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Research increasingly implicates glutamatergic dysfunction in the pathophysiologies of psychotic disorders. Auditory mismatch negativity (MMN) is an electroencephalography (EEG) waveform linked to glutamatergic neurotransmission and is consistently attenuated in schizophrenia (SCZ). MMN consists of two subcomponents, the repetition positivity (RP) and deviant negativity (DN) possibly reflecting different neural mechanisms. However, whether MMN reduction is present across different psychotic disorders, linked to distinct symptom clusters, or related to sex remain to be clarified. Four hundred participants including healthy controls (HCs; n = 296) and individuals with SCZ (n = 39), bipolar disorder (BD) BD typeI (n = 35), or BD type II (n = 30) underwent a roving MMN paradigm and clinical evaluation. MMN, RP and DN as well their memory traces were recorded at the FCZ electrode. Analyses of variance and linear regression models were used both transdiagnostically and within clinical groups. MMN was reduced in SCZ compared to BD (p = 0.006, d = 0.55) and to HCs (p < 0.001, d = 0.63). There was a significant group × sex interaction (p < 0.003) and the MMN impairment was only detected in males with SCZ. MMN amplitude correlated positively with Positive and Negative Syndrome Scale total score and negatively with Global Assessment of Functioning Scale score. The deviant negativity was impaired in males with SCZ. No group differences in memory trace indices of the MMN, DN, or RP. MMN was attenuated in SCZ and correlated with greater severity of psychotic symptoms and lower level of functioning. Our results may indicate sex-dependent differences of glutamatergic function in SCZ. [ABSTRACT FROM AUTHOR]

Abstract Background The distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders. Methods 808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types. Results Bipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later “bipolar” presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response. Conclusions Differences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder.

Background: The distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders. Methods: 808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types. Results: Bipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later "bipolar" presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response. Conclusions: Differences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder. [ABSTRACT FROM AUTHOR]

Objective: Compare patients diagnosed as DSM-5 type II bipolar disorder (BD2) vs. major depressive disorder (MDD).Methods: We compared characteristics of 3246 closely and repeatedly evaluated, consenting, adult patient-subjects (n = 706 BD2, 2540 MDD) at a specialty clinic using bivariate methods and multivariable modeling.Results: Factors more associated with BD2 than MDD included: [a] descriptors (more familial psychiatric, mood and bipolar disorders and suicide; younger at onset, diagnosis and first-treatment; more education; more unemployment; fewer marriages and children; higher cyclothymic, hyperthymic and irritable temperament ratings, lower anxious); [b] morbidity (more hypomanic, mixed or panic first episodes; more co-occurring general medical diagnoses, more Cluster B personality disorder diagnoses and ADHD; more alcohol and drug abuse and smoking; shorter depressive episodes and interepisode periods; lower intake ratings of depression and anxiety, higher for hypomania; far more mood-switching with antidepressants; lower %-time depressed; DMI > MDI course-pattern in BD2; more suicide attempts and violent suicidal behavior); [c] item-scores with intake HDRS21 higher for suicidality, paranoia, anhedonia, guilt, and circadian variation; lower somatic anxiety, depressed mood, insight, hypochondriasis, agitation, and insomnia; and [d] treatment (more lithium, mood-stabilizing anticonvulsants and antipsychotics, less antidepressants and benzodiazepines).Conclusions: BD2 and MDD subjects differed greatly in many descriptive, psychopathological and treatment measures, notably including more familial risk, earlier onset, more frequent recurrences and greater suicidal risk with BD2. Such differences can contribute to improving differentiation of the disorders and planning for their treatment. [ABSTRACT FROM AUTHOR]

In this open-label naturalistic study, we assess the feasibility, tolerability, and effectiveness of a repetitive transcranial magnetic stimulation protocol with a reduced total pulse number for treating patients suffering from bipolar disorder type II. All patients received one rTMS treatment session of 1000 pulses for 20 consecutive working days, accumulating to 20.000 rTMS pulses applied over 4 weeks. We measured the patients' symptoms before the start, halfway through, directly after, and one month after treatment. We quantified the depression symptoms using both the Beck depression inventory scale and the symptom checklist-90 depression subscale. Patients showed a significant reduction in depression symptoms directly after treatment and an even further reduction one month after treatment. The remission rates were at 26% halfway through treatment (after the 10th session), 61% directly after treatment (after the 20th session), and increased to 78% at the 1-month follow-up. Importantly, the protocol proved to be feasible and highly tolerable in this patient population, with no adverse effects being reported. Considering these positive results, further research should focus on replicating these findings in larger clinical samples with control groups and longer follow-up periods, while potentially adding maintenance sessions to optimize the treatment effect and stability for bipolar disorder type II patients. [ABSTRACT FROM AUTHOR]

• Bipolar disorder subtypes share pathophysiologic pathways on candidate-gene studies. • Subtype II has specific contributions of gene interactions and low-effect alleles. • In genome studies, subtypes contrasted in their relation to depression and psychosis. • Polygenic risk scores were able to differentiate bipolar disorder type II. • Research suggests transdiagnostic genetic backgrounds across the bipolar spectrum. The identification of bipolar disorder (BD) type II patients has both treatment and prognostic implications. Better understanding of its underlying genetics may yield useful diagnostic tools. A systematic review on BDII genetics was done using articles published in 2009–2019, following PRISMA recommendations. The most studied polymorphism was BDNF Val66Met with several gene-gene interactions within the dopaminergic system. Associations were reported within the monoaminergic systems (DRD3, ADH1B and SLC6A4) , calcium (CACNB2 and CACNG2) and cAMP (PDE1DA , PDE4B and DISC1) signal transduction pathways and the immune system (TNFα , IFNδ and IL-10). Chromosomes 2, 3 and 10 were associated with BDII and polygenic risk scores distinguished between BD subtypes and with major depressive disorder. Research on BDII stems from BDI findings, however with a stronger contribution of gene-gene interactions and low-effect alleles on known neuroplasticity and monoaminergic system genes. Genome studies point to transdiagnostic backgrounds, with wider associations across bipolar spectrum disorders. Findings able to accurately differentiate BDII remain elusive, dependent on better phenotypic characterization and new research methods. [ABSTRACT FROM AUTHOR]

Background: Two current theories regarding the neuroscientific bases of mood disorders involve alterations in glutamatergic neurotransmission and excessive activation of inflammatory pathways. We hypothesized that glutamate (Glu) levels and peripheral inflammatory markers would be associated with cognitive function, in patients with Bipolar Disorder Type II (BP-II), and that such factors would be associated with psychological treatment outcomes. Aims: The primary aim of this study was to explore the relationship between the neurotransmitter Glu, cytokines (CRP, IL_6, and TNFa) and neuropsychological and related functioning. The secondary aim was to assess cognitive functioning as a predictor of poor response to psychological therapy. Methods: Proton magnetic resonance spectroscopy data were acquired from the anterior cingulate cortex (ACC) of 15 participants with BP-II, and 13 healthy controls in a 3T magnetic resonance imaging scanner. The Digit Symbol Task (DST) for processing speed, TMT-B for executive function and Rey Auditory Verbal Learning Test (RAVLT) were administered to assess cognitive domains. Results: There was no significant difference in anterior cingulate Glu, or inflammatory markers between groups. Furthermore, we found no significant difference between groups in any cognitive tests. Scores on the DST were found to be significantly associated with poor response to psychological therapy. Conclusions: This study may highlight an association between neuropsychological dysfunction and treatment outcome in euthymic patients with BP-II. We did not find any association between peripheral inflammatory markers and brain Glu levels. This may have been in part due to the small sample size. [ABSTRACT FROM AUTHOR]

Affective instability is a psychophysiological symptom observed in some psychopathologies. It is a complex construct that encompasses (1) primary emotions, or affects, and secondary emotions, with each category having its own characteristics, amplitude, and duration, (2) rapid shifting from neutral or valenced affect to intense affect, and (3) dysfunctional modulation of emotions. Affective instability is often confused with mood lability, as in bipolar disorders, as well as with other terms. To clarify the concept, we searched databases for the term affective instability and read related articles on the topic. In this article we situate the term within the current affective nomenclature and human emotional experience, explore its psychophysiological features, and place it within the context of psychopathology. We explain why the term can potentially be confused with mood pathology and then define affective instability as an inherited temperamental trait modulated by developmental experience. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Bipolar Disorder I (BD I) and Bipolar Disorder II (BD II) vary considerably, with differences in symptomatology, management and prognosis. For patients with depression, the distinction between BD I and BD II is not always apparent, and hinges on the differentiation between manic/mixed and hypomanic episodes. Other putative differences between patients with BD I and II exist and may assist in distinguishing between these two conditions. Methods: Data were obtained from the National Epidemiological Survey on Alcohol and Related Conditions. A total of 1429 subjects were included in our analysis based on DSM-IV criteria, 935 with BD I and 494 with BD II. We examined for differences in a number of variables including demographics, clinical features, depressive symptoms, and co-morbid conditions using t-tests and chi-square analyses for a comparison of means as well as a logistic regression for variables found to be significant. Results: Key differences between BD I and BD II were identified in all categories in our comparison of means. In the regression analysis, a number of variables were determined to be predictors of BD I, including unemployment (OR=0.6), taking medications for depression (OR=1.7), a history of a suicide attempt (OR=1.8), depressive symptoms such as weight gain (OR=1.7), fidgeting (OR=1.5), feelings of worthlessness (OR=1.6) and difficulties with responsibilities (OR=2.2), as well as the presence of specific phobias (OR=1.8) and Cluster C traits (OR=1.4). Conclusions: Our results indicate that in addition to the differences between manic/mixed and hypomanic episodes, other significant differences exist that may be used to help differentiate BD I from BD II. [Copyright &y& Elsevier]

Abstract: High rates of anxiety disorders have been reported in bipolar disorders. The study aimed to investigate prevalence of anxiety disorders in remitted bipolar subjects and their influence on the illness severity. Bipolar subjects with anxiety disorders were younger, had earlier age at onset of illness, and were overrepresented by female subjects and those with earlier onset illness compared to those without anxiety disorder. The study demonstrated that (1) anxiety disorders are highly prevalent in bipolar subjects, (2) individual anxiety disorders, particularly SP and PD seem to have an effect on illness severity, (3) bipolar subjects with comorbid anxiety tend to have a poorer course and are less responsive to treatment, and (4) anxiety tends to be associated with an earlier age at onset of bipolar disorder (BPD) and results in a more complicated and severe disease course. [Copyright &y& Elsevier]