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Franco Benazzi - One of the best experts on this subject based on the ideXlab platform.
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Bipolar Disorder focus on Bipolar II Disorder and mixed depression
The Lancet, 2007Co-Authors: Franco BenazziAbstract:Bipolar II Disorder (recurrent depressive and hypomanic episodes) and related Disorders (united in the Bipolar spectrum) are understudied, despite a prevalence of about 5% in the community and about 50% in depressed outpatients. The apparent increase in prevalence of the Bipolar spectrum is related to several changes in diagnostic criteria, including improved probing for history of hypomania (focused more on overactivity than on mood change), lower minimum duration of hypomania, and inclusion of unipolar depressions with Bipolar signs (eg, family history of Bipolar Disorder, mixed depression). Prevalence of mixed depression, a combination of depression and manic or hypomanic symptoms, is high in patients with Bipolar Disorders. Controlled studies are needed to investigate treatment of mixed depression; antidepressants can worsen manic and hypomanic symptoms, and mood stabilising agents might be necessary.
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Bipolar II Disorder epidemiology diagnosis and management
CNS Drugs, 2007Co-Authors: Franco BenazziAbstract:Bipolar II Disorder (BP-II) is defined, by DSM-IV, as recurrent episodes of depression and hypomania. Hypomania, according to DSM-IV, requires elevated (euphoric) and/or irritable mood, plus at least three of the following symptoms (four if mood is only irritable): grandiosity, decreased need for sleep, increased talking, racing thoughts, distractibility, overactivity (an increase in goal-directed activity), psychomotor agitation and excessive involvement in risky activities. This observable change in functioning should not be severe enough to cause marked impairment of social or occupational functioning, or to require hospitalisation. The distinction between BP-II and Bipolar I Disorder (BP-I) is not clearcut. The symptoms of mania (defining BP-I) and hypomania (defining BP-II) are the same, apart from the presence of psychosis in mania, and the distinction is based on the presence of marked impairment associated with mania, i.e. mania is more severe and may require hospitalisation. This is an unclear boundary that can lead to misclassification; however, the fact that hypomania often increases functioning makes the distinction between mania and hypomania clearer. BP-II depression can be syndromal and subsyndromal, and it is the prominent feature of BP-II. It is often a mixed depression, i.e. it has concurrent, usually subsyndromal, hypomanic symptoms. It is the depression that usually leads the patient to seek treatment.DSM-IV Bipolar Disorders (BP-I, BP-II, cyclothymic Disorder and Bipolar Disorder not otherwise classified, which includes very rapid cycling and recurrent hypomania) are now considered to be part of the 'Bipolar spectrum'. This is not included in DSM-IV, but is thought to also include antidepressant/substance-associated hypomania, cyclothymic temperament (a trait of highly unstable mood, thinking and behaviour), unipolar mixed depression and highly recurrent unipolar depression.BP-II is underdiagnosed in clinical practice, and its pharmacological treatment is understudied. Underdiagnosis is demonstrated by recent epidemiological studies. While, in DSM-IV, BP-II is reported to have a lifetime community prevalence of 0.5%, epidemiological studies have instead found that it has a lifetime community prevalence (including the Bipolar spectrum) of around 5%. In depressed outpatients, one in two may have BP-II. The recent increased diagnosing of BP-II in research settings is related to several factors, including the introduction of the use of semi-structured interviews by trained research clinicians, a relaxation of diagnostic criteria such that the minimum duration of hypomania is now less than the 4 days stipulated by DSM-IV, and a probing for a history of hypomania focused more on overactivity (increased goal-directed activity) than on mood change (although this is still required for a diagnosis of hypomania). Guidelines on the treatment of BP-II are mainly consensus based and tend to follow those for the treatment of BP-I, because there have been few controlled studies of the treatment of BP-II. The current, limited evidence supports the following lines of treatment for BP-II. Hypomania is likely to respond to the same agents useful for mania, i.e. mood-stabilising agents such as lithium and valproate, and the second-generation antipsychotics (i.e. olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole). Hypomania should be treated even if associated with overfunctioning, because a depression often soon follows hypomania (the hypomania-depression cycle). For the treatment of acute BP-II depression, two controlled studies of quetiapine have not found clearcut positive effects. Naturalistic studies, although open to several biases, have found antidepressants in acute BP-II depression to be as effective as in unipolar depression; however, one recent large controlled study (mainly in patients with BP-I) has found antidepressants to be no more effective than placebo. Results from naturalistic studies and clinical observations on mixed depression, while in need of replication in controlled studies, indicate that antidepressants may worsen the concurrent intradepression hypomanic symptoms. The only preventive treatment for both depression and hypomania that is supported by several, albeit older, controlled studies is lithium. Lamotrigine has shown some efficacy in delaying depression recurrences, but there have also been several negative unpublished studies of the drug in this indication.
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the duration of hypomania in Bipolar II Disorder in private practice methodology and validation
Journal of Affective Disorders, 2006Co-Authors: Franco Benazzi, Hagop S AkiskalAbstract:Abstract Background DSM-IV 4-day minimum hypomania duration is not evidence-based. Epidemiologic data suggest that briefer hypomanias are prevalent in the community. We sought to find out the relative prevalence of short (2–3 days) versus long (≥ 4 days) hypomanias in private practice. Methods 206 Bipolar-II (BP-II) depressed outpatients (group B) and a group of 140 remitted BP-II (group R) were assessed with the DSM-IV Structured Clinical Interview, as modified by the authors. BP-II with short vs. longer hypomania were compared on such Bipolar validators as early age at onset, depressive recurrence, atypical feature specifier, depressive mixed state and Bipolar family history. In addition, to ascertain the Bipolar status of depressed patients with brief hypomanias, we included a comparison group of 178 major depressive Disorder (MDD) patients assessed when depressed. Results 27–30% of hypomanias (depending on whether assessment occurred when patients were depressed or in remission) had 2–3-day duration; 72% lasted less than 4 weeks. Except for the atypical feature specifier, BP-II with short vs. BP-II with longer hypomania were not significantly different on Bipolar validators. Moreover, BP-II with short, like its longer hypomanic counterpart, was significantly different from the comparison MDD group on all Bipolar indicators. Limitations Single interviewer and retrospective evaluation of duration of hypomania. Conclusions As BP-II patients almost never present clinically in a hypomanic episode, the retrospective assessment of the duration of these episodes is clinically unavoidable. Most hypomanias last from 2 days to a few weeks. BP-II with shorter vs. longer hypomanias had significantly higher rates of females, comorbidity and atypical features, but were otherwise indistinguishable on crucial Bipolar validators. Furthermore, such validators, including Bipolar family history, robustly distinguished BP-II with short hypomanias from the MDD group. The conservative 4-day threshold would misclassify one out of three BP-II as MDD. Such misclassification has relevant implications for treatment and outcome, as well as clinical research methodology for depressive and Bipolar Disorders.
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optimizing the detection of Bipolar II Disorder in outpatient private practice toward a systematization of clinical diagnostic wisdom
The Journal of Clinical Psychiatry, 2005Co-Authors: Hagop S Akiskal, Franco BenazziAbstract:Background We review a clinical diagnostic approach to validate a redefinition of Bipolar II Disorder (BPII), which bypasses several conservative steps in the DSM-IV Mood Module of the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) to make detection of BPII more "clinician-friendly." Method 563 consecutive private outpatients presenting with a DSM-IV-diagnosed major depressive episode (MDE) were included in the analyses. We used a modified SCID-CV in a semistructured way, used a duration of hypomania > or =2 days (rather than the 4-day floor cutoff recommended), did not follow the SCID-CV's stem (mood) skip-out instruction, focused more on past history of overactive behavior rather than mood change, and assessed hypomanic features both outside and during index MDE. Validation of BPII so-defined against major depressive Disorder (MDD) was undertaken in the Washington University tradition. The study was conducted from June 1999 to December 2003. Results BPII occurred in 56.8% of patients. Compared with MDD, BPII had a significantly earlier index age and age at onset of first MDE and higher rates of atypical features, depressive recurrences, hypomanic symptoms during MDE, trait mood lability, and Bipolar family history (p = .0000 for all variables). Conclusions Our experience suggests that when probing history for past hypomanic episodes, behavioral activation should be inquired first, thereby facilitating the patient's subsequent recall of euphoria and/or irritability during such activated periods. Information from significant others or past records is also crucial. In light of these clinical procedures, BPII emerged as more prevalent than MDD. We submit that clinicians have the distinct advantage of intimate knowledge of their patients, which, coupled with the procedures outlined herein, can maximize the yield of BPII diagnoses.
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agitated depression in Bipolar II Disorder
World Journal of Biological Psychiatry, 2005Co-Authors: Franco BenazziAbstract:Study aim: To test diagnostic validity or utility of agitated depression (AD) in Bipolar II Disorder (BP-II).Methods: Three hundred and twenty BP-II major depressive episode (MDE) outpatients interviewed with the Structured Clinical Interview for DSM-IV, Hypomania Interview Guide (HIG), and Family History Screen. AD defined as MDE with psychomotor agitation. Mixed depression defined as MDE with ≥4 hypomanic symptoms. AD, non-AD, mixed-AD, non-mixed-AD, and mixed-non-AD were compared versus diagnostic validators.Results: AD was present in 35.0%, 75.8% of AD were mixed, while only 14.3% of non-AD were mixed (P=0.0000). AD (n=112), versus non-AD (n=208), had significantly higher age, more females, recurrences, Bipolar I family history, and much more concurrent hypomanic symptoms. Mixed-AD (n=85), versus non-mixed-AD (n=27), was not significantly different, apart from more hypomanic symptoms (by definition), but there were clinically significant differences.Conclusions: Findings may partly support subtyping o...
Terence A Ketter - One of the best experts on this subject based on the ideXlab platform.
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american tertiary clinic referred Bipolar II Disorder versus Bipolar i Disorder associated with hastened depressive recurrence
International Journal of Bipolar Disorders, 2017Co-Authors: Saloni Shah, Laura D Yuen, Farnaz Hooshmand, Shefali Miller, Po W Wang, Bernardo Dellosso, Terence A KetterAbstract:Bipolar Disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000–2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of Bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan–Meier analyses assessed the relationships between Bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on Bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.
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differential prevalence and demographic and clinical correlates of second generation antipsychotic use in Bipolar i versus Bipolar II Disorder
Journal of Psychiatric Research, 2016Co-Authors: Dong Yeon Park, Kathryn C Goffin, Saloni Shah, Laura D Yuen, Jessica N Holtzman, Farnaz Hooshmand, Shefali Miller, Po W Wang, Terence A KetterAbstract:Abstract Aims To assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with Bipolar I Disorder (BDI) versus Bipolar II Disorder (BDII). Methods Stanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII. Results Among 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%). Limitations American tertiary Bipolar Disorder clinic referral sample, cross-sectional design. Conclusions Current SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust.
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different characteristics associated with suicide attempts among Bipolar i versus Bipolar II Disorder patients
Journal of Psychiatric Research, 2016Co-Authors: Kathryn C Goffin, Jessica N Holtzman, Farnaz Hooshmand, Shefali Miller, Po W Wang, Bernardo Dellosso, Terence A KetterAbstract:Abstract Background Suicide attempts are common in patients with Bipolar Disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with Bipolar I Disorder (BDI) versus Bipolar II Disorder (BDII)). Methods Outpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype. Results Among 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating Disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use Disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes. Limitations American tertiary Bipolar Disorder clinic referral sample, cross-sectional design. Conclusions Further studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.
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nosology diagnostic challenges and unmet needs in managing Bipolar Disorder
The Journal of Clinical Psychiatry, 2010Co-Authors: Terence A KetterAbstract:The spectrum of Bipolar Disorders includes the subtypes of Bipolar I Disorder, Bipolar II Disorder, cyclothymic Disorder, and Bipolar Disorder not otherwise specified (NOS). Because depression is the most pervasive symptom of Bipolar Disorder, this condition is frequently misdiagnosed as unipolar major depressive Disorder. As a result, patients often experience substantive delays in receiving the correct diagnosis and appropriate treatment. To help meet this important diagnostic challenge, various markers have been identified that have predictive value for a Bipolar outcome, including early onset of depression, family history of Bipolar Disorder, atypical depressive symptoms, and the presence of psychosis. Unmet needs in the management of Bipolar Disorder include an enhanced diagnostic process, more options for treating Bipolar depressive episodes, and safer, more tolerable medications for long-term maintenance treatment.
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impaired recognition of facial emotion in mania
American Journal of Psychiatry, 2002Co-Authors: Anna Lembke, Terence A KetterAbstract:OBJECTIVE: Recognition of facial emotion was examined in manic subjects to explore whether aberrant interpersonal interactions are related to impaired perception of social cues. METHOD: Manic subjects with Bipolar I Disorder (N=8), euthymic subjects with Bipolar I (N=8) or Bipolar II (N=8) Disorder, and healthy comparison subjects (N=10) matched pictures of faces to the words “fear,” “disgust,” “anger,” “sadness,” “surprise,” and “happiness.” RESULTS: The manic subjects showed worse overall recognition of facial emotion than all other groups. They showed worse recognition of fear and disgust than the healthy subjects. The euthymic Bipolar II Disorder subjects showed greater fear recognition than the manic and euthymic Bipolar I Disorder subjects. CONCLUSIONS: Impaired perception of facial emotion may contribute to behaviors in mania. Impaired recognition of fear and disgust, with relatively preserved recognition of other basic emotions, contrasts with findings for depression and is consistent with a mood-...
Bernardo Dellosso - One of the best experts on this subject based on the ideXlab platform.
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american tertiary clinic referred Bipolar II Disorder versus Bipolar i Disorder associated with hastened depressive recurrence
International Journal of Bipolar Disorders, 2017Co-Authors: Saloni Shah, Laura D Yuen, Farnaz Hooshmand, Shefali Miller, Po W Wang, Bernardo Dellosso, Terence A KetterAbstract:Bipolar Disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000–2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of Bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan–Meier analyses assessed the relationships between Bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on Bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.
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different characteristics associated with suicide attempts among Bipolar i versus Bipolar II Disorder patients
Journal of Psychiatric Research, 2016Co-Authors: Kathryn C Goffin, Jessica N Holtzman, Farnaz Hooshmand, Shefali Miller, Po W Wang, Bernardo Dellosso, Terence A KetterAbstract:Abstract Background Suicide attempts are common in patients with Bipolar Disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with Bipolar I Disorder (BDI) versus Bipolar II Disorder (BDII)). Methods Outpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype. Results Among 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating Disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use Disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes. Limitations American tertiary Bipolar Disorder clinic referral sample, cross-sectional design. Conclusions Further studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.
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american tertiary clinic referred Bipolar II Disorder compared to Bipolar i Disorder more severe in multiple ways but less severe in a few other ways
Journal of Affective Disorders, 2015Co-Authors: Kathryn C Goffin, Jessica N Holtzman, Farnaz Hooshmand, Shefali Miller, Po W Wang, Bernardo Dellosso, Natalie Portillo, Jennifer Dore, Shelley J HillAbstract:Abstract Background Prevalence and relative severity of Bipolar II Disorder (BDII) vs. Bipolar I Disorder (BDI) are controversial. Methods Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation. Results BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) Disorders, first-degree relative with mood Disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0±8.6 vs. 18.9±8.1 years), longer illness duration (19.0±13.0 vs. 16.1±13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1±1.4 vs. 3.7±1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%). Limitations American tertiary Bipolar Disorder clinic referral sample, cross-sectional design. Conclusions Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII.
Torbjorn Elvsashagen - One of the best experts on this subject based on the ideXlab platform.
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dentate gyrus cornu ammonis ca 4 volume is decreased and associated with depressive episodes and lipid peroxidation in Bipolar II Disorder longitudinal and cross sectional analyses
Bipolar Disorders, 2016Co-Authors: Erlend Boen, Torbjorn Elvsashagen, Birgitte Boye, Lars T Westlye, Dag Josefsen, Pedro ZuzarteAbstract:Objectives Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in Bipolar Disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with Bipolar II Disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. Methods We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). Results First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. Conclusions These results are consistent with a role for the dentate gyrus in the pathophysiology of Bipolar Disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in Bipolar Disorders.
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different impulsivity profiles in borderline personality Disorder and Bipolar II Disorder
Journal of Affective Disorders, 2015Co-Authors: Erlend Boen, Torbjorn Elvsashagen, Birgitte Boye, Stein Andersson, Ulrik Fredrik Malt, Benjamin Hummelen, Sigmund KarterudAbstract:Abstract Introduction Borderline personality Disorder (BPD) and Bipolar II Disorder (BP II) share clinical characteristics including impulsivity. Their relationship is disputed. In this study, we investigated self-reported impulsivity in these patient groups and in a healthy control group. Effects of current mood state and of traumatic childhood experiences were explored. Methods Twenty-five patients with BPD without comorbid Bipolar Disorder; 20 patients with BP II without comorbid BPD; and 44 healthy control subjects completed the UPPS questionnaire which yields assessments of four components of impulsivity: Urgency, Lack of Premeditation, Lack of Perseverance, and Sensation Seeking. Current mood state was rated using the Montgomery Asberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). Traumatic childhood experiences were assessed using the Childhood Trauma Questionnaire (CTQ). Group differences in UPPS levels; and effects of mood state and CTQ score on UPPS scores in patients were investigated. Results BPD patients showed significantly higher levels of Urgency and Lack of Perseverance than BP II patients and controls, and a significantly higher level of Lack of Premeditation than controls. BP II patients showed higher levels of Urgency and Lack of Perseverance than controls. In BP II, higher MADRS scores were associated with higher impulsivity scores. Also, higher CTQ scores were associated with higher Urgency scores in BP II. Limitations Relatively small sample size; cross-sectional assessment of influence of mood state. Conclusions BPD patients exhibited markedly elevated UPPS impulsivity scores compared with healthy controls and BP II patients, and the elevations were not related to current mood state. BP II patients showed moderately elevated impulsivity scores which were associated with a depressed mood state and to some extent with a history of childhood trauma. The findings suggest that BPD and BP II have different impulsivity profiles.
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Bipolar II Disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation
Bipolar Disorders, 2013Co-Authors: Erlend Boen, Torbjorn Elvsashagen, Ole A Andreassen, Lars T Westlye, Per Kristian Hol, Birgitte BoyeAbstract:Objectives The neurobiological substrate of Bipolar II Disorder (BD-II) remains largely unknown. A few previous studies have found evidence for cerebral cortical thinning in mixed samples of BD-II and Bipolar I Disorder patients; however, no study of cortical thickness or surface area has been limited to BD-II. In the present study, we compared magnetic resonance imaging (MRI)-based indices of cortical thickness and surface area between individuals with BD-II and healthy controls. Methods Thirty-six individuals with a DSM-IV diagnosis of BD-II and 42 controls underwent 3T MRI. Comparisons of thickness and relative surface areal expansion across the cerebral cortical mantle were performed using Freesurfer. Results Individuals with BD-II showed significant thinning in two prefrontal clusters primarily comprising the left subgenual anterior cingulate cortex, left perigenual ventromedial prefrontal cortex (PFC), bilateral dorsomedial PFC, and bilateral dorsolateral PFC (p < 0.0002 for both clusters, cluster size corrected) and in a left temporal cluster involving the superior, middle, and inferior temporal gyrus (p = 0.006, cluster size corrected). No group differences in cortical surface area were found. No significant effect of medication, mood state, illness duration, or family history of Bipolar Disorders on cortical thinning was observed. Conclusions These results indicate that BD-II is associated with thinning of prefrontal and temporal cortices implicated in the expression and regulation of negative and positive affect. Longitudinal studies are needed to clarify whether cortical thinning is a stable trait of BD-II, an illness effect that might progress during the course of the disease, or a combination of the two.
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evidence for reduced dentate gyrus and fimbria volume in Bipolar II Disorder
Bipolar Disorders, 2013Co-Authors: Torbjorn Elvsashagen, Erlend Boen, Birgitte Boye, Ole A Andreassen, Lars T Westlye, Stein Andersson, Ulrik Fredrik MaltAbstract:Objectives: Dentate gyrus (DG)-dependent inhibition of the stress response might play an important role in mood Disorders. During stress, hippocampal projections traversing the fimbria, a white matter bundle on the hippocampal surface, inhibit the hypothalamic–pituitary–adrenal (HPA) axis. The aim of the present study was to measure the volumes of the DG–cornu ammonis 4 (DG–CA4) and fimbria in patients with Bipolar II Disorder (BD-II) and healthy controls using a recently developed magnetic resonance imaging (MRI)-based technique. Methods: Thirty-seven individuals with a DSM-IV diagnosis of BD-II and 42 healthy controls underwent 3-Tesla MRI. Hippocampal subfield volumes were estimated using a novel segmentation algorithm implemented in FreeSurfer. Results: In patients with BD-II there was a significant reduction in the volume of the left [analysis of covariance (ANCOVA), F = 7.84, p = 0.006] and total (left + right) (F = 4.01, p = 0.047) DG–CA4 and left (F = 4.38, p = 0.040) and total (F = 4.15, p = 0.045) fimbria compared to healthy controls. Explorative analyses indicated a smaller left CA2–3 volume in subjects with BD-II compared to healthy controls, and a reduced left fimbria volume in unmedicated patients compared to medicated patients and controls. Conclusions: Our results provide evidence for the involvement of the DG and fimbria in BD-II. Longitudinal studies of the DG and fimbria with assessments of the HPA axis in BD-II are warranted.
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evidence for impaired neocortical synaptic plasticity in Bipolar II Disorder
Biological Psychiatry, 2012Co-Authors: Erlend Boen, Torbjorn Elvsashagen, Torgeir Moberget, Birgitte Boye, Nils O A Englin, Per O Pedersen, Ole A Andreassen, Espen DietrichsAbstract:Background Synaptic plasticity might play an important role in the pathophysiology and treatment of Bipolar Disorders. There is, however, a paucity of human evidence supporting this hypothesis, mainly due to a lack of methods for noninvasive assessment of synaptic plasticity. It has recently been demonstrated that plasticity of the visual evoked potential (VEP) induced by repeated visual stimulation might reflect synaptic plasticity. In this study, we examined VEP plasticity in healthy control subjects and patients with Bipolar II Disorder (BD-II). Methods Forty healthy control subjects and 26 individuals with a DSM-IV diagnosis of BD-II matched for age and gender participated. The VEPs were evoked by checkerboard reversal stimulation before and after a modulation block of prolonged (10 min) visual stimulation. Results The modulation block resulted in significant VEP plasticity in healthy control subjects. The VEP plasticity was significantly impaired in patients with BD-II. Explorative analyses indicated a trend toward a less severe impairment in medicated than in unmedicated patients. Conclusions Visual evoked potential plasticity might represent a reliable and robust assay for studies of synaptic plasticity in vivo in humans. In addition, our findings support the hypothesis of impaired synaptic plasticity in BD-II. Longitudinal studies are needed to fully clarify the effects of medication and mood state on VEP plasticity.
Ulrik Fredrik Malt - One of the best experts on this subject based on the ideXlab platform.
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different impulsivity profiles in borderline personality Disorder and Bipolar II Disorder
Journal of Affective Disorders, 2015Co-Authors: Erlend Boen, Torbjorn Elvsashagen, Birgitte Boye, Stein Andersson, Ulrik Fredrik Malt, Benjamin Hummelen, Sigmund KarterudAbstract:Abstract Introduction Borderline personality Disorder (BPD) and Bipolar II Disorder (BP II) share clinical characteristics including impulsivity. Their relationship is disputed. In this study, we investigated self-reported impulsivity in these patient groups and in a healthy control group. Effects of current mood state and of traumatic childhood experiences were explored. Methods Twenty-five patients with BPD without comorbid Bipolar Disorder; 20 patients with BP II without comorbid BPD; and 44 healthy control subjects completed the UPPS questionnaire which yields assessments of four components of impulsivity: Urgency, Lack of Premeditation, Lack of Perseverance, and Sensation Seeking. Current mood state was rated using the Montgomery Asberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). Traumatic childhood experiences were assessed using the Childhood Trauma Questionnaire (CTQ). Group differences in UPPS levels; and effects of mood state and CTQ score on UPPS scores in patients were investigated. Results BPD patients showed significantly higher levels of Urgency and Lack of Perseverance than BP II patients and controls, and a significantly higher level of Lack of Premeditation than controls. BP II patients showed higher levels of Urgency and Lack of Perseverance than controls. In BP II, higher MADRS scores were associated with higher impulsivity scores. Also, higher CTQ scores were associated with higher Urgency scores in BP II. Limitations Relatively small sample size; cross-sectional assessment of influence of mood state. Conclusions BPD patients exhibited markedly elevated UPPS impulsivity scores compared with healthy controls and BP II patients, and the elevations were not related to current mood state. BP II patients showed moderately elevated impulsivity scores which were associated with a depressed mood state and to some extent with a history of childhood trauma. The findings suggest that BPD and BP II have different impulsivity profiles.
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neurocognitive profiles in treatment resistant Bipolar i and Bipolar II Disorder depression
BMC Psychiatry, 2013Co-Authors: Ole A Andreassen, Ute Kessler, Helle K Schoeyen, Geir Egil Eide, Asa Hammar, Ulrik Fredrik MaltAbstract:The literature on the neuropsychological profiles in Bipolar Disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning. Acutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures. Neurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms. A high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant Bipolar depression, particularly in BD I. Trial registration number: NCT00664976
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evidence for reduced dentate gyrus and fimbria volume in Bipolar II Disorder
Bipolar Disorders, 2013Co-Authors: Torbjorn Elvsashagen, Erlend Boen, Birgitte Boye, Ole A Andreassen, Lars T Westlye, Stein Andersson, Ulrik Fredrik MaltAbstract:Objectives: Dentate gyrus (DG)-dependent inhibition of the stress response might play an important role in mood Disorders. During stress, hippocampal projections traversing the fimbria, a white matter bundle on the hippocampal surface, inhibit the hypothalamic–pituitary–adrenal (HPA) axis. The aim of the present study was to measure the volumes of the DG–cornu ammonis 4 (DG–CA4) and fimbria in patients with Bipolar II Disorder (BD-II) and healthy controls using a recently developed magnetic resonance imaging (MRI)-based technique. Methods: Thirty-seven individuals with a DSM-IV diagnosis of BD-II and 42 healthy controls underwent 3-Tesla MRI. Hippocampal subfield volumes were estimated using a novel segmentation algorithm implemented in FreeSurfer. Results: In patients with BD-II there was a significant reduction in the volume of the left [analysis of covariance (ANCOVA), F = 7.84, p = 0.006] and total (left + right) (F = 4.01, p = 0.047) DG–CA4 and left (F = 4.38, p = 0.040) and total (F = 4.15, p = 0.045) fimbria compared to healthy controls. Explorative analyses indicated a smaller left CA2–3 volume in subjects with BD-II compared to healthy controls, and a reduced left fimbria volume in unmedicated patients compared to medicated patients and controls. Conclusions: Our results provide evidence for the involvement of the DG and fimbria in BD-II. Longitudinal studies of the DG and fimbria with assessments of the HPA axis in BD-II are warranted.
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the load of short telomeres is increased and associated with lifetime number of depressive episodes in Bipolar II Disorder
Journal of Affective Disorders, 2011Co-Authors: Torbjorn Elvsashagen, Erlend Boen, Ole A Andreassen, Ulrik Fredrik Malt, Elsa Vera, Jorunn Bratlie, Dag Josefsen, Maria A BlascoAbstract:Abstract Background It has recently been hypothesized that Bipolar Disorders are associated with accelerated aging. Telomere dysfunction, a biomarker of aging, is determined by the load of short telomeres, rather than by the mean telomere length. To our knowledge, the load of short telomeres has not been reported in any psychiatric Disorder. The aims of the study were to examine the load of short telomeres and the mean telomere length and their relationships with illness duration and lifetime number of depressive episodes in Bipolar II Disorder (BD-II). Methods Twenty-eight patients (mean age = 34.8 ± 7.7) with a DSM-IV diagnosis of BD-II and 28 healthy control subjects (mean age = 34.8 ± 9.2) matched for age, sex, and education participated. The load of short telomeres (percentage of telomeres Results The load of short telomeres was significantly increased in patients with BD-II relative to healthy controls and may represent 13 years of accelerated aging. The load of short telomeres and the mean telomere length were associated with lifetime number of depressive episodes, but not with illness duration. Limitations Modest sample size and cross-sectional design. Conclusions Our results suggest that BD-II is associated with an increased load of short telomeres. Depressive episode-related stress may accelerate telomere shortening and aging. However, longitudinal studies are needed to fully clarify telomere shortening and its relationship with clinical variables in BD-II.