Body Stuff bibliografia sobre desordem bipolar

: All that wheezes is not asthma: bipolar disorder in primary care 1997-2007.

Manning JS.

Moses Cone Family Practice Residency, Greensboro, and the Department of Family Medicine, University of North Carolina, Chapel Hill, N.C.

PMID: 17607329 [PubMed - in process]

: Suicidal events and accidents in 216 first-episode bipolar I disorder patients: Predictive factors.

Khalsa HM, Salvatore P, Hennen J, Baethge C, Tohen M, Baldessarini RJ.

Department of Psychiatry, Harvard Medical School and the International Consortium for Bipolar Disorder Research, Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA.

BACKGROUND: Risks of life-threatening behaviors are high among bipolar disorder (BPD) patients, but early rates and associated risk factors for suicides and accidents remain ill-defined. METHODS: We assessed 216 DSM-IV BP-I patients prospectively for 4.2 years from first-lifetime hospitalization, using ordinal logistic-regression to estimate risks and associated demographic and clinical factors among risk-groups with: [1] no suicidal ideation, acts, or accidents, [2] suicidal ideation only, [3] suicides and attempts, [4] accidents, and [5] both suicidal acts and accidents. RESULTS: Suicidal thoughts or acts were identified in 127/216 subjects/4.2 years (14%/year), including suicidal ideation in 88 (9.7%/year), and acts in 39 (4.3%/year: 38 attempts [17.6%/year], 1 suicide [0.11%/year]); 87% of acts occurred within a year of a first-episode. Life-threatening accidents occurred in 20 cases (2.2%/year) with a mean latency of 3.8 years, including 12 with suicidal ideation or attempts (60% co-occurrence of accidents and suicidality); alcohol was implicated in 25% of accidents. The 53 cases of violent behaviors (5.84%/year) included a fatal car-wreck and a suicide, for a mortality risk of 0.22%/year (2/216/4.2 years). Suicidality was associated with initial mixed-state, proportion of follow-up weeks in mixed-states or depression, and prior suicide attempts; accidents were associated selectively with initial mania or psychosis, later mania or hypomania, and alcohol abuse. Violent acts also were associated with use of more psychotropic medicines/person, and with use of antipsychotics or sedative-anxiolytics. LIMITATIONS: Treatment was clinical and uncontrolled, illness relatively severe, and statistical power limited. CONCLUSIONS: Early in BP-I disorder, risks of suicidal acts and accidents were high, inter-related, and associated with particular types of initial and later morbidity, suggesting some predictability and potential for preventive intervention.

PMID: 17614135 [PubMed - as supplied by publisher]

: Progressive gray matter loss in patients with bipolar disorder.

Moorhead TW, McKirdy J, Sussmann JE, Hall J, Lawrie SM, Johnstone EC, McIntosh AM.

Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.

BACKGROUND: Structural brain abnormalities of the medial temporal lobe have been found in people with bipolar disorder (BPD). It is not known whether these abnormalities progress over the course of the illness or how they relate to neuropsychologic functioning. We sought to address these uncertainties in a prospective cohort study of people with bipolar I disorder. METHODS: Twenty patients with bipolar I disorder and 21 control subjects were recruited from the community. Participants were group matched for age, sex, and premorbid IQ. Longitudinal change in gray matter density was assessed using magnetic resonance imaging and evaluated using the technique of tensor-based morphometry with SPM2 software. Changes in gray and white matter density were estimated and compared with changes in cognitive function and clinical outcome. RESULTS: Patients with BPD showed a larger decline in hippocampal, fusiform, and cerebellar gray matter density over 4 years than control subjects. No significant changes in white matter density were found. Reductions in temporal lobe gray matter correlated with decline in intellectual function and with the number of intervening mood episodes over the follow-up period. CONCLUSIONS: Patients with BPD lose hippocampal, fusiform and cerebellar gray matter at an accelerated rate compared with healthy control subjects. This tissue loss is associated with deterioration in cognitive function and illness course.

PMID: 17617385 [PubMed - in process]

: Impact of anxiety disorder comorbidity on quality of life in euthymic bipolar disorder patients: differences between bipolar I and II subtypes.

Albert U, Rosso G, Maina G, Bogetto F.

BACKGROUND: Few studies investigated the impact of anxiety disorder comorbidity on health-related quality of life (HRQoL) of bipolar patients and none examined bipolar subtypes differences. The aim of the study was 1) to determine comorbidity rates for anxiety disorders in euthymic bipolar subjects, comparing bipolar type I and II disorders (BDI and BDII), and 2) to compare within each group HRQoL measures in subjects with and without anxiety comorbidity. METHODS: Comorbidity was evaluated through the SCID-I; HRQoL was assessed using the 36-Item Short-Form Health Survey (SF-36). All subjects were euthymic since at least 2 months, as confirmed by a HAM-D <8 and a YMRS <6. A comparison was made for SF-36 scores between subjects (all bipolars, BDI and BDII) with and without anxiety disorders. RESULTS: 105 patients were enrolled: 44 with BDI and 61 with BDII. Current and lifetime anxiety disorders comorbidities were 32.4% and 41.0% for all bipolars, 31.8% and 40.9% for BDI and 32.8% and 41.0% for BDII. BDI patients differed in several SF-36 domains from BDII subjects, which reported a poorer HRQoL. A current and lifetime comorbid anxiety disorder was associated with a poorer HRQoL considering all bipolars; when examining separately BDI and II subjects, however, the deleterious effect was restricted to BDI patients. LIMITATIONS: The cross-sectional assessment of HRQoL, the generic instrument used (SF-36) and the small sample size. CONCLUSIONS: Our study confirms the high comorbidity rates for anxiety disorders in bipolar subjects and provides evidence that anxiety comorbidity impacts HRQoL in subjects with BDI and not BDII.

PMID: 17617468 [PubMed - as supplied by publisher]

: Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with Lamotrigine monotherapy.

Haldane M, Jogia J, Cobb A, Kozuch E, Kumari V, Frangou S.

Section of Neurobiology of Psychosis, Institute of Psychiatry, PO66 De Crespigny Park London SE5 8AF, UK.

Verbal working memory and emotional self-regulation are impaired in Bipolar Disorder (BD). Our aim was to investigate the effect of Lamotrigine (LTG), which is effective in the clinical management of BD, on the neural circuits subserving working memory and emotional processing. Functional Magnetic Resonance Imaging data from 12 stable BD patients was used to detect LTG-induced changes as the differences in brain activity between drug-free and post-LTG monotherapy conditions during a verbal working memory (N-back sequential letter task) and an angry facial affect recognition task. For both tasks, LGT monotherapy compared to baseline was associated with increased activation mostly within the prefrontal cortex and cingulate gyrus, in regions normally engaged in verbal working memory and emotional processing. Therefore, LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation.

PMID: 17618089 [PubMed - as supplied by publisher]

6: Epidemiol Psichiatr Soc. 2007 Apr-Jun;16(2):109-17.

Longitudinal research on bipolar disorders.

Salvatore P, Tohen M, Khalsa HM, Baethge C, Tondo L, Baldessarini RJ.

Longitudinal assessment of the course of major psychiatric disorders has been advanced by studies from onset, but only rarely have large numbers of patients with a range of psychotic and major affective disorders been studied simultaneously and systematically from illness-onset. The decade-long McLean-Harvard First Episode Project & International Consortium for Bipolar Disorder Research has systematically followed-up large numbers of patients with DSM-IV bipolar or psychotic disorders from first-hospitalization. Major findings among patients with bipolar I disorder include: [a] full functional recovery from initial episodes was uncommon, and full symptomatic recovery, much slower than early syndromal recovery; [b] risks of relapse, recurrence, and switching were very high in the first two years; [c] most early morbidity was depressive-dysphoric, as reported in mid-course; [d] initial depression or mixed-states predicted more later depressive and overall morbidity, whereas initial mania or psychosis predicted later mania and a better prognosis; [e] based on within-subject modeling, most patients did not show progressive cycling over time, and illness-course was rather chaotic within and among patients; [f] treatment-latency or episode-counts were unassociated with responsiveness to long-term mood-stabilizing treatment; [g] very high rates of suicidal behavior and accidents occurred early; [h] early substance-use comorbidity associated with anxiety; [i] factor-analysis of prodromal symptoms predicted bipolar disorder much better than non-affective psychotic disorders. Project findings indicate that the course of bipolar I disorder is much less favorable than had been believed formerly, despite clinical treatment with modern mood-stabilizing and other treatments.

Publication Types:

PMID: 17619540 [PubMed - indexed for MEDLINE]

7: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Oct 1;31(7):1387-92. Epub 2007 Jun 14.

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Residual symptoms in bipolar disorder: the effect of the last episode after remission.

Kaya E, Aydemir O, Selcuki D.

Department of Psychiatry, Ok Meydani State Hospital, Istanbul, Turkiye.

In this study it is aimed to assess interepisode residual symptoms in remitted bipolar disorder patients with a hypothesis that the last episode recovered has implications on residual symptomatology. The study was carried out with 23 bipolar patients diagnosed as mania (BP-M) and 20 bipolar patients diagnosed as depression (BP-D) in their last episode, and with 22 healthy controls in a university hospital clinic. All patients were in remission for at least 6 months. In the assessment Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Stroop Test, Auditory Verbal Learning Test (AVLT), increased latency positive-evoked potentials (P300), Global Assessment of Functioning Scale (GAF), and Social Functioning Scale (SFS) were used cross-sectionally. In affective symptomatology, the BP-M group had higher YMRS scores, and the BP-D group had higher HAM-D scores compared to the controls. P300 test results revealed low amplitude in the BP-D group. In the AVLT, verbal learning and delayed recall were significantly lower in the two bipolar groups. The Stroop tasks were not different in the groups. Concerning the SFS, social withdrawal was impaired in the two bipolar groups, whereas dependency-competency was impaired in the BP-M and employment/occupation was impaired in the BP-D group. As a conclusion, bipolar patients recovering from depressive episode may experience more impairment in daily functioning due to residual depressive symptoms and impairment of attention and memory.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17628288 [PubMed - in process]

: Bipolar disorder: balancing mood states early in course of illness effects long-term prognosis.

Agren H, Backlund L.

Karolinska Institutet, Department of Clinical Neuroscience, Karolinska University Hospital Huddinge, Stockholm, Sweden. hans.agren@ki.se

The importance of observing swings above euthymic normality in patients with affective disorders has been emphasized by many research groups. The concept of mood bipolarity has not only established a Bipolar II disorder (with only hypomania, not mania, but also opened up for discussion of a Bipolar Spectrum, that would necessitate treatment with a broader range of agents, i.e., not only antidepressants. In order to understand the determinants of the patterns of mood swings in individuals with bipolar disorder we have used a computerized life-charting technique to analyze a large amount of clinical information in 100 patients with bipolar mood swings. In a cross-sectional set-up, we demonstrate clear evidence of achieving a better long-term stabilization when starting patients on mood stabilizer early after the first evidence of the mood disorder.

PMID: 17631368 [PubMed - in process]

: Quality of life among bipolar disorder patients misdiagnosed with major depressive disorder.

Awad AG, Rajagopalan K, Bolge SC, McDonnell DD.

Humber River Regional Hospital, Toronto, Ontario, Canada ; AstraZeneca Pharmaceuticals, LP, Wilmington, Del. ; and Consumer Health Sciences, Princeton, N.J.

Objective: Bipolar disorder is frequently misdiagnosed as major depressive disorder (MDD). We aim to quantify the prevalence of misdiagnosed bipolar disorder among the depression population and evaluate the quality-of-life (QOL) impact of misdiagnoses.Method: Data were collected from 2 self-administered, cross-sectional studies in 2003. Patients participating in The Bipolar Disorder Misdiagnosis Study (N = 1156) were previously diagnosed with depression, experienced a depressive episode within the past year, and had no previous diagnosis of bipolar disorder or schizophrenia. Patients who experienced a manic episode in the past year, based on DSM-IV criteria, were classified as misdiagnosed. Patients participating in The Bipolar Disorder Project (N = 1214) self-reported a diagnosis of bipolar disorder and were recruited through community mental health centers and support groups. Quality of life was assessed via the Psychological General Well-Being (PGWB) Index and Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). Demographic differences between groups were controlled using linear regression models.Results: Of the diagnosed MDD sample, 14.3% met criteria for misdiagnosed bipolar disorder. When controlling for demographic differences, the PGWB overall score for the misdiag-nosed averaged 12.77 (p < .001) points lower than that of MDD patients and 9.55 (p < .001) points lower than that of diagnosed bipolar disorder patients. The average SF-8 mental component summary score for the misdiagnosed was 5.85 (p < .001) points lower than that of MDD patients and 3.18 (p = .002) points lower than that of diagnosed bipolar disorder patients.Conclusion: Misdiagnosis is associated with poorer QOL than MDD or diagnosed bipolar disorder, which are recognized as having a considerable impact on QOL.

PMID: 17632652 [PubMed - in process]

: Dark therapy for bipolar disorder using amber lenses for blue light blockade.

Phelps J.

Corvallis Psychiatric Clinic, 3517 Samaritan Drive, Corvallis, OR 97330, United States.

"Dark Therapy", in which complete darkness is used as a mood stabilizer in bipolar disorder, roughly the converse of light therapy for depression, has support in several preliminary studies. Although data are limited, darkness itself appears to organize and stabilize circadian rhythms. Yet insuring complete darkness from 6 p.m. to 8 a.m. the following morning, as used in several studies thus far, is highly impractical and not accepted by patients. However, recent data on the physiology of human circadian rhythm suggests that "virtual darkness" may be achievable by blocking blue wavelengths of light. A recently discovered retinal photoreceptor, whose fibers connect only to the biological clock region of the hypothalamus, has been shown to respond only to a narrow band of wavelengths around 450nm. Amber-tinted safety glasses, which block transmission of these wavelengths, have already been shown to preserve normal nocturnal melatonin levels in a light environment which otherwise completely suppresses melatonin production. Therefore it may be possible to influence human circadian rhythms by using these lenses at night to blunt the impact of electrical light, particularly the blue light of ubiquitous television screens, by creating a "virtual darkness". One way to investigate this would be to provide the lenses to patients with severe sleep disturbance of probable circadian origin. A preliminary case series herein demonstrates that some patients with bipolar disorder experience reduced sleep-onset latency with this approach, suggesting a circadian effect. If amber lenses can effectively simulate darkness, a broad range of conditions might respond to this inexpensive therapeutic tool: common forms of insomnia; sleep deprivation in nursing mothers; circadian rhythm disruption in shift workers; and perhaps even rapid cycling bipolar disorder, a difficult- to -treat variation of a common illness.

PMID: 17637502 [PubMed - as supplied by publisher]

11: BMC Psychiatry. 2007 Jul 19;7:33.

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The management of bipolar mania: a national survey of baseline data from the EMBLEM study in Italy.

Bellantuono C, Barraco A, Rossi A, Goetz I.

Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Italy. Cesario.bellantuono@univr.it

BACKGROUND: Although a number of studies have assessed the management of mania in routine clinical practice, no studies have so far evaluated the short- and long-term management and outcome of patients affected by bipolar mania in different European countries.The objective of the study is to present, in the context of a large multicenter survey (EMBLEM study), an overview of the baseline data on the acute management of a representative sample of manic bipolar patients treated in the Italian psychiatric hospital and community settings. EMBLEM is a 2-year observational longitudinal study that evaluates across 14 European countries the patterns of the drug prescribed in patients with bipolar mania, their socio-demographic and clinical features and the outcomes of the treatment. METHODS: The study consists of a 12-week acute phase and a < or = 24-month maintenance phase. Bipolar patients were included into the study as in- or out-patients, if they initiated or changed, according to the decision of their psychiatrist, oral antipsychotics, anticonvulsants and/or lithium for the treatment of an episode of mania.Data concerning socio-demographic characteristics, psychiatric and medical history, severity of mania, prescribed medications, functional status and quality of life were collected at baseline and during the follow-up period. RESULTS: In Italy, 563 patients were recruited in 56 sites: 376 were outpatients and 187 inpatients. The mean age was 45.8 years. The mean CGI-BP was 4.4 (+/- 0.9) for overall score and mania, 1.9 (+/- 1.2) for depression and 2.6 (+/- 1.6) for hallucinations/delusions. The YMRS showed that 14.4% had a total score < 12, 25.1% > or = 12 and < 20, and 60.5% > or = 20. At entry, 75 patients (13.7%) were treatment-naïve, 186 (34.1%) were receiving a monotherapy (of which haloperidol [24.2%], valproate [16.7%] and lithium [14.5%] were the most frequently prescribed) while 285 (52.2%) a combined therapy (of which 8.0% were represented by haloperidol/lithium combinations). After a switch to an oral medication, 137 patients (24.8%) were prescribed a monotherapy while the rest (415, 75.2%) received a combination of drugs. CONCLUSION: Data collected at baseline in the Italian cohort of the EMBLEM study represent a relevant source of information to start addressing the short and long-term therapeutic strategies for improving the clinical as well as the socio-economic outcomes of patients affected by bipolar mania. Although it's not an epidemiological investigation and has some limitations, the results show several interesting findings as a relatively late age of onset of bipolar disorder, a low rate of past suicide attempts, a low lifetime rate of alcohol abuse and drug addiction.

Publication Types:

PMID: 17640381 [PubMed - indexed for MEDLINE]

12: Neuropsychobiology. 2007;55(3-4):123-31. Epub 2007 Jul 18.

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Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder.

Einat H, Yuan P, Szabo ST, Dogra S, Manji HK.

University of Minnesota, College of Pharmacy, Duluth, MN 55812, USA. heinat@d.umn.edu

RATIONALE: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. OBJECTIVES: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. METHODS: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. RESULTS: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. CONCLUSIONS: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder. (c) 2007 S. Karger AG, Basel.

Publication Types:

PMID: 17641532 [PubMed - in process]

13: Neuroscientist. 2007 Aug;13(4):392-404.

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Bipolar disorder and epilepsy: a bidirectional relation? Neurobiological underpinnings, current hypotheses, and future research directions.

Mazza M, Di Nicola M, Della Marca G, Janiri L, Bria P, Mazza S.

Institute of Psychiatry, Bipolar Disorders Unit, Catholic University of Sacred Heart, Rome, Italy. marianna.mazza@rm.unicatt.it

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. In bipolar patients, changes in second-messenger systems, such as G-proteins, phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate, or calcium activity have been described, along with changes in c-fos expression. Common mechanisms at the level of ion channels might include the antikindling and the calcium-antagonistic and potassium outward current-modulating properties of antiepileptic drugs. All these lines of research appear to be converging on a richer understanding of neurobiological underpinnings between bipolar disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders.

Publication Types:

Review

PMID: 17644769 [PubMed - indexed for MEDLINE]

14: J Clin Psychiatry. 2007;68 Suppl 6:24-5.

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Treatment of bipolar disorder with antipsychotic medication: issues shared with schizophrenia.

Young AH.

Department of Psychiatry, University of British Columbia Institute of Mental Health, Vancouver, Canada. alyoung@interchange.ubc.ca

Atypical antipsychotics are increasingly used in bipolar disorder as antimanic, antidepressant, and maintenance treatments. Many of the clinical issues related to switching antipsychotics are similar between schizophrenia and bipolar disorder. These include similar motivations for switching due to limited efficacy and unacceptable adverse effects. Particular attention must be paid to the phase of treatment and coprescribed medications.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17650056 [PubMed - indexed for MEDLINE]

: The long-term impact of treatment with electroconvulsive therapy on discrete memory systems in patients with bipolar disorder.

MacQueen G, Parkin C, Marriott M, Bégin H, Hasey G.

Mood Disorder Program, St. Joseph's Healthcare, McMaster University, Hamilton, Ont. macqueng@mcmaster.ca

OBJECTIVE: Electroconvulsive therapy (ECT) has been controversially associated with long-lasting memory problems. Verbal learning and memory deficits are commonly reported in studies of people with bipolar disorder (BD). Whether memory deficits can be exacerbated in patients with BD who receive ECT has, to our knowledge, not been systematically examined. We aimed to examine whether long-term effects of ECT on discrete memory systems could be detected in patients with BD. METHODS: We studied several domains of memory in 3 groups of subjects who were matched for age and sex: a group of healthy comparison subjects, a group of people with BD who had received ECT at least 6 months before memory assessment and another group with BD that had an equal past illness burden but had never received ECT. Memory was assessed with the California Verbal Learning Test, the Continuous Visual Memory Test and a computerized process dissociation task that examines recollection and habit memory in a single paradigm. RESULTS: Compared with healthy subjects, patients had verbal learning and memory deficits. Subjects who had received remote ECT had further impairment on a variety of learning and memory tests when compared with patients with no past ECT. This degree of impairment could not be accounted for by illness state at the time of assessment or by differential past illness burden between patient groups. CONCLUSIONS: From a clinical perspective, it is unlikely that such findings, even if confirmed, would significantly change the risk-benefit ratio of this notably effective treatment. Nonetheless, they may highlight the importance of attending to cognitive factors in patients with BD who are about to receive ECT; further, they raise the question of whether certain strategies that minimize cognitive dysfunction with ECT should be routinely employed in this patient group.

PMID: 17653292 [PubMed - indexed for MEDLINE]

16: Acta Psychiatr Scand. 2007 Sep;116(3):189-94.

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Development of the bipolar inventory of symptoms scale.

Bowden CL, Singh V, Thompson P, Gonzalez JM, Katz MM, Dahl M, Prihoda TJ, Chang X.

Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. bowdenc@uthscsa.edu

OBJECTIVE: Most rating scales for bipolar disorders (BDs) do not encompass the spectrum of symptomatology now established as characterizing the illness. We report the rationale, format, reliability and initial validity studies of the Bipolar Inventory of Symptoms Scale (BISS), a 44-item scale designed to encompass the spectrum of behavioral disturbances in BDs. METHOD: Structured video interviews of 20 patients representing four bipolar syndromal subtypes were rated by nine raters. RESULTS: Generally, high inter-rater reliability and internal consistency were established for the depression and mania subscales and the BISS total score. The BISS discriminated across subtypes of bipolar patients with depressed, manic/hypomanic, mixed manic or recovered status. CONCLUSION: The BISS has adequate reliability, concurrent validity and is capable of discriminating between bipolar subtypes. It also provides a comprehensive scale to assess discrete behavioral components of BD.

Publication Types:

Research Support, N.I.H., Extramural

PMID: 17655560 [PubMed - indexed for MEDLINE]

: Examining ventral and dorsal prefrontal function in bipolar disorder: A functional magnetic resonance imaging study.

Frangou S, Kington J, Raymont V, Shergill SS.

Section of Neurobiology of Psychosis, Institute of Psychiatry, Kings College London, London, UK.

Several lines of research suggest both dorsal and ventral prefrontal cortical dysfunction in bipolar disorder (BD). We used functional magnetic resonance imaging to compare patterns of brain activation in remitted BD patients and controls whilst performing tasks selected for their relative specificity in engaging either the dorsal (n-back sequential-letter working memory task) or ventral (gambling task) PFC. Seven BD patients were selected from participants of the Maudsley Bipolar Disorder Project on the basis of clinical remission, absence of cognitive deficits, and monotherapy with mood stabilisers. Subjects were individually matched by gender, age, and IQ to an equal number of healthy controls. In the n-back task, group differences were only present in response to increasing memory load. Patients did not show the predicted dynamic response in the dorsal PFC, but had increased activation in the parietal cortices. During the gambling task, controls showed significant activation in the ventral and dorsal PFC; this was attenuated in BD patients where increased activation was seen in lateral temporal and polar regions. Our findings suggest that there are trait abnormalities in dorsal and ventral PFC function in BD that may be more pronounced during tasks that rely on ventral-dorsal PFC interaction.

PMID: 17656073 [PubMed - as supplied by publisher]

: Art, alpha-1-antitrypsin polymorphisms and intense creative energy: Blessing or curse?

Schmechel DE.

Department of Medicine, Duke University Medical Center, Medical Director, The Falls Neurology and Memory Center, 4355 Hickory Boulevard (US 321), Granite Falls, NC 28630, United States.

Persons heterozygous for Z, S and rare alpha-1-antitrypsin (AAT, SERPIN1A) polymorphisms (ca. 9% of population) are often considered 'silent' carriers with increased vulnerability to environmentally modulated liver and lung disease. They may have significantly more anxiety and bipolar spectrum disorders, nutritional compromise, and white matter disease [Schmechel DE, Browndyke J, Ghio A. Strategies for the dissection of genetic-environmental interactions in neurodegenerative disorders. Neurotoxicology 2006;27:637-57]. Given association of art and mood disorders, we examined occupation and artistic vocation from this same series. One thousand five hundred and thirty-seven consecutive persons aged 16-90 years old received comprehensive work-up including testing for AAT 'phenotype' and level, nutritional factors, and inflammatory, iron and copper indices. Occupations were grouped by Bureau of Labor Standards classification and information gathered on artistic activities. Proportion of reactive airway disease, obstructive pulmonary disease, and pre-existing anxiety disorder or bipolar disorder were significantly increased in persons carrying AAT non-M polymorphisms compared to normal MM genotype (respectively, 10, 20, 21, and 33% compared to 8, 12, 11, and 9%; contingency table, pulmonary: chi(2)=37, p=0.0001; affective disorder: chi(2)=171, p=0.0001). In persons with artistic avocation (n=189) or occupation (n=57), AAT non-M polymorphisms are significantly increased (respectively, proportions of 44 and 40% compared to background rate of 9%; contingency table, avocation: chi(2)=172, p=0.0001; occupation: chi(2)=57, p=0.0007). Artistic ability and 'anxiety/bipolar spectrum' mood disorders may represent phenotypic attributes that had selective advantage during recent human evolution, an 'intensive creative energy' (ICE) behavioral phenotype. Background proportion of ICE of 7% consists of 49 of 1312 persons with AAT MM genotype (4%), and 58 of 225 persons with non-MM genotypes (26%) (contingency table, chi(2)=222, p=0.0001). Penetrance of ICE increases in genotypes with lower AAT levels: PiMS, 18%; PiMZ, 44%; PiSS and PiZZ, 100% (five cases). At all ages, persons with non-MM genotype had significantly higher proportion of thiamine deficiency (50% in PiMZ), reactive hypoglycemia (20% in PiMZ), and possibly fatty liver (thiamine: chi(2)=28, p=0.0001; hypoglycemia: chi(2)=92, p=0.0001). In older persons, PiMZ genotype had significantly increased proportion (46%) of brain MRI T2 white matter abnormalities (chi(2)=49, p=0.003). Persons with ICE and MM genotype showed increased prevalence of pulmonary disorders and same signature as S and Z carriers and homozygotes (see above). Z polymorphism was associated with delayed age of onset (average 7 years) for persons with toxic environmental or occupational exposures (log rank, p=0.0001) and more stable cognitive change in persons with neurodegenerative illness (p<0.05). At all ages, ICE phenotype and Z polymorphism were associated with altered copper homeostasis with low or absent non-ceruloplasmin bound copper (p<0.05). AAT polymorphisms which affect iron, lipid and copper metabolism may affect early events in nervous system development, function and response to environmental exposures. AAT may also be a 'switch' for copper metabolism and low 'free' copper would be theorized to provide protection for lipid oxidation and favorably affect beta-amyloid and other aggregation, but possibly alter early 'critical' period of CNS development. AAT polymorphisms may define an important and treatable subset of persons presenting with CNS disorders. This new proposed phenotype for AAT transcends classic pattern of strictly liver and lung disease, and should be considered for proper evaluation and management of patients presenting with classic AAT-related disorders, affective disorders, persons with ICE, white matter disease or multisystem disorders of memory.

PMID: 17659342 [PubMed - in process]

19: J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(8):1070-9.

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Facial emotion processing in acutely ill and euthymic patients with pediatric bipolar disorder.

Schenkel LS, Pavuluri MN, Herbener ES, Harral EM, Sweeney JA.

Department of Psychiatry, University of Illinois at Chicago, USA.

OBJECTIVE: Past investigations indicate facial emotion-processing abnormalities in pediatric bipolar disorder (PBD) subjects. However, the extent to which these deficits represent state- and trait-related factors is unclear. We investigated facial affect processing in acutely ill and clinically stabilized children with PBD and matched healthy subjects. METHOD: Subjects (N = 86) consisted of unmedicated/acutely ill (n = 29) and medicated/clinically stabilized (n = 29) PBD youths and matched healthy subjects (n = 28) who completed tasks of facial affect identification and differentiation. RESULTS: Subjects with PBD, regardless of clinical and treatment status, showed marked impairments in the ability to correctly identify emotionally intense happy and sad facial expressions, with both groups tending to misjudge extreme facial expressions as being moderate to mild in intensity. However, when differentiating subtle variations of happy or sad expressions, only unmedicated/acutely ill PBD patients performed more poorly than healthy subjects. Younger age at onset was associated with more impaired emotion processing only in the PBD sample. PBD subjects with comorbid attention-deficit/hyperactivity disorder (ADHD) performed more poorly than subjects without ADHD when processing sad facial expressions, but not happy ones. CONCLUSIONS: This study found evidence of both state-of-illness and trait-related deficits in emotion processing in PBD. Treatments are needed to better reduce this impairment and to reduce its developmental impact on interpersonal functioning.

Publication Types:

PMID: 17667485 [PubMed - indexed for MEDLINE]

20: Am J Psychiatry. 2007 Aug;164(8):1229-37.

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Erratum in:

Am J Psychiatry. 2007 Oct;164(10):1616.

The bipolar disorder phenome database: a resource for genetic studies.

Potash JB, Toolan J, Steele J, Miller EB, Pearl J, Zandi PP, Schulze TG, Kassem L, Simpson SG, Lopez V; NIMH Genetics Initiative Bipolar Disorder Consortium, MacKinnon DF, McMahon FJ.

Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21287-7419, USA. jpotash@jhmi.edu

OBJECTIVE: The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies. METHOD: Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies. Clinicians reviewed the interview items and derived variable definitions that were used to extract data from the original datasets. The combined data were subjected to range and logic assessments, and a subset was re-verified against the original data. Inconsistent data and variables that were deemed unreliable were excluded. Several of the resulting variables were characterized in the total cohort and tested for familial clustering, heritability, and statistical power in genetic linkage and association studies. RESULTS: The combined database of phenotypic variables contained 197 variables on 5,721 subjects in 1,177 families. Deoxyribonucleic acid (DNA) samples are available for 5,373 of these subjects. The clinical presentation of bipolar disorder varied markedly. Most subjects suffered from serious and often disabling illness. Many phenotypic variables are strongly familial, and some quant