Course Of Affective Disorders Research Articles

S18 * LESCH TYPOLOGY (LAT): FROM BASIC RESEARCH TO TREATMENT * S18.1 * LESCH ALCOHOLISM TYPOLOGY AND TEMPERAMENTS: THEIR ROLE IN ETIOLOGY, COURSE AND TREATMENT

S18 * LESCH TYPOLOGY (LAT): FROM BASIC RESEARCH TO TREATMENT * S18.1 * LESCH ALCOHOLISM TYPOLOGY AND TEMPERAMENTS: THEIR ROLE IN ETIOLOGY, COURSE AND TREATMENT

The impact of brief depressive episodes on the outcome of bipolar disorder and major depressive disorder: A 1-year prospective study

Brief depressive episodes (BDEs) cause psychosocial impairment and increased risk of suicide, worsening the outcome and long-term course of affective disorders. The aim of this naturalistic observational study was to assess the frequency of BDEs and very brief depressive episodes (VBDEs) and their impact on clinical outcome in a sample of patients with major depressive disorder (MDD) and bipolar disorder (BD). Seventy patients with a diagnosis of MDD or BD were followed up and monthly visited for a period of 12 months, assessing the eventual occurrence of BDEs and/or VBDEs. Clinical and demographic variables of the total sample and of the groups divided according to the presence of BDEs or VBDEs were collected and compared by one-way ANOVAs. Hamilton Depression Rating Scale 21 items (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression (severity of illness) (CGIs) and the Short Form Health Survey (SF-36-item 1) were administered at baseline and logistic regression was performed to evaluate whether baseline scores were predictive of the onset of BDEs or VBDEs. BDEs (88.6% of the total sample), VBDEs (44.3% of the total sample) and BDEs+VBDEs (40.0% of the total sample) were found to occur frequently across the sample. BDE patients showed more death thoughts during major depressive episodes (χ(2) = 4.14, df = 1, p = 0.04, Phi = 0.24) compared to patients without BDEs. Indeed VBDE patients showed a higher rate of hospitalization (χ(2) = 5.71, df = 1, p = 0.031, phi = 0.29), a more frequent prescription of a combined treatment (χ(2) = 13.07, df = 7, p = 0.03, phi = 0.43) and higher scores at SF-36 item 1 (F = 6.65, p = 0.01) compared to patients without VBDEs. Finally, higher SF-36 item 1 scores were found to be predictive of VBDEs (odds ratio = 2.81, p = 0.03). Major depressives, either unipolar or bipolar, with BDEs or VBDEs showed a worse outcome, represented by a more severe psychopathology and higher rates of hospitalization. VBDEs were predicted by a negative subjective general health perception. Studies with larger samples and longer follow-up are warranted to confirm the results of the present study.

Selbst und Körper in der Depression: Herausforderungen an die Therapie

Depression can be considered to be the result of multiple neurobiological, psychological and social factors which are related to one another. Clinical experience underlines the importance of psychomotor symptoms in depression. These are correlated both to subjective experience and the underlying somatic processes in the course of affective disorders. The main aim of this article is to analyse the inter-relationship between the self, self-concepts and subjective experience of depressed patients and neurobiological processes of depression, particularly from a psychotherapeutical perspective. Reflecting the concept of depression as a psychosomatosis of affect regulation, different empirical approaches are demonstrated focussing on the self-body relationship in depression. In a series of combined studies operationalised subjective psychological characteristics and prefrontal cortical activation patterns during emotional-motor stimulation, explored by using functional magnetic resonance imaging (fMRI), were investigated. The Repertory Grid Technique, an idiographical procedure, was used to explore the individual features of the depressed patients. In the first study phase catatonic patients in an acute and post-acute state who also had an underlying affective disorder were investigated. Subjective operationalised psychological characteristics in both the acute and post-acute state showed a significant lack of contact, decreased self-esteem and reduced emotional arousal (compared to non-catatonic psychiatric and healthy controls). fMRI revealed significant dysfunctional activation patterns in the orbito-frontal cortex and alterations in the medial pre-frontal and pre-motor cortex during negative emotional stimulation. The results support the hypothesis that emotional arousal plays a central role in depressive stupor and that orbito-frontal cortical dysfunction may be closely related to regression to somatic defence mechanisms as paradigmatically observed in depressive stupor. Further results from combined neuropsychological and fMRI/MRS investigations of the neurophysiological basis of depressive symptomatology and its therapeutically induced effects are demonstrated. In these studies a pathological functional interaction between lateral and medial prefrontal cortical regions and a disturbed balance between left and right dorso-lateral prefrontal cortex was found. This emotional-cognitive dysbalance may be correlated with the dominant negative emotions and cognitive deficits in depression.The results of current studies reveal a possible dissociation between cognitive and psychopatho-logical symptoms in the course of depression. These combined neuropsychological and neuroimaging approaches may contribute to the development of specific neuronal and metabolic diagnostic markers for depression and thus to more specific, effective and sustainable treatment. Furthermore, the therapeutical challenges arising from the multi-dimensionality of depressive disorders (especially the inhibitions reflected in psychomotor symptoms) and the subjective experience of the individual depressive patient are discussed. Finally, the development of a therapeutic relationship is an important precondition in enabling the patient to overcome the vicious circles of depression.

S100B Serum Levels and Word Memory Processing in Remitted Major Depression as Reflected by Brain Potentials

Objective: Memory processes, as reflected by ‘old/new’ effects of event-related potentials (ERPs), have been shown to be impaired in depressed patients. This variability might be partly explained by biological factors. S100B is a glial calcium-binding protein with neuroplastic properties; S100B serum levels have been shown to be increased in depressive patients. The pathophysiologic role of S100B in depression, however, is not yet sufficiently understood. Methods: In the present study, ERPs recorded in a visual continuous word recognition paradigm were therefore investigated in patients with remitted major depression in relation to S100B serum levels. Results: Patients with moderately increased S100B serum levels (n = 6) showed a normal old/new effect in contrast to a reduced old/new effect in patients with normal S100B levels (n = 6) compared to aged-matched controls. Conclusions: These findings provide evidence of an association between S100B levels and memory processes in patients with recurrent depression and further suggest a neuroprotective role of moderately increased S100B serum levels in the course of affective disorders.

Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder

In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD). In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls. A trend was found for a protective effect of the exon 9beta polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9beta had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons. We conclude that the exon 9beta polymorphism and the TthIIII polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.

Netherlands study of depression and anxiety (NESDA): examining the long-term course of affective disorders

Background and aims:The Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is an ongoing study to: 1) describe the long-term course and consequences of depressive and anxiety disorders, and 2) to examine the demographic, psychosocial, somatic, biological and genetic determinants of this course. This presentation describes NESDA's rationale, sampling frame and methods.Methods:The design is an 8-year longitudinal cohort study following 2,850 participants aged 18 through 65 years. The sample consists of 1600 persons with a current (6 month recency) diagnosis of depression or anxiety disorder, 850 persons at risk (because of high symptomatology, family or life-time history), and 400 healthy controls. Recruitment takes place in the community, through 65 general practitioners (using a three-stage screening procedure), and through 17 mental health care institutions in order to include patients reflecting various settings and stages of psychopathology. The 4-hour baseline assessment includes questionnaires, interviews, a medical exam, a computer task and blood (including DNA and RNA) and saliva collections. Follow-up assessments are repeated after 1, 2, 4 and 8 years.Results:Over 2500 respondents with more than 2100 current diagnoses of depression or anxiety disorders, were recruited in November 2006 (mean age = 41 years, 67% female). Expected end date of recruitment is in February 2007.Discussion:NESDA is expected to provide more insight into (predictors of) the course of affective disorders. NESDA is open for collaboration (including data utilization) with other European research groups, which we hope to stimulate by a presentation of its design and methods.

Inanspruchnahme eines psychoedukativen Gruppenangebotes für Angehörige von Patienten mit affektiven Störungen

The relevance of family interactions in the course of affective disorders has been well described. In contrast to the situation regarding schizophrenic disorders, there are few systematic concepts for involvement of the relatives of patients with affective disorders in treatment. The goal of this study was the development and evaluation of a standardised psychoeducational treatment programme. We determined the number and characteristics of relatives accepting the offer of such a group. Relatives of almost half of 55 patients with major depression and a bipolar disorder participated in the group. Relatives of male patients were more likely to take part than relatives of female patients. Relatives of patients with a bipolar disorder were more likely to take part than relatives of patients with unipolar depression. The patients whose relatives attended the group showed a more favourable understanding of the illness and more knowledge about affective disorders, but on the other hand, felt themselves to be more strongly criticised by their relatives and had less social support than the other patients. These results emphasise the importance of differential family-focused treatment modalities in affective disorders.

The Munich vulnerability study on affective disorders: premorbid neuroendocrine profile of affected high-risk probands

One of the most characteristic alterations in depression is a disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. A function test combining the pre-treatment of 1.5 mg dexamethasone (DEX) with a challenge of 100 μg corticotropin-releasing hormone (CRH) reveals a pathological increase in the adrenocorticotropin and cortisol release in patients with major depression. These changes partially persist after successful treatment with remission and therefore, might represent trait or vulnerability markers. To further address this question, we were investigating the premorbid neuroendocrine profile of 74 healthy high-risk probands (HRPs) with a positive family history for affective disorders. The aim was to identify premorbid vulnerability factors. During the observation period, 19 HRPs developed an affective disorder. Their premorbid DEX/CRH test results were compared with 19 age- and sex matched controls. No significant differences could be observed between these two groups. Our results suggest that a dysregulated HPA system indicated by this function test can rather be regarded as a neurobiological scar developing during the course of affective disorders.

Modèles de sensibilisation comportementale et troubles psychiques : aspects actuels

Behavioral sensitization is a preclinical model which can be defined as an augmentation in the behavioral effect of a psychostimulant upon re-administration. It has two phases, induction and expression. Induction refers to the transient sequence of events precipitated by psychostimulant administration that leads to the enduring changes in neural functions responsible for behavioral augmentation. Expression corresponds to the enduring neural alterations arising from the induction process that directly mediate the augmented behavorial response. These two processes are not only temporally but also anatomically and biochemically distinct. Induction seems to require the stimulation of dopamine D1 receptors in the ventral tegmental area (VTA) either directly by dopamine (DA) agonists, or indirectly via GABAergic inhibition; the stimulation of excitatory amino acid (EEA) receptor in the VTA, the amygdala and the hippocampus may also have a central role in the induction process. Contrary to its induction the expression of sensitization depends on the stimulation of the DA terminal fields and appears to be D2 mediated, whereas GABA and EEA do not seem to play a role. These processes result in an enhanced DA efflux induced by repeated exposure to stimulants. At least three different subcellular cascades have been involved in the molecular mechanisms of sensitization. Activation of these cascades induce changes in expression of neuritogenesis and synaptogenesis genes and remodelling of neural networks. First used to conceptualize various aspects of the course of affective disorders, behavioral sensitization models have been recently applied to the pathophysiology of schizophrenia, as a consequence of a better understanding of their neurobiologic underpinnings. Other psychiatric syndroms such as anxious disorders and drug addiction have been concerned too. Behavioral sensitization helps understand syndrome progression manifested by either increasing frequency, severity or spontaneity of psychiatric episodes, as well as the deteriorative course of some psychotic illnesses since sensitization, if sustained can lead to potential neurotoxic effects producing structural alterations. This model has found many applications in the psychopharmacological domain. Repeated application of stimulants either parenterally or directly into the brain may also produce a progressive increase in neural excitability, eventually producing major motor seizures in response to a previously subthreshold dose of drug. This could explain why anticonvulsants may be effective in psychiatric disorders in which behavioral sensitization is deemed to be involved. Recent data show that drugs like valproate are not only useful for treating affective illness but are also efficient in schizophrenia and anxious disorders. Contrary to lithium, valproate appears to prevent not only the induction but also the expression of behavioral sensitization in rodents. Drugs like olanzapine have, in addition to their D2 blockade effect, the capacity to block D1 receptors which may be linked to their antimanic and mood stabilising properties, considering the role of D1 receptors in the induction of sensitization phenomena. It is also possible that 5HT2 blockade play a role in this respect, as these receptors have been involved too in the development of behavioral sensitization. Finally the model allows specific predictions about the course of some psychiatric illnesses and particularly regarding the fact that treatment intervention that limit duration and number of psychiatric episodes may prevent progression of brain pathology. However such hypotheses have still to be tested through futures studies.

RECURRENT AFFECTIVE DISORDERS: NONLINEAR AND STOCHASTIC MODELS OF DISEASE DYNAMICS

Affective disorders tend to be recurrent and progressive and illness patterns typically evolve from isolated episodes at the beginning to more rapid, rhythmic and finally irregular "chaotic" mood patterns. Chararacteristic timecourse and disease patterns have prompted the consideration of nonlinear dynamics and chaos. In this paper we review some of our recent work where we addressed the relevance of nonlinear, stochastic and resulting cooperative dynamics for disease patterns and temporal course of affective disorders by use of a computational approach.

Target evaluation processing and serum levels of nerve tissue protein S100B in patients with remitted major depression

Selective attention processes (N2 and P3 components of event-related potentials (ERPs)) have been shown to be impaired in depressed patients but findings have been mixed. Part of this variability might be explained by neurobiological factors. ERPs (Go/Nogo paradigm) were investigated in patients with remitted major depression in relation to S100B. S100B, an astroglial protein with neuroplastic properties, has been shown to be increased in depression. Its pathophysiologic role in depression, however, is not yet sufficiently understood. Patients with increased S100B serum levels ( n=6) showed a normal N2- and P3-amplitude in contrast to a reduced N2- and P3-amplitude in patients with normal S100B serum levels ( n=6). These findings provide evidence of a correlation between S100B levels and attentional processes in patients with recurrent depression and further substantiate S100B's role as a marker in the course of affective disorders.

The High-affinity Non-peptide CRH1Receptor Antagonist R121919 Attenuates Stress-induced Alterations in Plasma Oxytocin, Prolactin, and Testosterone Secretion in Rats

Evidence from basic and clinical research suggests that hyperactivity of central corticotropin-releasing hormone (CRH) circuits contributes to causality and course of affective disorders. Therefore, CRH receptor antagonists have attracted attention as potential therapeutics. We could previously show that the novel high-affinity non-peptide CRH 1 receptor antagonist R121919 significantly inhibits stress-induced corticotropin release and displays anxiolytic effects in rats selectively bred for high anxiety-related behavior. These animals are characterized by their innate hyper-reactivity of the hypothalamic-pituitary-adrenocortical system linked to an increased emotionality and therefore are suitable for the evaluation of CRH 1 receptor antagonists. Here we show that in addition to its effects on anxiety-related behavior and corticotropin secretion, R121919 attenuates the stress-induced release of corticosterone, prolactin, and oxytocin. Moreover, the decrease in plasma testosterone following exposure to stress is abolished by R121919. Our data indicate that antagonism of CRH 1 receptors may prevent stress-associated endocrine alterations.

Self-esteem, social adjustment and suicidality in affective disorders

Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients.

Is there evidence for a latent class called ‘hypomanic temperament’?

Background: Affective disorders belong to the most common psychiatric disorders. Several risk factors have been postulated and empirically investigated. Researchers like Akiskal [Interpersonal Factors in the Origin and Course of Affective Disorders, Gaskell, London, 1996] have pointed out the associations between sub-affective temperaments and affective disorders. However, no study has dealt with the issue whether there is a latent class of such sub-affective temperaments or if such temperaments are best conceptualized as fully dimensional. We investigated whether the Hypomanic Personality Scale [J. Abnorm. Psychol. 121 (1986) 214–222] as an indicator of hyperthymia is taxonic in structure. Methods: We chose two different samples to address this issue: A sample of young adults ( n=1966) and another sample of adolescents ( n=4045). We ran MAXCOV-HITMAX analyses based on identical subsets of items in both samples. Results: Neither in the sample of young adults nor in the sample of adolescents there was evidence for a latent class called ‘hypomanic temperament’. Limitation: Only one indicator for vulnerability and one procedure to test for latent classes was used. Furthermore, we do not know how many of our sample had a life-time history or current affective disorders. Conclusions: The hypomanic–hyperthymic temperament is best conceptualized as a dimension in the general population. However, before drawing final conclusions about the taxonicity of the risk for affective disorders, more research is needed using different measures, samples and methods to resolve this question of the dimensionality of vulnerability. Additionally, the question remains open how to conceptualize mania itself.

AFFECTIVE DISORDERS IN CULTURAL CONTEXT

This article reviews epidemiologic and ethnographic evidence for the cultural shaping of the causes, symptomatology, and course of affective disorders. Cross-cultural research demonstrates much overlap of depression with anxiety, somatoform, and dissociative disorders, raising questions about the universality of the prototypical representation of depression in North American psychiatry. Culture-specific symptoms may lead to under-recognition or misidentification of syndromes of mania and depression in many ethnocultural groups. Cultural idioms of distress may employ symptoms related to affective disorders to express sentiments and perceptions that do not in themselves indicate psychopathology. Socially mediated cognition about the self and specific modes of interpersonal interaction influence the course of depression. This article discusses some implications of these findings for the recognition and treatment of affective disorders among culturally diverse populations in primary care and mental health care settings.

On the impact of episode sensitization on the course of recurrent affective disorders

Sensitization of an organism by recurrent disease episodes is postulated as a key mechanism governing the progressive long-term course of affective disorders. The particular significance is that episode sensitization could underly the transition from externally triggered disease episodes to autonomous episode generation. Functionally, this transition might be explained by positive feedback between a disease episode and the activity state of an organism which includes the introduction of a memory trace for generated disease episodes. Here we consider the functional consequences of episode sensitization for the course of recurrent affective disorders. We use a computational approach and extend our previously introduced model for the course of affective disorders by a feedback mechanism for episode sensitization. Depending on sensitization timescale and amount, triggered episodes leave the model in a sustained sensitized state or induce autonomous disease progression. Runaway activation can end in saturation. Remarkably, however, over a broad parametric range the progression ends in intermediate states with fluctuating disease patterns. This behavior results from the model's nonlinear dynamics and represents a situation where the feedback intermittently changes between positive and negative directions. Our simulations strongly support episode sensitization as an important disease mechanism for affective disorders. From a nonlinear standpoint, this mechanism offers an explanation not only for autonomous disease progression but also for occurence and stability of irregular rapid-cycling disease states.

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat.

The mechanisms whereby antidepressant drugs exert their therapeutic effects remain unknown. Responses to stressful stimuli are currently thought to contribute to the onset and course of affective disorders. It has been postulated that antidepressants might act by ameliorating response patterns to challenging life events, such as processes of reactivity and/or habituation. Using the olfactory bulbectomy (OBX) rat model, this study examined the effects of various antidepressants on measures of reactivity and habituation in behavioral tests assessing responses to novel stimuli. Sham-operated and OBX rats received 21 daily injections of fluoxetine (10 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), buspirone (3 mg/kg), or vehicle. Forty-eight hours after the last injection, animals were tested in the open field, elevated plus maze, and startle apparatus. For each test, time series data were collected and fit with exponential random effects models, in which estimated parameters assessed behavioral reactivity and habituation. Relative to sham controls, OBX rats displayed increased total locomotor activity in the open field and exhibited increased open arm behavior in the elevated plus maze. Through comparison with zinc sulfate-treated anosmic controls, these OBX-induced increases were attributed to both an augmentation of initial reactivity due to anosmia and an attenuation of the average rate of habituation. Chronic antidepressant treatment did not reduce the anosmia-related initial reactivity levels of OBX rats to that of sham controls. Rather, the antidepressants evoked their restorative effects by increasing the rate of habituation. These findings suggest that antidepressants restore normal responding by permitting more effective adaptation to novel stimuli.

Predictors of recurrence in affective disorder — analyses accounting for individual heterogeneity

Background: Previous studies suggest that gender, age at onset, and marital status act as risk factors for further recurrence initially during the course of affective disorder but not at a later stage. These studies did, however, not take the individual liability to recurrence into account. Method: The effect of predictors of recurrence was estimated with the use of generalised linear mixed models in a case register study including a random sample of all patients admitted with primary affective disorder in Denmark during 1971–1993. Results: In total, 7047 first admission patients with a diagnosis of affective disorder, depressive or manic/circular type were included in the analyses. The study confirmed that the effect of the type of disorder, age at first admission, and never being married decreased during the course of illness even when the individual liability to recurrence was taken into account. No differences in the effect of gender and in the effect of a recent divorce were found between early and later episodes and the effect of a recent death of a spouse seemed to increase during the course of illness. The risk of recurrence increased with every new episode for all sub-groups of patients. Conclusion: The effect of some, but not all, predictors of recurrence decline during the course of affective illness. The number of previous episodes predicts recurrence in most subgroups of patients. Limitation: The data relate to re-admissions rather than recurrence. Clinical relevance: The study underscores the importance of the illness process itself.

Recovery from episodes during the course of affective disorder: a case-register study.

The aim of the study was to investigate whether the duration of treated episodes changes during the course of unipolar and bipolar affective disorder. The rate of recovery from successive hospitalized episodes was estimated with survival analyses in a case-register study including all hospital admissions with primary affective disorder in Denmark during the period 1971-1993. A total of 9174 patients with recurrent episodes were followed from their first admission. The rate of recovery from hospitalized episodes did not change with the number of episodes in unipolar or bipolar disorder. Furthermore, the rate of recovery was constant across episodes, regardless of the combination of age, gender and type of disorder. Initially in the course of the illness, the rate was a little faster for bipolar than for unipolar patients, but later in the course of the illness the rate of recovery was the same for the two disorders. It is concluded that, in modern treatment settings, the duration of affective episodes appears to be stable during the course of unipolar and bipolar disorder.

Consequences of deterministic and random dynamics for the course of affective disorders

Background: Uni- and bipolar affective disorders tend to be recurrent and progressive. Illness patterns can evolve from isolated episodes to more rapid, rhythmic, and “chaotic” mood patterns. Nonlinear deterministic dynamics are currently proposed to explain this progression. However, most natural systems are nonlinear and noisy, and cooperative behavior of possible clinical relevance can result. Methods: The latter issue has been studied with a mathematical model for progression of disease patterns in affective disorders. Results: Deterministic dynamics can reproduce a progression from stable, to periodic, to chaotic patterns. Noise increases the spectrum of dynamic behaviors, enhances the responsiveness to weak activations, and facilitates the occurrence of aperiodic patterns. Conclusions: Noise might amplify subclinical vulnerabilities into disease onset and could induce transitions to rapid-changing dysrhythmic mood patterns. We suggest that noise-mediated cooperative behavior, including stochastic resonance, should be considered in appropriate models for affective illness.