Onset Of Affective Disorders Research Articles

T3. METACOGNITIVE BELIEFS IN SEVERE MENTAL DISORDERS

BackgroundAffective dysregulation and psychotic experiences or symptoms often co-occur in the general population as well as in bipolar and psychotic disorders, suggesting a complex interplay. Early trauma is hypothesised to be important for the aetiology of both, and individuals with early traumatic experiences often develop disorders characterised by an admixture of affective and psychotic symptoms. Early emotional abuse seems to be particularly relevant for both disorders. Studies of common factors associated with affective dysregulation and psychosis in bipolar and psychotic disorders could help further theoretical understanding and tailor therapeutic interventions. Metacognitive beliefs – beliefs that outline the importance or consequence of thoughts – have been proposed as one possible common factor. Compared to healthy controls, patients with affective or psychotic disorders hold higher levels of metacognitive beliefs that could be maladaptive. Metacognitive beliefs have been linked to affective and/or psychotic diagnoses and symptoms in these disorders, and to early trauma in general. However, little is known about the specific relationships between symptoms of bipolar/psychotic disorders, early emotional abuse, and metacognitive beliefs.This project had three objectives: (1) to examine the prevalence of metacognitive beliefs in bipolar and psychotic disorders, compared to controls; (2) explore whether illness-related factors were linked to metacognitive beliefs; (3) examine if symptomatic responses (depression or positive symptoms) to early emotional abuse were mediated by metacognitive beliefs.MethodsPatients with a bipolar or psychotic disorder, and healthy controls, were included through the on-going Thematically Organised Psychosis (TOP) Study in Oslo, Norway. Analyses included t-tests for group comparisons, regression analyses, and regression based mediation pathway analyses where the indirect effects were tested with bootstrapped confidence intervals.ResultsPatients with bipolar or psychotic disorders reported higher levels of metacognitive beliefs compared to controls. Metacognitive beliefs were significantly related to depression for all patients. Higher levels of metacognitive beliefs were also related to illness-factors related to a poorer long-term outcome, specifically an earlier age at onset of affective disorder in bipolar disorders, and poorer premorbid social adjustment in psychotic disorders. Metacognitive beliefs significantly mediated the relationship between early emotional abuse and depression. The combination of metacognitive beliefs and depression significantly mediated the relationship between early emotional abuse and positive symptoms. The mediation models explained a moderate amount of the variance in symptoms (R2 = .21 and .29) compared to direct models of early emotional abuse impacting on symptomatic responses directly (R2 = .04 and .03)DiscussionOur results show that patients with bipolar or psychotic report higher levels of metacognitive beliefs compared to controls, and that such beliefs relate to current symptoms of depression in both patient groups. Our results also suggest that metacognitive beliefs relate to factors present before or at the onset of illness, which are often linked to a poorer long-term outcome in the disorders. Further, our findings suggest that in regards to early emotional abuse, metacognitive beliefs could play a role in an affective pathway to psychosis. Metacognitive beliefs could thus be relevant treatment targets in regards to depression and positive symptoms in bipolar and psychotic disorders.

An exploration of metacognitive beliefs and thought control strategies in bipolar disorder

BackgroundMetacognitive factors influence depression, but are largely unexplored in bipolar disorders. We examined i) differences in metacognitive beliefs and thought control strategies between individuals with bipolar disorder and controls, and ii) to what extent clinical characteristics were related to levels of metacognitive beliefs and thought control strategies in bipolar disorder. MethodEighty patients with bipolar disorder were assessed for age at onset of affective disorder, number of affective episodes, symptoms of mania and depression, metacognitive beliefs (MCQ-30) and thought control strategies (TCQ). Control subjects (N=166) completed MCQ-30 and TCQ. Factors impacting on metacognitive beliefs and thought control strategies were explored with multiple linear regressions. ResultsPatients with bipolar disorder reported higher levels of unhelpful metacognitive beliefs and thought control strategies than controls. Metacognitive beliefs were mainly influenced by depressive symptoms, and age at onset of affective illness. Thought control strategies were mainly influenced by metacognitive beliefs and age at onset of affective illness. ConclusionOur findings suggest that metacognitive beliefs and control strategies are relevant in bipolar disorder. Depression and age at onset of affective disorder could contribute to metacognitive beliefs in bipolar disorder, and influence the use of thought control strategies. This indicates potential relationships that warrant further investigation for clinical relevance.

Affective disorders as potential complication of anti-acne treatment with isotretinoin: A case series

ObjectiveTo analyse cases of 9 patients (18-27 yo) who were consequently admitted to our department and treated with affective disorders (AD) while undergoing isotretinoin (INN) therapy. MethodsA semi-structured questionnaire designed by the authors was used to analyse many variables related to demographic characteristics, dermatologic and psychiatrics symptoms, AD course and treatment, family history of mental disorders, building on medical histories of patients and their families, and available medical records. ResultsPatients were diagnosed (DSM-IV-TR) with: a major depressive episode (4 patients), a recurrent major depressive episode (3), a bipolar mixed episode (1), and rapid cycling bipolar I disorder (1). The mean time from the first use of INN to: I. the onset of mental disorders was approximately 2 months (1–6 months), II. a visit with a psychiatrist was about 12 months (1–38 months). The predictors of occurrence of AD included a family history of AD and a prior episode of mental disorders. The onset of AD was in most cases preceded by prodromal symptoms such as headaches, sleep disorders, fatigue, drowsiness, or general weakness. Five patients reported suicidal ideation, four patients showed suicidal tendencies, and two persons attempted to commit suicide during the treatment. ConclusionsPsychiatrists should pay special attention to isotretinoin as a drug that may trigger episodes of AD, particularly in patients with a family history of AD or prior episodes of mental disorders. Isotretinoin therapy of patients with acne and a family history of AD or prior episodes of mental disorders requires special care and, if symptoms of depression develop or worsen during the INN treatment, collaboration between a dermatologist and a psychiatrist is needed.

Ernst Rüdin and the State of Science

Ernst Rüdin and the State of Science

What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12–30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD (‘AR’), b) participants from families without mental illness (‘controls’), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.

Proteomic Changes in Female Rat Hippocampus Following Exposure to a Terrified Sound Stress

Stress plays a profound role in the onset of affective disorders, including an elevation in risk factors for depression and anxiety. Women are twice as vulnerable to stress as men because of greater sensitivity to a substance produced during times of anxiety. To better define the abnormal proteins implicated in cognitive deficits and other stress-induced dysfunction, female rats were exposed to terrified sound stress, and two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) were utilized to determine the differential protein expression in the hippocampus in sound-stressed female rats compared with controls. Quantitative differences were found in 44 protein spots which were differentially expressed between the stressed and control groups (fold change of >2; p < 0.01). Eighteen protein spots were downregulated, and 26 protein spots were upregulated in the stressed group. The seven most differentially expressed proteins were identified and validated as follows: dihydropyrimidinase-related protein 2 (DRP-2), creatine kinase B type, dynamin-1 protein, alpha-internexin, glial fibrillary acidic protein beta, gamma-enolase, and peptidyl-prolyl cis-trans isomerase A. Changes in protein levels were detected in the hippocampus of female rats subjected to terrified sound stress. The findings herein may open new opportunities for further investigations on the modulation induced in the hippocampus by stress at the molecular level, especially with respect to females stress.

Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder

Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction with the BDNF Val66Met polymorphism predict onset of affective disorder in healthy individuals at heritable risk for affective disorder. In a high-risk study, we assessed whole blood levels of BDNF in 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high and low risk twins, respectively). Participants were followed up longitudinally with questionnaires at 6-month intervals for mean seven years and then reassessed with a personal interview to obtain information about whether they had developed psychiatric illness. At follow-up 36 participants (15.4%) had developed psychiatric disorder. Cox regression analysis revealed that BDNF levels at baseline were not associated with onset of illness in this explorative study. Further, two-way interactions between BDNF levels and the Val66Met polymorphism or between familial risk and the Val66Met polymorphism did not predict illness onset.

Is there evidence for an emotion-related bias in verbal learning or memory in individuals putatively high at risk for mania?

There is broad evidence that individuals with bipolar disorder show deficits in verbal memory and learning. Such deficits seem to be independent of acute mood episodes and to manifest after the onset of the disorder. Less research has been conducted in relation to more specific memory functions, particularly to verbal memory and learning for emotional information. Therefore, the objective of the present study is to investigate if there is evidence for an affective memory bias in at-risk individuals before the onset of affective disorder. We applied the Emotional Auditive Verbal Learning Test to individuals at risk for mania and at risk for depression, as well as to a control group. We hypothesized a mania-related memory bias for individuals at risk of mania. We found no evidence for an overall learning or memory deficit in the high-risk groups. All groups performed better learning and remembering neutral words compared to emotionally valenced words, however, contrary to our hypothesis there was no specific emotion-related learning or memory bias in the two high-risk groups. There was no evidence of impairments in verbal learning and memory overall and for emotional contents before the onset of affective disorders.

Atypical prodromal onset in affective disorders

Serra, Ga; Manfredi, Ga,b; Faedda, Gc; De Chiara, La; Sani, Ga,b; Koukopoulos, Aa,b; Koukopoulos, Ab; Girardi, Pa,b Author Information

Risk of affective disorders following prenatal exposure to severe life events: A Danish population-based cohort study

Objective To examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring. Methods In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothers were considered exposed if one (or more) of their close relatives died or was diagnosed with serious illness up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of affective disorder or 31 December 2007; hospital admissions were identified by linkage to the Central Psychiatric Register. Log-linear Poisson regression was used for data analysis. Results The risk of affective disorders was increased in male offspring whose mothers were exposed to severe life events during the second trimester (adjusted RR 1.55 [95% CI 1.05–2.28]). There was an increased risk of male offspring affective disorders in relation to maternal exposure to death of a relative in the second trimester (adjusted RR 1.74 [95% CI 1.06–2.84]) or serious illness in a relative before pregnancy (adjusted RR 1.44 [95% CI 1.02–2.05]). There was no evidence for an association between prenatal exposure to severe life events and risk of female offspring affective disorders. Conclusions Our population-based study suggests that prenatal maternal exposure to severe life events may increase the risk of affective disorders in male offspring. These findings are consistent with studies of populations exposed to famine and earthquake disasters which indicate that prenatal environment may influence the neurodevelopment of the unborn child.

P01-47 - A comparison of life events in patients with adult-onset unipolar disorder, adult-onset bipolar disorder and controls

ObjectiveThe present study aimed to explore the association between stressful life events (LE) and the development of affective psychopathology.MethodThirty patients with unipolar disorder and 30 patients with bipolar disorder were compared to 60 matched healthy controls as regards the rate of stressful LE. Measures included the Beck Depression Inventory, the Adult Life Events Checklist and the Childhood Life Events Questionnaire.ResultsThe entire sample had more LE in general, more negative and loss-related LE in the year preceding their first depressive episode as compared to normals. Subjects with unipolar disorder had more positive LE and more achievement LE, whereas subjects with bipolar disorder had more uncontrollable LE in the year preceding the first depressive episode. The relationship between LE and manic episodes was prominent in the year preceding the first manic episode, with bipolar subjects reporting more LE in general and more ambiguous events in that year. A significant relationship was found between childhood LE and the development of affective disorders in adulthood, with unipolars exhibiting less positive and achievement LE.ConclusionsThe major impact of LE on the onset of affective disorders was found in the year prior to the first depressive or manic episodes, in the unipolar and bipolar groups. This suggests that the accumulation of LE at this crucial period contributes to the precipitation of a pathological response mechanism. Once established, this mechanism would be reactivated in the future by even less numerous and less severe stressors, compatible with the kindling hypothesis.

A comparison of life events in patients with unipolar disorder or bipolar disorder and controls

Objective The present study aimed to explore the association between stressful life events (LEs) and the development of affective psychopathology. Method Thirty patients with unipolar disorder and 30 patients with bipolar disorder were compared to 60 matched healthy controls in regard to the rate of stressful LEs. Assessment measures included the Beck Depression Inventory, the Adult Life Events Questionnaire, and the Childhood Life Events List. Results The entire sample of affective patients had more LEs in general, more negative LEs, and more loss-related LEs in the year preceding their first depressive episode as compared with normal controls. Subjects with unipolar disorder had more positive LEs and more achievement LEs, whereas subjects with bipolar disorder had more uncontrollable LEs in the year preceding the first depressive episode. The relationship between LEs and manic episodes was prominent in the year preceding the first manic episode, with subjects with bipolar disorder reporting more LEs in general and more ambiguous events in that year. Almost no significant differences on LE frequency were observed in the year before the last depressive and manic episodes in the patient groups with unipolar and bipolar disorder. A significant relationship was found between childhood LEs and the development of affective disorders in adulthood, with patients with unipolar disorder exhibiting less positive and achievement LEs. Conclusions In both the unipolar and the bipolar groups, the major impact of LEs on the onset of affective disorders was found in the year before the first depressive or manic episodes. This suggests that the accumulation of stressful LEs at this crucial period contributes to the precipitation of a pathological response mechanism. Once established, this mechanism would be reactivated in the future by even less numerous and less severe stressors, compatible with the kindling hypothesis.

Individual Differences in Typical Reappraisal Use Predict Amygdala and Prefrontal Responses

Participants who are instructed to use reappraisal to downregulate negative emotion show decreased amygdala responses and increased prefrontal responses. However, it is not known whether individual differences in the tendency to use reappraisal manifests in similar neural responses when individuals are spontaneously confronted with negative situations. Such spontaneous emotion regulation might play an important role in normal and pathological responses to the emotional challenges of everyday life. Fifty-six healthy women completed a blood oxygenation-level dependent functional magnetic resonance imaging challenge paradigm involving the perceptual processing of emotionally negative facial expressions. Participants also completed measures of typical emotion regulation use, trait anxiety, and neuroticism. Greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These associations were not attributable to variation in trait anxiety, neuroticism, or the use of another common form of emotion regulation, namely suppression. These findings suggest that, like instructed reappraisal, individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation might predict successful coping with emotional challenges as well as the onset of affective disorders.

The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women

A growing literature suggests that hormonal fluctuations occurring across the menstrual cycle, during and after pregnancy, and during the menopausal transition are associated with onset of affective disorders or exacerbation of existing disorders. This influence of the neuroendocrine system on psychiatric disorders is thought to be mediated by an abnormality in central nervous system response to neuroactive steroids such as estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO). This interplay is considerably complex as neuroactive steroids modulate the function of multiple neurotransmitter systems throughout various stages of development. While one could choose to study any number of steroid–neurotransmitter interactions, our group in addition to others has focused our investigative efforts on unraveling the contribution of neuroactive steroids to psychiatric syndromes and disorders via their modulation of gamma aminobutyric acid (GABA), the brain's major inhibitory neurotransmitter. The goal of this article is two-fold: to synthesize the clinical and preclinical research focusing on the interplay between neuroactive steroids and GABA as they relate to neuropsychiatric and substance use disorders in women and to integrate data from our laboratory using proton magnetic resonance spectroscopy into this context.

Age-at-First-Registration and Heterogeneity in Affective Psychoses

Previous research into age of onset in affective disorders has produced conflicting results. This paper examines the influence of heterogeneity on the age-at-first-registration distribution for the ICD-9 diagnostic group 'affective psychosis'. For 1979-1991, data for age-at-first-registration for 4985 individuals diagnosed with affective psychosis (ICD-9 296.x) were extracted from a name-linked mental health register. These data were divided into (i) '296.1 only', a category used to code unipolar depression (males = 700; females = 1321); and (ii) '296 other', all 296 cases other than 296.1 (males = 1280; females = 1684). Inception rates for each 5-year age division were adjusted for the background population age-structure as a rate per 100,000 population. The age-at-first-registration distribution for affective psychosis has a wide age range, with women outnumbering men. There is a near-linear increase in inception rates for both men and women with 296.1 only, while the bulk of those with affective psychoses (296 other) have an inverted U-shaped age distribution. Males have an earlier modal age-at-first-registration for 296 other compared to females. The heterogeneity in terms of subtypes and sex in affective psychosis clouds the interpretation of age-at-first-registration. Separating those with unipolar psychotic depression from other subclassifications and differentiating by sex may provide clues to factors that precipitate the onset of affective psychosis.

Rapid cycling bipolar affective disorder in people with intellectual disability: a systematic review.

Rapid cycling bipolar affective disorder has attracted renewed interest in the general adult psychiatric literature, particularly as the response to lithium prophylaxis is poor in this subgroup of patients. The present paper describes a systematic Medline/Psyclit review of case studies and small series of patients with rapid cycling bipolar affective disorder in people with intellectual disability (ID). Rapid cycling bipolar affective disorder in people with ID may differ from its occurrence in the non-ID population in terms of a relative preponderance of males, an increased likelihood of rapid cycling onset in those with an early (prepubertal) onset of affective disorder and a different response to prophylactic drugs. The efficacy of treatment and prophylaxis of rapid cycling illnesses needs further investigation in the population with ID.

The effect of gender and age at onset of depression on mortality.

Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness.

Maladaptive coping and affective disorders among cancer patients.

Coping has attracted much attention in research as a possible mediator of the psychological impact of cancer. Yet, conceptual ambiguity and methodological limitations have resulted in weak and contradictory findings. A major shortcoming has been the use of designs which do not represent adequately the complexity or the diversity of demands which arise from the diagnosis and treatment of cancer. The neglect of appraisal in the assessment of the relationship between coping and mental health is of particular concern, given the role it has been found to play in the onset and maintenance of affective disorders. In a prospective study 673 newly diagnosed cancer patients were interviewed 4 to 8 weeks and 1 year later to assess the effects of their appraisals, coping responses and resolution of any concerns on subsequent mental health. Logistic regression analyses, adjusted for possible confounding variables, were used to investigate the relationships between coping variables and affective disorders. When examined separately the degree of threat appraised, the reporting of a helpless response and perceived success of primary responses in resolving concerns all predicted subsequent effective disorder. However, in a multivariate model only appraisal and success of the response in resolving the concern were significant. No response was found to prevent affective disorders, however certain types of responses were associated with the resolution of specific concerns. The results highlight the importance of assessing the whole coping process and the need to address the complex and multifaceted characteristics of cancer demands. On the basis of our findings we describe a maladaptive cycle of coping, which we believe contributes to the later onset of affective disorders in cancer patients.

Affective disorders in people with autism: A review of published cases

The presentation of affective disorders in people with autism and autistic-like disorders is discussed based upon a review of 17 published cases. Half of the patients were female and almost all of the patients had IQs in the mentally retarded range. 35% of the patients had the onset of affective disorder in childhood. Of the cases mentioning family history, 50% had a family history of affective disorder or suicide. Changes in mood, self-attitude, and vital sense were rarely reported by the patients. A change in mood, attitude toward self and others, and vegetative changes were inferred based on the observations of others. Difficulties in diagnosing affective disorders in autistic people are presented and suggestions are made for diagnosis, treatment, and research.

Headache syndromes and psychiatric disorders: Association and familial transmission

This paper examines the association between psychiatric disorders and headache syndromes in a longitudinal epidemiologic sample of young adult who were selected from the general population of Zurich, Switzerland. Headache syndromes were defined according to the newly introduced diagnostic criteria of the International Headache Society in 1988. The prevalence rates of psychiatric disorders, according to specific headache subtypes, were examined both cross-sectionally and longitudinally. In the cross-sectional data, migraine with aura was associated with hypomania, recurrent brief depression, and all of the anxiety disorders, whereas only the phobic disorders and panic were elevated among subjects with migraine without aura. Similar findings emerged for the longitudinal data, with the exception that major depression was associated with both subtypes of migraine. Subjects with tension-type headaches did not differ from controls with respect to any of the affective or anxiety disorders in both the cross-sectional and longitudinal data. Prospective study data indicated that the age of onset of anxiety disorders generally preceded that of migraine and that the onset of affective disorders in the majority of comorbid subjects followed that of the onset of migraine. In order to investigate the mechanism for the associations between anxiety/depression syndromes and migraine, patterns of co-transmission of migraine and anxiety/depression were examined in data from a controlled family history study of migraine. The results were consistent with a syndromic relationship between migraine and anxiety/depression, rather than their representing discrete manifestations of shared underlying etiology. The implications of these data for research and clinical work are discussed.