HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

AbstractSchizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.

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Deficits in explicit emotion regulation in bipolar disorder: a systematic review

International Journal of Bipolar Disorders ◽

10.1186/s40345-021-00221-9 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Marcel Kurtz ◽

Pia Mohring ◽

Katharina Förster ◽

Michael Bauer ◽

Philipp Kanske

Keyword(s):

At Risk ◽

Bipolar Disorder ◽

Emotion Regulation ◽

Mood State ◽

Bipolar Disorders ◽

Protective Measure ◽

Behavioral Measures ◽

Increased Risk ◽

Regulation Strategies ◽

Depressive Episodes

Abstract Background This study aimed to compile and synthesize studies investigating explicit emotion regulation in patients with bipolar disorder and individuals at risk of developing bipolar disorder. The importance of explicit emotion regulation arises from its potential role as a marker for bipolar disorders in individuals at risk and its potent role in therapy for bipolar disorder patients. Methods To obtain an exhaustive compilation of studies dealing specifically with explicit emotion regulation in bipolar disorder, we conducted a systematic literature search in four databases. In the 15 studies we included in our review, the emotion-regulation strategies maintenance, distraction, and reappraisal (self-focused and situation-focused) were investigated partly on a purely behavioral level and partly in conjunction with neural measures. The samples used in the identified studies included individuals at increased risk of bipolar disorder, patients with current affective episodes, and patients with euthymic mood state. Results In summary, the reviewed studies' results indicate impairments in explicit emotion regulation in individuals at risk for bipolar disorder, patients with manic and depressive episodes, and euthymic patients. These deficits manifest in subjective behavioral measures as well as in neural aberrations. Further, our review reveals a discrepancy between behavioral and neural findings regarding explicit emotion regulation in individuals at risk for bipolar disorders and euthymic patients. While these groups often do not differ significantly in behavioral measures from healthy and low-risk individuals, neural differences are mainly found in frontostriatal networks. Conclusion We conclude that these neural aberrations are a potentially sensitive measure of the probability of occurrence and recurrence of symptoms of bipolar disorders and that strengthening this frontostriatal route is a potentially protective measure for individuals at risk and patients who have bipolar disorders.

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Bipolar Disorders: Antipsychotic Drug Therapy of Aripiprazole an Open Label Study

Neuroscience and Neurological Surgery ◽

10.31579/2578-8868/036 ◽

2018 ◽

Vol 3 (1) ◽

pp. 01-02

Author(s):

Amycus Alecto

Keyword(s):

Bipolar Disorder ◽

Early Adulthood ◽

Indirect Costs ◽

Bipolar Disorders ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Direct And Indirect Costs ◽

The Us ◽

Depressive Episodes

Patients with bipolar disorder are exceptionally challenging to manage because of the dynamic, chronic, and fluctuating nature of their disease. Typically, the symptoms of bipolar disorder first appear in adolescence or early adulthood, and are repeated over the patient's lifetime, expressed as unpredictable recurrences of hypomanic/manic or depressive episodes. The lifetime prevalence of bipolar disorder in adults is reported to be approximately 4%, and its management was estimated to cost the US healthcare system in 2009 $150 billion in combined direct and indirect costs.

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A systematic review on neuropsychological function in bipolar disorders type I and II and subthreshold bipolar disorders—something to think about

CNS Spectrums ◽

10.1017/s1092852918001463 ◽

2019 ◽

Vol 24 (1) ◽

pp. 127-143 ◽

Cited By ~ 3

Author(s):

Sinead King ◽

James M Stone ◽

Anthony Cleare ◽

Allan H Young

Keyword(s):

Bipolar Disorder ◽

Bipolar Disorders ◽

Cochrane Library ◽

Type I ◽

Neuropsychological Dysfunction ◽

Visual Spatial ◽

Significant Difference ◽

Major Depressive Episodes ◽

Depressive Episodes ◽

Disorder Type

Neuropsychological dysfunction is a well-established finding in individuals with bipolar disorder type I (BP-I), even during euthymic periods; however, it is less clear whether this also pertains to bipolar disorder type II (BP-II) or those with subthreshold states (SBP; subthreshold bipolar disorder), such as bipolar not otherwise specified (BP-NOS). Herein, we compare the literature regarding neuropsychological performance in BP-II vs BP-I to determine the extent of relative impairment, and we present and review all related studies on cognition in SBP. After systematically searching PubMed, Medline, PsycINFO, and The Cochrane Library, we found 17 papers that comprise all the published studies relevant for this review. The areas that are consistently found to be impaired in BP are executive function, verbal memory, visual spatial working memory, and attention. More studies than not show no significant difference between BP-I and BP-II, particularly in euthymic samples. Preliminary evidence suggests that patients experiencing major depressive episodes who also meet criteria for SBP show similar profiles to BP-II; however, these results pertain only to a depressed sample. SBP were found to perform significantly better than both MDD and healthy controls in a euthymic sample. A consensus on mood state, patient selection, and neuropsychological testing needs to be agreed on for future research. Furthermore, no studies have used the most recent DSM-5 criteria for SBP; future studies should address this. Finally, the underlying bases of cognitive dysfunction in these diagnostic groups need to be further investigated. We suggest recommendations on all of the above current research challenges.

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Evidence that bipolar disorder is the poor outcome fraction of a common developmental phenotype: an 8-year cohort study in young people

Psychological Medicine ◽

10.1017/s0033291709006138 ◽

2009 ◽

Vol 40 (2) ◽

pp. 289-299 ◽

Cited By ~ 43

Author(s):

M. J. A. Tijssen ◽

J. van Os ◽

H.-U. Wittchen ◽

R. Lieb ◽

K. Beesdo ◽

...

Keyword(s):

Mental Health ◽

Health Care ◽

Bipolar Disorder ◽

Mental Health Care ◽

Health Care Use ◽

Symptom Scale ◽

Childhood Disorders ◽

Manic Symptoms ◽

Dsm Iv ◽

Depressive Episodes

BackgroundReported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts.MethodIn 1395 adolescents aged 14–17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms (‘mania symptom scale’) were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI).ResultsIncidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/105 person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050–0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex.ConclusionsThis study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for care.

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Comorbidity Between ADHD and Symptoms of Bipolar Disorder in a Community Sample of Children and Adolescents

Twin Research and Human Genetics ◽

10.1375/twin.8.5.459 ◽

2005 ◽

Vol 8 (5) ◽

pp. 459-466 ◽

Cited By ~ 24

Author(s):

Wendy Reich ◽

Rosalind J. Neuman ◽

Heather E. Volk ◽

Cynthia A. Joyner ◽

Richard D. Todd

Keyword(s):

Bipolar Disorder ◽

Children And Adolescents ◽

Latent Class ◽

Community Sample ◽

Control Sample ◽

Bipolar Disorders ◽

Adhd Subtypes ◽

Population Prevalence ◽

Increased Risk ◽

Dsm Iv

AbstractThe prevalence and frequency of comorbidity of possible bipolar disorder was examined with attention-deficit hyperactivity disorder (ADHD) in a nonreferred population of twins. Children and adolescents aged 7 to 18 years with a history of manic symptoms were identified from a population-based twin sample obtained from state birth records (n = 1610). The sample was enriched for ADHD; however, there was also a random control sample (n = 466), which allowed a look at the population prevalence of the disorder. Juveniles with threshold or below threshold manic episodes were further assessed for comorbidity with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and population-defined ADHD subtypes (from latent class analysis) using Fisher's exact test. Nine juveniles who exhibited DSM-IV manic (n = 1), hypomanic (n = 2) or below threshold episodes (n = 6) were identified. The population prevalence of broadly defined mania in the random sample was 0.2%. The possible manic episodes showed significant comorbidity with population-defined severe combined and talkative ADHD subtypes. It can be concluded that there is a significant association of bipolar symptoms with two population-defined subtypes of ADHD. Episodes of possible bipolar disorders as defined by DSM-IV are uncommon in this nonreferred sample. Children and adolescents with ADHD appear to be only modestly at increased risk for bipolar disorders.

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Regional lithium prescription rates and recurrence in bipolar disorder

International Journal of Bipolar Disorders ◽

10.1186/s40345-021-00223-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Martin Sköld ◽

Sindre Rolstad ◽

Erik Joas ◽

Mathias Kardell ◽

Erik Pålsson ◽

...

Keyword(s):

Bipolar Disorder ◽

Bipolar Disorders ◽

Population Level ◽

Bipolar I Disorder ◽

Not Otherwise Specified ◽

Number Of Patients ◽

Bipolar Ii ◽

National Quality ◽

Prescription Rates ◽

Depressive Episodes

Abstract Background Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes. Aims To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden. Method Data from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately. Results Lithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately. Conclusions The advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

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DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder

International Journal of Molecular Sciences ◽

10.3390/ijms19103026 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3026 ◽

Cited By ~ 14

Author(s):

Charanraj Goud Alladi ◽

Bruno Etain ◽

Frank Bellivier ◽

Cynthia Marie-Claire

Keyword(s):

Dna Methylation ◽

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Treatment Response ◽

Bipolar Disorders ◽

Mental Illnesses ◽

Mood Stabilizers ◽

Major Depressive ◽

Meta Analyses

So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.

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Bipolar Disorders: Antipsychotic Drug Therapy of Aripiprazole an Open Label Study

Neuroscience and Neurological Surgery ◽

10.31579/2578-8868/156 ◽

2018 ◽

Vol 3 (1) ◽

pp. 01-02

Author(s):

Amycus Alecto

Keyword(s):

Bipolar Disorder ◽

Early Adulthood ◽

Indirect Costs ◽

Bipolar Disorders ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Direct And Indirect Costs ◽

The Us ◽

Depressive Episodes

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Depression and Bipolar Disorder: Is Prevention of Mania Possible? Critical Issues on Diagnostic Criteria

European Psychiatry ◽

10.1016/s0924-9338(09)70482-1 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

S. Gorini Amedei ◽

M. Catena ◽

F. Lejeune ◽

S. Duma ◽

M.A. Scarpato ◽

...

Keyword(s):

Bipolar Disorder ◽

Diagnostic Criteria ◽

Antidepressant Drugs ◽

Epidemiological Survey ◽

Careful Examination ◽

Negative Consequences ◽

Manic Depressive ◽

Critical Issues ◽

Dsm Iv ◽

Depressive Episodes

Diagnostic criteria for bipolar disorder in DSM IV require the occurrence of a manic or hypomanic episode. The scant appropriateness of these criteria compared with Kraepelin"s concept of manic depressive insanity has been repeatedly reported and the concept of bipolar spectrum has been proposed for more than 30 years. The negative consequences of pure adherence to operational diagnostic criteria on clinical needs are presented in terms of community epidemiology results and in terms of clinical evidences and the inadequate treatment of depressive and anxiety episodes and the risk of manic switch with antidepressant drugs are discussed.The epidemiological survey conducted in Sesto Fiorentino showed that depressive episodes in patients with subthreshold mania or hypomania were different from the clinical presentation of pure unipolar depressives episodes confirming not only the numeric impact but also qualitative differences between these groups of patients.Our clinical study where predictors of mania have been prospectively evaluated in a trans nosographic sample of outpatients demonstrated that aspects related to bipolarity predicted manic shift regardless of the diagnosis. DSM IV criteria seem not to be able to detect and describe a group of patients relevant both on epidemiological and on clinical level. These findings underline the need of a careful examination of patients treatment and validate the rule of further research in definition of mood disorders boundaries for prevention strategies.

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Bipolar disorder and personality disorder

European Psychiatry ◽

10.1016/s0924-9338(03)80010-x ◽

2003 ◽

Vol 18 (S1) ◽

pp. 9s-12s ◽

Cited By ~ 7

Author(s):

Charles Bowden ◽

Wolfgang Maier

Keyword(s):

Bipolar Disorder ◽

Depressive Symptoms ◽

Personality Disorder ◽

Mental Disorders ◽

Personality Disorders ◽

Bipolar Disorders ◽

Wide Range ◽

Patients Experience ◽

Depressive Episodes

Patients with bipolar disorders experience cyclical changes in mood that present as a range of different syndromes. In classical mania, patients experience episodes of euphoria, whereas in depressive episodes they suffer from depression. In hypomania, patients experience a milder form of mania, and in mixed mania, patients may experience both manic and depressive symptoms simultaneously, or alternate between them rapidly. Because of this wide range of symptoms, bipolar disorders can appear to overlap with other mental disorders, especially personality disorders.

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