late 1970s. The sixth interview in 1999 provides the basis to investigate and update the participation and drop-out patterns of the Zurich subjects. METHOD: Aside from descriptive analyses, particular attention was paid to the Symptom Checklist 90-R (SCL-90-R), used initially to stratify the Zurich sample. RESULTS: The initial proportions of high-scorers vs. low-scorers (two-thirds vs. one-third) have not changed significantly in the 367 subjects who participated in the 1999 interview. More detailed analyses indicate a selective and changing dependence of participation/drop-out on health status as measured by the SCL-90 R. In recent interviews drop-out has become more likely in subjects with extremely high SCL scores and in subjects with low SCL scores. CONCLUSION: Drop-out in the Zurich Study is associated with extreme SCL scores.

Risk factors for the bipolar and depression spectra.

OBJECTIVE: To identify risk factors for mood disorders in a community sample studied from the ages of 20 to 35 years. METHOD: Social characteristics, a family history of mood disorders and some personality features were analysed as risk factors for bipolar and depressive disorders by means of logistic regression. RESULTS: Frequent 'ups and downs' of mood were the strongest risk factor for both bipolar and depressive disorders; a weaker risk factor for both was emotional/vegetative lability (neuroticism). An additional risk factor for bipolar disorders was a positive family history of mania, whereas for depression it was a positive family history of depression/fatigue. As a risk factor for bipolar disorders, 'ups and downs' were much stronger than a positive family history of mania. Frequent ups and downs were independent of the family history of mood disorders. CONCLUSION: The results suggest that mood regulation should be investigated as a new, very important independent risk factor for mood disorders.

Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies.

BACKGROUND: While there is ample evidence that the prevalence rates for major depressive disorder (MDD) in the general population are higher in women than in men, there is little data on gender differences as regard to symptoms, causal attribution, help-seeking, coping, or the consequences of depression. METHOD: The large DEPRES Study dataset covering representative population samples of six European countries (wave I: 38,434 men and 40,024 women; wave II: 563 men and 1321 women treated for depression) was analyzed for gender differences. RESULTS: In wave I marked gender differences were found in the six-month prevalence rate for major depression but less so for minor depression; the gender differences for major depression persisted across all age groups. Even after stratification by clinically significant impairment and paid employment status, men reported fewer symptoms than women; as a consequence, men reached the diagnostic threshold less often. In wave II there were clear gender differences in causal attribution and in coping. Men coped by increasing their sports activity and consumption of alcohol and women through emotional release and religion. Women felt the effects of depression in their quality of sleep and general health, whereas men felt it more in their ability to work. LIMITATIONS: The second wave of the study comprises treated depressives only and may be less representative than the first wave.

Localization of MDMA-induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA).

3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5-HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA-naïve volunteers. Thirty-one-channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA-specific EEG pattern with that of various 5-HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior.

Gender differences in the subjective effects of MDMA.

RATIONALE: 3.4-Methylenedioxymethamphetamine (MDMA) mainly releases serotonin (5-HT) and is contained in the recreational drug Ecstasy. 5-HT is known to play an important role in mood and anxiety disorders, for which there is a female preponderance. To date, there are no systematic data on gender differences in the subjective effects of MDMA. OBJECTIVES: The present work analyzed the pooled data from three controlled studies on the psychological and physiological effects of MDMA in healthy volunteers with no or minimal MDMA experience. A particular focus of the analyses were possible gender differences. METHODS: A total of 74 subjects (54 male, 20 female) participated in all three studies. MDMA in oral doses ranging from 70-150 mg (1.35-1.8 mg/kg) was administered under double-blind placebo-controlled conditions. Subjective peak changes were assessed by standardized psychometric rating scales. Physiological measures were blood pressure, heart rate, and peripheral body temperature. Adverse drug effects were assessed during the experimental session and after 24 h. RESULTS: Psychoactive effects of MDMA were more intense in women than in men. Women especially had higher scores for MDMA-induced perceptual changes, thought disturbances, and fear of loss of body control. The dose of MDMA positively correlated with the intensity of perceptual changes in women. Acute adverse effects and sequelae were also more frequent in female than in male subjects. In contrast, men showed higher increases in blood pressure than woman. CONCLUSIONS: The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with an increased susceptibility of women to the 5-HT-releasing effects of MDMA. Our results also indicate that increasing doses of MDMA produce more hallucinogen-like perceptual alterations, particularly in women.

No difference in brain activation during cognitive performance between ecstasy (3,4-methylenedioxymethamphetamine) users and control subjects: a [H2(15)O]-positron emission tomography study.

The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use.

Concurrent psychiatric comorbidity and multimorbidity in a community study: gender differences and quality of life.

This study analysis of a community cohort at the age of 35 focused on the effects of gender and multimorbidity on quality of life and subjective distress. Consistent with an earlier analysis, quality of life decreased with increasing numbers of concurrent psychiatric diagnoses. Women generally reported lower quality of life and higher distress than men. Relative to men, well-being in women was subject to more diagnostic (alcohol abuse/dependence, depression, generalized anxiety disorder, bulimia) and social influences (partner, promotion). The same factors predicted women's psychological and physical well-being, indicating a more holistic experience in women. Men's physical well-being did not correlate with any of the diagnostic or social variables measured.

3,4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H(2)(15)O]-PET in healthy humans.

[H(2)(15)O]-Positron Emission Tomography (PET) was used to examine regional cerebral blood flow (rCBF) after administration of a single oral dose of the serotonin realeaser and uptake inhibitor MDMA (1.7 mg/kg) or placebo to 16 MDMA-naïve subjects. Psychological changes were assessed by psychometric rating scales. MDMA produced distributed changes in regional blood flow including increases in ventromedial frontal and occipital cortex, inferior temporal lobe and cerebellum; and decreases in the motor and somatosensory cortex, temporal lobe including left amygdala, cingulate cortex, insula and thalamus. Concomitant with these changes, subjects experienced heightened mood, increased extroversion, slight derealization and mild perceptual alterations. MDMA also produced increases in blood pressure and several side effects such as jaw clenching, lack of appetite and difficulty concentrating. These results indicate that a distributed cluster of brain areas underlie the various effects of MDMA in humans.

Psychological and physiological effects of MDMA ("Ecstasy") after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans.

MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") mainly releases serotonin and dopamine. In animals, pretreatment with 5-HT(2) antagonists has been shown to attenuate neurochemical and behavioral effects of MDMA. In humans, the role of 5-HT(2) receptors in the action of MDMA has not been studied. We investigated the effect of pretreatment with the 5-HT(2A/C) antagonist ketanserin (50 mg p.o.) on subjective responses to MDMA (1.5 mg/kg p.o.) in 14 healthy volunteers using a double-blind placebo-controlled within-subject design. Subjective effects were rated by psychometric rating scales. Physiological effects measured were blood pressure, heart rate, and body temperature. Adverse effects were assessed during the sessions, and after one and three days. Ketanserin attenuated MDMA-induced perceptual changes, emotional excitation, and acute adverse responses but had little effect on MDMA-induced positive mood, well-being, extroversion, and short-term sequelae. Body temperature was lower under MDMA plus ketanserin compared to MDMA alone. The results suggest a contributing role for 5-HT(2) receptors in the action of MDMA in humans.

Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are attenuated by the serotonin uptake inhibitor citalopram.

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.