Exploring the genetics of lithium response in bipolar disorders
Marisol Herrera-RiveroMazda AdliKazufumi AkiyamaNirmala AkulaAzmeraw T. AmareRaffaella ArdauBárbara AriasJean‐Michel AubryLena BacklundFrank BellivierAntonio BenabarreSusanne BengesserAbesh Kumar BhattacharjeeJoanna M. BiernackaArmin BirnerMicah CearnsPablo CervantesHsi‐Chung ChenCaterina ChillottiSven CichonScott ClarkFrancesc ColomCristiana CruceanuPiotr M. CzerskiNina DalknerFranziska DegenhardtMaria Del ZompoJ. Raymond DePauloBruno ÉtainPeter FalkaiEwa Ferensztajn‐RochowiakAndreas J. ForstnerJosef FrankLouise FrisénMark A. FryeJanice M. FullertonCarla GalloSébastien GardJulie GarnhamFernando S. GoesMaria Grigoroiu‐SerbânescuPaul GrofRyota HashimotoRoland HaslerJoanna HauserUrs HeilbronnerStefan HermsPer HoffmannLiping HouYi‐Hsiang HsuStéphane JamainEsther JiménezJean‐Pierre KahnLayla KassemTadafumi KatoJohn R. KelsoeSarah Kittel‐SchneiderPo‐Hsiu KuoIchiro KusumiBarbara KönigGonzalo LajeMikael LandénCatharina LavebrattMarion LeboyerSusan G. LeckbandMario MajMirko ManchiaCynthia Marie‐ClaireLina MartinssonMichael J. McCarthySusan L. McElroyVincent MillischerMarina MitjansFrancis M. MondimorePalmiero MonteleoneCaroline M. NievergeltTomáš NovákMarkus M. NöthenClaire O’DonovanNorio OzakiSergi PapiolAndrea PfennigClaudia PisanuJames B. PotashAndreas ReifEva Z. ReininghausHélène Richard-LepourielGloria RobertsGuy A. RouleauJanusz RybakowskiMartin SchallingPeter R. SchofieldKlaus Oliver SchubertEva C. SchulteBarbara SchweizerGiovanni SeverinoTatyana ShekhtmanPaul D. ShillingKatzutaka ShimodaChristian SimhandlClaire SlaneyAlessio SquassinaThomas StammPavla StopkováFabian StreitFasil Tekola‐AyeleAnbupalam ThalamuthuAlfonso TortorellaGustavo TureckiJulia VeehEduard VietaBiju ViswanathStephanie H. WittPeter P. ZandiMartin AldaMichael BauerFrancis J. McMahonPhilip B. MitchellMarcella RietschelThomas G. SchulzeBernhard T. Baune
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Abstract Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.Keywords:
Depression
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Hypomania
Bipolar II disorder
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A specific family history or genetic background may be used to distinguish valid subgroups in patients who show similar symptoms. Also, a familial background may predict differences in other characteristics, i.e. course of illness, response to treatment or biological characteristics. Two hundred and fifty-one bipolar patients were separated according to their family history, 20 with a family history of mania with or without depression, 86 with a family history of depression only, and 145 with a family history of neither mania nor depression. The group that had a family history of mania was notable in that it showed more episodes of affective illness and was more likely to be readmitted to hospital. This difference in course suggests a familial association with multiple episodes and mania. In other respects than in course of illness, the groups separated by family history were similar.
Depression
Bipolar illness
History of depression
Psychiatric history
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Objective: A recent study reported an 8% increase in bipolar diagnoses in public and community mental health services in New South Wales from 2003 to 2014, an increase interpreted by the authors as reflecting increasing diagnostic boundaries of bipolar disorder, and bipolar II in particular. If valid, we would expect an increase in hospital admissions for hypomania as well as for mania and so analysed a relevant dataset to test that hypothesis. Methods: Data were examined for 27,255 individuals hospitalised in NSW psychiatric hospitals over a 14-year period (2000–2014) for ICD-10 diagnosed mania or hypomania and with analyses examining rates of hospitalisation/per year for both mania and for hypomania. Results: While overall admissions for mania and hypomania increased over the study period by 16.4%, admissions for mania increased by 31.0% and admissions for hypomania actually decreased by 32.1%. Conclusion: The increased rate in admissions of those with a bipolar disorder appears to reflect a trend over more than four decades. The hypothesis that any increase in the diagnostic boundaries of bipolar II disorder would be associated with an increase in hospitalisation rates was rejected, with the converse trend being identified.
Hypomania
Bipolar II disorder
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Bipolar disorder (BD) is a mood disorder where moods can fluctuate from depression to elevated moods referred to as mania. BD is currently divided into three types. All three types involve clear changes in mood, energy, and activity levels. BD-I is the most severe disorder and symptoms of mania can be so severe that they can require psychiatric hospitalization. BD-II has the same symptoms as BD-I; however, it was described as hypomania because they are less severe than in pure mania. Cyclothymia, also known as a cyclothymic disorder, is a minor mood disorder characterized by fluctuating low-level depressive symptoms and periods of mild mania, similar to BD-II. Mood stabilizers and second-generation antipsychotics are first-line for treating and maintaining a stable mood. This study related to a case report on slurred speech and tremors induced by antipsychotics in a patient suffering from BD.
Hypomania
Depression
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Objectives: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. Methods: Clinician‐adjusted self‐ratings of mood were completed daily for one year for naturalistically treated outpatients with bipolar I (n = 405) or bipolar II (n = 102) disorder. Ratings were analyzed for mean time spent euthymic, depressed, manic, hypomanic, and cycling, and the percentages of time spent ill were compared between the two groups. Results: Percentages of time spent ill for bipolar I versus II patients were: euthymia 47.7% versus 50.2%; depression 36.0% versus 37.0%; hypomania 11.5% versus 9.8%; mania 1.0% versus 0.2%; and cycling 3.7% versus 2.8%. The depression/mania ratio was 2.9 in the bipolar I and 3.8 in bipolar II sub‐groups. Conclusions: Depression represents the predominant abnormal mood state for treated outpatients with bipolar I and II disorder. In contrast to other studies, we found that depression/mania ratios were of a similar magnitude, suggesting the same tendency towards mood instability in both sub‐groups.
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Depression
Bipolar II disorder
Mood stabilizer
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Episode duration, recurrence rates, and time spent in manic and depressive phases of bipolar disorder (BD) is not well defined for subtypes of the disorder.We reviewed the course, timing, and duration of episodes of mania and depression among 1130 clinically treated DSM-IV-TR BD patients of various types, and compared duration and rates as well as total proportion of time in depressive versus manic episodes during 16.7 average years at risk.As expected, episodes of depressions were much longer than manias, but episode-duration did not differ among BD diagnostic types: I, II, with mainly mixed-episodes (BD-Mx), or with psychotic features (BD-P). Recurrence rates (episodes/year) and proportion of time in depression and their ratios to mania were highest in BD-II and BD-Mx subjects, with more manias/year in psychotic and BD-I subjects. In most BD-subtypes, except with psychotic features, there was more time in depressive than manic morbidity, owing mainly to longer depressive than manic episodes. The proportion of time in depression was highest among those who followed a predominant DMI course, whereas total time in mania was greatest in BD with psychotic features and BD-I. and with an MDI course.Subtypes of BD patients differed little in episode-duration, which was consistently much longer for depression. The findings underscore the limited control of bipolar depression with available treatments.
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Bipolar I disorder
Polarity (international relations)
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The substance use is common among people with a diagnosis of bipolar disorder. In addition, alcoholism and bipolar disorder coexist with a high frequency. This association is higher in men than in women, and this consumption is thefactor that most strongly influences the hospitalization. To analyze the clinical, epidemiological, diagnostic approach and evolution of bipolar disorder andalcoholism. Review of thesubject on recent articles of alcoholism in bipolar disorder. The stages of mania associated with alcohol consumption up to 40% of casesand are more common at this stage that in depressive. This association isgreater than that which occurs between alcoholism and schizophrenia ordepression. Patients with bipolar disorder who have mixed and irritative statesand those with rapid cycling have a prevalence of alcohol consumption and sustanceuse higher than those who do not use substances. It has also been observed thatthe consumption of alcohol, and substance use can change the symptoms of maniaand turn them into a mixed state symptoms. It also states that rapid cycles canbe precipitated by increased alcohol consumption during rotation from mania todepression. The associationof bipolar disorder with addictive behaviors is a factor that worsens theprognosis and comorbid alcohol itself is associated with a poor prognosis. Close monitoring of bipolar patients and especially in those who consumealcohol is very important.
Dual diagnosis
Bipolar I disorder
Alcohol Dependence
Alcohol use disorder
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Introduction The substance use is common among people with a diagnosis of bipolar disorder. In addition, alcoholism and bipolar disorder coexist with a high frequency. This association is higher in men than in women, and this consumption is the factor that most strongly influences the hospitalization. Objectives To analyze the clinical, epidemiological, diagnostic approach and evolution of bipolar disorder and alcoholism. Methods Review of the subject on recent articles of alcoholism in bipolar disorder. Results The stages of mania associated with alcohol consumption up to 40% of cases and are more common at this stage that in depressive. This association is greater than that which occurs between alcoholism and schizophrenia or depression. Patients with bipolar disorder who have mixed and irritative states and those with rapid cycling have a prevalence of alcohol consumption and substance use higher than those who do not use substances. It has also been observed that the consumption of alcohol and substance use can change the symptoms of mania and turn them into a mixed state symptoms. It also states that rapid cycles can be precipitated by increased alcohol consumption during rotation from mania to depression. Conclusions The association of bipolar disorder with addictive behaviors is a factor that worsens the prognosis and comorbid alcohol itself is associated with a poor prognosis. Close monitoring of bipolar patients and especially in those who consume alcohol is very important. Disclosure of interest The authors have not supplied their declaration of competing interest.
Dual diagnosis
Bipolar I disorder
Alcohol Dependence
Depression
Alcohol use disorder
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Abstract Objective: Unipolar mania is not included in the diagnostic and statistical manual of mental disorders-5 (DSM-5) as a separate diagnosis, although it is defined by widely accepted diagnostic criteria. The aim of this study was to investigate the differences between unipolar mania and bipolar disorder in terms of clinical and inflammatory parameters. Methods: The data of 495 hospitalised patients with bipolar disorder diagnoses were analysed retrospectively. Forty met the diagnostic criteria for unipolar mania. Two patients refused to participate in the study. Thirty-eight unipolar mania patients and 42 randomly selected patients with bipolar disorder diagnosis were included in the study. The two groups were compared in terms of sociodemographic, clinical characteristics, serum brain-derived neurotrophic factor, C-reactive protein (CRP), leucocyte and cytokine levels. Results: A total of 40 (8.08%) of 495 patients diagnosed with bipolar disorder met the unipolar mania diagnostic criteria. The number of manic episodes and the number of hospitalisations were statistically higher in the unipolar mania group than in the bipolar disorder group. Among all the manic symptoms, the incidence of symptoms such as euphoria, increased sexual interest, grandiosity and delusions were found to be statistically higher in the unipolar mania group. Interleukin (IL)-6 and CRP levels were significantly higher in the unipolar mania group than in the bipolar disorder group. Conclusion: Unipolar mania differs from bipolar disorder in terms of clinical features and serum IL-6 and CRP levels.
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Bipolar I disorder
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