Influence of light exposure during early life on the age of onset of bipolar disorder

BackgroundEnvironmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association.MethodsData collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation.ResultsMore hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model.ConclusionsLight exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.     

Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression

Fiedorowicz JG, Endicott J, Solomon DA, Keller MB, Coryell WH. Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression. Bipolar Disord 2012: 14: 664–671. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: In a well‐defined sample, we sought to determine which clinical variables, some of potential nosological relevance, influence subsequent course following prospectively observed initial episodes of hypomania or mania (H/M). Methods: We identified 108 individuals in the National Institute of Mental Health Collaborative Depression Study diagnosed with unipolar major depression at intake who subsequently developed H/M. We assessed time to repeat H/M based on whether one had been started on an antidepressant or electroconvulsive therapy within eight weeks of developing H/M, had longer episodes, or had a family history of bipolar disorder. Results: Modeling age of onset, treatment‐associated H/M, family history of bipolar disorder, duration of index H/M episode, and psychosis in Cox regression analysis, family history of bipolar disorder (n = 21) was strongly associated with repeat episodes of H/M [hazard ratio (HR) = 2.01, 95% confidence interval (CI): 1.06–3.83, p = 0.03]. Those with treatment‐associated episodes (n = 12) were less likely to experience subsequent episodes of H/M, although this was not significant in the multivariate model (HR = 0.25, 95% CI: 0.06–1.05, p = 0.06). These individuals also had a later age of onset for affective illness and were more likely to be depressed. Duration of illness with a temporal resolution of one week, psychosis, and age of onset were not associated with time to repeat H/M episode. Conclusions: A family history of bipolar disorder influences the course of illness, even after an initial H/M episode. In this select sample, treatment‐associated H/M did not appear to convey the same risk for a course of illness characterized by recurrent H/M episodes.     

Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder

Singh MK, Chang KD, Chen MC, Kelley RG, Garrett A, Mitsunaga MM, Bararpour L, Howe M, Reiss AL, Gotlib IH. Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder.
Bipolar Disord 2012: 14: 585–596. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S. Objectives: A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities. Methods: Anatomical images from magnetic resonance imaging of 26 13‐ to 18‐year‐old adolescents with bipolar I disorder and 24 age‐comparable healthy controls with no personal or family history of psychopathology were analyzed using whole‐brain voxel‐based morphometry (VBM). Results: Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p < 0.05, family‐wise error (FWE)‐corrected]. Conclusions: Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.     

Early determinants of four-year clinical outcomes in bipolar disorder with psychosis

Carlson GA, Kotov R, Chang S‐W, Ruggero C, Bromet EJ. Early determinants of four‐year clinical outcomes in bipolar disorder with psychosis. Bipolar Disord 2012: 14: 19–30. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar disorder with psychosis is common in inpatient settings and is associated with diverse outcomes after hospital discharge, which can range from a return to premorbid functioning with no recurrence, to a chronic or recurring illness. Less is known, however, about factors that can predict a better or worse clinical outcome. The present study sought to assess four‐year clinical outcomes and their predictors in patients hospitalized for bipolar I disorder with psychosis. Methods: Participants from the Suffolk County Mental Health Project (SCMHP) with a baseline diagnosis of bipolar I disorder with psychotic features (N = 126) were reassessed using face‐to‐face interviews at six months, two years, and four years following their first hospitalization. At each time point, clinical status, role functioning, and treatment were assessed by highly trained interviewers using standardized instruments. Results: The majority of participants (73.2%) returned to their premorbid level of role functioning by the four‐year follow‐up and the median percentage of time ill during the interval was less than 20%. Nevertheless, almost half of the sample (46.9%) was rehospitalized at least once. Psychotic symptoms at baseline (particularly Schneiderian symptoms), depressive phenomenology, childhood psychopathology, and younger age at first hospitalization predicted worse outcome, whereas mood‐incongruent psychotic features and age of mood disorder onset did not. Conclusions: The four‐year outcomes of a first‐admission cohort with bipolar I disorder with psychosis were generally favorable. Poorer premorbid functioning, Schneiderian delusions, greater depressive symptoms, and a younger age of first hospitalization portend a worse course.     

Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment

Hajek T, Cullis J, Novak T, Kopecek M, Höschl C, Blagdon R, O’Donovan C, Bauer M, Young L T, MacQueen G, Alda M. Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.
Bipolar Disord 2012: 14: 261–270. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). Methods: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non‐Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li‐naïve, young BD participants (15–30 years of age) and 18 sex‐ and age‐matched healthy controls. We compared hippocampal volumes obtained from 1.5‐T magnetic resonance imaging (MRI) scans using optimized voxel‐based morphometry with small volume correction. Results: The non‐Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li‐naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. Conclusions: Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li‐naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.     

Age at onset of bipolar disorder and risk for comorbid borderline personality disorder

Objectives: The relationship between bipolar disorder and cluster B personality disorders remains phenomenologically complex and controversial. We sought to examine the relationship between early age at onset of bipolar disorder and development of comorbid borderline personality disorder. Methods: A total of 100 adults in an academic specialty clinic for bipolar disorder underwent structured diagnostic interviews and clinical assessments to determine lifetime presence of comorbid borderline personality disorder, histories of childhood trauma, and clinical illness characteristics. Results: Logistic regression indicated that increasing age at onset of bipolar disorder was associated with a lower probability of developing comorbid borderline personality disorder (odds ratio = 0.91, 95% confidence interval: 0.83–0.99) while controlling for potential confounding factors, including a history of severe child trauma/abuse. Conclusion: Early onset of bipolar disorder increases the probability of developing comorbid borderline personality disorder, independent of the effects of severe childhood trauma/abuse. In patients with borderline personality disorder, prospective studies of new‐onset bipolar disorder may underestimate the prevalence of true comorbidity unless they capture the primary risk window for first‐episode mania arising before the end of adolescence.     

Mental disorders in offspring of parents with bipolar and major depressive disorders

Vandeleur C, Rothen S, Gholam‐Rezaee M, Castelao E, Vidal S, Favre S, Ferrero F, Halfon O, Fumeaux P, Merikangas KR, Aubry J‐M, Burstein M, Preisig M. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 2012: 14: 641–653. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. Methods: A total of 376 offspring (aged 6.0–17.9 years; mean = 11.5 years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co‐parents were interviewed by psychologists blind to proband diagnoses, using a semi‐structured diagnostic interview. Results: Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). Conclusions: These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.     

Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder

Lu LH, Zhou XJ, Fitzgerald J, Keedy SK, Reilly JL, Passarotti AM, Sweeney JA, Pavuluri M. Microstructural abnormalities of white matter differentiate pediatric and adult onset bipolar disorder. Bipolar Disord 2012: 14: 597–606. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: White‐matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white‐matter deviation may be more pronounced in pediatric than adult‐onset BD. The present study aimed to examine how white‐matter microstructure deviates from a typical maturational trajectory in BD. Methods: Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9–42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract‐based spatial statistics were used to examine the center of white‐matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post‐hoc analyses. Results: The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult‐onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity. Conclusions: The ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater susceptibility to illness.     

Cognitive decline in elderly bipolar disorder patients: a follow‐up study

Schouws SNTM, Stek ML, Comijs HC, Dols A, Beekman ATF. Cognitive decline in elderly bipolar disorder patients: a follow‐up study. Bipolar Disord 2012: 14: 749–755. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Older individuals with bipolar disorder may exhibit greater cognitive decline over time compared to mentally healthy elderly individuals. We aimed to investigate neurocognitive performance in bipolar disorder over a period of two years. Methods: A comprehensive neuropsychological test battery was applied at baseline and two years later to 65 euthymic elderly outpatients with bipolar disorder (mean age = 68.35, range: 60–90 years) and to a demographically comparable sample of 42 healthy elderly controls. A general linear model was used to measure changes over time for the two groups. The impact of baseline illness characteristics on intra‐individual change in neurocognitive performance within the bipolar group was studied by using logistic regression analysis. Results: At baseline and at follow up, bipolar disorder patients performed worse on all neurocognitive measures compared to the healthy elderly group. However, there was no significant group‐by‐time interaction between the bipolar disorder patients and the comparison group. Conclusions: Although older bipolar disorder patients have worse cognitive function than normal controls, they did not have greater cognitive decline over a period of two years.     

Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients

Hardy C, Rosedale M, Messinger JW, Kleinhaus K, Aujero N, Silva H, Goetz RR, Goetz D, Harkavy‐Friedman J, Malaspina D. Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients.
Bipolar Disord 2012: 14: 109–117. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder. Methods: We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM‐IV bipolar disorder patients and 44 control subjects. Results: The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = ?0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p = 0.024) and social fear (r = 0.610, p = 0.046). Conclusions: Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex‐stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.     

The role of disturbed sleep in the early recognition of bipolar disorder: a systematic review

Ritter PS, Marx C, Bauer M, Lepold K, Pfennig A. The role of disturbed sleep in the early recognition of bipolar disorder: a systematic review.
Bipolar Disord 2011: 13: 227–237. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Severely disturbed sleep is known to occur during and shortly prior to the onset of mood episodes in bipolar disorder. Whether alterations in sleep occur parallel and as part of the disease process or whether they represent a trait existent before the onset of the disorder itself remains unclear. Methods: A systematic review evaluating all published data on the occurrence of disordered sleep prior to the onset of the first mood episode was conducted. Results: The evidence cited within this paper suggests that sleep disturbances frequently precede bipolar disorder by several years and convey an elevated long‐term risk for developing any kind of mood disorder. Disordered sleep appears to emerge about the time of puberty and remains persistently elevated in individuals at high risk. Conclusion: Disturbed sleep appears to be an early symptom of bipolar disorder but further research, especially longitudinal studies in individuals at high risk, will be required to characterize the type and patterns more precisely.     

Birth‐cohort and dual diagnosis effects on age‐at‐onset in Brazilian patients with bipolar I disorder

Objective: Substance use disorders and birth‐cohort have been associated with an earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter‐relations of these factors in age‐at‐onset in bipolar illness. Method: Two‐hundred and thirty patients with bipolar I disorder were cross‐sectionally evaluated. Patients were categorized into four age groups for analysis. Lifetime comorbidity and age‐at‐onset were derived from the Structured Clinical Interview for DSM‐IV. Results: There was a strong linear association between age group and age‐at‐onset. Lifetime alcohol and drug use disorders were also associated with age‐at‐onset. Illicit drug and alcohol use disorders and age group remained significant in the multivariate model. No interactions appeared. Conclusion: Both age group and dual diagnoses had strong and independent impacts on age‐at‐onset in out‐patients with BD. Substance abuse may be partly accountable for earlier symptom onset, but other features of BD in younger generations are still in need to be accounted for.     

Sleep apnea risk and clinical correlates in patients with bipolar disorder

Soreca I, Levenson J, Lotz M, Frank E, Kupfer DJ. Sleep apnea risk and clinical correlates in patients with bipolar disorder. Bipolar Disord 2012: 14: 672–676. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Despite the high prevalence of risk factors for obstructive sleep apnea (OSA) among individuals with bipolar disorder, the presence of sleep‐disordered breathing has not been systematically assessed in this population. In this study, we sought to determine the level of risk for OSA in a population of remitted individuals with a diagnosis of bipolar I disorder. Methods: A total of 72 individuals with a diagnosis of bipolar I disorder, all of whom were overweight by the World Health Organization criteria, completed the Berlin Questionnaire, a self‐assessment tool to establish risk for OSA. Results: Over half of this study population (54.1%) was found to be in the high‐risk category for OSA. Participants at high risk for OSA scored significantly higher on measures of both depression and mania, even when sleep items were not counted in the total scores. Conclusions: Sleep apnea may be prevalent in patients with bipolar I disorder. Considering the substantial overlap of symptoms between OSA and depression and the potentially harmful effects of sleep disruption in patients with mood disorders, a systematic screening to assess prevalence and associated features of OSA in patients with bipolar disorder is warranted.     

Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder

Olsson SK, Sellgren C, Engberg G, Landén M, Erhardt S. Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder. Bipolar Disord 2012: 14: 719–726. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Kynurenic acid (KYNA), an end metabolite of tryptophan degradation, antagonizes glutamatergic and cholinergic receptors in the brain. Recently, we reported elevated levels of cerebrospinal fluid (CSF) KYNA in male patients with bipolar disorder. Here, we investigate the relationship between symptomatology and the concentration of CSF KYNA in patients with bipolar I disorder. Methods: CSF KYNA levels from euthymic male {n = 21; mean age: 41 years [standard deviation (SD) = 14]} and female [n = 34; mean age: 37 years (SD = 14)] patients diagnosed with bipolar I disorder were analyzed using high‐performance liquid chromatography (HPLC). Results: Euthymic bipolar I disorder patients with a lifetime occurrence of psychotic features had higher CSF levels of KYNA {2.0 nm [standard error of the mean (SEM) = 0.2]; n = 43} compared to patients without any history of psychotic features [1.3 nm (SEM = 0.2); n = 12] (p = 0.01). Logistic regression, with age as covariate, similarly showed an association between a history of psychotic features and CSF KYNA levels [n = 55; odds ratio (OR) = 4.9, p = 0.03]. Further, having had a recent manic episode (within the previous year) was also associated with CSF KYNA adjusted for age (n = 34; OR = 4.4, p = 0.03), and the association remained significant when adjusting for a lifetime history of psychotic features (OR = 4.1, p = 0.05). Conclusions: Although the causality needs to be determined, the ability of KYNA to influence dopamine transmission and behavior, along with previous reports showing increased brain levels of the compound in patients with schizophrenia and bipolar disorder, may indicate a possible pathophysiological role of KYNA in the development of manic or psychotic symptoms.     

Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study

Fan A, Berg A, Bresee C, Glassman LH, Rapaport MH. Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study. Bipolar Disord 2012: 14: 206–210. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Background: Allopurinol promotes the salvage of purines, possibly increasing endogenous adenosine levels. Recent studies suggest that adenosine has neuroprotective and inhibitory effects. Two previous inpatient trials demonstrated that allopurinol has anti‐manic activity. Our objective was to test allopurinol as an adjunct to standard medications in bipolar disorder manic outpatients. Methods: In this double‐blind, placebo‐controlled trial, 27 subjects who met DSM‐IV criteria for bipolar disorder and scored ≥ 14 on the Young Mania Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo for six weeks. The primary efficacy measure was the YMRS. The primary safety measure was the Treatment Emergent Symptom Scale. Results: The effect of allopurinol augmentation in decreasing mean YMRS scores was modest, with an overall effect size of ?0.25 (Cohen’s d). Allopurinol‐treated individuals who abstained from caffeine (n = 4) had a greater decrease in YMRS scores (?15.3 ± 1.8) than subjects using caffeine (n = 5) (?9.6 ± 3.4, p = 0.219), with an effect size of ?0.86. Conclusion: In this small outpatient pilot study, allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms. Subjects with restricted caffeine use showed a greater effect size compared to caffeine users. This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol’s anti‐manic effect in previous studies.     

State‐related alterations of gene expression in bipolar disorder: a systematic review

Munkholm K, Vinberg M, Berk M, Kessing LV. State‐related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684–696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Alterations in gene expression in bipolar disorder have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state‐related alterations in gene expression have the potential to point to markers of disease activity, and trait‐related alterations might indicate vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related. Methods: A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guideline for reporting systematic reviews, based on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications. Results: A total of 17 studies were included, comprising 565 patients and 418 control individuals. Six studies evaluated intraindividual alterations in gene expression across mood states. Two of five studies found evidence of intraindividual alterations in gene expression between a depressed state and a euthymic state. No studies evaluated intraindividual differences in gene expression between a manic state and a euthymic state, while only one case study evaluated differences between a manic state and a depressed state, finding altered expression in seven genes. No study investigated intraindividual variations in gene expression between a euthymic state and multiple states of various polarities (depressive, manic, hypomanic). Intraindividual alterations in expression of the same genes were not investigated across studies. Only one gene (the brain‐derived neurotrophic factor gene; BDNF) was investigated across multiple studies, showing no alteration between bipolar disorder patients and control individuals. Conclusions: There is evidence of some genes exhibiting state‐related alterations in expression in bipolar disorder; however, this finding is limited by the lack of replication across studies. Further prospective studies are warranted, measuring gene expression in various affective phases, allowing for assessment of intraindividual differences.     

The role of vascular risk factors in late onset bipolar disorder

BACKGROUND: The association between late life depression and cerebro-vascular risk and cerebro-vascular disease is well established. Do similar links exist with late onset bipolar disorder? AIMS AND OBJECTIVES: Patients with early onset (less than 60 years of age) bipolar disorder were compared with those of late onset (aged 60 and above) in relation to cognitive function, physical health and vascular risk factors. METHOD: Cross-sectional survey of elderly bipolar disorder patients (above 65 years) involved with secondary care mental health services. Thirty patients with early onset were compared with 20 patients with a late onset bipolar disorder. Diagnosis of bipolar disorder was according to ICD-10 criteria and without an associated clinical diagnosis of dementia. Assessment of cognition included tests of frontal-executive function, and cerebro-vascular risk was quantified with the Framingham stroke risk score. RESULTS: The late onset group had a higher stroke risk score than the early onset group, this difference persisting despite taking age and gender differences into account. However, late onset patients' cognitive function (including frontal lobe tests) and physical health status was no different to the early onset group. CONCLUSION: There is higher 'cerebrovascular risk' in elderly patients with late onset bipolar disorder, compared to patients with an early onset. This suggests that cerebrovascular risk may be an important factor for the expression of bipolar disorders in later life, and has significant management implications for older bipolar patients.     

Will disruptive mood dysregulation disorder reduce false diagnosis of bipolar disorder in children?

Margulies DM, Weintraub S, Basile J, Grover PJ, Carlson GA. Will disruptive mood dysregulation disorder reduce false diagnosis of bipolar disorder in children? Bipolar Disord 2012: 14: 488–496. © 2012 The Authors Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The frequency of diagnosis of bipolar disorder has risen dramatically in children and adolescents. The DSM‐V Work Group has suggested a new diagnosis termed disruptive mood dysregulation disorder (DMDD) (formerly temper dysregulation disorder with dysphoria) to reduce the rate of false diagnosis of bipolar disorder in young people. We sought to determine if the application of the proposed diagnostic criteria for DMDD would reduce the rate of diagnosis of bipolar disorder in children. Patients and methods: Eighty‐two consecutively hospitalized children, ages 5 to 12 years, on a children’s inpatient unit were rigorously diagnosed using admission interviews of the parents and the child, rating scales, and observation over the course of hospitalization. Results: Overall, 30.5% of inpatient children met criteria for DMDD by parent report, and 15.9% by inpatient unit observation. Fifty‐six percent of inpatient children had parent‐reported manic symptoms. Of those, 45.7% met criteria for DMDD by parent‐report, though only 17.4% did when observed on the inpatient unit. Conclusion: Although DMDD does decrease the rate of diagnosis of bipolar disorder in children, how much depends on whether history or observation is used.     

Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder

Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder. Bipolar Disord 2012: 14: 856–862. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such clinical commentary exists for improved detection of borderline personality disorder in depressed patients. Clinical experience suggests that borderline personality disorder is as disabling as bipolar disorder; however, no studies have directly compared the two disorders. For this reason we undertook the current analysis from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project comparing unemployment and disability rates in patients with bipolar disorder and borderline personality disorder. Methods: Patients were interviewed with semi‐structured interviews. We compared three non‐overlapping groups of depressed patients: (i) 181 patients with DSM–IV major depressive disorder and borderline personality disorder, (ii) 1068 patients with major depressive disorder without borderline personality disorder, and (iii) 84 patients with bipolar depression without borderline personality disorder. Results: Compared to depressed patients without borderline personality disorder, depressed patients with borderline personality disorder were significantly more likely to have been persistently unemployed. A similar difference was found between patients with bipolar depression and major depressive disorder without borderline personality disorder. No differences were found between patients with bipolar depression and depression with borderline personality disorder. Conclusions: Both bipolar disorder and borderline personality disorder were associated with impaired occupational functioning and thus carry a significant public health burden. Efforts to improve detection of borderline personality disorder in depressed patients might be as important as the recognition of bipolar disorder.     

Cognition in older adults with bipolar disorder versus major depressive disorder

Gildengers AG, Butters MA, Chisholm D, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF III, Mulsant BH. Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 2012: 14: 198–205. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction in older age during both acute mood episodes and remitted states. The purpose of this study was to investigate for the first time the similarities and differences in the cognitive function of older adults with BD and MDD that may shed light on mechanisms of cognitive decline. Methods: A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages ≥ 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using comprehensive measures of cognitive function and cognitive–instrumental activities of daily living (C‐IADLs). Test results were standardized using a group of mentally healthy individuals (n = 92) of comparable age and education level. Results: Subjects with BD and MDD were impaired across all cognitive domains compared with controls, most prominently in Information Processing Speed/Executive Function. Despite the protective effects of having higher education and lower vascular burden, BD subjects were more impaired across all cognitive domains compared with MDD subjects. Subjects with BD and MDD did not differ significantly in C‐IADLs. Conclusion: In older age, patients with BD have worse overall cognitive function than patients with MDD. Our findings suggest that factors intrinsic to BD appear to be related to cognitive deterioration and support the understanding that BD is associated with cognitive decline.