Early Schizophrenia and Bipolar Disorder Patients Display Reduced Neural Prepulse Inhibition

Background: Altered sensorimotor gating has been demonstrated by Prepulse Inhibition (PPI) tests in patients with psychosis. Recent advances in signal processing methods allow assessment of neural PPI through electroencephalogram (EEG) recording during acoustic startle response measures (classic muscular PPI). Simultaneous measurements of muscular (eye-blink) and neural gating phenomena during PPI test may help to better understand sensorial processing dysfunctions in psychosis. In this study, we aimed to assess simultaneously muscular and neural PPI in early bipolar disorder and schizophrenia patients. Method: Participants were recruited from a population-based case-control study of first episode psychosis. PPI was measured using electromyography (EMG) and EEG in pulse alone and prepulse + pulse with intervals of 30, 60, and 120 ms in early bipolar disorder (n = 18) and schizophrenia (n = 11) patients. As control group, 15 socio-economically matched healthy subjects were recruited. All subjects were evaluated with Rating Scale, Hamilton Rating Scale for Depression, and Young Mania Rating Scale questionnaires at recruitment and just before PPI test. Wilcoxon ranked sum tests were used to compare PPI test results between groups. Results: In comparison to healthy participants, neural PPI was significantly reduced in PPI 30 and PPI60 among bipolar and schizophrenia patients, while muscular PPI was reduced in PPI60 and PPI120 intervals only among patients with schizophrenia. Conclusion: The combination of muscular and neural PPI evaluations suggested distinct impairment patterns among schizophrenia and bipolar disorder patients. Simultaneous recording may contribute with novel information in sensory gating investigations.

Mitochondrial modulators in the treatment of bipolar depression: a systematic review and meta-analysis

Mitochondrial dysfunction has been implicated in the risk, pathophysiology, and progression of mood disorders, especially bipolar disorder (BD). Thus, the objective of this meta-analysis was to determine the overall antidepressant effect of mitochondrial modulators in the treatment of bipolar depression. Outcomes included improvement in depression scale scores, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) score. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of diverse mitochondrial modulators were pooled to determine standard mean differences (SMDs) compared with placebo.13 RCTs were identified for qualitative review. The overall effect size of mitochondrial modulators on depressive symptoms was −0.48 (95% CI: −0.83 to −0.14, p = 0.007, I2 = 75%), indicative of a statistically significant moderate antidepressant effect. In the subgroup analysis, NAC improved depressive symptoms compared with placebo (−0.88, 95% CI: −1.48 to −0.27, I2 = 81%). In addition, there was no statistical difference between mitochondrial modulators and placebo in YMRS. Although mitochondrial modulators were superior to placebo in CGI-S score (−0.44, 95% CI: −0.83 to −0.06, I2 = 71%), only EPA was superior to placebo in subgroup analysis. Overall, a moderate antidepressant effect was observed for mitochondrial modulators compared with placebo in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

Case Report: Repeated Transcranial Magnetic Stimulation Improves Comorbid Binge Eating Disorder in Two Female Patients With Treatment-Resistant Bipolar Depression

Introduction: Binge eating disorder (BED) is the most common eating disorder, affecting a large population worldwide. It is characterized by recurrent episodes of binge eating, with no compensatory behaviors. BED is often associated with psychiatric comorbidities, and still represents a challenge in terms of treatment strategies. In the last years, neuromodulation has represented a promising approach in the treatment of BED. We report the cases of two women, affected by Bipolar Disorder Type II (BD-II) and comorbid BED, whose BED symptoms improved after a course of accelerated intermittent Theta Burst Stimulation (iTBS).Methods: We carried out a clinical study, involving neurostimulation on six patients with a treatment-resistant depressive episode. The trial consisted of a 3-week accelerated iTBS treatment, delivered to the left dorsolateral pre-frontal cortex. Clinical evaluation scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Young Mania Rating Scale) were administered at baseline, after 2 weeks, and at the end of the stimulation cycle. Pharmacotherapy was maintained unchanged during iTBS treatment. Patients gave their informed consent both for the protocol and for the publication.Results: The treatment was well-tolerated. Depressive symptoms only slightly improved; however, patients' binge episodes remitted completely, which was a serendipitous finding. BED symptomatology complete remission lasted up to 12 weeks follow-up.Discussion: This is the first study regarding iTBS use in BED in comorbidity with BD-II. Further research is still needed to assess the efficacy of this technique in BED treatment.

Eye Movements and Cognitive Functioning in Patients With Schizophrenia Spectrum Disorders: Network Analysis

Background: Eye movement parameters are often used during cognitive functioning assessments of patients with psychotic spectrum disorders. It is interesting to compare these oculomotor parameters with cognitive functions, as assessed using psychometric cognitive tests. A network analysis is preferable for understanding complex systems; therefore, the aim of this study was to determine the multidimensional relationships that exist between oculomotor reactions and neurocognition in patients with schizophrenia spectrum disorders.Materials and Methods: A total of 134 subjects (93 inpatients with schizophrenia spectrum disorders (ICD-10) and 41 healthy volunteers) participated in this study. Psychiatric symptom severity was assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Young Mania Rating Scale. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale, and akathisia was assessed using the Barnes Akathisia Rating Scale. Eye movements were recorded using an eye-tracker SMI RED 500, and cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. The statistical analyses were conducted using Minitab 17 Statistical Software, version 17.2.1. Data visualization and additional analyses were performed in the R 4.0.3 environment, using RStudio V 1.3.1093 software.Results: A network model of neurocognitive and oculomotor functions was constructed for the patients. In the full network (which includes all correlations) the median antisaccade latency value is the central element of the oculomotor domain, and the Symbol Coding test, the Digit Sequencing test, and the Verbal Fluency test are central elements in the neurocognitive domain. Additionally, there were connections between other cognitive and oculomotor functions, except for the antisaccade error latency in the oculomotor domain and the Token Motor Task in the neurocognitive domain.Conclusion: Network analysis provides measurable criteria for the assessment of neurophysiological and neurocognitive abnormalities in patients with schizophrenic spectrum disorders and allows to select key targets for their management and cognitive remediation.

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice.Objectives: To present clinical and pharmacokinetic data of nine mother–infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006–2018).Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother–infant pairs at delivery, and at days 1–5, 7–11, 30, and 60 postpartum, and monthly until 6-months.Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02–1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum.Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.

Comparison of Adjunctive Quetiapine Versus Adjunctive Haloperidol in Combination with Sodium Valproate for Treatment of Patients with Mania or Mixed Feature Bipolar I Disorder: A Randomized Double-Blind Clinical Trial Study

Background: Acute mania causes many problems for the patient and others. Therefore, it is very important to eliminate the symptoms quickly. Objectives: The present study made the individual comparison of the therapeutic effects of sodium valproate combined with quetiapine or haloperidol as an add-on among patients with bipolar I disorder experiencing an episode of mania or mixed feature admitted to a Psychiatric Center in Tehran. Methods: The present study was a double-blind clinical randomized trial conducted on 36 patients. All patients were investigated by the Young Mania Rating Scale (YMRS). The study lasted six weeks in total (after raising drug dosage to the maximum level). We prescribed sodium valproate 15 mg/kg plus quetiapine 500 mg daily in one group and sodium valproate 15 mg/kg plus haloperidol 10 mg daily in the other group. In addition, an equivalent dosage of quetiapine and haloperidol was prescribed. This study used different data analysis methods such as Paired t test, ANOVA, and chi-square test. Results: The YMRS scores did not show any statistically significant difference between quetiapine and haloperidol receiving groups (P > 0.05). Conclusions: This paper argued that a combination of sodium valproate with either quetiapine or haloperidol could be effective in the management of acute mania or mixed bipolar I disorder to reduce the severity and duration of symptoms, although there was no statistically significant difference between the efficacy of these two pharmacological therapies.

Resilience Predicts Self-Stigma and Stigma Resistance in Stabilized Patients With Bipolar I Disorder

The identification of factors that prevent self-stigma and on the other hand promote stigma resistance are of importance in the long-term management of bipolar disorder. Accordingly, the aim of the current study was to investigate the association of factors deemed relevant in this context, i.e., resilience, premorbid functioning, and residual mood symptoms, with self-stigma/stigma resistance. Sixty patients diagnosed with bipolar I disorder were recruited from a specialized outpatient clinic. Self-stigma and stigma resistance were measured by the Internalized Stigma of Mental Illness (ISMI) Scale. The presence and severity of symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). Resilience and premorbid functioning were measured by the Resilience Scale (RS-25) and the Premorbid Adjustment Scale (PAS), respectively. Resilience correlated negatively with self-stigma and positively with stigma resistance and was a predictor for self-stigma/stigma resistance in multiple linear regression analysis. Residual depressive symptoms correlated positively with self-stigma and negatively with stigma resistance. There were no significant correlations between sociodemographic variables, premorbid functioning as well as residual manic symptoms and self-stigma/stigma resistance. The findings of this study implicate that resilience may be considered as an important component of self-stigma reduction interventions.

Impact of modification to DSM-5 criterion A for hypomania/mania in newly diagnosed bipolar patients: findings from the prospective BIO study

Background DSM-IV states that criterion A for diagnosing hypomania/mania is mood change. The revised DSM-5 now states that increased energy or activity must be present alongside mood changes to diagnose hypomania/mania, thus raising energy/activity to criterion A. We set out to investigate how the change in criterion A affects the diagnosis of hypomanic/manic visits in patients with a newly diagnosed bipolar disorder. Results In this prospective cohort study, 373 patients were included (median age = 32; IQR, 27–40). Women constituted 66% (n = 245) of the cohort and 68% of the cohort (n = 253) met criteria for bipolar type II, the remaining patients were diagnosed bipolar type I. Median number of contributed visits was 2 per subject (IQR, 1–3) and median follow-up time was 3 years (IQR, 2–4). During follow-up, 127 patients had at least one visit with fulfilled DSM-IV criterion A. Applying DSM-5 criterion A reduced the number of patients experiencing a hypomanic/manic visit by 62% at baseline and by 50% during longitudinal follow-up, compared with DSM-IV criterion A. Fulfilling DSM-5 criterion A during follow-up was associated with higher modified young mania rating scale score (OR = 1.51, CL [1.34, 1.71], p < 0.0001) and increased number of visits contributed (OR = 1.86, CL [1.52, 2.29], p < 0.0001). Conclusion Applying the stricter DSM-5 criterion A in a cohort of newly diagnosed bipolar patients reduced the number of patients experiencing a hypomanic/manic visit substantially, and was associated with higher overall young mania rating scale scores, compared with DSM-IV criterion A. Consequently, fewer hypomanic/manic visits may be detected in newly diagnosed bipolar patients with applied DSM-5 criterion A, and the upcoming ICD-11, which may possibly result in longer diagnostic delay of BD as compared with the DSM-IV.

Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study

Dopamine-β-hydroxylase (DβH) is an enzyme converting dopamine to norepinephrine, a key neurotransmitter in mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Due to overlapping symptomology of unipolar and bipolar depression, the present study attempted to explorer if the plasma DβH activity could discriminate the depressive episodes of BD from MDD. The aim of this study was to compare the plasma DβH activity among MDD patients (n = 104), BD patients (n = 101), and healthy controls (n = 160). Clinical characteristics and cognitive function were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Patient Health Questionnaire-9 (PHQ-9), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Our data showed a lower plasma DβH activity in patients with BD, not MDD, than that in controls. For the BD patients, the plasma DβH activities were negatively correlated with HAM-D scores and HAM-A scores. However, there was no significant correlation between plasma DβH activity and severity of depressive symptoms in MDD patients. No significant correlation between DβH activities and cognitive assessments neither in BD nor in MDD patients. The present study provides evidence that BD is associated with decreased circulating DβH activity.