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Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in current research. Serum neurofilament light (sNfL), a marker for neuro-axonal injury, is increased in various acute and chronic neurological disorders, but also neuro-psychiatric conditions, including affective disorders. The aim of our study was to determine a potential relation between a neuron-specific marker like sNfL and different clinical states of BD. Methods: In the current investigation, 51 patients with BD and 35 HC were included. Mood ratings with the Hamilton depression scale (HAM D) and the Young mania rating scale (YMRS) have been included. Illness duration was defined as the period from the time of diagnosis out of self-report and medical records. sNFL was quantified by a commercial ultrasensitive single molecule array (Simoa). There was a significant positive correlation between the number of manic episodes in the past and sNfL, controlled for age and duration of illness. (R = 0.49, p = 0.03) Depressive episodes were not associated to sNfL values. (R = 0.311, p = n.s.) Patients with >3 years of illness duration showed significantly higher levels of sNfL (M18.59; SD 11.89) than patients with shorter illness duration (M = 12.38, p = 0.03) and HC (M = 11.35, p = 0.02). Patients with <3 years of illness and HC did not differ significantly in sNfL levels. Interestingly, individuals with BD and HC did not differ in sNFL levels in general. Nevertheless, looking at the BD cohort more specifically, we found that individuals with BD with longer duration of illness (>3 years) had higher levels of sNfL than those with an illness duration below 3 years. Our results confirm previous reports on the relation of neuro-axonal injury as evidenced by sNfL and illness specific variables in bipolar disorder. Further studies are needed to clarify if sNfL may predict the disease course and/or indicated response to treatment regimes. • Individuals with BD with duration of illness >3 years had higher levels of sNfL than those below 3 years. • Individuals with an illnessduration over 3 years are also showing higher NfL levels than HC. • Current manic symptoms are showing a positive correlation with sNfL. [ABSTRACT FROM AUTHOR]

BackgroundLittle is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches.MethodsThis study examined the longitudinal course of mood symptoms and functioning ratings in 126 youth at high risk for BD based on family history and early mood symptoms. Participants were enrolled in a randomized trial of family-focused therapy and followed longitudinally (mean 2.0 years, SD = 53.6 weeks).ResultsUsing latent class growth analyses (LCGA), we observed three mood trajectories. All youth started the study with active mood symptoms. Following the index mood episode, participants were classified as having a "significantly improving course" (n = 41, 32.5% of sample), a "moderately symptomatic course" (n = 21, 16.7%), or a "predominantly symptomatic course" (n = 64, 50.8%) at follow-up. More severe depression, anxiety, and suicidality at the study's baseline were associated with a poorer course of illness. LCGA also revealed three trajectories of global functioning that closely corresponded to symptom trajectories; however, fewer youth exhibited functional recovery than exhibited symptomatic recovery.LimitationsMood trajectories were assessed within the context of a treatment trial. Ratings of mood and functioning were based on retrospective recall.ConclusionsThis study suggests considerable heterogeneity in the course trajectories of youth at high risk for BD, with a significant proportion (32.5%) showing long-term remission of symptoms. Treatments that enhance psychosocial functioning may be just as important as those that ameliorate symptoms in youth at risk for BD.

Objective: To develop and internally validate risk prediction models for adolescent onset and persistence of eating disorders. Methods: N = 963 Australian adolescents (11–19 years) in the EveryBODY Study cohort completed online surveys in 2018 and 2019. Models were built to predict 12‐month risk of (1) onset, and (2) persistence of a DSM‐5 eating disorder. Results: Onset Model. Of the n = 687 adolescents without an eating disorder at baseline, 16.9% were identified with an eating disorder after 12 months. The prediction model was based on evidence‐based risk factors for eating disorder onset available within the dataset (sex, body mass index percentile, strict weight loss dieting, history of bullying, psychological distress, weight/shape concerns). This model showed fair discriminative performance (mean AUC =.75). The most important factors were psychological distress, weight and shape concerns, and female sex. Diagnostic Persistence Model. Of the n = 276 adolescents with an eating disorder at baseline, 74.6% were identified as continuing to meet criteria for an eating disorder after 12 months. The prediction model for diagnostic persistence was based on available evidence‐based risk factors for eating disorder persistence (purging, distress, social impairment). This model showed poor discriminative performance (mean AUC =.65). The most important factors were psychological distress and self‐induced vomiting for weight control. Discussion: We found preliminary evidence for the utility of a parsimonious model for 12‐month onset of an eating disorder among adolescents in the community. Future research should include additional evidence‐based risk factors and validate models beyond the original sample. Public Significance: This study demonstrated the feasibility of developing parsimonious and accurate models for the prediction of future onset of an eating disorder among adolescents. The most important predictors in this model included psychological distress and weight and shape concerns. This study has laid the ground work for future research to build and test more accurate prediction models in diverse samples, prior to translation into a clinical tool for use in real world settings to aid decisions about referral to early intervention. [ABSTRACT FROM AUTHOR]

Abstract Background Using a personality typing approach, we investigated the relationship between personality profiles and the prediction of longterm illness severity in patients with bipolar disorder (BD). While previous research suggests associations between BD and traits from the NEO-FFI profiles, the current study firstly aimed to identify latent classes of NEO-FFI profiles, and, secondly, to examine their impact on the longterm prognosis of BD. Methods Based on the NEO-FFI profiles of 134 euthymic patients diagnosed with BD (64.2% female, mean age = 44.3 years), successive latent profile analyses were conducted. Subsequently, a subsample (n = 80) was examined prospectively by performing multiple regression analysis of the latent classes to evaluate the longitudinal course of the disease (mean: 54.7 weeks) measured using a modified Morbidity Index. Results The latent profile analyses suggested a 3-class model typifying in a resilient (n = 68, 51%), vulnerable (n = 55, 41%) and highly vulnerable (n = 11, 8%) class. In the regression analysis, higher vulnerability predicted a higher longterm Morbidity Index (R 2 = 0.28). Conclusions Subgroups of patients with BD share a number of discrete personality features and their illness is characterized by a similar clinical course. This knowledge is valuable in a variety of clinical contexts including early detection, intervention planning and treatment process.

[Background] Bipolar disorder (BD) is a highly recurrent psychiatric condition. While combined pharmacological and psychosocial treatments improve outcomes, not much is known about potential moderators that could affect these treatments. One potential moderator might be the quality of interpersonal relations in families, for example, familial attitudes and perceived criticism. [Method] To explore this question we conducted a post-hoc analysis that used an existing data set from a previous study by our group that compared cognitive behavioral therapy (CBT) and supporting therapy (ST) in remitted BD. In the present study, we used Cox proportional hazard models. [Results] We found that the relatives’ ratings of criticism predicted the likelihood of depressive recurrences, especially in the ST condition. The patients’ ratings of negative familial attitudes predicted the risk of recurrences in general, irrespective of the therapy condition. [Conclusion] These results suggest that it might be important to assess perceived criticism and familial attitudes as potential moderators of treatment outcome in BD.

Background: Using a personality typing approach, we investigated the relationship between personality profiles and the prediction of longterm illness severity in patients with bipolar disorder (BD). While previous research suggests associations between BD and traits from the NEO-FFI profiles, the current study firstly aimed to identify latent classes of NEO-FFI profiles, and, secondly, to examine their impact on the longterm prognosis of BD. Methods: Based on the NEO-FFI profiles of 134 euthymic patients diagnosed with BD (64.2% female, mean age = 44.3 years), successive latent profile analyses were conducted. Subsequently, a subsample (n = 80) was examined prospectively by performing multiple regression analysis of the latent classes to evaluate the longitudinal course of the disease (mean: 54.7 weeks) measured using a modified Morbidity Index. Results: The latent profile analyses suggested a 3-class model typifying in a resilient (n = 68, 51%), vulnerable (n = 55, 41%) and highly vulnerable (n = 11, 8%) class. In the regression analysis, higher vulnerability predicted a higher longterm Morbidity Index (R2 = 0.28). Conclusions: Subgroups of patients with BD share a number of discrete personality features and their illness is characterized by a similar clinical course. This knowledge is valuable in a variety of clinical contexts including early detection, intervention planning and treatment process. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Little is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches.Methods: This study examined the longitudinal course of mood symptoms and functioning ratings in 126 youth at high risk for BD based on family history and early mood symptoms. Participants were enrolled in a randomized trial of family-focused therapy and followed longitudinally (mean 2.0 years, SD = 53.6 weeks).Results: Using latent class growth analyses (LCGA), we observed three mood trajectories. All youth started the study with active mood symptoms. Following the index mood episode, participants were classified as having a "significantly improving course" (n = 41, 32.5% of sample), a "moderately symptomatic course" (n = 21, 16.7%), or a "predominantly symptomatic course" (n = 64, 50.8%) at follow-up. More severe depression, anxiety, and suicidality at the study's baseline were associated with a poorer course of illness. LCGA also revealed three trajectories of global functioning that closely corresponded to symptom trajectories; however, fewer youth exhibited functional recovery than exhibited symptomatic recovery.Limitations: Mood trajectories were assessed within the context of a treatment trial. Ratings of mood and functioning were based on retrospective recall.Conclusions: This study suggests considerable heterogeneity in the course trajectories of youth at high risk for BD, with a significant proportion (32.5%) showing long-term remission of symptoms. Treatments that enhance psychosocial functioning may be just as important as those that ameliorate symptoms in youth at risk for BD. [ABSTRACT FROM AUTHOR]

Introduction A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. Methods Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. Results Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. Discussion This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time. [ABSTRACT FROM AUTHOR]

Abstract Background Although bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF) and prospective illness course in patients with BD, and explores the effects of current mood state on self-reported BPF profiles. Methods The study included 375 patients who participated in the former Stanley Foundation Bipolar Network. All patients met DSM-IV criteria for bipolar-I disorder (n = 294), bipolar-II disorder (n = 72) or bipolar disorder NOS (n = 9). BPF were assessed with the self-rated Personality Diagnostic Questionnaire. Illness course was based on 1-year clinician rated prospective daily mood ratings with the life chart methodology. Regression analyses were used to estimate the relationships among these variables. Results Although correlations were weak, results showed that having more BPF at baseline is associated with a higher episode frequency during subsequent 1-year follow-up. Of the nine BPF, affective instability, impulsivity, and self-mutilation/suicidality showed a relationship to full-duration as well as brief episode frequency. In contrast all other BPF were not related to episode frequency. Conclusions Having more BPF was associated with an unfavorable illness course of BD. Affective instability, impulsivity, and self-mutilation/suicidality are associated with both rapid cycling BD and BPD. Still, many core features of BPD show no relationship to rapid cycling BD and can help in the differential diagnosis.

Bipolar disorder (BD) is a chronic and disabling psychiatric condition that is linked to significant disability and psychosocial impairment. Although current neuropsychological, molecular, and neuroimaging evidence support the existence of neuroprogression and its effects on the course and outcome of this condition, whether and to what extent neuroprogressive changes may impact the illness trajectory is still poorly understood. Thus, this selective review was aimed toward comprehensively and critically investigating the link between BD and neurodegeneration based on the currently available evidence. According to the most relevant findings of the present review, most of the existing neuropsychological, neuroimaging, and molecular evidence demonstrates the existence of neuroprogression, at least in a subgroup of BD patients. These studies mainly focused on the most relevant effects of neuroprogression on the course and outcome of BD. The main implications of this assumption are discussed in light of specific shortcomings/limitations, such as the inability to carry out a meta-analysis, the inclusion of studies with small sample sizes, retrospective study designs, and different longitudinal investigations at various time points.

Abstract Recent reviews and treatment guidelines regard trauma-focused cognitive-behavior therapies as the treatments of choice for chronic post-traumatic stress disorder (PTSD). However, many patients do not engage in this treatment when it is available, drop out before completion, or do not respond. Medications remain widely used, alone and in conjunction with psychotherapy, although the limitations of traditional monoamine-based pharmacotherapy are increasingly recognized. This article will review recent developments in psychopharmacology for PTSD, with a focus on current clinical data that apply putative neurobiologic mechanisms to medication use—i.e., a theranostic approach. A theranostic approach however, also requires consideration of timing, pre, peri or post trauma in conjunction with underlying dynamic processes affecting synaptic plasticity, the HPA axis, hippocampal activation, PFC-amygdala circuitry and fear memory. Highlights • PTSD clinical pharmacology is reviewed with considerations of both neurobiology and timing • No trials have addressed predisposing genetic or epigenetic factors pre-traumatically • Some medications given acutely post-trauma have been shown to prevent later PTSD • Other agents have shown benefit as trauma-focused psychotherapy augmentation • Medications given chronically have shown variable results based on timing factors [ABSTRACT FROM AUTHOR]

Background: Although bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF) and prospective illness course in patients with BD, and explores the effects of current mood state on self-reported BPF profiles. Methods: The study included 375 patients who participated in the former Stanley Foundation Bipolar Network. All patients met DSM-IV criteria for bipolar-I disorder ( n = 294), bipolar-II disorder ( n = 72) or bipolar disorder NOS ( n = 9). BPF were assessed with the self-rated Personality Diagnostic Questionnaire. Illness course was based on 1-year clinician rated prospective daily mood ratings with the life chart methodology. Regression analyses were used to estimate the relationships among these variables. Results: Although correlations were weak, results showed that having more BPF at baseline is associated with a higher episode frequency during subsequent 1-year follow-up. Of the nine BPF, affective instability, impulsivity, and self-mutilation/suicidality showed a relationship to full-duration as well as brief episode frequency. In contrast all other BPF were not related to episode frequency. Conclusions: Having more BPF was associated with an unfavorable illness course of BD. Affective instability, impulsivity, and self-mutilation/suicidality are associated with both rapid cycling BD and BPD. Still, many core features of BPD show no relationship to rapid cycling BD and can help in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective Although bipolar disorder (BD) is a common recurrent condition with highly heterogeneous illness course, data are limited regarding clinical implications of interactions between gender and onset age. We assessed relationships between onset age and demographic/illness characteristics among BD patients stratified by gender. Methods Demographic and unfavorable illness characteristics, descriptive traits, and clinical correlates were compared in 502 patients from Stanford University BD Clinic patients enrolled in the Systematic Treatment Enhancement Program for BD between 2000 and 2011, stratified by gender, across pre-, peri-, and post-pubertal (<12, 13–16, and >17 years, respectively) onset-age subgroups. Results Among 502 BD patients, 58.2% were female, of whom 21.9% had pre-pubertal, 30.7% peri-pubertal, and 47.4% post-pubertal onset. Between genders, although demographics, descriptive characteristics, and most clinical correlates were statistically similar, there were distinctive onset-age related patterns of unfavorable illness characteristics. Among females, rates of 6/8 primary unfavorable illness characteristics were significantly higher in pre-pubertal and peri-pubertal compared to post-pubertal onset patients. However, among males, rates of only 3/8 unfavorable illness characteristics were significantly higher in only pre-pubertal versus post-pubertal onset patients, and none between peri-pubertal versus post-pubertal onset patients. Limitations Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability, onset age based on retrospective recall. Discussion We describe different phenotypic presentations across age at illness onset groups according to gender. Among females and males, peri-pubertal and post-pubertal onset age groups were more different and more similar, respectively. Further investigation is warranted to assess implications of gender-by-onset-age interactions to more accurately delineate distinctive BD phenotypes. [ABSTRACT FROM AUTHOR]

BackgroundRecent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.MethodResting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.ResultsYoung adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.ConclusionsThis is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness. [ABSTRACT FROM PUBLISHER]

Objectives Results from magnetic resonance imaging ( MRI) studies are heterogeneous with regard to hippocampal and amygdala volume alterations in bipolar disorder ( BD). Lithium treatment may influence both structures. It is unknown if lithium treatment has distinct effects on hippocampal subfield volumes and if subfield volumes change over the course of illness in BD. Methods MRI scans were obtained for 34 lithium-treated patients with BD (Li+), 147 patients with BD who were not treated with lithium (Non-Li), and 300 healthy controls. Hippocampal total and subfield volumes and amygdala volumes were automatically estimated using Freesurfer. General linear models were used to investigate volume differences between groups and the effects of illness course and lithium treatment. Results The Non-Li BD group displayed significantly smaller bilateral cornu ammonis ( CA) 2/3 and CA4/dentate gyrus ( DG) subfields, total hippocampal volumes, right CA1 and right subiculum subfields, and left amygdala volume compared to healthy controls. There were no differences between the Li+ BD and either the Non-Li BD or the healthy control groups. In patients with numerous affective episodes, Non-Li BD patients had smaller left CA1 and CA2/3 volumes compared to Li+ BD patients and healthy controls. There were positive associations between lithium treatment duration and left amygdala volume. Conclusions Hippocampal subfield and amygdala volumes were reduced in Non-Li BD patients compared to healthy controls, whereas the Li+ BD volumes were no different from those in Non-Li BD patients or healthy controls. Over the course of BD, lithium treatment might counteract reductions specifically in the left CA1 and CA2/3 hippocampal subfields and amygdala volumes, in accordance with the suggested neuroprotective effects of lithium. [ABSTRACT FROM AUTHOR]

Background and objectives Dysregulated affect is a hallmark feature of acute episodes of bipolar disorder (BD) and persists during inter-episode periods. Its contribution to course of illness is not yet known. The present report examines the prospective influence of inter-episode affect dysregulation on symptoms and functional impairment in BD. Methods Twenty-seven participants diagnosed with inter-episode bipolar I disorder completed daily measures of negative and positive affect for 49 days (±8 days) while they remained inter-episode. One month following this daily assessment period, symptom severity interviews and a measure of functional impairment were administered by telephone. Results More intense negative affect and positive affect during the inter-episode period were associated with higher depressive, but not manic, symptoms at the one-month follow-up assessment. More intense and unstable negative affect, and more unstable positive affect, during the inter-episode period were associated with greater impairment in home and work functioning at the follow-up assessment. All associations remained significant after controlling for concurrent symptom levels. Limitations The findings need to be confirmed in larger samples with longer follow-up periods. A more comprehensive assessment of functional impairment is also warranted. Conclusions The findings suggest that a persistent affective dysregulation between episodes of BD may be an important predictor of depression and functional impairment. Monitoring daily affect during inter-episode periods could allow for a more timely application of interventions that aim to prevent or reduce depressive symptoms and improve functioning for individuals with BD. [ABSTRACT FROM AUTHOR]

Learning about possible factors influencing, positively or negatively, the Quality of Life (QoL) of patients with psychosis is an important task for both, research and treatment. The study examined the association of illness course with QoL in a sample of Mexican patients with psychosis. It was hypothesized that illness perception would mediate the relation of illness course to QoL. Sixty-one (56 % female) patients were interviewed and assessed for illness course (relapses, residual symptoms, and diagnosis), QoL, and illness perception. Mediation analyses (simple and multiple) with bootstrapping procedures were applied, including residual symptoms as the predictor of QoL, and illness perception dimensions as candidate mediators. Residual symptoms, rather than a relapsing course or a diagnosis of schizophrenia, have a diminishing effect in the subjective QoL. This effect is fully mediated by illness perception, particularly by the cognitive and the emotional representations. Results underscore the importance that patients' beliefs have on their perceived QoL, encouraging further research and development of interventions targeting illness perceptions. [ABSTRACT FROM AUTHOR]

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Abstract: Background: Gene–environment interactions may contribute to bipolar disorder (BD) clinical course variability. We examined effects of brain-derived neurotrophic factor (BDNF) val66met genotype and early life stress (ELS) upon illness severity and chronicity in adult BD patients. Methods: 80 patients (43 BD I, 33 BD II, 4 BD not otherwise specified, mean ± SD age 46.4 ± 14.0 years, 63.7% female) receiving open evidence-based and measurement-based care in the Stanford Bipolar Disorders Clinic for at least 12 months underwent BDNF val66met genotyping and completed the Childhood Trauma Questionnaire. BDNF met allele carrier genotype and history of childhood sexual and physical abuse were evaluated in relation to mean prior-year Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (MPY-CGI-BP-OS) score and clinical and demographic characteristics. Results: BDNF met allele carriers (but not non-met allele carriers) with compared to without childhood sexual abuse had 21% higher MPY-CGI-BP-OS scores (3.5 ± 0.7 versus 2.9 ± 0.7, respectively, t = −2.4, df = 28, p = 0.025) and 35% earlier BD onset age (14.6 ± 5.7 versus 22.8 ± 7.9 years, respectively, t = 3.0, df = 27, p = 0.006). Regression analysis, however, was non-significant for a BDNF-childhood sexual abuse interaction. Limitations: small sample of predominantly female Caucasian insured outpatients taking complex medication regimens; only one gene polymorphism considered. Conclusions: Between group comparisons suggested BDNF met allele carrier genotype might amplify negative effects of ELS upon BD illness severity/chronicity, although with regression analysis, there was not a significant gene-environment interaction. Further studies with larger samples are warranted to assess whether BDNF met allele carriers with ELS are at risk for more severe/chronic BD illness course. [Copyright &y& Elsevier]

Introduction: The illness course of bipolar disorder (BD) is highly heterogeneous with substantial variation between individuals with the same BD subtype and within individuals over time. This heterogeneity is not well-delineated and hampers the development of more targeted treatment. Furthermore, although lifestyle-related behaviors are believed to play a role in the illness course, such mechanisms are poorly understood. To address some of these knowledge gaps, we aimed to develop an app for collection of multi-dimensional longitudinal data on BD-relevant symptoms and lifestyle-related behaviors., Methods: An app named MinDag was developed at the Norwegian Center for Mental Disorders Research in Oslo, Norway. The app was designed to tap into selected areas: mood, sleep, functioning/activities (social, occupational, physical exercise, leisure), substance use, emotional reactivity, and psychotic experiences. Ethical, security and usability issues were highly prioritized throughout the development and for the final app solution. We conducted beta- and pilot testing to eliminate technical problems and enhance usability and acceptability., Results: The final version of MinDag comprises six modules; three which are presented for the user once daily (the Sleep module in the morning and the Mood and Functoning/Activities modules in the evening) and three which are presented once weekly (Substance Use, Emotional Reactivity, and Psychotic Experiences modules). In general, MinDag was well received in both in the beta-testing and the pilot study, and the participants provided valuable feedback that was taken into account in the final development. MinDag is now in use as part of the research protocol at the NORMENT center and in a specialized treatment unit for BD at Oslo University Hospital in Norway., Discussion: We believe that MinDag will generate unique longitudinal data well suited for capturing the heterogeneity of BD and clarifying important unresolved issues such as how life-style related behavior may influence BD symptoms. Also, the experiences and knowledge derived from the development of MinDag may contribute to improving the security, acceptability, and benefit of digital tools in mental health., (Copyright © 2022 Bjella, Collier Høegh, Holmstul Olsen, Aminoff, Barrett, Ueland, Icick, Andreassen, Nerhus, Myhre Ihler, Hagen, Busch-Christensen, Melle and Lagerberg.)

Background and objectives The identification of prognostic factors in patients with schizophrenia and related psychotic disorders should enhance our understanding of the aetiology of these disorders and improve their treatment. The first years following an initial episode of psychosis are a «critical period» for biological and psychosocial influences that affect future outcome. Both, short-term outcome and baseline predictors, have been defined by different measures, making the comparison among studies difficult. Studies of the predictive value of baseline demographic and clinical characteristics in the Mexican population are still limited. Hence, the present study aims to: 1. replicate the prognostic value of selected patient characteristics previously related to the short-term course of psychosis in Mexican first-episode psychosis patients, and 2. retrospectively assess their prognostic value in the prediction of diagnosis, presence of psychotic residual symptoms, and number of psychotic episodes at least three-years later. Methods Information on baseline predictor variables (sociodemographic, premorbid phase, context of the first episode, dimensions of psychopathology) and clinical outcome (diagnosis, residual symptomatology, psychotic episodes) was obtained from the clinical records of 51 patients with a short-term course of psychosis and whose available follow-up period was at least three years long (mean=5.8, SD=2.1). Results Poor premorbid adjustment and hospitalization at first psychotic episode were significant predictors of a schizophrenia diagnosis. Lower educational level and an insidious type of onset significantly predicted the presence of residual symptoms. Hospitalization at first psychotic episode and higher scores on the psychotic dimension at onset significantly predicted subsequent psychotic episodes. Discussion Low educational level increased the risk of residual symptoms, possibly because it hinders treatment continuity. Poor premorbid adjustment was related to a schizophrenia diagnosis at the follow-up assessment, supporting previous findings of their high ratings for premorbid impairment, including social withdrawal and dysfunctional peer relationship. Insidious onset was predictive of persistent residual symptoms; an association possibly mediated by the duration of untreated psychosis (DUP). Being hospitalized at first episode was a significant prognostic factor for schizophrenia diagnosis and multiple psychotic episodes; the severity and nature of symptoms at first episode that require hospitalization might account for these associations. Replicating previous findings, multiple-episode patients scored significantly higher than the single-episode patients on the psychoticism dimension. Most baseline factors did not predict diagnosis. This seems congruent with a dimensional view of psychosis suggesting that even though schizophrenic and non-schizophrenic psychoses are classified as separate families of disorders, they exist along a continuum of psychosis that crosses diagnostic boundaries, sharing aetiological and risk factors. Currently, both the amelioration of severe psychotic symptoms and the improvement of psychosocial functioning and quality of life are feasible aims. Symptom exacerbation and hospitalizations might cause cumulative deterioration and impair the patient's social reintegration. Thus, relapse prevention is an important objective in treatment. The identification of reliable predictors of illness course has significant implications for treatment and service planning. Conclusions The predictive value of several factors was replicated in this sample of patients with psychotic illnesses, although predictors seem to relate differently to the three short-term course measures. Comprehensively mapping the development and outcome of the first episode of psychosis requires the use of standardized measurement tools and the longitudinal assessment of multiple outcome measures. [ABSTRACT FROM AUTHOR]

Bopp JM, Miklowitz DJ, Goodwin GM, Stevens W, Rendell JM, Geddes JR. The longitudinal course of bipolar disorder as revealed through weekly text messaging: a feasibility study. Bipolar Disord 2010: 12: 327–334. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: To examine the feasibility of collecting course of illness data from patients with bipolar I and II disorder, using weekly text-messaged mood ratings, and to examine the time trajectory of symptom ratings based on this method of self-report. Methods: A total of 62 patients with bipolar I (n = 47) or II (n = 15) disorder provided mood data in response to weekly cell phone text messages (n = 54) or e-mail prompts (n = 8). Participants provided weekly ratings using the Altman Self-Rating Mania Scale and the Quick Inventory of Depressive Symptoms–Self Report. Patients with bipolar I and II disorder, and men and women, were compared on percentages of time in depressive or manic mood states over up to two years. Results: Participants provided weekly ratings over an average of 36 (range 1–92) weeks. Compliance with the procedure was 75%. Overall, participants reported depressive symptoms 47.7% of the time compared to 7% of entries reflecting manic symptoms, 8.8% reflecting both depressive and manic symptoms, and 36.5% reflecting euthymic mood. Participants with bipolar I disorder reported more days of depression and were less likely to improve with time than participants with bipolar II disorder. Gender differences observed at the beginning of the study were not observed at follow-up. Conclusions: The results are similar to those of other longitudinal studies of bipolar disorder that use traditional retrospective, clinician-gathered mood data. Text-message-based symptom monitoring during routine follow-up may be a reliable alternative to in-person interviews. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Gender differences in psychotic disorder have been observed in terms of illness onset and course; however, past research has been limited by inconsistencies between studies and the lack of epidemiological representative of samples assessed. Thus, the aim of this study was to elucidate gender differences in a treated epidemiological sample of patients with first episode psychosis (FEP). Methods: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics of 661 FEP consecutive patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Results: Prior to onset of psychosis, females were more likely to have a history of suicide attempts (p =.011) and depression (p =.001). At service entry, females were more likely to have depressive symptoms (p =.007). Conversely, males had marked substance use problems that were evident prior to admission (p <.001) and persisted through treatment (p <.001). At service entry, males also experienced more severe psychopathology (p <.001) and lower levels of functioning (GAF, p =.008; unemployment/not studying p =.004; living with family, p =.003). Treatment non-compliance (p <.001) and frequent hospitalisations (p =.047) were also common for males with FEP. At service discharge males had significantly lower levels of functioning (GAF, p =.008; unemployment/not studying p =.040; living with family, p =.001) compared to females with FEP. Conclusions: Gender differences are evident in illness course of patients with FEP, particularly with respect to past history of psychopathology and functioning at presentation and at service discharge. Strategies to deal with these gender differences need to be considered in early intervention programs. [Copyright &y& Elsevier]

Objectives: Most prior research has focused on functional impairment as a consequence, rather than a predictor, of mood symptoms in bipolar disorder (BD). Yet the majority of this research has been cross-sectional, thus limiting conclusions regarding directionality of effects. Indeed, just as functional impairment may represent an important outcome of BD, it may also serve as a risk factor for future affective symptoms or episodes. Thus, the primary aim of this study was to evaluate functional impairment as a predictor of mood symptoms in BD. Methods: Ninety-two patients with bipolar I disorder, recruited from hospital settings, were administered the Modified Hamilton Rating Scale for Depression, Bech–Rafaelson Mania Scale, and UCLA Social Attainment Survey (SAS) at baseline and at four-month follow-up. Results: Overall, patients evidenced a moderate level of functional impairment at both time points. Whereas baseline functional impairment was not associated with subsequent manic symptoms, baseline functional impairment was significantly predictive of depressive symptom levels at four-month follow-up. When individual SAS subscales were evaluated, impaired romantic relationship functioning and activity involvement were each significantly predictive of subsequent depressive symptoms, whereas baseline peer functioning was not. Conclusions: The study results suggest that functional impairment may be predictive of subsequent depressive, but not manic, symptoms over a relatively short-term follow-up period. Future studies that evaluate illness course over longer follow-up periods would be useful to further clarify the potential bidirectional relationship between depression and functional impairment in BD. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes is becoming more prevalent and its successful management relies on patients' self-care behaviours. Measures focusing on patients' perceptions can be effective behavioural interventions. Aim To gain insight into the perceptions of patients with diabetes, especially ideas of the illness course and perceived severity, and their impacts on self-care behaviour. Design of study Qualitative approach with in-depth patient interviews (n = 22) and seven focus groups (n = 53). Setting A rural town in Taiwan. Method The interview protocol was mainly derived from Kleinman's explanatory model. Purposive sampling strategies of maximum variation were used. The transcript of the interviews was analysed with editing and immersion/crystallisation styles. Results Diabetes is regarded as an incurable, inevitably deteriorating disorder of sugar metabolism with many chronic complications. Patients thought that renal injury, followed by blindness, leg amputation, and poor peripheral circulation, were the most frequent complications. They also assessed their perceived severity of the disease at specific points in time through different indicators in their daily lives, such as sugar level, presence of complications, and medications used. Patients felt that these aspects progressed concurrently and that the illness course followed a unidimensional process. The ever-increasing doses of medication was considered by these patients to be a side-effect of the drugs taken. Conclusion Physicians should clarify with their patients that the risks of uraemia, blindness, and leg amputation are less prevalent than expected and that patients should pay more attention to cardiovascular complications. Certain oral hypoglycaemic agents may not cause a vicious cycle of ever-increasing doses of medication and the drugs that need to be taken should not be seen as indicators of severity but, rather, measures taken to prevent the diabetes becoming severe in the future. [ABSTRACT FROM AUTHOR]

Neria Y, Bromet EJ, Carlson GA, Naz B. Assaultive trauma and illness course in psychotic bipolar disorder: findings from the suffolk county mental health project.Acta Psychiatr Scand 2005: 111: 380–383.© Blackwell Munksgaard 2005.Little is known about the relationship of assaultive trauma to clinical and functional outcome in patients with bipolar disorder.We assessed trauma histories in a cohort of 109 first-admission bipolar patients with psychosis using structured interviews and medical records. Assaultive trauma included rape, physical attacks, and physical threats. Outcome was assessed using standardized ratings.Forty percent reported a history of assaultive trauma, mostly in childhood (≤16 years). Exposed patients were more symptomatic at each follow-up than unexposed. Sixteen percent of exposed patients remitted after one episode compared with 38.5% of the non-exposed. Patients exposed as adults were the most symptomatic at 6 months, while patients exposed in childhood were the most symptomatic at 24 months.Our findings supported the salient role of trauma history as a risk factor for poor course in severe bipolar disorder. Given the high prevalence of such exposure, clinical awareness in first-admission psychotic bipolar patients is critical. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate whether the presence of comorbid personality disorder influences the course of bipolar illness. Methods: Fifty-two euthymic male bipolar I out-patients were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID II). Bipolar patients with an axis II diagnosis were compared with those without an axis II diagnosis on retrospectively obtained demographic, clinical and course of illness variables. Results: Thirty-eight percent of the bipolar patients met criteria for an axis II diagnosis. Two (4%) met criteria for (only) a Cluster A disorder, four (8%) for (only) a Cluster B, and six (12%) for (only) a Cluster C disorder. One (2%) bipolar patient met criteria a disorder in both Clusters A and B, and one (2%) for a disorder in Clusters B and C. Five (10%) met criteria for at least one disorder in Clusters A and C, and one met criteria for disorders in Clusters A, B, and C. The presence of a personality disorder was significantly associated with a lower rate of current employment, a higher number of currently prescribed psychiatric medications, and a higher incidence of a history of both alcohol and substance use disorders compared with the bipolar patients without axis II pathology. Conclusions: Our results extend previous findings of an association between comorbid personality disorder in bipolar I patients and factors that suggest a more difficult course of bipolar illness. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a highly recurrent psychiatric condition. While combined pharmacological and psychosocial treatments improve outcomes, not much is known about potential moderators that could affect these treatments. One potential moderator might be the quality of interpersonal relations in families, for example, familial attitudes and perceived criticism., Method: To explore this question we conducted a post-hoc analysis that used an existing data set from a previous study by our group that compared cognitive behavioral therapy (CBT) and supporting therapy (ST) in remitted BD. In the present study, we used Cox proportional hazard models., Results: We found that the relatives' ratings of criticism predicted the likelihood of depressive recurrences, especially in the ST condition. The patients' ratings of negative familial attitudes predicted the risk of recurrences in general, irrespective of the therapy condition., Conclusion: These results suggest that it might be important to assess perceived criticism and familial attitudes as potential moderators of treatment outcome in BD., Competing Interests: The authors have declared that no competing interests exist.

Bipolar disorder (BD) is a chronic and disabling psychiatric condition that is linked to significant disability and psychosocial impairment. Although current neuropsychological, molecular, and neuroimaging evidence support the existence of neuroprogression and its effects on the course and outcome of this condition, whether and to what extent neuroprogressive changes may impact the illness trajectory is still poorly understood. Thus, this selective review was aimed toward comprehensively and critically investigating the link between BD and neurodegeneration based on the currently available evidence. According to the most relevant findings of the present review, most of the existing neuropsychological, neuroimaging, and molecular evidence demonstrates the existence of neuroprogression, at least in a subgroup of BD patients. These studies mainly focused on the most relevant effects of neuroprogression on the course and outcome of BD. The main implications of this assumption are discussed in light of specific shortcomings/limitations, such as the inability to carry out a meta-analysis, the inclusion of studies with small sample sizes, retrospective study designs, and different longitudinal investigations at various time points. [ABSTRACT FROM AUTHOR]

Past research has subtyped patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) according to factors related to illness onset, illness duration, and age. However, no classification system fully accounts for the wide range of symptom severity, functional disability, progression, and prognosis seen among patients. This study examined whether illness trajectories among individuals with CFS were predictive of different levels of symptomology, functional disability, and energy expenditure. Of the participants ( N=541 ), the majority described their illness as Fluctuating (59.7%), with 15.9% Constantly Getting Worse, 14.1% Persisting, 8.5% Relapsing and Remitting, and 1.9% Constantly Getting Better. The illness courses were associated with significant differences in symptomology on select domains of the DSQ, functioning on select subscales of the SF-36, and on overall levels of energy expenditure. The significant symptomatic and functional differences between groups suggest that subtyping patients with CFS according to illness course is a promising method for creating more homogeneous groups of patients.

Objective: To analyze the differences in the quality of life of patients with psychosis according to the course of the illness., Method: Clinical records and SCID-I interviews were used to establish the course of the illness and to categorize it according to 3 criteria: a) relapses, b) residual symptoms, and c) clinical diagnosis. Subjective quality of life was assessed with the Seville Questionnaire., Results: Sixty one patients (56% women) participated, reporting a mostly adequate quality of life. An illness course characterized by the presence of residual symptoms, rather than by the occurrence of any relapse or the progression of a first-episode psychosis into schizophrenia, showed a negative effect on the perceived quality of life of patients., Conclusions: The clinical services provided to patients with psychosis should focus not only on symptoms remission and relapse prevention, but also achieving a recovery with a satisfactory quality of life. Having identified residual symptoms as a crucial factor negatively affecting quality of life, clinicians must carefully assess them and treat them, in order to achieve the best possible recovery., (Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.)