The clinical trajectory of emerging bipolar disorder among the high-risk offspring of bipolar parents: current understanding and future considerations.

Relatively little is known about the onset of bipolar disorder, yet the early illness course is already associated with significant morbidity and mortality. Therefore, characterizing the bipolar illness trajectory is key to risk prediction and early intervention advancement. In this narrative review, we discuss key findings from prospective longitudinal studies of the high-risk offspring of bipolar parents and related meta-analyses that inform us about the clinical trajectory of emerging bipolar disorder. Challenges such as phenotypic and etiologic heterogeneity and the non-specificity of early symptoms and syndromes are highlighted. Implications of the findings for both research and clinical practice are discussed. Bipolar disorder in young people at familial risk does not typically onset with a hypomanic or manic episode. Rather the first activated episode is often preceded by years of impairing psychopathological states that vary over development and across emerging bipolar subtype. Taking heterogeneity into account and adopting a more comprehensive approach to diagnosis seems necessary to advance earlier identification and our understanding of the onset of bipolar disorder

The performance of the Health of the Nation Outcome Scales as measures of clinical severity.

The aim of this study was to examine the performance of the Health of the Nation Outcome Scales (HoNOS) against other measures of functioning and mental health in a full three-year cohort of admissions to a psychiatric hospital. A sample of N=1719 patients (35.3% females, aged 17-78 years) was assessed using observer-rated measures and self-reports of psychopathology at admission. Self-reports were available from 51.7% of the sample (34.4% females, aged 17-76 years). Functioning and psychopathology were compared across five ICD-10 diagnostic groups: substance use disorders, schizophrenia and psychotic disorders, affective disorders, anxiety/somatoform disorders and personality disorders. Associations between the measures were examined, stratifying by diagnostic subgroup. The HoNOS were strongly linked to other measures primarily in psychotic disorders (except for the behavioral subscale), while those with substance use disorders showed rather poor links. Those with anxiety/somatoform disorders showed null or only small associations. This study raises questions about the overall validity of the HoNOS. It seems to entail different levels of validity when applied to different diagnostic groups. In clinical practice the HoNOS should not be used as a stand-alone instrument to assess outcome but rather as part of a more comprehensive battery including diagnosis-specific measures

The Use of the Health of the Nation Outcome Scales for Assessing Functional Change in Treatment Outcome Monitoring of Patients with Chronic Schizophrenia.

Schizophrenia is a severe mental disorder that is characterized not only by symptomatic severity but also by high levels of functional impairment. An evaluation of clinical outcome in treatment of schizophrenia should therefore target not only assessing symptom change but also alterations in functioning. This study aimed to investigate whether there is an agreement between functional- and symptom-based outcomes in a clinical sample of admissions with chronic forms of schizophrenia. A full 3-year cohort of consecutive inpatient admissions for schizophrenia (N = 205) was clinically rated with the Positive and Negative Symptom Scale (PANSS) and the Health of the Nation Outcome Scales (HoNOS) as measures of functioning at the time of admission and discharge. The sample was stratified twofold: first, according to the degree of PANSS symptom improvement during treatment with the sample being divided into three treatment response groups: non-response, low response, and high response. Second, achievement of remission was defined using the Remission in Schizophrenia Working Group criteria based on selected PANSS symptoms. Repeated measures analyses were used to compare the change of HoNOS scores over time across groups. More than a half of all admissions achieved a symptom reduction of at least 20% during treatment and around one quarter achieved remission at discharge. Similarly, HoNOS scores improved significantly between admission and discharge. Interaction analyses indicated higher functional improvements to be associated with increasing levels of treatment response. Functional improvement in individuals treated for schizophrenia was linked to a better clinical outcome, which implies a functional association. Thus, improvement of functioning represents an important therapeutic target in the treatment of schizophrenia

Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated

Discrepancies between clinical needs and helpseeking behaviors in co-occurring posttraumatic stress and alcohol use disorders.

OBJECTIVE: The aim of the study was to compare subjects dually diagnosed with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) to those with only one or none of these conditions regarding helpseeking needs and behaviors. METHOD: Data from a large community sample (N=3694) were used to assess the associations among lifetime PTSD and AUD, other psychiatric disorders, clinical characteristics and lifetime helpseeking behaviors derived from a semi-structured interview. RESULTS: Comorbid individuals had more severe clinical profiles and were more impaired than individuals with either PTSD or AUD alone or those with no/other psychiatric conditions. However, they did not differ in overall helpseeking behavior from any other group. Those with comorbid PTSD/AUD were even less likely than the other groups to seek help for depression and anxiety disorders through specific treatment facilities or the use of prescribed psychotropic drugs. CONCLUSIONS: Despite a greater need for treatment the comorbid group did not seek more help than the others. Their lower use of prescribed drugs supports the self-medication hypothesis, suggesting that those individuals relieve their symptoms through higher alcohol use instead. Our findings underline the need for health care facilities to encourage helpseeking behavior in the aftermath of stressful life events

Childhood adversities as specific contributors to the co-occurrence of posttraumatic stress and alcohol use disorders.

There is much evidence that alcohol use disorders (AUD) often co-occur with posttraumatic stress disorders (PTSD), and that the comorbid condition is associated with a more severe clinical profile than that of PTSD without AUD. However, little is known about the role of childhood adversities as specific risk factors for the development of AUD in individuals presenting with PTSD. The aim of the study was to explore whether specific stressors from the spectrum of trauma and childhood adversities contribute to the development of AUD among subjects with PTSD. From a large community sample, of N=140 individuals with PTSD, N=24 (17.14%) received an additional diagnosis of AUD with an onset after the onset of PTSD. Those with comorbid PTSD/AUD and those with PTSD only were compared regarding type and features of their trauma, childhood adversities and psychiatric comorbidity. Compared to PTSD alone, PTSD/AUD was associated with higher levels of stress in terms of childhood adversities; in particular, sexual abuse below the age of 16, but also with having been brought up in a foster home. PTSD/AUD was also associated with an earlier age of adverse events. Treatment of AUD should include standardized assessments of trauma, especially of trauma experienced during childhood

Development and validation of a risk calculator for major mood disorders among the offspring of bipolar parents using information collected in routine clinical practice.

Family history is a significant risk factor for bipolar disorders (BD), but the magnitude of risk varies considerably between individuals within and across families. Accurate risk estimation may increase motivation to reduce modifiable risk exposures and identify individuals appropriate for monitoring over the peak risk period. Our objective was to develop and independently replicate an individual risk calculator for bipolar spectrum disorders among the offspring of BD parents using data collected in routine clinical practice. Data from the longitudinal Canadian High-Risk Offspring cohort study collected from 1996 to 2020 informed the development of a 5 and 10-year risk calculator using parametric time-to-event models with a cure fraction and a generalized gamma distribution. The calculator was then externally validated using data from the Lausanne-Geneva High-Risk Offspring cohort study collected from 1996 to 2020. A time-varying C-index by age in years was used to estimate the probability that the model correctly classified risk. Bias corrected estimates and 95% confidence limits were derived using a jackknife resampling approach. The primary outcome was age of onset of a major mood disorder. The risk calculator was most accurate at classifying risk in mid to late adolescence in the Canadian cohort (n = 285), and a similar pattern was replicated in the Swiss cohort (n = 128). Specifically, the time-varying C-index indicated that there was approximately a 70% chance that the model would correctly predict which of two 15-year-olds would be more likely to develop the outcome in the future. External validation within a smaller Swiss cohort showed mixed results. Findings suggest that this model may be a useful clinical tool in routine practice for improved individualized risk estimation of bipolar spectrum disorders among the adolescent offspring of a BD parent; however, risk estimation in younger high-risk offspring is less accurate, perhaps reflecting the evolving nature of psychopathology in early childhood. Based on external validation with a Swiss cohort, the risk calculator may not be as predictive in more heterogenous high-risk populations. The Canadian High-Risk Study has been funded by consecutive operating grants from the Canadian Institutes for Health Research, currently CIHR PJT Grant 152796 he Lausanne-Geneva high-risk study was and is supported by five grants from the Swiss National Foundation (#3200-040,677, #32003B-105,969, #32003B-118,326, #3200-049,746 and #3200-061,974), three grants from the Swiss National Foundation for the National Centres of Competence in Research project "The Synaptic Bases of Mental Diseases" (#125,759, #158,776, and #51NF40 - 185,897), and a grant from GlaxoSmithKline Clinical Genetics

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders

Social Phobia Is Associated with Delayed Onset of Chickenpox, Measles, and Mumps Infections.

Evidence showing that infectious diseases in childhood play an important role in the etiopathogenesis of neurodevelopmental and other mental disorders is growing. The aim of this study was to explore the timing of common childhood diseases in early-onset anxiety disorders. We analyzed data from PsyCoLaus, a large Swiss Population Cohort Study (N = 3720). In this study, we regressed overanxious disorder, separation anxiety disorder, social phobia, and specific phobias on the age of onset of several childhood diseases, always adjusting for the other anxiety disorders listed above and for sex. The timing of viral childhood diseases (chickenpox, measles, and mumps) was consistently delayed in social phobia, notably both in men and women. We found no evidence for a reversed sequence of onset of phobia symptoms before that of the infections included. Social phobia was the only early anxiety disorder to show an association with a delayed onset of common viral childhood diseases

Barley plasma membrane intrinsic proteins (PIP aquaporins) as water and CO2 transporters

We identified barley aquaporins and demonstrated that one, HvPIP2;1, transports water and CO2. Regarding water homeostasis in plants, regulations of aquaporin expression were observed in many plants under several environmental stresses. Under salt stress, a number of plasma membrane-type aquaporins were down-regulated, which can prevent continuous dehydration resulting in cell death. The leaves of transgenic rice plants that expressed the largest amount of HvPIP2;1 showed a 40% increase in internal CO2 conductance compared with leaves of wild-type rice plants. The rate of CO2 assimilation also increased in the transgenic plants. The goal of our plant aquaporin research is to determine the key aquaporin species responsible for water and CO2 transport, and to improve plant water relations, stress tolerance, CO2 uptake or assimilation, and plant productivity via molecular breeding of aquaporins.</p