Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life

Objectives: Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders. We addressed these issues by examining data from a prospective longitudinal community study to (i) determine the cumulative incidence of mood episodes and disorders in the first three decades of life; (ii) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa; and (iii) determine the clinical and treatment characteristics of these subjects. Methods: Using the Munich‐Composite International Diagnostic Interview, clinically trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects (aged 14–24 at baseline and 21–34 at third follow‐up). Results: The estimated cumulative incidence at age 33 was 2.9% for manic, 4.0% for hypomanic, 29.4% for major depressive, and 19.0% for minor depressive episodes; overall, 26.0% had unipolar major depression, 4.0% bipolar depression, 1.5% unipolar mania, and 3.6% unipolar hypomania (no major depression). Overall, 0.6% and 1.8% had unipolar mania or hypomania, respectively, without indication for even minor depression. A total of 3.6% of the initial unipolar major depression cases subsequently developed (hypo)mania, with particularly high rates in adolescent onset depression (< 17 years: 9%). A total of 49.6% of the initial unipolar mania cases subsequently developed major depression and 75.6% major or minor depression. While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases, bipolar cases did not significantly differ in mania characteristics from unipolar mania cases. Conclusions: Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood, a time period when both the recognition and the intervention rates by the healthcare system are rather low. ‘Conversion’ to bipolar disorder is limited in initial unipolar depression, but common in initial unipolar mania. The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings.     

Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes.

Cerebrospinal fluid neurotransmitter metabolite levels were studied to assess whether measures of central serotonin, dopamine, or norepinephrine function are associated with severity of abnormal eating patterns in patients with bulimia nervosa. In comparison with healthy controls (N = 17), hospitalized bulimic patients with a history of binge eating more frequently than twice daily (N = 11) had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. For the total patient group (N = 29), levels of both metabolites were significantly inversely correlated with binge frequency. On the basis of preclinical studies, these results were examined in the context of speculative models in which low central serotonin function might contribute to blunted satiety responses in bulimic patients, while low central dopamine activity might play a role in abnormal hedonic responses to food.     

Mood,performance, and pain sensitivity: Changes induced by food constituents

We examined the behavioral effects of the dietary constituents tryptophan and tyrosine on human mood, sensorimotor performance and pain sensitivity. Tryptophan and tyrosine are neurotransmitter precursors present in varying amount in protein-containing foods. Tryptophan (50 mg/kg) increased subjective drowsiness and fatigue but unlike many hypnotics did not impair sensorimotor performance. Tryptophan also decreased human pain sensitivity in a manner that was more specific than certain analgesic drugs.     

The object relations of bulimic women in context: an integration of two studies

The purpose of this paper is to investigate and contextualize the object relations of bulimic women. Two independent studies, one quantitative and one qualitative, were conducted. In the quantitative study, 77 undergraduate women completed self-report measures of eating behavior, interpersonal dependency, and object relations. In the qualitative study, four bulimic women participated in semi-structured interviews that were coded for relational themes and contextualized through a feminist socio-cultural analysis. Results supported the strong association between dependency and eating disorders and demonstrated that the object relationships of the participants were characterized by both insecure attachment and egocentricity. Socio-cultural analysis suggests that the development of these object relations can be partially accounted for by conflicting cultural expectations for women.     

Mood disorders in children and adolescents: an epidemiologic perspective.

Epidemiologic studies show that major depression is comparatively rare among children, but common among adolescents, with up to a 25% lifetime prevalence by the end of adolescence. Mania is much less common, with no more than a 2% lifetime prevalence by the end of adolescence. Developmental studies that include assessments of both hormonal changes and social changes through the pubertal transition are needed to investigate joint biological and environmental influences on the emergence of the gender difference in depression in puberty. Although subthreshold mood disorder symptoms are common, controversy exists about their clinical significance. This controversy is made more complex by methodologic uncertainties regarding inconsistent symptom reports obtained from parents, teachers, and children and by the pervasive existence of comorbidity. Retrospective reports about age of onset in adult studies suggest that at least 50% of youngsters with major depression and 90% of those with mania continue to have adult recurrences. These recurrences are mediated by adverse role transitions, such as truncated educational attainment and teenage childbearing, that typically occur before the time of initial treatment. Aggressive outreach and early treatment aimed at preventing the occurrence of adverse role effects might help decrease the persistence of child and adolescent mood disorders. Long-term follow-up studies are needed to resolve current uncertainties regarding nosology, methodology, and long-term treatment effects. Innovative epidemiologic research designs aimed at more quickly providing provisional information are also needed to advance understanding of long-term developmental processes.     

Anorexic and bulimic eating disorders

Anorexic and bulimic eating disorders today are rather frequent in adolescent girls and young women of developed industrial countries. News media frequently report such patients, and lay people are interested. For scientists, it is not easy to explain the etiology and pathophysiology of these eating disorders. Clinically, treatment is a challenge. General risk factors for the development of anorexic and bulimic eating disorders are (1) female gender, (2) adolescence, and (3) living in an industrial country. Special risk factors are (1) obesity or mental disorders (eating, depression, substance use), (2) premorbid characteristics (early menarche, childhood obesity, anxiety disorder, low self-esteem, and perfectionism), and (3) premorbid stresses. Biological and sociocultural factors and personally threatening experiences all play a role in the etiology. Especially in early phases of the illness, affected patients do not appear to suffer, are reluctant to admit symptoms, and may avoid necessary treatment. Progress has recently been made in the understanding and treatment of anorexic and bulimic eating disorders.     

From fetish object to transitional object: the analysis of a chronically self-mutilating bulimic patient

This paper challenges the view that food, or the patient's own body, functions as a transitional object for bulimics during the binge-purge cycle or symptomatic equivalents of self-harm. The author proposes that the bulimic patient's actions in and on her body more closely approximate the use of a fetish, which temporarily enhances a deficient and unstable body image and assuages separation anxiety, but does not promote progressive development. To illustrate these distinctions, the author presents an analysis of a self-mutilating bulimic patient who used her body as a fetish until a more integrated "me" evolved within the "shared skin" of her treatment. At that point, a transitional object and an idealizing selfobject fantasy were created, and the patient was able to engage the question of "not me," relinquish her self-mutilation, and resume the process of separation and growth.     

Shaping of the cat paw for food taking and object manipulation: an X-ray analysis

The kinematics of the cat distal forelimb during food-taking were analysed to obtain information on the movement processes within the paw before and during object taking in a species without monosynaptic cortico-motoneuronal projections. The behaviour was investigated with two tests: either the table test (TT, food offered on a table located at ground level in a reaching distance of 22 and 28 cm) or the horizontal test (HT, food offered in a small container located at shoulder level, height 18–25 cm, reaching distance 6–12 cm). In five animals, the changes in configuration and the conjoint actions of the wrist, the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were assessed with three-dimensional X-ray cinematography (time resolution 20 ms, spatial resolution 1 mm) and video analysis. While approaching the target, the digits were first extended and subsequently abducted. This ‘preshaping’ consisted of combined angular changes in the MCP and PIP joints, thereby attaining an adequate grip aperture. Each cat used a stable strategy, but different cats used different strategies. In the TT, preshaping involved an MCP extension and a PIP flexion. In the HT, predominant extension of the MCP, predominant extension of the PIP, or a combination of both were used, followed by MCP flexion and PIP flexion. The grip aperture started to decrease before object contact, earlier in the TT, later in the HT. Grasping was achieved by flexion of first the PIP and later the MCP. The X-ray analysis gave evidence for individuated digit movements. Correlation analysis of the angular position of the joints between the different phalanges showed that digits 3 and 4 acted in concert, as did digits 2 and 5, but with clear independence between the different pairs. Furthermore, the different phalanges served different purposes during the grasp. Digits 3, 4 established object contact, digits 2, 5 were mainly used to stabilize the paw onto the surface. The cat distal forelimb displays a refined movement repertoire during the preshaping and grasping phase of food-taking. During the preshaping phase, the kinematics resembled in some aspects the situation in humans. The results demonstrate the ability of the polysynaptic projections from the cortico-motoneuronal system to organize differentiated distal limb movements, including individuated movements of the digits.     

Interpersonal relation pattern in families with a bulimic member- interaction analysis

Basic hypotheses concerning the interaction in families of bulimic patients are tested. Family therapy sessions of 20 female patients of an outpatient therapy unit for eating-disorders were coded with a micro-analytic instrument (G?ttinger Familieninteraktions-Skalen) and analysed. The siblings relationships were systematically included in the study. The parental dyad turned out to be significantly more conflictual than the other dyads were. In the relationship between the patient and the parents a relatively stable pattern of interactional behaviour was found. The relationship between mother and bulimic daughter was more conflictual than that between father and daughter. The father-sibling-dyad was not significantly more conflictual than the father-patient-dyad. Especially the impact of sibling relationships on the family interaction of bulimic patients needs further elucidation.     

Hypnotizability in bulimic patients and controls

Summary Various studies have indicated that bulimics are more easily hypnotized and dissociate more readily than control groups and patients with other eating disorders. A comparison is reported of 15 inpatients with bulimia nervosa (DSM III-R) with 15 subjects in a control group comparable in age and education. The instrument used was the Harvard Group Scale of Hypnotic Susceptibility/Form A (HSGHS: A), which includes 12 standardized test suggestions. The results show that bulimics have higher scores in hypnotizability than the control group. A method study (comparison of self-evaluation with a video recording) shows that this is a result of the behaviour itself and not of the answering pattern used by the subjects in the questionnaire. It is possible that differing expectations regarding the experiment may have influenced the results. Considerations concerning the increased ability of bulimics to dissociate as a causal factor versus an accompanying phenomenon of the disorder are discussed.     

Effects of an antiandrogenic oral contraceptive on appetite and eating behavior in bulimic women

High androgen levels in women with bulimia nervosa may promote bulimic behavior. The aim of the present study was to investigate the effects of an antiandrogenic oral contraceptive (OC) on appetite and eating behavior in women with bulimia nervosa compared to healthy controls. Twenty-one women with bulimia nervosa and 17 healthy controls matched for age and body mass index participated in the study. Basal and meal-related appetite and secretions of the satiety peptide cholecystokinin (CCK) and the appetite-stimulating peptide ghrelin were studied before and after 3 months of treatment with an antiandrogenic OC (30 microg ethinyl estradiol combined with 3 mg drospirenone). Bulimic behavior was evaluated in relation to changes in hormone levels. Before treatment, bulimic women had higher frequency of menstrual disturbances, acne and hirsutism and higher levels of testosterone but lower meal-related CCK secretion than controls. OC treatment reduced meal-related hunger and gastric distention in bulimics. CCK secretion in response to the meal was unchanged in bulimic women but decreased in the controls. Ghrelin secretion was comparable between groups and did not change in response to OC treatment. The treatment improved bulimic behavior in relation to a decline in testosterone levels in the entire group. Our results support the suggestion that androgens play a role in bulimic behavior. Treatment with an antiandrogenic OC may serve as a new strategy for treatment of bulimia nervosa and particularly in those patients with hyperandrogenic symptoms.     

Pathogenesis of stroke-like episodes in MELAS: analysis of neurovascular cellular mechanisms

The pathogenesis of stroke-like episodes in mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) is not fully understood although two main theories have been proposed; ischemic vascular hypothesis caused by "mitochondrial angiopathy" and generalized cytopathic hypothesis caused by "mitochondrial cytopathy". Crucial molecular mechanism includes the lack of taurine modification at the wobble uridine of mutant transfer RNAsLeu(UUR) resulting in defective translation of cognate codons due to a defect in codon-anticodon interaction. Whereas recent clinical studies have shed light on the neuronal hyperexcitability, which may potentially initiate a cascade of stroke-like events. Stroke-like episodes are characterized by neuronal hyperexcitability, neuronal vulnerability, increased capillary permeability, and focal hyperaemia. It is recognized that stroke-like lesions not only evolve in the area incongruent to a vascular territory, but also potentially spread into the surrounding cortex with concomitant vasogenic edema presumably provoked by prolonged epileptic activities. Based on the clinical observations, we speculate that stroke-like episodes appear to be non-ischemic neurovascular events; once neuronal hyperexcitability developed in a localized brain region as a result from either mitochondrial dysfunction in the capillary endothelial cells, or in neurons or astrocytes, epileptic activities may depolarize the adjacent neurons leading to propagation of epileptic activities in the surrounding cortex. Increased capillary permeability provoked by epileptic activities in the presence of mitochondrial capillary angiopathy may cause unique edematous brain lesions predominantly involving the cortex. As a consequence, susceptible neuronal population in the cortex may result in neuronal loss with a laminar or pseudo-laminar distribution.     

Syncope: A videometric analysis of 56 episodes of transient cerebral hypoxia

To investigate the clinical features of transient cerebral hypoxia, syncope was induced in 56 of 59 healthy volunteers through a sequence of hyperventilation, orthostasis, and Valsalva maneuver. All events were monitored on video by two cameras. Complete syncope with falling and loss of consciousness was observed in 42 subjects, lasting 12.1 ± 4.4 seconds. Myoclonic activity occurred in 38 of these 42 episodes (90%). The predominant movement pattern consisted of multifocal arrhythmic jerks both in proximal and distal muscles. Superposition of generalized myoclonus was common. Additional movements such as head turns, oral automatisms, and righting movements occurred in 79%. Eyes remained open throughout syncope in most subjects and initial upward deviation was common. Sixty percent reported visual and auditory hallucinations. Thirteen subjects had incomplete syncope with falls but partially preserved consciousness. These episodes were shorter and usually not accompanied by myoclonus and hallucinations. Transient amnesia and unresponsiveness without falling occurred in 1 subject.