Family History Of Affective Disorder Research Articles

APOE Genotype, ApoE Plasma Levels, Lipid Metabolism, and Cognition in Monozygotic Twins with, at Risk of, and without Affective Disorders.

Background: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel therapeutic approaches. Methods: We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR). Results: The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L, p = 0.037). Limitations: The present study could benefit from a larger sample size. We did not assess dietary habits. Conclusions: The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.

Persistent increase over time in oxidatively stress generated RNA and DNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives – An up to 5-year prospective study

ObjectivesIncreased oxidative stress generated nucleoside damage seems to play a crucial role in bipolar disorder (BD) pathophysiology. It may contribute to accelerated ageing and reduced life expectancy in patients with BD. MethodsIn the five-year prospective “Bipolar Illness Onset study”, we investigated repeated measurements of oxidative stress generated RNA and DNA damage in 357 patients with newly diagnosed/first-episode BD (880 visits), 132 of their unaffected first-degree relatives (236 visits) and 198 healthy age- and sex-matched control persons with no personal or first-degree family history of affective disorder (432 visits). Amongst patients with BD, we further investigated associations of oxidative stress generated RNA- and DNA damage with affective phases and measures of illness load. ResultsPatients newly diagnosed with BD and their unaffected relatives had higher levels of oxidative stress generated RNA damage than healthy control individuals and these differences persisted over time, whereas DNA damage was less consistently elevated. Neither illness load nor affective phase impacted the levels in patients with BD. ConclusionsOur findings support elevated oxidative stress generated RNA damage being a trait phenomenon in BD as indicated by persistent increase in RNA damage over time in patients newly diagnosed with BD and in their unaffected first-degree relatives compared with healthy control individuals. We did not detect state alterations in levels of oxidative stress.

Influence of Socio-Demographic Factors on Perceived Stress in Outpatients with Depression and Anxiety in Remission During the COVID-19 Pandemic

Abstract Objective: The study aimed at identifying the influence of socio-demographic factors on perceived stress during the first and the second “waves” of the COVID-19 pandemic among patients with depression and anxiety in remission compared to controls. Method: The study was designed as case-control, cross-sectional and non-interventional, and included 60 outpatients with depressive and anxiety disorders in remission and 60 controls with or without family history of affective disorder. A self-assessment scale (Perceived Stress Scale, PSS-10) was used to evaluate perceived stress. The remission was objectified by the Clinical Global Impression scale (CGI-S ≤ 2) and a questionnaire about the socio-demographic features and clinical characteristics of the disorders was completed. Results: By using multiple logistic regression, it was found that the diagnostic category and/or the relevant family history did not predict higher levels of perceived stress during the COVID-19 pandemic (p > 0.05). Females were associated with higher risk of moderate or high stress (OR = 2.613, p = 0.017), as well as those working from home during the pandemic (OR = 4.00, p = 0.026). Conclusions: Addressing the COVID-19 effects on mental health in a biopsychosocial manner, the study shows the impact of socio-demographic factors such as gender and work environment in times of a psychosocial crisis. The lack of differences in stress perception by the patients in remission and healthy controls implicates the importance of adequate maintenance treatment and easy access to mental health services in times of crisis.

Early-onset late-life depression: Association with body mass index, obesity, and treatment response

Early-onset (EOD) and late-onset (LOD) late-life depression might differ in etiology, clinical features, and treatment response. While EOD is more frequently associated with a family history of affective disorders and personality aspects, LOD is thought to be more strongly driven by acquired cerebrovascular risk factors associated with vascular pathology, executive dysfunction, and poor treatment response. However, in a systematic review, EOD and LOD only differed in the frequency of affective disorders in the family history. We compared EOD versus LOD using medical records. In this retrospective chart review, elderly depressed patients (N = 108; mean age: 69.0 ± 7.2 years) were characterized by sociodemographic, psychiatric, and somatic variables and divided according to age-at-onset (cut-off: 60 years): EOD (N = 67, mean age-at-onset: 40.2 ± 13.6 years) and LOD (N = 41, 67.5 ± 6.3 years). A family history of affective disorders was more common in EOD than LOD patients (49.2% vs. 19.5%). EOD patients had a higher body mass index (mean: 27.0 kg/m2 vs. 23.1 kg/m2) and were more often obese compared with LOD patients (20% vs. 0%). There were fewer treatment responders in the EOD group than in the LOD group on trend level significance (46.3% vs. 63.4%). Higher frequency of affective disorders in the family history is compatible with a greater genetic risk of EOD. The larger metabolic burden of EOD might stem from the longer duration of depressive illness.

Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

Vascular depression – regarding a case report

IntroductionAge-related vascular changes have long been documented as an etiopathogenic factor of some geriatric depressive syndromes. More recently, it has emerged the concept of “Vascular Depression” recognizing that cardiovascular disease may predispose, precipitate or perpetuate late life depression. This condition was defined by an episode of major depressive disorder within the preceding 12 months in elderly with cardiovascular/cerebrovascular disease, or major cardiovascular risk factors. Vascular Depression isn`t described in DSM-V, and that difficults clinical recognition and affects clinically informed systematic studies.ObjectivesRegarding a clinical case, we enphasize the clinical impact of Vascular Depression`s hypothesis.MethodsWe present a qualitative review of this topic using the Pubmed Central database.Results74 years old male patient, with major depressive disorder about ten years. Depressive and cognitive symptoms didn`t respond to antidepressive treatment and his functional state has gradually declined.ConclusionsVascular depression develops after the 60 – 65 years in the absence of personal and family history of affective disorder. The key symptoms are low energy, anhedonia, deficits in selfinitiation, psychomotor retardation, reduced processing speed and lack of insight into mood symptoms. Clinical assessment includes a review of history of vascular risk factors or/and disease, but also an imagiological evidence demonstrating subcortical white matter abnormalities. Insidious and chronic course tends to delay its recognition and management. This becomes critical because Vascular Depression is associated with poor response to antidepressant treatment and persistent depressive symptoms. It`s also associated with poor selfmanagement of comorbidities and impairment in daily function. Increased mortality from all causes is widely documented.

Family history of affective disorders, the gender factor and clinical characteristics of depression

Analysis of clinical features of development and course of depression in patients with FH of mood disorders taking into account sex differences. This multicenter cross-sectional study included patients over 18 years of age with depressive episode/recurrent depressive disorder. Clinical characteristics of depression, presence of comorbid mental illness and family history (FH) information were obtained in a structured clinical interview. One hundred and seventy-one patients (mean age (M (SD)) 40.87 (15.86) y.o.), including 64.5% of women, were enrolled in the study. FH was revealed in 30.2% of patients. The proportion of FH did not differ in men and women (p=0.375). Generalized anxiety disorder (GAD) was more frequent in FH positive patients (p=0.016). Logistic regression also revealed that FH is a risk factor for concomitant GAD (p=0.019, OR=2.4). The GLM demonstrated a significant joint effect of FH and sex on the maximum duration of a depressive episode (p=0.044), as well on the number of suicide attempts (p=0.055) and the number of depressive episodes as a trend (p=0.072). We have demonstrated the specific interaction of FH of mood disorders with sex on clinical course of depression. Thus, the manifestation of a genetic influence on the clinical phenotype of depression can be significantly moderated by sex.

Hippocampal subfield morphology in monozygotic twins discordant for affective disorders.

Unipolar and bipolar disorders aggregate in families and have been associated with a reduced gray-matter volume in hippocampal and prefrontal cortex. Here we used structural MRI to clarify whether abnormalities in hippocampal subfield and prefrontal cortical morphology are associated with familial vulnerability (i.e., changes present both in patients and unaffected relatives compared to healthy individuals), resilience (i.e., changes differentiating unaffected relatives and patients), or sequalae of illness in a sample of monozygotic twins. We investigated regional differences in gray-matter volume extracted using FreeSurfer 6.0 between remitted affected twins (AT) with either unipolar or bipolar disorder (n = 67), unaffected discordant co-twins (UT, n = 39), and low-risk twins (LT, n = 31) with no personal or first-degree family history of affective disorders. The UT showed greater bilateral hippocampal volumes compared to AT. Between group differences in left hippocampal volume were driven by greater cornu ammonis 1-3 and 4, subiculum and subfield of dentate gyrus. For the right hippocampus, differences were driven by greater hippocampal tail and subiculum. There was a trend for UT having a larger left hippocampus than LT, but no significant differences in hippocampal volumes between AT and LT. Outside the hippocampus, AT showed a smaller volume of left dorsomedial prefrontal cortex compared to LT. Our results suggest that larger volume of specific hippocampal subfields may be associated with resilience in healthy relatives of patients with an affective illness. Moreover, a smaller volume of left dorsomedial prefrontal cortex may reflect a sequalae of illness.

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex.

Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal history of childhood maltreatment. We included a total of 342 healthy subjects from the FOR2107 cohort (www.for2107.de). An emotional face-matching task was used to identify the medial prefrontal cortex and right amygdala. Dynamic Causal Modeling (DCM) was conducted and neural coupling parameters were obtained for healthy controls with and without particular risk factors for depression. We assigned a genetic risk if subjects had a first-degree relative with an affective disorder and an environmental risk if subjects experienced childhood maltreatment. We then compared amygdala inhibition during emotion processing between groups. Amygdala inhibition by the medial prefrontal cortex was present in subjects without those two risk factors, as indicated by negative model parameter estimates. Having a genetic risk (i.e., a family history) did not result in changes in amygdala inhibition compared to no risk subjects. In contrast, childhood maltreatment as environmental risk has led to a significant reduction of amygdala inhibition by the medial prefrontal cortex. We propose a mechanistic explanation for the amygdala hyperactivity in subjects with particular risk for depression, in particular childhood maltreatment, caused by a malfunctioned amygdala downregulation via the medial prefrontal cortex. As childhood maltreatment is a major environmental risk factor for depression, we emphasize the importance of this potential early biomarker.

S100B and brain derived neurotrophic factor in monozygotic twins with, at risk of and without affective disorders

BackgroundThe calcium binding protein S100B and brain derived neurotrophic factor (BDNF) are both biomarkers implicated in neuronal processes in the central nervous system and seem to be associated with affective disorders. Here we investigated both markers in a sample of monozygotic (MZ) twins with, at risk of and without affective disorders, aiming to evaluate whether these markers have a role as causal factors- or trait markers for affective disorders. MethodWe measured serum S100B and plasma BDNF levels in 204 monozygotic twins (MZ) with unipolar or bipolar disorder in remission or partial remission (affected), their unaffected co-twins (high-risk) and twins with no personal or family history of affective disorder (low-risk). ResultsNo significant group differences in S100B and BDNF levels were found between the three groups. Exploratory analysis revealed that higher S100B levels were correlated with lower cognitive performance. LimitationsThe cross-sectional design cannot elucidate the two neuronal biomarkers role as causal factors. We would have preferred a higher sample size in the high- and low-risk groups. ConclusionThe present result did not support a role for S100B and BDNF as neither causal factors nor trait markers for affective disorders. Elevated S100B levels may associate with impaired cognition, but further studies are warranted.

Diagnostic Stability in Bipolar Disorder: A Narrative Review

After participating in this activity, learners should be better able to:• Evaluate diagnostic stability in bipolar disorder• Analyze the factors contributing to diagnostic stability OBJECTIVE: Diagnostic stability is the degree to which a diagnosis remains unchanged during follow-up. It is an important measure of predictive validity in bipolar disorder (BD). In this study, we review the literature concerning diagnostic stability in BD, analyze the factors contributing to diagnostic stability, and describe the implications of diagnostic boundaries and diagnostic delay. A comprehensive literature search of MEDLINE and EMBASE databases was conducted, including all studies published from 1980 to 2016, to evaluate the diagnostic stability of BD. Thirty-seven articles were included: 6 focusing mainly on BD, 18 on psychotic disorders, 10 on depression, and 3 on diagnostic stability in psychiatric disorders in general. Data analysis was performed in standardized fashion using a predefined form. Despite a high variability of the methodological approaches taken, an acceptable degree of diagnostic stability was found. The most common criteria for evaluating diagnostic stability were prospective consistency and retrospective consistency. The mean prospective and retrospective consistencies were 77.4% and 67.6%, respectively. A large majority of studies were performed in Europe or in North America (67.5%), compared to 21.6% in Asia and only 10.8% in Africa, Oceania, and South America. Extreme ages, female gender, psychotic symptoms, changes to treatment, substance abuse, and family history of affective disorder have been related to diagnostic instability. Several factors appear to have a negative impact on the diagnostic stability, but the evidence is insufficient to draw any robust conclusions. Nevertheless, despite variable prospective and retrospective consistencies, the overall diagnostic stability is good. Standardized methods need to be used to obtain more accurate assessments of stability.

Thirty-year cardiovascular risk score in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives.

Bipolar disorder is associated with a decreased life expectancy of 8-12 years. Cardiovascular disease is the leading cause of excess mortality. For the first time, we investigated the Framingham 30-year risk score of cardiovascular disease in patients with newly diagnosed/first-episode bipolar disorder, their unaffected first-degree relatives and healthy individuals. In a cross-sectional study, we compared the Framingham 30-year risk score of cardiovascular disease in 221 patients with newly diagnosed/first-episode bipolar disorder, 50 of their unaffected first-degree relatives and 119 healthy age- and sex-matched individuals with no personal or first-degree family history of affective disorder. Among patients with bipolar disorder, we further investigated medication- and illness-related variables associated with cardiovascular risk. The 30-year risk of cardiovascular disease was 98.5% higher in patients with bipolar disorder (p = 0.017) and 85.4% higher in unaffected first-degree relatives (p = 0.042) compared with healthy individuals in models adjusted for age and sex. When categorizing participants in low cardiovascular risk without considering age and sex distribution among participants, 81% of patients were at low risk, versus 92% of unaffected relatives and 89% of healthy individuals. Of the patients 209 (94.6%) were diagnosed within the preceding 2 years. Smoking was more prevalent among patients with bipolar disorder (45.2%) and their unaffected first-degree relatives (20.4%) compared with healthy individuals (12.8%). Similarly, dyslipidemia was more common among patients with bipolar disorder compared with healthy individuals. Treatment with psychotropic medication with metabolic adverse effects was associated with higher 30-year cardiovascular disease risk score, whereas we did not find illness-related variables associated with cardiovascular risk among patients with bipolar disorder. We found an enhanced cardiovascular disease risk score in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives, which points to a need for specific primary preventive interventions against smoking and dyslipidemia in these populations.

Factors predicting re-hospitalization for inpatients with bipolar mania––A naturalistic cohort

Patients with bipolar mania often require re-hospitalization, which can be a social-economic burden. This study aimed to investigate the factors affecting time to re-hospitalization for inpatients with acute bipolar mania. In this 6-year naturalistic study we reviewed the charts of inpatients with acute bipolar mania. Potential dichotomous factors including sex, family history of affective disorder, suicide history, and discharge against medical advice, involuntary admission, psychotic features, substance use disorder, and remission at discharge were recorded. Continuous variables including age, age at onset of affective episodes, and number of previous hospitalizations were also recorded. We used survival analysis with a univariate Cox proportional hazard regression model, along with forward multivariate model, to identify the potential factors. Of the 165 patients, 23% achieved symptomatic remission at discharge. In the forward Cox model, psychotic features, discharge against medical advice and higher number of previous hospitalizations were significant risk factors for re-admission. Remission at discharge was significantly associated with preventing re-hospitalization. We identified several predictors for re-hospitalization among inpatients with bipolar mania. Further studies are needed in other real-world settings to validate our results.

Expressed emotion, emotional distress, and individual and familial history of affective disorder among parents of adolescents with bipolar disorder

Parental expressed emotion (EE) attitudes are important prognostic indicators in the course of bipolar disorder (BD) in adolescents and adults. This study examined the hypothesis that parents’ own susceptibility to affective disturbances contributes to their likelihood of high-EE attitudes. We examined past-week levels of emotional distress, lifetime affective diagnoses, and family histories of affective disorder among high- and low-EE parents of 86 adolescents with bipolar I or II disorder who were recovering from an episode of depression or (hypo) mania. High EE parents endorsed higher concurrent levels of depression, anxiety, and anger/hostility than low EE parents, and reported a greater familial history of depression and BD. No differences between high and low EE parents were found in concurrent levels of interpersonal sensitivity, lifetime rates of affective disorders, or familial loading of anxiety disorder. Parents’ distress at the time of the EE assessment was the strongest correlate of EE. The results suggest that susceptibility to affective psychopathology may be an important contributor to the development of EE attitudes among parents of adolescents with BD.

Hair cortisol in newly diagnosed bipolar disorder and unaffected first-degree relatives

ObjectiveHair cortisol is a promising new biomarker of retrospective systemic cortisol concentration. In this study, we compared hair cortisol concentrations in patients with newly diagnosed bipolar disorder (BD), their unaffected first-degree relatives and healthy individuals and identified potential predictors of hair cortisol concentrations in patients with BD. MethodIn a cross-sectional design, we compared hair cortisol concentrations in 181 patients with newly diagnosed/first episode BD, 42 of their unaffected first-degree relatives and 101 healthy age- and sex-matched individuals with no personal or first-degree family history of affective disorder. In patients with BD, we further investigated whether medication- and illness related variables, as well as measures of stressful life events in the preceding 12 months and childhood trauma, were associated with hair cortisol concentrations. ResultsHair cortisol concentrations were 35.1% (95%CI: 13.0–61.5) higher in patients with BD (P = 0.001) compared with healthy individuals in models adjusted for age and sex. Hair cortisol concentrations in unaffected first-degree relatives did not differ from healthy individuals (P = 0.8). In patients, neither medication, illness duration nor stress related variables were associated with hair cortisol concentrations. ConclusionWe found elevated hair cortisol concentrations in patients newly diagnosed with BD indicating the presence of physiological stress in early stages of BD.

Clinical Characteristics, Life Adversities and Personality Traits in Monozygotic Twins With, at Risk of and Without Affective Disorders.

Background: Affective disorders have a long-term impact on psychiatric health and are caused by multiple interacting factors including familial risk, childhood adversity, life events and personality traits.Methods: In this study, monozygotic twins (MZ) at familial risk (indexed by affective disorder in their co-twin; high-risk group), affected MZ twins (indexed by a diagnosis with affective disorder) and MZ twins with no family history of affective disorder (low-risk group) were identified through cross-linking of nation-wide Danish registers. In total, 204 MZ twins were included and psychopathology, personality traits and life adversity were evaluated by semi-structured interviews and questionnaires.Results: Affected MZ twins presented with more subclinical affective symptoms and were functionally impaired as evidenced by higher unemployment rates and reduced functional status. The affected and the high-risk groups reported more childhood adversity and had experienced more stressful life events than the low-risk group. A direct comparison within the discordant twin pairs showed that the high-risk twins presented fewer affective symptoms, better functional status, more extraversion and lower neuroticism scores than their affected co-twins although they had equal levels of life adversity as their affected co-twins.Conclusion: These findings add to the evidence indicating that patients experience higher neuroticism, persistent subclinical symptoms and reduced socio-occupational function after affective episodes. Additionally, neuroticism and extraversion seem capable of moderating the sensitivity to exposure from the environment.

Clock genes polymorphisms in male bipolar patients with comorbid alcohol abuse

BackgroundPsychiatric comorbidity affects 24–65% patients with bipolar disorder (BD), 45% of which have alcohol abuse/dependence (AAD). Despite the fact that BD has an equal incidence in both genders, AAD more often occurs in men. We hypothesized that the presence of BD and AAD, reported as a secondary diagnosis, may result from a common genetic background. However, specific genetic factors predispose to gender differences. MethodsBased on the relationship between circadian clock genes pathway and BD/AAD we decided to test the connection of four core clock genes with common genetic background of both diseases. We analyzed 436 patients with BD, among which 17% were diagnosed with AAD. The control group consisted of 417 healthy subjects. We analyzed 44 SNPs of the previously described core molecular clock genes: CLOCK, ARNTL, TIMELESS and PER3. ResultWe found association of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms with an increased risk of BD/AAD in a group of male patients. We also found that two other polymorphisms of PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. LimitationsPossible factors that could have influenced the results are: relatively small sample size, gender disproportion and unverifiable data form the patient interview. ConclusionsOur study confirms the existence of a link between clock genes and increased risk of alcohol abuse/dependence in male patients and the accumulation of risk genes in patients with a positive family history.

Is aberrant affective cognition an endophenotype for affective disorders? - A monozygotic twin study.

Identification of endophenotypes can improve prevention, detection and development of new treatments. We therefore investigated whether aberrant affective cognition constitutes an endophenotype for affective disorders by being present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative to twins with no family history of affective disorder (i.e. low-risk). We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ twins using Danish population-based registers in recruitment. Twins attended one test session involving neurocognitive testing, clinical ratings and questionnaires. Main outcomes were attention to and recognition of emotional facial expressions, the memory of emotional self-referential words, emotion regulation and coping strategies. Participants were 103 affected, 44 high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and showed comparable non-affective cognitive performance. We observed no aberrant affective cognition in affected and high-risk relative to low-risk twins. However, high-risk twins displayed attentional avoidance of emotional faces (ps ⩽ 0.009) and more use of task-oriented coping strategies (p = 0.01) compared with affected twins. In contrast did affected twins show more emotion-oriented coping than high- and low-risk twins (ps ⩽ 0.004). Our findings provide no support of aberrant affective cognition as an endophenotype for affective disorders. High-risk twins' attentional avoidance of emotional faces and greater use of task-oriented coping strategies may reflect compensatory mechanisms.

Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome.

The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration). Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio. Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other. Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

The Bipolar Illness Onset study: research protocol for the BIO cohort study

IntroductionBipolar disorder is an often disabling mental illness with a lifetime prevalence of 1%–2%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide...