Onset Of Bipolar Disorder Research Articles

Impact of sunlight on the age of onset of bipolar disorder

Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p=0.006), controlling for each country's median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

High Behavioral Approach System (BAS) sensitivity, reward responsiveness, and goal-striving predict first onset of bipolar spectrum disorders: A prospective behavioral high-risk design.

A prospective, behavioral high-risk design provided a theoretically guided examination of vulnerability to first onset of bipolar spectrum disorder based on the Behavioral Approach System (BAS) model. Adolescents (ages 14-19) at an "age of risk" for bipolar disorder onset were screened on BAS sensitivity by interviewers blind to current symptoms, lifetime history, and family history of psychopathology. Participants were selected with high versus moderate levels of BAS sensitivity and administered a lifetime diagnostic interview. Those with a bipolar spectrum disorder, psychosis, or hypomanic episode with onset prior to the BAS sensitivity assessment were excluded. High BAS (n = 171) and moderate BAS (n = 119) sensitivity participants in the final sample completed baseline measures of symptoms, goal-setting, and reward responsiveness and were followed prospectively with semistructured diagnostic interviews every 6 months. Consistent with the vulnerability hypothesis of the BAS model of bipolar disorder, high BAS participants had a greater likelihood, and shorter time to onset, of bipolar spectrum disorder than moderate BAS participants across an average of 12.8 months of follow-up (12.9% vs. 4.2%), controlling for baseline depressive and hypomanic symptoms, and family history of bipolar disorder. High reward responsiveness on a behavioral task and ambitious goal-striving for popular fame and financial success (but not impulsivity) also predicted first onset of bipolar spectrum disorder controlling for the covariates and BAS risk group, and ambitious goal-striving partially mediated the BAS risk group effect. We discuss implications of the findings for the BAS model of bipolar disorder and early intervention efforts.

Family Functioning and the Course of Adolescent Bipolar Disorder

The symptoms of bipolar disorder affect and are affected by the functioning of family environments. Little is known, however, about the stability of family functioning among youth with bipolar disorder as they cycle in and out of mood episodes. This study examined family functioning and its relationship to symptoms of adolescent bipolar disorder, using longitudinal measures of family cohesion, adaptability, and conflict. Parent- and adolescent-reported symptom and family functioning data were collected from 58 families of adolescents with bipolar disorder (mean age =14.48±1.60; 33 female, 25 male) who participated in a 2-year randomized trial of family-focused treatment for adolescents (FFT-A). Cohesion and adaptability scores did not significantly change over the course of the study. Parent-reported conflict prior to psychosocial treatment moderated the treatment responses of families, such that high-conflict families participating in FFT-A demonstrated greater reductions in conflict over time than low-conflict families. Moreover, adolescent mania symptoms improved more rapidly in low-conflict than in high-conflict families. For all respondents, cohesion, adaptability, and conflict were longitudinally correlated with adolescents’ depression scores. Finally, decreases in parent-reported conflict also predicted decreases in adolescents’ manic symptoms over the 2-year study. Findings suggest that family cohesion, adaptability, and conflict may be useful predictors of the course of adolescent mood symptoms. Family conflict may be an important target for family intervention in early onset bipolar disorder.

Family Treatment for Bipolar Disorder and Substance Abuse in Late Adolescence

The initial onset of bipolar disorder occurs in childhood or adolescence in about 50% of patients. Early-onset forms of the disorder have a poorer prognosis than adult-onset forms and are frequently characterized by comorbid substance abuse. Clinical trials research suggests that family psychoeducational approaches are effective adjuncts to medication in stabilizing the symptoms of bipolar disorder in adults and youth, although their efficacy in patients with comorbid substance use disorders has not been systematically investigated. This article describes the family-focused treatment (FFT) of a late adolescent with bipolar disorder and polysubstance dependence. The treatment of this patient and family required adapting FFT to consider the family's structure, dysfunctional alliance patterns, and unresolved conflicts from early in the family's history. The case illustrates the importance of conducting manual-based behavioral family treatments with a psychotherapeutic attitude, including addressing unstated emotional conflicts and resistances that may impede progress.

Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage‐dependent calcium channels in psychiatric disorders

The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7 kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17-26 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.

Influence of parental consanguineous marriages on age at onset of bipolar disorder

The present study was performed to investigate the association between parental consanguineous marriages and age at onset of bipolar disorder (BPD). A total of 195 BPD patients participated in the study. Kaplan–Meier analysis revealed that relationships between age at onset and cumulative proportion of patients have different patterns with respect to types of parental marriages. Among early onset cases, the age at onset was higher for offspring of consanguineous than unrelated marriages, whereas in late onset cases the age at onset was lower for offspring of consanguineous than unrelated marriages. However, there was no difference between consanguineous and unrelated marriages for intermediate age at onset.

Behavioral Approach System (BAS)-Relevant Cognitive Styles in Individuals with High Versus Moderate BAS Sensitivity: A Behavioral High-Risk Design

This study used a behavioral high-risk design to evaluate cognitive styles relevant to the Behavioral Approach System (BAS) among individuals at high (n = 171) versus low (n = 119) risk of first onset of bipolar disorder based on BAS sensitivity, a known risk factor for bipolar disorder. Cognitive styles in high-BAS participants paralleled those implicated in bipolar disorder. Linear regressions indicated that individuals with high BAS sensitivity exhibited greater levels of goal striving, positive overgeneralization, rumination on positive affect, depressive brooding, perfectionism, and hypomanic personality. Furthermore, of the cognitive styles, emotion-focused rumination on positive affect mediated the association between BAS sensitivity and current levels of hypomanic symptoms. These results provide evidence that individuals at risk for the development of bipolar disorder have higher levels of BAS-relevant cognitive styles and hypomanic personality than do individuals with lower risk, indicating that these styles are not simply markers of prior (hypo)manic episodes.

Neuroimaging can help identify biomarkers of early onset bipolar disorder

(2012). Neuroimaging can help identify biomarkers of early onset bipolar disorder. Klinik Psikofarmakoloji Bulteni-Bulletin of Clinical Psychopharmacology: Vol. 22, No. 1, pp. 1-4.

Increased hippocampal volumes in lithium treated adolescents with bipolar disorders: A structural MRI study

Structural neuroimaging studies in bipolar disorder (BD) have consistently identified several anatomical abnormalities in many brain areas related to mood regulation. Hippocampus is one of the key components of emotional regulatory networks in the brain. Evidence about hippocampal changes in BD is quite limited and inconsistent particularly for adolescent onset BD. It is aimed to compare hippocampus volumes of euthymic BD-I adolescents with healthy controls using structural MRI. Hippocampal volumes of seventeen youths between 13 and 19 age period with DSM-IV BD (seven boys) and twelve healthy comparison subjects (five boys) were compared using structural MRI. Differences in hippocampal volumes between groups were tested. There was no significant difference between the right and left hippocampus volumes of patients with BD and the control group. However boys tended to have significantly larger right hippocampal volumes than girls both in BD and control group. Right hippocampal volumes were enlarged in lithium treated bipolar patients. This enlargement is not related to sex. Future, longitudinal follow-up studies need large enough sample sizes of both sexes and a sex-matched healthy comparison group to sort out developmental, gender and medication influences on brain structures over time in BD. Lithium treatment in adolescent-onset BD has a significant effect on hippocampus volumes.

Brain Structural Abnormalities at the Onset of Schizophrenia and Bipolar Disorder: A Meta-analysis of Controlled Magnetic Resonance Imaging Studies

A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI), found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophrenic and bipolar patients significant overall effect sizes were demonstrated for intracranial, whole brain, total grey and white matter volume reduction as well as for an increase of lateral ventricular volume at disease onset. Thus, the available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenia or bipolar disorder and that there is a significant overlap of brain abnormalities in affective and non-affective psychotic disorders at the onset of the disease. However, whole grey matter volume deficits and lateral ventricular enlargement appear to be more prominent in first-episode schizophrenia whereas white matter volume reduction seems more prominent in bipolar disorder. The common vs specific trajectories of brain pathomorphology in schizophrenia and bipolar disorder are discussed.

Rationale and First Results of Developing At-Risk (Prodromal) Criteria for Bipolar Disorder

Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for individuals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk criteria (BAR). This criteria comprises the peak age range of the first onset of bipolar disorder, genetic risk, presenting with sub-threshold mania, cyclothymic features or depressive symptoms. An initial pilot evaluation of the BAR criteria in 22 subjects indicated conversion rates to proxies of first-episode mania of 23% within 265 days on average, and high specificity and sensitivity of the criteria. If prospective studies confirm the validity of the BAR criteria, then the criteria would have the potential to open up new avenues of research for indicated prevention in BD and might therefore offer opportunities to ameliorate the severity of, or even prevent BD.

Age at onset versus family history and clinical outcomes in 1,665 international bipolar-I disorder patients

Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age<12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD-I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co-morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset.

Factitious disorder comorbid with bipolar I disorder. A case report

We describe a case of factitious disorder with physical and psychological symptoms comorbid with bipolar I disorder in a 37-year-old woman. Since the onset of bipolar disorder, which occurred at the age of 31, she increasingly complained of physical symptoms, compulsively seeking medical and surgical interventions. She has been hospitalised several times and her Munchausen-type factitious disorder recently appeared to be developing into Munchausen by proxy, involving her 11-year-old daughter. The patient adhered poorly to stabilising and antipsychotic drug treatment and did not improve through the years. We here analyse her mood phases, which were always associated with changes in the quality of factitious symptoms, according to whether the disorder was in its depressive phase (somatic complaints and suicidal ideation prevail), or in its manic or mixed phase (medical intervention-seeking and manipulation of clinicians to obtain surgical interventions). We also briefly discuss some important forensic issues to consider in similar cases, mainly stemming from the psychotic aspects of these two co-occurring disorders. Clinicians should be aware of some patients' ability to produce signs and symptoms of physical and/or psychological illness and consult psychiatrists before giving consent to invasive diagnostic procedures or surgery.

Early life stress exacerbates cognitive dysfunction induced by d-amphetamine: amelioration by valproic acid

It has been demonstrated that experiences taking place early in life have a profound influence on brain development, interacting with the genetic background and determining differences in the vulnerability to the onset of bipolar disorder when the individual is exposed to a second adverse event later in life. Here, we investigated the effects of exposure to an early adverse life event (maternal deprivation) and to a later adverse life event [D-amphetamine (AMPH)] on cognition in an animal model of mania. We have previously demonstrated that that repeated AMPH exposure produces severe and persistent cognitive impairment, which was more pronounced when the animals were maternal deprived, suggesting that the early adverse life event could be potentiating the effects of the exposure to the second adverse life event later in life. Here, we show that valproic acid ameliorated the cognitive deficits induced by AMPH, but it was not effective when the animals were exposed to both stressors: maternal deprivation and AMPH treatment.

Amygdala and insula volumes prior to illness onset in bipolar disorder: A magnetic resonance imaging study

There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328days – UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippocampus, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippocampal volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched samples.

P-216 - Continuity and discontinuity of psychopathological characteristics of bipolar disorder patient with adult versus pediatric onset

By contrast to adult bipolar disorder(A-BD), there has been considerably controversy about the existence and diagnosis of pediatric bipolar disorder(P-BD).We assessed outcome and psychopathological characteristics of A-BD vs. P-BD. We examined medical records of inpatients with DSM-IV-diagnoses of bipolar disorder. Patients were divided in two groups pediatric versus adult(>18 yrs) onset of bipolar disorder and compared for demographic and clinical data. All admitted patients were evaluated by a rating scale assessing their temperament(TEMPS-A) and DSM-IV diagnosis(MINI). Among seventy-eight patients(pediatric-BD N = 24 vs. Adult-BD N = 54; aged 34.79 ± 11.46 vs. 43.59 ± 12.75), 69% patients had an adult onset of the bipolar disorder. Pediatric-BD patients had a significant longer time of untreated full-blown psychiatric symptoms before first psychiatric contact(DUB) compared to A-BD (Mean pediatric DUB 11.04 ± 12.35 vs. adult DUB 2.23 ± 4.28,p < 0001). At onset P-BD patients had diagnosis of mood disorder in 50% cases compared to A-BD with 77.7% cases(Mood disorder diagnosis N = 12 vs. N = 42, p = .033). Regarding P-BD, most frequently polarity of onset was mixed (N = 12, 52%) versus adult-BD with depressive (N = 28, 58.3%, p = .036). Patients with P-onset showed greater psychosis lifetime compared to A-BD(1.1 vs. 0.6,p = .05). Pediatric-BD had temperament characteristics ranked hyperthimic>cyclothimic>depressive> irritable=anxious, versus adult onset hyperthimic > depressive = irritable > anxious >cyclothimic (p = 03). In our sample patients with early onset tend to maintain over time specific psychopathological characteristics compared to adult onset; this characteristics are often misdiagnosed with a variety of psychiatric diagnosis before the diagnosis of bipolar disorder and specific treatment. No differences were found for outcome measures probabily related to small sample.

A Clinical Study of Phenomenology and Comorbidity of Paediatric Bipolar Disorder

Background: Considerable controversy exists regarding clinical presentation, diagnosis, and comorbidities especially with Attention Deficit Hyperactivity Disorder (ADHD), in paediatric Bipolar Disorder (BPD). Aims and objectives: To describe phenomenology and comorbidities of paediatric BPD. Method: 78 Subjects (6-16 years) attending child and adolescent psychiatry services of C.S.M.M.U. Lucknow, who fulfilled DSM-IV-TR 2000 criteria for BPD were assessed using K-SADS-PL, child mania rating scale (CMRS),child depression rating scale (CDRS), Attention Deficit Hyperactivity Disorder rating scale (ADHD-RS) and Clinical Global Assessment Scale (C-GAS). Results: All the subjects were diagnosed as BPD-I. There mean chronological age was 13.4±2.1 years. The mean age at onset of BPD was 12.2 ± 2.3 years. The most common symptoms found in manic subjects were increased goal directed activities (100%), distractibility (100%), elation (98.7%), grandiosity (90.5%), physical restlessness (82.4%), poor judgment (82.4%) and decreased need for sleep (81.1%). 19 (24.3%) cases of BPD had other current comorbid disorders. The common comorbidities were Mental Retardation (10.26%), ADHD (10.26%), oppositional defiant disorder (6.41%), and substance abuse (3.85%). Conclusions: In children and adolescents elation/grandiosity was more common presentation than Irritability. Comorbidities were seen in 24.3% children in paediatric BPD. Differentiation of comorbid disruptive behaviour disorders especially ADHD from BPD is possible with respect to age of onset, quality of the disturbed mood, and the course of each disorder.

P-296 - A clinical study of phenomenology and comorbidity of paediatric bipolar disorders (BPD) from indian subcontinent

Introduction Considerable controversy exist regarding clinical presentation, diagnosis, and comorbidities specially Attention Deficit Hyperactivity Disorder (ADHD), in paediatric BPD. Objectives To describe phenomenology and comorbidities of paediatric BPD. Aims To clinically study the Phenomenology and Comorbidity of Pediatric BPD and to clinically study the comorbidity of ADHD in Pediatric BPD. Method 78 Subjects (6–16 years) attending child and adolescent psychiatry services of C.S.M.M.U. Lucknow, who fulfilled DSM-IV-TR 2000 criteria for BPD were assessed using K-SADS-PL, child mania rating scale (CMRS),child depression rating scale (CDRS) ADHD-RS and C-GAS. Results All the subjects were diagnosed as BPD-I. Their mean chronological age was 13.4 ± 2.1 years. The mean age at onset of BPD was 12.2 ± 2.3 years. The most common symptoms found in manic subjects were increased goal directed activities (100%), distractibility (100%), elation (98.7%), grandiosity (90.5%), physical restlessnesss (82.4%), poor judgment (82.4%) and decreased need for sleep (81.1%). 19 (24.5%) cases of BPD had other current comorbid disorders. The commonest comorbidities were MR (10.26%) and ADHD (10.26%), accompanied by Seizure disorders (2.56%), Oppositional Defiant Disorder (6.41%), substance abuse (3.85%), Anxiety Disorders (2.56%), and Enuresis (1.28). Conclusions In children and adolescents elation/grandiosity is more common presentation than Irritability. Comorbidities are rare in paediatric BPD-I. Differentiation of comorbid disruptive behaviour disorders especially ADHD from BPD is possible with respect to age of onset, quality of the disturbed mood, and the course of each disorder.

O-22 - Examining the comorbidity of bipolar disorder and autism spectrum disorders: a large controlled analysis of phenotypic and familial correlates in youth with bipolar disorder

Objective This study examines the clinical and familial correlates of bipolar disorder (BPD) when it occurs with and without autism spectrum disorders (ASD) comorbidity in a well characterized research referred population of youth with BPD. We hypothesized that in youth with BPD the clinical and familial correlates of BPD will be comparable irrespective of the comorbidity with ASD. Method Clinical correlates and familial risk was assessed using data from a large family study of youth with bipolar I disorder (BPD-I; probands N = 157; relatives N = 487). Findings in BPD-I youth were compared with those of youth with ADHD without BPD-I (probands N = 162; relatives N = 511) and age and sex matched controls without BPD-I or ADHD (probands N = 136; relatives N = 411). All subjects were comprehensively assessed using structured diagnostic interviews and a wide range of non overlapping measures assessing multiple dimensions of functioning. Results Thirty percent (47/155) of the BPD-I probands met criteria for ASD. The age at onset of BPD was significantly earlier in the presence of ASD comorbidity (4.7±2.9 vs. 6.3±3.7 years; p = 0.01). The phenotypic and familial correlates of BPD were similar in youth with and without ASD comorbidity. Conclusion A clinically significant minority of youth with BPD-I suffers from comorbid ASD. Phenotypic and familial correlates of BPD were typical of the disorder in the presence of ASD comorbidity. BPD-I comorbidity with ASD represents a very severe psychopathologic state in youth.

AS04-02 - Development of a scale for the assessment of prodromal states

While early detection strategies have been developed for schizophrenia, affective psychoses have long been relatively neglected in this domain. However, considering the difficulties met when attempting to define the onset of bipolar disorder, we felt prodrome to first episode mania would be a clinically relevant initial target for study. Based on an extensive literature review we identified symptoms, risk factors and associated clinical features that may be present in the phase preceding first episode mania onset. In a sample of 20 first episode mania patients, we explored which of these elements were present in at least 50% of cases. The study confirmed that a prodrome phase can be identified before onset of first episode mania. The symptoms presented felt under 3 categories (sleep problems, irritability, mood symptoms) and were rather unspecific. Various risk factors and markers of vulnerability could be identifed. On this basis a multi-dimensional scale grouped in 3 sub-scales was constructed. Our exploration suggests that identification of patients in the prodromal phase to first episode mania needs to be based on a combination of dimensions rather than on symptoms only. The scale still needs to be validated prospectively.