The normal 14-18 gestational weeks "parasagittal complex" view of the fetal brain. A 3D transvaginal neurosonographic study.

OBJECTIVE: To study the early second trimester development of brain hemispheres, lateral ventricles, choroid plexus, and ganglionic eminence/basal ganglia complex (GEBG). METHODS: A retrospective analysis of TVUS 3D volumes of 14-18 gestational weeks (GW) fetuses. Hemispheres were analyzed for wall thickness, choroid plexus extension, GEBG height and length, lamination pattern (intermediate zone and the subplate border, IZ-SP), ventricle height, width, and angle. Measurements were correlated with GW and assessed for symmetry and impact of probe resolution. RESULTS: We included 84 fetuses (168 hemispheres). The CP location is variable at 14-16 GW, becoming consistently and symmetrically posterior at 18 GW. Hemispheric thickness, GEBG height and length grow significantly with fetal age, whereas ventricle height, width, and angle regress. The detection rate of the IZ-SP line at 14, 15, 16, 17, and 18 weeks was 0%, 24%, 78.26%, 100%, and 100%, respectively. The ratio between the upper and lower segments of the cerebral lamination grows with GW. For all brain structures, the asymmetry between sides was significant only for ventricular height. The transducer type did not have a significant effect on any outcome except for ventricle height. CONCLUSION: These normal features of the parasagittal view should aid clinicians in fetal brain assessment during the early weeks of the second trimester.

Decreased Psychological Well-Being in Patients With Bipolar Disorder in Remission.

BACKGROUND: The goals of this study were to introduce psychological well-being as an important subject of inquiry in bipolar disorder, to compare well-being in a cohort of patients with bipolar disorder with that of a normative sample, and to assess whether common measures of well-being and mood measure empirically distinct phenomena. METHODS: Participants were outpatients with bipolar I disorder in remission (N=37) from the Enhancing Emotion Regulation in Bipolar Disorder (EERBD) study and a matched community normative sample from the Midlife in the United States (MIDUS) survey (N=6297). The Psychological Well-Being Scale (PWBS) was used to measure psychological well-being. We calculated means and SD of scores on the PWBS and evaluated the differences between the scores of the bipolar I and community samples. We also tested the association between raw and change scores in depression [Hamilton Rating Scale for Depression (HAM-D)] and eudaimonic well-being (PWBS) using Spearman correlation coefficients. RESULTS: The MIDUS survey sample (N=6297) was 48% male, with a mean age of 47 years (SD=13 y). The EERBD sample (N=37) was 27% male, with a mean age of 41 years (SD=11 y). In the bipolar sample, the baseline mean score on the HAM-D was 12.7 (SD=6.0) and the mean score on the Young Mania Rating Scale was 6.1 (SD=6.2). The baseline mean sum score on the PWBS in the normative community MIDUS sample was 100 (SD=14), while that of the bipolar I EERBD sample was 79 (SD=15) at baseline, 84 (SD=13) posttreatment, and 84 (SD=12) at the 3-month follow-up assessment. The effect sizes of the differences at all timepoints were large (Hedges g=1.42 at baseline, 1.11 at the end of treatment, and 1.06 at the 3-mo follow-up). No association was found between the PWBS and depression scores. CONCLUSIONS: Outpatients with bipolar disorder in remission demonstrated substantially impaired psychological well-being, despite low levels of depressive symptoms, compared with a normative community sample.

Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response.

BACKGROUND: Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response. METHODS: We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models. RESULTS: Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response. LIMITATIONS: Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors. CONCLUSIONS: Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression.

The Influence of Substance Abuse on Inhibition Capacities and Risky Decision in a Group of Outpatient Schizophrenia Patients.

OBJECTIVE: Substance abuse is common among patients with schizophrenia, is related to worse course and outcome of illness. Unfortunately, little is known about how substance abuse affects the cognitive function of schizophrenia patients, whose cognitive function is often already comprised. Neurocognitive functioning includes inhibition control and decision-making, and both schizophrenia and substance use disorder are related to impairments of inhibition control. However, the influence of substance abuse on inhibition capacities among schizophrenia patients is unclear. Methods: This study measured the influence of substance use disorder on inhibition capacities and risky decision-making in a group of 39 schizophrenia patients that were evaluated using a socio-demographic questionnaire and clinical assessment using the Positive and Negative Syndromes Scale for Schizophrenia. To assess inhibition control we utilized the Matching Familiar Figure Test (MFFT) and the Stroop task, and to evaluate decision-making we used the Iowa Gambling Task (IGT) and self-report questionnaire, the Barratt Impulsiveness Scale. Results: Univariate analysis found significant differences between the groups with regard to criminal history (χ2 = 5.97, p=.015), smoking status (χ2 = 12.30, p<.001), and total BIS score (t= -2.69, df = 37, p=.01). Our model did not find a significant effect of substance abuse on the first response time and number of errors on the MFFT or in the total interference index of Stroop performance and net score on risky decision-making in the IGT. The two groups did not differ significantly either in first response time or in number of errors on the MFFT (F = 0.54, p=.47, d = 0.24, 95% CI [-0.4, 0.88]; F = 0.28, p=.60, d = 0.61, 95% CI [0, 1.26], respectively), nor did they differ in the total interference index of the Stroop task (F(1)=0.49, p=.49, d = 0.25, 95% CI [-0.38, 0.88]). Conclusion: The analyses did not detect any statistically significant effect of substance abuse on inhibition control or risky decision-making processes in outpatients diagnosed with schizophrenia, despite increased impulsivity, criminal history and smoking status. These results neither support nor disprove previous findings.

Psychotic symptoms during bipolar depressive episodes and suicidal ideation.

BACKGROUND: Psychotic symptoms during bipolar depressive episodes, especially in outpatients, are under recognized and studied by clinicians and researchers. We examined the relationship between psychotic symptoms during a depressive episode and suicidal ideation in bipolar patients. METHODS: Participants (N = 351) were adult, depressed outpatients with bipolar disorder (BD) in a comparative effectiveness study of quetiapine versus lithium. Psychotic symptoms were assessed via Bipolar Inventory of Signs and Symptoms Scale (BISS) and depressive episodes via Mini-International Neuropsychiatric Interview (MINI). Because only 4.84% (N = 17) endorsed psychotic symptoms, we performed iterative multivariate matching with non-psychotic participants. On every matched population, a multiple regression analysis examined whether psychotic symptoms were associated with suicidal ideation, via the Concise Health Risk Taking scale (CHRT-12). RESULTS: Averaged across the 50 matched populations, current psychotic symptoms predicted active suicidal ideation on the CHRT, but not a passive propensity toward suicide or total CHRT scores, after adjusting for common correlates of suicidality (e.g., previous suicidal behavior) (ß=0.59, p=.01, R2= 0.41). LIMITATIONS: Our study was limited by three factors. First, the generalizability of our study was limited as the sample included only outpatients. Next, the analysis was cross-sectional and does not allow for causal interpretation. Lastly, our study lacked information regarding the content and mood congruency of participants' psychosis. CONCLUSION: While a small proportion of BD outpatients had current symptoms of psychosis during their depressive episode, those who did were more likely to endorse active suicidal thoughts, including suicide methods and plans.

Targeting Mitochondrial Dysfunction for Bipolar Disorder.

People with bipolar disorder (BD) all too often have suboptimal long-term outcomes with existing treatment options. They experience relapsing episodes of depression and mania and also have interepisodic mood and anxiety symptoms. We need to have a better understanding of the pathophysiology of BD if we are to make progress in improving these outcomes. This chapter will focus on the critical role of mitochondria in human functioning, oxidative stress, and the biological mechanisms of mitochondria in BD. Additionally, this chapter will present the evidence that, at least for some people, BD is a product of mitochondrial dysregulation. We review the modulators of mitochondria, the connection between current BD medication treatments and mitochondria, and additional medications that have theoretical potential to treat BD.

Familial severe psychiatric history in bipolar disorder and correlation with disease severity and treatment response.

BACKGROUND: Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder. METHODS: The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response. RESULTS: Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms. CONCLUSIONS: Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history.

Cognitive enhancement drug use among resident physicians: Prevalence and motivations for use - results from a survey.

Background: Non-medical use of prescription drugs for the enhancement of cognitive functioning has gained popularity in recent years, especially among young educated adults. To our knowledge, no previous study investigated this phenomenon among resident physicians.Objective: To analyze cognitive enhancement drugs use motivations and patterns among resident physicians.Methods: A survey and statistical analysis regarding the use of drugs traditionally prescribed for the treatment of Attention Deficit Hyperactivity Disorder: stimulants, amphetamines and modafinil.Participants: 1,453 residents who took their written residency exam in the summer of 2017. The response rate was 32.3%.Results: 28.1% of responders reported past use, with 73.67% of them reporting use without a related medical diagnosis. Almost half of the users (47.1%) acquired the drug with a prescription, but without a diagnosis of a related medical disorder. The first use was predominantly during residency (54.3%), with 45% reporting it as related to the residency exam.Factors found to positively impact non-medical use include: declaring undiagnosed Attention Deficit Hyperactivity Disorder, fear of failing the exam, a belief that more than 30% of other examinees take cognitive enhancements drugs, and a learning disability diagnosis. Self-reports of being a competitive person and being a parent, were negatively correlated with non-medical use.Conclusions: The use of drugs that are taken traditionally for the treatment of Attention Deficit Hyperactivity Disorder is common among resident physicians, both with and without related medical indication. Interestingly, factors associated with the fear of being "left behind" increase non-medical use and not the desire to succeed.

An evaluation of suicidal risk in bipolar patients with comorbid posttraumatic stress disorder.

BACKGROUND: While bipolar disorder (BD) and posttraumatic stress disorder (PTSD) frequently co-occur and individually have a higher risk of suicide compared to the general population, few studies have examined the impact of comorbid PTSD on suicidal ideation in patients with BD. METHODS: We analyzed baseline data from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for bipolar disorder study (Bipolar CHOICE), a 6-month, pharmacological comparative effectiveness trial of individuals with BD. Bipolar CHOICE enrolled 482 individuals. A hierarchical multiple regression analysis assessed whether comorbid PTSD was associated with increased suicidal ideation as assessed by the Concise Health Risk Tracking Scale (CHRT) total and factor scores, while controlling for common correlates of suicidal ideation in this population such as a current major depressive episode, comorbid anxiety disorders, severity of illness and previous suicide attempts. RESULTS: Consistent with our hypothesis, diagnosis of comorbid PTSD was a significant predictor of the CHRT total score (ß=2.59, p=.03). Comorbid PTSD was also a significant predictor of the CHRT propensity factor (ß=2.32, adjusted p=.04), but was not a significant predictor of the active suicidal thoughts factor. Additionally, all participants with comorbid PTSD (N = 58) endorsed current suicidal ideation (p=.005) and were more likely to have had a previous suicide attempt (p<.001) compared to those without PTSD. LIMITATIONS: Generalizability beyond outpatient settings is limited, mixed affective states were not assessed, and analyses were cross-sectional. CONCLUSIONS: Patients have an increased risk of suicidal ideation when PTSD is comorbid with BD.

Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients.

Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of "Magen" neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.