BACKGROUND: Current treatment options for the management of depressive episodes in bipolar disorder are often sub-optimal, with some treatments either noted to be only partially effective or to require long durations of treatment prior to a therapeutic response. Therefore, pharmaco-therapeutic options that reduce depressive symptoms in a more rapid manner might provide a viable therapeutic option for some people. Intravenous (IV) scopolamine, a pan muscarinic antagonist, has been demonstrated in a number of studies to confer a rapid antidepressant effect, albeit no study to date has exclusively evaluated its potential therapeutic effect in a cohort consisting solely of individuals with bipolar disorder.
METHODS: Individuals with bipolar disorder who are currently experiencing a depressive episode of at least moderate severity will be included in this study. Eligible participants will undergo a screening and placebo-run in visit and will be randomised at visit 3 to the treatment or placebo group. Participants will receive the three blinded infusions over the course of 2 weeks, with two subsequent follow-up visits, 1 and 3 weeks after the last infusion visit. The total duration of the study will be approximately 6 weeks. Patients will continue their regular treatment regime in addition to study medication. Objective and subjective mood questionnaires, cognitive assessments and other psychometric instruments will be administered and recorded.
CONCLUSIONS: To our knowledge, this is the first study to investigate the antidepressant effects of IV scopolamine in an exclusively bipolar disorder cohort. Trial findings will contribute to the evidence base regarding the cholinergic hypothesis of mood disorders and specifically might result in an additional safe therapeutic option for the management of depressive episodes in bipolar disorder.
BACKGROUND: ClinicalTrials.gov NCT04211961 . December 26, 2019. EudraCT Number 2017-003112-39.

Magnetic seizure therapy (MST) is a new convulsive therapy that is as effective as traditional electroconvulsive therapy (ECT) in treating depression but with fewer cognitive side effects. The aim of this study was to compare the efficacy and cognitive effects between MST (100 Hz applied over the vertex) and bifrontal ECT for treating patients with depressive episodes.
Forty-five patients with depressive episodes were enrolled, with 18 receiving MST and 27 receiving ECT. MST was administered over the vertex with 100 Hz frequency. Treatment consisted of six sessions. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was used to assess the severity of depression. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognition. Assessments were performed at baseline and after the third and sixth treatment sessions.
Both MST and ECT improved the patients\' depressive symptoms significantly, yet no significant difference was found between the two groups (p > .05). The response rates and remission rates of MST and ECT were 72.2% versus 81.5% and 61.1% versus 63.0%, respectively. The MST group showed significant improvements in immediate memory (p < .001), delayed memory (p = .002), and attention (p < .001) than ECT. The recovery times for consciousness (p < .001), spontaneous breathing (p < .001), and orientation (p < .001) were shorter in MST group than ECT group. RBANS improvements were negatively correlated with the recovery time for orientation (r = .561, p < .001).
Magnetic seizure therapy showed similar efficacy to bifrontal ECT for treating depressive episodes. While MST may be an effective alternative to ECT, larger randomized trials are needed.

Affective disorders are associated with increased risk of dementia, yet most studies focus on the association of major depressive disorder or depressive episodes of bipolar disorder with increased dementia risk. The association of manic/mixed episodes of bipolar disorder with increased dementia risk is unclear.
Between January 1, 2001 and December 31, 2009, 20,535 individuals aged 45-80 years with bipolar disorder and 82,140 age- and sex-matched comparisons were enrolled and followed up to December 2011 in Taiwan. Those who developed dementia (ICD-9-CM codes: 290.0-290.4, 294.1-294.2, and 331.0-331.2) during the follow-up period were identified.
Cox proportional hazards models were used to examine the relationship between manic/mixed/depressive episodes of bipolar disorder and incident dementia. We also assessed the association between the frequency of psychiatric admissions (total, manic/mixed, and depressive episodes per year) for bipolar disorder and dementia risk.
Bipolar disorder was associated with increased risk of incident dementia (hazard ratio [HR]: 7.52, 95% confidence interval [CI]: 6.86-8.25). Greater frequency of manic/mixed (>2/year: HR: 4.50, 3.50-5.79; 1-2/year: HR: 3.17, 2.31-4.36) and depressive episodes (>2/year: HR: 7.84, 5.93-10.36; 1-2/year: HR: 2.93, 2.05-4.19) were associated with increased risk of incident dementia.
Not only depressive episode of bipolar disorder, but manic/mixed episodes of bipolar play a role as a risk factor of incident dementia, especially for those patients with more than two manic/mixed episodes per year. These findings remind the clinicians the importance of preventing the relapse of bipolar disorder for the potential subsequent cognitive decline and disease.

The second part of this study investigates the correlates and background factors of major depression in young people. The study sample consisted of 744 high school students, (439 males and 305 females), aged 14 to 23 years, and attending 15 high schools in the North of France. Among them, 32 (18 males and 14 females) had a major depressive episode according to DSM-III-R criteria. Data were collected by means of a questionnaire devised for the study in order to investigate sociodemographic, behavioral, medical and environmental factors associated with depression. Antisocial behavior, more frequently found in males, was the only factor significantly differentiating male from female depressed students. On the other hand, school difficulties, health problems, impairments in interpersonal relationships and family history disorders were most often found significantly associated with major depression in males but not in females. According to these findings, the authors examine the concept of \"masked depression\" and advance some hypotheses about the reasons why major depression in young people is so often underdiagnosed.

The first part of this study investigates the prevalence and clinical manifestations of major depressive episodes in young people. The sample for this investigation consisted of 744 high school students (439 males and 305 females), aged 14 to 23 years, and attending 15 high schools in the North of France. Assessment of major depressive episodes according to DSM-III-R criteria was performed by medical doctors using a semi-structured interview and by means of the French version of the Center for Epidemiologic Studies-Depression Scale (CES-D). Thirty-two students (18 males and 14 females) were found to have a major depressive episode with a prevalence of 4.1% in males and 4.7% in females. However, the results also showed that the significant manifestations of major depression differed according to sex and suggested that manifestations of major depression in female young people might differ from those observed in adults more markedly than in males. This may explain that the diagnostic performance of the CES-D was found to be higher in males than in females and that the female prevalence of major depression was found to be lower than those usually obtained with adolescent-specific diagnostic criteria.

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety-eight patients with BD-I who were hospitalized with a depressive episode between 2005 and 2013 were retrospectively followed for 6-months and 1-year rehospitalization rates, as well as time to rehospitalization, according to treatment at discharge: MSs and/or AAPs with or without AD. Multivariable survival models adjusted for covariates known to influence rehospitalization were conducted. Six-months and 1-year rehospitalization rates were significantly lower in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%, P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89, respectively). Time to rehospitalization within 6-months and 1-year was significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P = .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at discharge reduced significantly the adjusted risk of rehospitalization within 6-months (HR = 0.081, 95% CI: 0.016-0.412, P = 0.002) and 1-year (HR = 0.149, 95% CI: 0.041-0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to MS/AAP at discharge from BD-I depressive episode hospitalization is associated with a lower rate of and a longer time to rehospitalization during a 1-year follow up period.

BACKGROUND: The present study aims to examine if autism spectrum disorder (ASD) is a risk factor for suicide attempts among adult depressed patients and to elucidate the characteristics of suicide attempts in adult depressed patients with ASD.
METHODS: We conducted a case-control study. Subjects consisted of 336 retrospectively recruited first-time visit patients to our outpatient clinic with a current major depressive episode; 31 of the 336 patients had attempted suicide. The demographic backgrounds (i.e., age, gender, personal/family history of suicidality); specific psychopathology like bipolarity, agitation, and psychotic features; and comorbidity such as physical diseases, alcohol abuse, cluster B personality disorder, and ASD including pervasive developmental disorder not otherwise specified (PDD-NOS) were examined as potential risk factors for suicide attempts. We compared these variables between the suicide attempters and non-attempters. In addition, we compared suicide attempters to non-attempters within the ASD group and non-ASD group. Binary logistic regression analysis was performed using the significant independent variables from the comparisons between the suicide attempters and non-attempters, and the odds ratios (OR) and 95% confidence intervals (CI) were calculated.
RESULTS: Logistic regression analysis demonstrated that agitation during a depressive episode (OR = 7.15, 95% CI = 2.88-17.74), past suicidal behaviors (OR = 4.32, 95% CI =1.70-10.98), and comorbid PDD-NOS (OR = 4.04, 95% CI = 1.20-13.54) were significantly associated with suicide attempts. The most prevalent suicidal method was drug overdose (59.1%) among non-ASD attempters while hanging was the most prevalent (44.4%) in ASD attempters.
CONCLUSIONS: Depressed adults with comorbid atypical autistic traits are at higher risk for suicide attempts and may engage in methods that are more lethal.

OBJECTIVE: Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration.
METHODS: Patients with bipolar disorder (n = 43) admitted to a mental health center, both with depressive and manic episodes, were retrospectively followed between 2005 and 2013. Fluid balance and electrolyte serum indices were compared between their manic and depressive episodes. We adjusted for physical and psychiatric comorbidities and for psychotropic treatment, using two-way analysis of variance with repeated measures.
RESULTS: There was a significant reduction in serum fluid balance indices during mania compared to depression: mean hemoglobin concentration 13.9 ± 1.4 g/dL versus 14.5 ± 1.4 g/dL, paired t = -4.2, p < 0.0005; mean hematocrit 41.1 ± 4.1% versus 42.3 ± 3.7%, paired t = -3.0, p < 0.005; mean albumin concentration 4.2 ± 0.3 g/dL versus 4.5 ± 0.3 g/dL, paired t = -4.5, p < 0.0001; and mean sodium concentration 140.3 ± 2.0 mEq/L versus 141.0 ± 2.0 mEq/L, paired t = -2.1, p = 0.04, respectively. Controlling for physical and psychiatric comorbidities and psychotropic treatment did not alter these associations.
CONCLUSIONS: Our results support the notion of an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive for relative hemoconcentration during depressive episodes and relative hemodilution during manic episodes. These findings may eventually lead to novel therapeutic targets.

Outcome in bipolar patients is affected by comorbidity. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. This pilot study examined a series of 40 euthymic bipolar patients (DSM-IV criteria) (bipolar I disorder 31, bipolar II disorder 9) to assess the effect of clinical variables and the influence of comorbid personality on the clinical course of bipolar illness. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with \"pure\" bipolar patients (n = 10) with regard to demographic, clinical, and course of illness variables. Comorbid personality disorder was diagnosed in 75% of patients according to ICD-10 criteria, with obsessive-compulsive personality disorder being the most frequent type. Sixty-three per cent of subjects had more than one comorbid personality disorder. Bipolar patients with and without comorbid personality disorder showed no significant differences regarding features of the bipolar illness, although the group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness. In subjects with comorbid personality disorders, the number of hospitalizations correlated significantly with depressive episodes and there was an inverse correlation between age at the first episode and duration of bipolar illness. These findings, however, should be interpreted taking into account the preliminary nature of a pilot study and the contamination of the sample with too many bipolar II patients.