The developmental trajectory of bipolar disorder

BackgroundBipolar disorder is highly heritable and therefore longitudinal observation of children of affected parents is important to mapping the early natural history.AimsTo model the developmental trajectory of bipolar disorder based on the latest findings from an ongoing prospective study of the offspring of parents with well-characterised bipolar disorder.MethodA total of 229 offspring from families in which 1 parent had confirmed bipolar disorder and 86 control offspring were prospectively studied for up to 16 years. High-risk offspring were divided into subgroups based on the parental long-term response to lithium. Offspring were clinically assessed and DSM-IV diagnoses determined on masked consensus review using best estimate procedure. Adjusted survival analysis and generalised estimating equations were used to calculate differences in lifetime psychopathology. Multistate models were used to examine the progression through proposed clinical stages.ResultsHigh-risk offspring had an increased lifetime risk of a broad spectrum of disorders including bipolar disorder (hazard ratio (HR) = 20.89; P = 0.04), major depressive disorder (HR = 17.16; P = 0.004), anxiety (HR = 2.20; P = 0.03), sleep (HR = 28.21; P = 0.02) and substance use disorders (HR = 2.60; P = 0.05) compared with controls. However, only offspring from lithium non-responsive parents developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder and evidence supported a progressive transition through clinical stages, from non-specific psychopathology to depressive and then manic or psychotic episodes.ConclusionsFindings underscore the importance of a developmental approach in conjunction with an appreciation of familial risk to facilitate earlier accurate diagnosis in symptomatic youth.

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Progressive cortical thinning might identify children at risk of developing psychotic spectrum symptoms

10.13056/acamh.15013 ◽

2021 ◽

Keyword(s):

At Risk ◽

Bipolar Disorder ◽

Brain Structure ◽

Familial Risk ◽

Low Risk ◽

Children At Risk ◽

Long Term Outcomes ◽

Cortical Thinning ◽

Increased Risk

Offspring of patients with schizophrenia or bipolar disorder have an increased risk of developing these conditions. However, our capacity to predict the long-term outcomes of these at-risk individuals is limited. Now, researchers have investigated whether longitudinal changes in brain structure differ in individuals at high familial risk who develop psychotic spectrum symptoms, compared to those who do not and to low-risk controls.

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Early interventions for youths at high risk for bipolar disorder: a developmental approach

European Child & Adolescent Psychiatry ◽

10.1007/s00787-015-0773-6 ◽

2015 ◽

Vol 25 (3) ◽

pp. 217-233 ◽

Cited By ~ 15

Author(s):

Xavier Benarous ◽

Angèle Consoli ◽

Vanessa Milhiet ◽

David Cohen

Keyword(s):

Bipolar Disorder ◽

High Risk ◽

Early Interventions ◽

Developmental Approach

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Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

Psychological Medicine ◽

10.1017/s0033291717003087 ◽

2017 ◽

Vol 48 (9) ◽

pp. 1532-1539 ◽

Cited By ~ 8

Author(s):

E. Neilson ◽

C. Bois ◽

T.-K. Clarke ◽

L. Hall ◽

E. C. Johnstone ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Familial Risk ◽

Positive Association ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Score Analysis ◽

Increased Risk ◽

Heritable Disorder ◽

Diagnostic Symptoms

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

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Mortality in offspring of mothers with psychotic disorder

Psychological Medicine ◽

10.1017/s0033291707002383 ◽

2007 ◽

Vol 38 (8) ◽

pp. 1203-1210 ◽

Cited By ~ 9

Author(s):

J. Suvisaari ◽

L. Häkkinen ◽

J. Haukka ◽

J. Lönnqvist

Keyword(s):

High Risk ◽

General Population ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Suicide Attempts ◽

Risk Group ◽

High Risk Group ◽

Suicide Mortality ◽

Increased Risk ◽

Maternal Suicide

BackgroundPrevious studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders.MethodThe Helsinki High-Risk Study follows up offspring (n=337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population.ResultsWithin the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24, p=0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p<0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p<0.0001).ConclusionsOffspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.

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Long term outcomes of acute and transient psychotic disorders: The missed opportunity of preventive interventions

European Psychiatry ◽

10.1016/j.eurpsy.2018.05.004 ◽

2018 ◽

Vol 52 ◽

pp. 126-133 ◽

Cited By ~ 16

Author(s):

Grazia Rutigliano ◽

Sergio Merlino ◽

Amedeo Minichino ◽

Rashmi Patel ◽

Cathy Davies ◽

...

Keyword(s):

High Risk ◽

Psychotic Disorders ◽

Cumulative Risk ◽

Acute Onset ◽

Kaplan Meier ◽

Schizophrenia Spectrum ◽

National Health Service Trust ◽

Icd 10

AbstractBackground:Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear.Methods:Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1 st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals.Results:A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83–17.47%), 28.41% at 2-year (95%CI 26.80–30.09%), 33.96% at 3-year (95% CI 32.25–35.75%), 36.85% at 4-year (95%CI 35.07–38.69%), 40.99% at 5-year (95% CI 39.12–42.92%), 42.58% at 6-year (95%CI 40.67–44.55%), 44.65% at 7-year (95% CI 42.66–46.69%), and 46.25% at 8-year (95% CI 44.17–48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09–38.27%).Conclusions:Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes.

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Abstract 13943: Hypertrophic Cardiomyopathy with Left Ventricular Apical Aneurysm Represents a High-Risk Subgroup Necessitating Aggressive Preventive Therapy: A Long-term Follow-Up Study

Circulation ◽

10.1161/circ.130.suppl_2.13943 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Ethan J Rowin ◽

Barry J Maron ◽

Tammy S Haas ◽

John R Lesser ◽

Mark S Link ◽

...

Keyword(s):

Heart Failure ◽

Hypertrophic Cardiomyopathy ◽

High Risk ◽

Sudden Death ◽

Left Ventricular ◽

Increased Risk ◽

Long Term Follow Up ◽

Apical Aneurysm

Background: Increasing penetration of high spatial resolution cardiovascular magnetic resonance (CMR) imaging into routine cardiovascular practice has resulted in more frequent identification of a subset of hypertrophic cardiomyopathy (HCM) patients with thin-walled, scarred left ventricular (LV) apical aneurysms. Prior experience involved relatively small numbers of patients with short follow-up and therefore the risk associated with this subgroup remains incompletely defined. Therefore, we assembled a large HCM cohort with LV apical aneurysms and long-term follow-up in order to clarify clinical course and prognosis. Methods and Results: Of 2,400 HCM patients, 60 (2.5%) were identified by CMR with LV apical aneurysm, 24 to 86 years of age, including 19 (32%) <45 years old; 70% male, and followed for 5.6 ± 3.5 years. Over the follow-up period, 24 patients experienced 31 adverse disease-related complications including: appropriate implantable cardioverter-defibrillator discharge for VT/VF (n=11), received or listed for heart transplant (n=6), heart failure death (n=5), nonfatal thromboembolic events (n=4), resuscitated out-of-hospital cardiac arrest (n=3), and sudden death (n=2). In addition, an intracavitary thrombus was identified in the apical aneurysm in 9 patients without a thromboembolic history. Combined HCM-related death and aborted life threatening event rate was 8.6% per year, nearly 6-fold greater than the 1.5% annual mortality rate reported in the general HCM population. Conclusions: Patients with LV apical aneurysms represent a high-risk subgroup within the diverse HCM spectrum, associated with substantial increased risk for disease-related morbidity and mortality, including advanced heart failure, thromboembolic stroke and sudden death. Identification of this unique HCM phenotype should prompt consideration for primary prevention ICD, and anticoagulation for stroke prophylaxis.

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What Diagnoses Are Associated with Psychosis?

The First Episode of Psychosis ◽

10.1093/med-psych/9780190920685.003.0003 ◽

2021 ◽

pp. 35-48

Author(s):

Beth Broussard ◽

Michael T. Compton

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Healthcare Provider ◽

Psychotic Disorders ◽

Definitive Diagnosis ◽

Psychotic Symptoms ◽

Specific Diagnosis ◽

Substance Related Disorders

In this chapter we discuss the different diagnoses associated with psychosis. Schizophrenia is one of several primary psychotic disorders, a group of psychiatric disorders that primarily cause psychosis. Other disorders can cause psychotic symptoms—or symptoms similar to these—but are not considered psychotic disorders. A few examples of such disorders are major depressive disorder, bipolar disorder, and some substance-related disorders. It is often difficult to make a specific diagnosis when long-term information is not available at first. In instances in which a definitive diagnosis is uncertain, a working diagnosis allows the healthcare provider to begin effective treatments for psychosis even before a more certain diagnosis is made.

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The Neurobiology and Treatment of Bipolar Disorder

10.1093/med/9780190681425.003.0020 ◽

2017 ◽

Author(s):

Katherine E. Burdick ◽

Luz H. Ospina ◽

Stephen J. Haggarty ◽

Roy H. Perlis

Keyword(s):

Bipolar Disorder ◽

High Risk ◽

Genetic Risk ◽

Biological Models ◽

Increased Risk ◽

Psychotic Features ◽

Prodromal Syndrome ◽

Abnormal Sleep ◽

Epigenetic Processes ◽

High Risk Children

Bipolar disorder (BPD) is a severe mood disorder that often has psychotic features. Its most severe forms are more common and significantly more likely to cause disability than originally thought. Studies of high-risk children have found them to be at increased risk for a variety of symptoms and neurobiological abnormalities. In contrast to schizophrenia, there is no formal prodromal syndrome that has been identified, and cognitive abnormalities do not precede the onset of the disorder. Abnormal sleep and circadian rhythms are prominent and have led to intriguing biological models. Neurobiological experiments have primarily focused on candidate pathways and include circadian abnormalities, epigenetic processes including histone modification, WNT/GSK3 signaling, other modulators of neuroplasticity, and mitochondrial dysfunction. Recent data suggest that BPD is a highly polygenic disease and that integration of prior modeling and data with the wide variety of new genetic risk loci will be productive in the future.

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Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample

The British Journal of Psychiatry ◽

10.1192/bjp.bp.108.049536 ◽

2008 ◽

Vol 193 (5) ◽

pp. 378-382 ◽

Cited By ~ 155

Author(s):

Ian Kelleher ◽

Michelle Harley ◽

Fionnuala Lynch ◽

Louise Arseneault ◽

Carol Fitzpatrick ◽

...

Keyword(s):

Domestic Violence ◽

High Risk ◽

Childhood Trauma ◽

Psychotic Disorders ◽

Traumatic Events ◽

High Risk Group ◽

Traumatic Experiences ◽

Psychotic Symptoms ◽

High Risk Population ◽

Increased Risk

BackgroundChildren and adolescents who report psychotic symptoms appear to be at increased risk for psychotic disorders in adulthood – a putative ‘symptomatic’ high-risk group. However, little research has investigated whether those in this high-risk population have increased rates of exposure to traumatic events in childhood, as seen in patients who have a psychotic illness.AimsTo examine whether adolescents with psychotic symptoms have an increased rate of traumatic experiences.MethodPsychiatric interviews were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about a number of early traumatic events including physical and sexual abuse, exposure to domestic violence and bullying.ResultsFourteen adolescents (6.6% of those interviewed) reported experiencing at least one psychotic symptom. Adolescents who reported psychotic symptoms were significantly more likely to have been physically abused in childhood, to have been exposed to domestic violence and to be identified as a bully/victim (that is, both a perpetrator and victim of bullying) than those who did not report such symptoms. These findings were not confounded by comorbid psychiatric illness or family history of psychiatric history.ConclusionsOur findings suggest that childhood trauma may increase the risk of psychotic experiences. The characteristics of bully/victims deserve further study.

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Breast Cancer in Young Women after Treatment with Irradiation for Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v108.11.3333.3333 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3333-3333

Author(s):

Linda Lee ◽

Melania Pintilie ◽

David Hodgson ◽

Michael Crump

Keyword(s):

Breast Cancer ◽

High Risk ◽

Breast Density ◽

Young Women ◽

Cumulative Incidence ◽

Breast Mri ◽

Increased Risk

Abstract BACKGROUND: Women who are survivors of Hodgkin’s Lymphoma (HL) are at increased risk of developing breast cancer (BCa) as a long-term complication due to the use of extended field (mantle) irradiation (RT) of disease above the diaphragm. Many young women are at significantly increased risk of BCa prior to the age at which routine screening mammography is recommended for the general population. The sensitivity of mammography is lower in these women, in part due to increased breast tissue density characteristic of young pre-menopausal women. Currently, there is a paucity of information on the optimal screening modality and surveillance frequency for these women. METHODS: We reviewed the current BCa screening strategies used for this high risk group at our centre and described the incidence, method of detection, and characteristics of secondary BCas in a cohort of 115 women who received supradiaphragmatic RT for HL before age 30 between 1965 and 2000 at Princess Margaret Hospital (PMH) and who subsequently accepted long-term follow-up in a high-risk screening clinic. RESULTS: Median age at treatment was 22 (range 9–30). Radiation fields were mantle in 106 women, modified mantle in 6, and involved field in 3 (median dose delivered: 35 Gy, range 15–60). RT alone was used for 44 patients while 71 received combined modality therapy, of which 45 (65%) received MOPP. Treatment induced amenorrhea occurred in 15 women (median age 38); hormone replacement therapy was subsequently used by 9. Of the 107 women who participated in annual radiographic BCa screening, 95 were screened with mammogram alone, 1 with breast MRI alone, 8 with mammogram and MRI, and 3 with mammogram and ultrasound. Median age at first mammogram was 36; however, median age decreased with more recent year of HL diagnosis (age 40 for women diagnosed before 1985 compared to age 33 for women diagnosed after 1985, p<0.0001). Women with high breast density received MRI screening more often (p=0.02); however, breast density was not significantly associated with previous breast radiation dose or age at last follow-up. Twelve women were diagnosed with BCa in this cohort, following active breast surveillance for a median of 5 years (representing 584 person-years). The 20-year cumulative incidence of breast cancer was 10.9% (95% CI 5.3–18.8%) in this group of women. This was comparable to the 20-year cumulative incidence of breast cancer of 12% (95% CI 8–17%) in all 448 women with HL treated with supradiaphragmatic radiation before age 30 at PMH during the same time period. BCa occurred after a median of 17 years after treatment for HL (range 13–28). Median age at BCa diagnosis was 40 (range 31–51). Seven cancers were detected by physical exam (6 node-positive invasive BCas, 1 in-situ BCa) and 5 were detected on annual mammograms (1 node-positive invasive BCa, 4 in-situ BCas). CONCLUSIONS: Although women in the more recent treatment cohort are receiving their first mammogram at a younger age, the majority of BCas were still detected clinically, and these BCas had less favorable pathological characteristics. More frequent breast imaging should be considered in women who have had supradiaphragmatic RT for HL. Prospective evaluation of breast MRI as a screening strategy for HL survivors has been initiated at PMH in an effort to detect BCa at an earlier stage.

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