Liisa Hantsoo

Omega-3 fatty acid monotherapy for pediatric bipolar disorder: A prospective open-label trial

BACKGROUND To test the effectiveness and safety of omega-3 fatty acids (Omegabrite(R) brand) in the treatment of pediatric bipolar disorder (BPD). METHOD Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-IV diagnosis of BPD and Young Mania Rating Scale (YMRS) score of >15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). RESULTS Subjects experienced a statistically significant but modest 8.9+/-2.9 point reduction in the YMRS scores (baseline YMRS=28.9+/-10.1; endpoint YMRS=19.1+/-2.6, p<0.001). Adverse events were few and mild. Red blood cell membrane levels of EPA and DHA increased in treated subjects. CONCLUSIONS As only 35% of these subjects had a response by the usual accepted criteria of >50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD.

Hot flashes and panic attacks: A comparison of symptomatology, neurobiology, treatment, and a role for cognition.

Despite decades of research, the causal mechanisms of hot flashes are not adequately understood, and a biopsychosocial perspective on hot flashes remains underdeveloped. This article explores overlooked parallels between hot flashes and panic attacks within 5 areas: course and symptomatology, physiological indicators, neurocircuitry and biochemical mechanisms, pharmacotherapy, and psychological treatment, noting both similarities and important differences between the 2 events. An integrative conceptual model is presented that identifies key ways in which psychological factors may influence the experience of hot flashes, with clinical implications and areas of future research. This model yields readily testable hypotheses and may provide a template for exploring the role of cognition in the frequency and severity of hot flashes and, in turn, a basis for the development of nonpharmacological treatments.

Comparison of open-label, 8-week trials of olanzapine monotherapy and topiramate augmentation of olanzapine for the treatment of pediatric bipolar disorder.

BACKGROUND The aim of this study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents. METHOD Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23). RESULTS Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg. CONCLUSIONS Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.

Premenstrual Dysphoric Disorder: Epidemiology and Treatment.

Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD’s profile, characterized by cognitive–affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD’s clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD’s pathophysiology, including neurosteroids and stress, and explore potential treatment targets.

“One end has nothing to do with the other:” Patient attitudes regarding help seeking intention for depression in gynecologic and obstetric settings

Many women rely on their obstetrician/gynecologist (OB/GYN) as their primary contact with the health care delivery system. There have been few studies exploring patient views on getting help for depression from these providers. The purpose of this study is to assess help seeking intention for depression and identify beliefs which moderate this intention. Telephone interviews of women following a routine gynecologic visit or in the immediate postpartum period (regarding prenatal care) were used to assess intention to seek help from their providers in a case of depression. For women who lacked this intention, related beliefs were elicited with the open ended question “why not?” Among the 225 women in the study more than half receiving gynecologic care (59%) and nearly a third of women who received prenatal care (29%; p < 0.001) stated they would not seek help from their OB/GYN for depression. Report that a prenatal provider had mentioned depression was associated with help seeking intention for depression but was not independent of confounding variables. Beliefs among women who lacked help seeking intention clustered into two attitude themes: 1) an OB/GYN is the wrong doctor for depression care and 2) OB/GYN is not a good setting for depression care. Many women have attitudes which reduce their intention to seek help for depression from their OB/GYN. Interventions aiming to increase delivery of depression care in these settings should consider these beliefs in their design.

Gender and cognitive-emotional factors as predictors of pre-sleep arousal and trait hyperarousal in insomnia

OBJECTIVE Elevated pre-sleep arousal has been consistently associated with insomnia, yet the cognitive-emotional mechanisms involved in sleep-related arousal remain unclear. The purpose of this study was to identify predictors of pre-sleep arousal and trait hyperarousal from a set of variables that included self-reported affect, sleep-related cognitions, locus of control, and gender. METHODS Cross-sectional data were analyzed for 128 participants (89 females) who met criteria for psychophysiological insomnia and completed a set of questionnaires that included the beliefs and attitudes about sleep (BAS), positive and negative affect schedule (negative subscale (nPANAS) and positive subscale (pPANAS)), sleep locus of control (SLOC), Pre-Sleep Arousal Scale (PSAS), hyperarousal scale (HAS) and demographic information. Step-wise regression was conducted with a set of independent variables, with PSAS and HAS serving as separate dependent variables. RESULTS Trait hyperarousal was associated with higher levels of both negative and positive emotionality, as well as negative beliefs about sleep, in both genders. Pre-sleep arousal was associated with greater negative emotionality and internal sleep locus of control, varying by gender. Among women, high pre-sleep arousal was associated with negative emotionality, while in men greater pre-sleep arousal was associated with an internal sleep locus of control. CONCLUSION These findings have clinical implications, suggesting that men and women may require different cognitive targets when addressing pre-sleep arousal.

Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice

BACKGROUND Adverse childhood experiences (ACEs) are one of the greatest predictors of affective disorders for women. Periods of dynamic hormonal flux, including pregnancy, exacerbate the risk for affective disturbance and promote hypothalamic-pituitary-adrenal (HPA) axis dysregulation, a key feature of affective disorders. Little is understood as to how stress experienced in late childhood, defined as preadolescence, alters the programming unique to this period of brain maturation and its interaction with the hormonal changes of pregnancy and postpartum. METHODS Preadolescent female mice were exposed to chronic stress and examined for changes in their HPA axis during pregnancy and postpartum, including assessment of maternal-specific stress responsiveness and transcriptomics of the paraventricular nucleus of the hypothalamus. Translationally, pregnant women with low or high ACEs were examined for their maternal stress responsiveness. RESULTS As predicted, preadolescent stress in mice resulted in a significant blunting of the corticosterone response during pregnancy. Transcriptomic analysis of the paraventricular nucleus revealed widespread changes in expression of immediate early genes and their targets, supporting the likely involvement of an upstream epigenetic mechanism. Critically, in our human studies, the high ACE women showed a significant blunting of the HPA response. CONCLUSIONS This unique mouse model recapitulates a clinical outcome of a hyporesponsive HPA stress axis, an important feature of affective disorders, during a dynamic hormonal period, and suggests involvement of transcriptional regulation in the hypothalamus. These studies identify a novel mouse model of female ACEs that can be used to examine how additional life adversity may provoke disease risk or resilience.

A Mobile Application for Monitoring and Management of Depressed Mood in a Vulnerable Pregnant Population

OBJECTIVE This study tested whether a mood tracking and alert (MTA) mobile application (app) improved mental health care delivery in a high-risk obstetric population. METHODS Pregnant women with depressive symptomatology at <32 weeks gestation were followed for eight weeks after randomization to a control patient portal (PP) app alone or with the MTA app. The MTA app monitored activity, assessed mood, and alerted obstetric providers of signs of worsening mood. RESULTS Seventy-two women enrolled (PP, N=24; MTA, N=48). MTA users had significantly more contacts addressing mental health, and as gestational age increased, they rated ability to manage their own health significantly better than women in the control group. Women who received telephone contact from a provider triggered by an MTA app alert were significantly more likely to receive a mental health specialist referral. CONCLUSIONS A mobile MTA app improved service delivery and patient engagement among patients with perinatal depression symptoms.

Basal and stress-activated hypothalamic pituitary adrenal axis function in postmenopausal women with overactive bladder

Introduction and hypothesisThe aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB.MethodsPostmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST).ResultsBaseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction.ConclusionsPreliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.

Movement patterns in women at risk for perinatal depression: use of a mood-monitoring mobile application in pregnancy

Objectives To examine, using a smartphone application, whether mood is related to daily movement patterns in pregnant women at risk for perinatal depression. Materials and Methods Thirty-six women with elevated depression symptoms (PHQ-9 ≥ 5) in pregnancy used the application for 8 weeks. Mood was reported using application-administered surveys daily (2 questions) and weekly (PHQ-9 and GAD-7). The application measured daily mobility (distance travelled on foot) and travel radius. Generalized linear mixed-effects regression models estimated the association between mood and movement. Results Women with milder depression symptoms had a larger daily radius of travel (2.7 miles) than women with more severe symptoms (1.9 miles), P  = .04. There was no difference in mobility. A worsening of mood from the prior day was associated with a contracted radius of travel, as was being in the group with more severe symptoms. No significant relationships were found between anxiety and either mobility or radius. Discussion We found that the association of mood with radius of travel was more pronounced than its association with mobility. Our study also demonstrated that a change in mood from the prior day was significantly associated with radius but not mood on the same day that mobility and radius were measured. Conclusion This study lays the groundwork for future research on how smartphone mood-monitoring applications can combine actively and passively collected data to better understand the relationship between the symptoms of perinatal depression and physical activity that could lead to improved monitoring and novel interventions.