Subthreshold Bipolar Disorder Research Articles

Preliminary results from the Australian Genetics of Bipolar Disorder Study: A nation-wide cohort.

The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage. A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18-90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data. Most participants were living with bipolar I disorder (n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I (p = 2.0E-26) and females (p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine. Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.

A new approach for the treatment of subthreshold bipolar disorders: Targeted high dose levothyroxine and repetitive transcranial magnetic stimulation for mitochondrial treatment.

Bipolar spectrum disorder includes Bipolar I, Bipolar II and subthreshold bipolar disorders (BD). The condition is highly prevalent, disabling and associated with high mortality. Failure of diagnosis is high. Subthreshold presentations present as 4 or more changes in polarity, are generally less responsive to standard treatment and as a result, drug combinations are often needed. High Dose Levothyroxine (HDT) has been reported to be safe and effective with this condition. Treatment response has been associated with mutations in thyroid activating enzymes and intra cerebral transporter protein carrier. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to be effective in bipolar depression and has been proved to have neuroplastic effect. Present authors had reported clinical evidence of safe and effective use of a combination treatment protocol. Potential mechanisms of action of the combined treatment protocol and the role of mitochondria function are discussed.

Genetic and environment effects on structural neuroimaging endophenotype for bipolar disorder: a novel molecular approach

We investigated gene–environment effects on structural brain endophenotype in bipolar disorder (BD) using a novel method of combining polygenic risk scores with epigenetic signatures since traditional methods of examining the family history and trauma effects have significant limitations. The study enrolled 119 subjects, including 55 BD spectrum (BDS) subjects diagnosed with BD or major depressive disorder (MDD) with subthreshold BD symptoms and 64 non-BDS subjects comprising 32 MDD subjects without BD symptoms and 32 healthy subjects. The blood samples underwent genome-wide genotyping and methylation quantification. We derived polygenic risk score (PRS) and methylation profile score (MPS) as weighted summations of risk single nucleotide polymorphisms and methylation probes, respectively, which were considered as molecular measures of genetic and environmental risks for BD. Linear regression was used to relate PRS, MPS, and their interaction to 44 brain structure measures quantified from magnetic resonance imaging (MRI) on 47 BDS subjects, and the results were compared with those based on family history and childhood trauma. After multiplicity corrections using false discovery rate (FDR), MPS was found to be negatively associated with the volume of the medial geniculate thalamus (FDR = 0.059, partial R2 = 0.208). Family history, trauma scale, and PRS were not associated with any brain measures. PRS and MPS show significant interactions on whole putamen (FDR = 0.09, partial R2 = 0.337). No significant gene–environment interactions were identified for the family history and trauma scale. PRS and MPS generally explained greater proportions of variances of the brain measures (range of partial R2 = [0.008, 0.337]) than the clinical risk factors (range = [0.004, 0.228]).

Pragmatic issues and prescribing patterns in bipolar disorder: A mental health professional's survey.

There is substantial treatment gap between the suggested guidelines and pragmatic clinical practice for psychotropic usage in bipolar disorder (BD) due to the lack of naturalistic studies and not taking into account the transcultural differences and diverse background. We intend to study this treatment gap and elucidate the preference of psychotropics and prescription patterns, critical clinical issues faced and related pragmatics in BD by conducting the mental health professionals survey. After focused discussions, Canadian Network for Mood and Anxiety Treatments guidelines being the primary anchor, a 46-item online survey questionnaire was prepared. With 25.4% response rate, 127 psychiatrists were evaluated using Survey Monkey® electronic platform on the demographics, predominant polarity; usage of antipsychotics, antidepressants, and electroconvulsive therapy, psychotropic's preference (monotherapy vs. polytherapy) in the acute and maintenance phase of BD. Majority of the participants were males (70.9%) and placed in government institute or medical colleges. Majority agreed that child and adolescent and old age bipolar probands are not routinely seen but subthreshold BD cases are frequent; did not prefer mood stabilizer in pregnancy (61.4%) and antidepressants, preferred polytherapy in acute but monotherapy in maintenance phase (after 3rd episode), seldom preferred ECT as an option (more in suicidality), agreed to a subset of BD being refractory and neuroprogressive. This study elucidates the importance of treatment preferences, prescribing patterns and pragmatic issues faced by the clinicians. These patterns if studied longitudinally in a systematic manner would help in modifying the potential treatment strategies and reduce treatment gap.

An epidemiological study of externally determined and self-identified mental and physical disability across the spectrum of bipolar disorders

Background: Studies exploring disability in bipolar disorder (BD) have primarily assessed clinical samples of full-threshold BD-I and BD-II alongside so-called objective criteria such as unemployment or receipt of government disability payments. This study extends research on disability by examining externally determined and self-identified disability in a community sample and by including subthreshold BD (BDS). Methods: Data were extracted from the USA Collaborative Psychiatric Epidemiology Surveys about individuals who met recognized criteria for BD-I, BD-II and BDS who had completed self-ratings of physical and mental disability, comorbidities, and health risk factors (e.g., obesity). Rates of disability were estimated, and logistic regression analyses were used to determine demographic and clinical variables associated with externally determined and self-identified of disability. Results: Of 408 individuals who met eligibility criteria (BD-I = 100; BD-II=104; BDS=204), 35% met criteria for externally determined disability, about 40% self-reported mental disability and about 23% self-reported physical disability. The odds were three-fold (Odds Ratio (OR): 3.05; 95% Confidence Intervals (CI): 1.69, 5.53) that someone with self-identified physical disability would meet criteria for externally determined disability, but associations with mental disability were non-significant (OR: 1.06; 95% CI: 0.63, 1.80). Regression analyses demonstrated that mental disability was associated with being a current or past smoker and physical disability was associated with BD-I. Limitations: the adequacy of the assessments of disability and definition of BDS can be questioned. Conclusions: Future clinical and community studies need to consider both externally determined and self-identified disability across the entire Bd spectrum.

Suicidal behavior is four times more frequent in university students with bipolar disorder assessed by an online version of Mood Disorder Questionnaire

Introduction: Bipolar disorder (BD) in young people is frequently associated with suicidal behavior. The main objective of this research is to evaluate if university students who have BD show more suicidal behavior than those who do not have BD. Materials and Methods: 583 university students from Fortaleza, Brazil, participated in this study. Volunteers over 18 years of age who were attending public or private universities from March to December 2019 were able to participate. A sociodemographic and clinical questionnaire and the Mood Disorder Questionnaire (MDQ) were filled out. According to MDQ, participants were classified into three groups: 1) individuals without BD (n=318); 2) individuals with subthreshold BD symptoms (n=160); 3) individuals with BD (n=105). Results: Compared to those who do not have BD, individuals with BD had four times less plans for the future (x2=16.00; p=0.000), considered four times life less worth living (x2=13.44; p=0.001), assumed two times more frequently death as welcome if it comes (x2=19.10; p=0.000), thought two times more about getting hurt (x2=75.32; p=0.000), had seven times more specific plans to die (x2=39.93; p=0.000) and had four times more suicide attempts (x2=33.50; p=0.000). Conclusions: Suicidal behavior was four times more prominent in university students with BD than in those who did not have BD.

Childhood trauma and bipolar spectrum: a population-based sample of young adults.

Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Prevalence and correlates of bipolar spectrum disorders in Singapore: Results from the 2016 Singapore Mental Health Study (SMHS 2016)

BackgroundPrevalence estimates of Bipolar Spectrum Disorders (BSD) remain scant in Southeast Asia. This study aims to investigate the prevalence of BSD, its correlates with sociodemographic factors, and the associations between the BSD subgroups and clinical severity, impairment, and disability in Singapore. MethodsThis study utilizes data gathered from the second Singapore Mental Health Study (SMHS)- a nationwide cross-sectional survey conducted between 2016 and 2018 (response rate: 69.5%). Respondents were randomly selected and administered, in a single visit, interviewer-led surveys of the World Health Organization Composite International Diagnostic Interview version 3.0 (CIDI 3.0) in their preferred language (i.e. Chinese, Malay, Tamil, or English). A total of 6126 residents completed the study. ResultsThe lifetime weighted prevalence of BSD, Bipolar I, II, and subthreshold bipolar disorder was 3.1%, 1.5%, 0.03%, and 1.6% respectively. A higher prevalence of Bipolar Disorders (BPD) was significantly associated with younger age, being divorced or separated, and being unemployed. Lifetime comorbidity of BSD with at least one other psychiatric or physical condition was 45% and 51% respectively. BSD was most comorbid with Obsessive Compulsive Disorder (psychiatric condition) and Chronic pain (physical condition). LimitationsThis study relies on self-report data which may be subject to unintended response biases leading to the under or over-reporting of results. DiscussionIn addition to the high prevalence of BPD, there is also a concerning shift and increase in the proportion of those who experience severe symptoms of mania/hypomania and depression. Subthreshold bipolar disorder is found to be clinically significant and cross-culturally valid in a multi-cultural setting.

Treatment of trichotillomania and subthreshold bipolar disorder with lithium.

Treatment of trichotillomania and subthreshold bipolar disorder with lithium.

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

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.

A Case of Simultaneous Mania and Idiopathic Normal Pressure Hydrocephalus: Etiology or Comorbidity?

Normal pressure hydrocephalus (NPH), typically associated with the triad of gait disturbance, dementia and urinary incontinence, rarely presents with symptoms of mania, depression or psychosis and psychiatric disorders may complicate the diagnosis. Few cases of NPH and psychiatric disease comorbidity have been reported so far. In most of these cases, NPH was associated with depression and psychotic symptoms. Mania symptoms were also reported in a few cases those of which were associated with a history of bipolar disorder (BPD) or subthreshold BPD symptoms. In this paper, we present a case of late-onset mania symptoms simultaneously presenting with NPH in a healthy individual without a history of psychiatric disorder.

Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response

BackgroundThis study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC). MethodsOne hundred and six young (15–30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition. ResultsSignificant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p < 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(p = 0.04). ConclusionFindings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD. Trial registrationNCT01811147.

A Pilot Study of the Effectiveness of Lithium Versus Quetiapine Immediate Release Monotherapy in Patients With Bipolar Spectrum Disorders

The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase. Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared. Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups. The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.

Is ‘subthreshold’ bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy.

Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample: focus on depressive features.

Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention. In total 287 participants aged 12-30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes. At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of 'conversion' to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania. This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.

Epidemiology of bipolar spectrum disorder: Results from the general population survey of South Korea

IntroductionPatients with subthreshold bipolar disorder (sub-BP) experience severe clinical courses and functional impairments, which are comparable to those with bipolar I and II disorders (BP-I and -II). Nevertheless, lifetime prevalence, socioeconomic correlates and diagnostic overlaps of bipolar spectrum disorder (BPS) have not yet been estimated in the general population of South Korean adults.AimsThis study aimed to estimate the lifetime prevalence, correlates and diagnostic comorbidities of BPS using a validated screening instrument in the nationwide general population of South Korea.MethodsA total of 3013 adults among the 2011 Korean Epidemiologic Catchment Area survey (KECA-2011) completed face-to-face interviews using the Korean versions of the composite international diagnostic interview 2.1 and mood disorder questionnaire (K-CIDI and K-MDQ).ResultsThe lifetime prevalence of BPS in the South Korean adults was measured to be 4.3% (95% CI 2.6–6.9). Nearly 80% of the subjects with BPS were codiagnosed with other DSM-IV nonpsychotic mental disorders: 35.4% (95% CI 24.2–48.5) for major depression and dysthymic disorder, 35.1% (95% CI 27.7–43.3) for anxiety disorders and 51.9% (95% CI 40.5–63.1) for alcohol and nicotine use disorders. Younger age (18–34 years) was the only sociodemographic predictor of BPS positivity (P = 0.014) and the diagnostic overlap patterns were different between men and women.ConclusionsPositivity for BPS was estimated to be much greater than the prevalence of DSM-IV BP in South Korea. Most of the respondents with BPS were diagnosed with other major mental disorders and this might be related with mis and/or underdiagnosis of clinically relevant Sub-BP.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Antipsychotics in chronic schizoaffective disorder: A naturalistic study

In spite of the beneficial effects of antipsychotics (AP) on the course of schizoaffective disorder (SAD) in general, there is an evidence for some negative aspects of their application. The objective of the study was to investigate the clinical manifestations and the course of resistant SAD while treated by the different AP. At present, the research includes 63 patients with SAD and duration of psychotic and/or affective symptoms more than six months. The research was naturalistic follow-up. The first group of patients (n = 18) were treated with SGA. An average duration of hospitalization was 61.2 days. After a reduction of acute psychotic condition, subthreshold psychotic and anxiety symptoms were still remaining. The total PANSS score was 71 ± 8. The second group (n = 24) was treated with a combination of FGA and SGA. An average duration of hospitalization was 53.8 days, the total PANSS score was 79 ± 6. It has been prevailed subthreshold bipolar symptoms. The third group of patients (n = 21) were treated with FGA. An average duration of hospitalization was 45.5 days; the total PANSS score was 63 ± 10. The negative symptoms and subthreshold depressions have been prevailed among the patients.To conclude, the treatment of SAD by the SGA and combination of SGA and FGA are more likely associated with persistence of subthreshold psychotic and/or bipolar disorder and the longer duration of hospitalizations. On the other hand, application of FGA in SAD is more likely associated with negative symptoms and depressions after a reduction of acute psychotic condition.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clinical Practice Guidelines for Management of Bipolar Disorder.

Bipolar disorder (BPAD) is a serious mental disorder characterized by episodes of depression, hypomania/mania and mixed episodes, with interepisodic recovery. However, many patients with BPAD continue to exhibit residual symptoms in the interepisodic period. The illness usually starts in adolescence or early adulthood and has significant negative impact on the life of the sufferer and their caregivers. Patients with BPAD encounter educational difficulties, job related problems, interpersonal difficulties, psychosocial dysfunction, disability, marital problems, multiple suicidal attempts, completed suicide and medication side effects. Additionally patients with BPAD have high rates of physical and psychiatric comorbidity. The prevalence rates of BPAD vary from country to country. A large multinational study suggests that lifetime prevalence of BPAD-I ranges from 0-1% with a mean of 0.6 (SD-0.4). The prevalence rate of BPAD-II ranges from 0 to 1.1% with a mean of 0.4 (SD-0.3). Additionally a significant proportion of patients have been shown to have subthreshold BPAD with a range of 0.1 to 2.4% with a mean of 1.4 (SD-0.8). There is no nationwide study to evaluate the prevalence rates of BPAD in India. In a country like India, patients have limited resources, poor knowledge about the disorder and treatment; have inadequate access to the health care facilities, which makes treatment of BPAD a challenge. Indian Psychiatric Society (IPS) made first attempt to formulate Clinical Practice Guidelines (CPGs) for management of BPAD in 2005. Since then, over the last one decade there have been several developments, especially in the form of emergence of new evidence for some of the pharmacological agents. Accordingly, these new guidelines attempt to update the previous guidelines published by IPS. These guidelines should be read along with the earlier version of the CPGs, published by IPS in 2005.

Lifetime prevalence, sociodemographic correlates, and diagnostic overlaps of bipolar spectrum disorder in the general population of South Korea

BackgroundPatients with subthreshold bipolar disorder (Sub-BP) experience severe clinical courses and functional impairments which are comparable to those with bipolar I and II disorders (BP-I and -II). Nevertheless, lifetime prevalence, socioeconomic correlates and diagnostic overlaps of bipolar spectrum disorder (BPS) have not yet been estimated in the general population of South Korean adults. MethodsA total of 3013 adults among the 2011 Korean Epidemiologic Catchment Area survey (KECA-2011) completed face-to-face interviews using the Korean versions of the Composite International Diagnostic Interview 2.1 and Mood Disorder Questionnaire (K-CIDI and K-MDQ). ResultsThe lifetime prevalence of BPS in the South Korean adults was measured to be 4.3% (95% CI 2.6–6.9). Nearly 80% of the subjects with BPS were co-diagnosed with other DSM-IV non-psychotic mental disorders: 35.4% (95% CI 24.2–48.5) for major depression and dysthymic disorder, 35.1% (95% CI 27.7–43.3) for anxiety disorders, and 51.9% (95% CI 40.5–63.1) for alcohol and nicotine use disorders. Younger age (18–34 years) was the only sociodemographic predictor of BPS positivity (P=0.014), and the diagnostic overlap patterns were different between men and women. LimitationsThe prevalence of BPS and other mental disorders could have been influenced by recall bias due to the retrospective nature of this study. ConclusionsPositivity for BPS was estimated to be much greater than the prevalence of DSM-IV BP in South Korea. Most of the respondents with BPS were diagnosed with other major mental disorders and this might be related with mis- and/or under-diagnosis of clinically relevant Sub-BP.

Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder

Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-β1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression.