Neural and Endocrine Correlates of Early Life Abuse in Youth With Depression and Obesity

Depression and insulin resistance are becoming increasingly prevalent in younger populations. The origin and consequence of insulin resistance in depressed youth may, in part, be rooted in exposure to environmental stressors, such as early life abuse, that may lead to aberrant brain motivational networks mediating maladaptive food-seeking behaviors and insipient insulin resistance. In this paper, we aimed to investigate the impact of early life abuse on the development of insulin resistance in depressed and overweight youth aged 9 to 17 years. We hypothesized that youth with the greatest burden of early life abuse would have the highest levels of insulin resistance and corresponding aberrant reward network connectivities. To test this hypothesis, we evaluated sixty-nine depressed and overweight youth aged 9 to 17, using multimodal assessments of early life abuse, food-seeking behavior, and insulin resistance. Based on results of the Childhood Trauma Questionnaire (CTQ), we separated our study participants into two groups: 35 youth who reported high levels of the sum of emotional, physical, or sexual abuse and 34 youth who reported insignificant or no levels of any abuse. Results of an oral glucose tolerance test (OGTT) and resting state functional connectivity (RSFC), using the amygdala, insula, and nucleus accumbens (NAcc) as seed-based reward network regions of interest, were analyzed for group differences between high abuse and low abuse groups. High abuse youth exhibited differences from low abuse youth in amygdala-precuneus, NAcc-paracingulate gyrus, and NAcc-prefrontal cortex connectivities, that correlated with levels of abuse experienced. The more different their connectivity from of that of low abuse youth, the higher were their fasting glucose and glucose at OGTT endpoint. Importantly, level of abuse moderated the relation between reward network connectivity and OGTT glucose response. In contrast, low abuse youth showed hyperinsulinemia and more insulin resistance than high abuse youth, and their higher OGTT insulin areas under the curve correlated with more negative insula-precuneus connectivity. Our findings suggest distinct neural and endocrine profiles of youth with depression and obesity based on their histories of early life abuse

Association between solar insolation and a history of suicide attempts in bipolar I disorder

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.Peer reviewe

Increased depressive symptoms in menopausal age women with bipolar disorder: age and gender comparison

OBJECTIVE: Emerging data suggest the menopausal transition may be a time of increased risk for depression. This study examines the course of bipolar disorder focusing on depressive symptoms in menopausal transition age women, compared to similar-aged men as well as younger adult women and men. METHODS: Outpatients with bipolar disorder were assessed with the systematic treatment enhancement program for bipolar disorder (STEP-BD) affective disorders evaluation and longitudinally monitored during naturalistic treatment with the STEP-BD clinical monitoring form. Clinical status (syndromal/subsyndromal depressive symptoms, syndromal/subsyndromal elevation or mixed symptoms, and euthymia) was compared between menopausal transition age women (n=47) and pooled similar-aged men (n=30) 45-55 years old, younger women (n=48) and men (n=39) 30-40 years old. RESULTS: Subjects included 164 bipolar disorder patients (67 type I, 82 type II, and 15 not otherwise specified), 34% were rapid cycling and 58% women. Bipolar II disorder/bipolar NOS was more common in women. Monitoring averaged 30+/-22 months, with an average of 0.9+/-0.5 clinic visits/month. Menopausal age women had a significantly greater proportion of visits with depressive symptoms (p\u3c0.05), significantly fewer euthymic visits (p\u3c0.05) and no difference in proportion of visits with elevated/mixed symptoms compared to pooled comparison group. CONCLUSIONS: Menopausal transition age women with bipolar disorder experience a greater proportion of clinic visits with depressive symptoms compared to similarly aged men, and younger women and men with bipolar disorder. Further systematic assessment on the influence of the menopausal transition and reproductive hormones upon mood is needed to better inform clinical practice in treating women with bipolar disorder

Mood disorders and fertility in women: a critical review of the literature and implications for future research

A medline literature review of fertility and mood disorder articles published since 1980 was performed in order to critically review the literature regarding a relationship between mood disorders, fertility and infertility treatment. Previous studies suggests that mood disorders, both in the bipolar and unipolar spectrum, may be associated with decreased fertility rates. Most studies report that women seeking treatment for infertility have an increased rate of depressive symptoms and possibly major depression (none showed evaluated mood elevations). Many, but not all, studies found that depressive symptoms may decrease the success rate of fertility treatment. Treatments for infertility may independently influence mood through their effects on estrogen and progesterone, which have been shown to influence mood through their actions on serotonin. Studies are limited in scope and confounding variables are many, limiting the strength of the results. In conclusion, a range of existing studies suggests that fertility and mood disorders are related in a complex way. Future studies should use clinical interviews and standardized and validated measures to confirm the diagnosis of mood disorders and control for the variables of medication treatment, desire for children, frequency of sexual intercourse, age, FSH levels, menstrual cycle regularity in assessing an interrelationship between mood disorders and fertility

Increased frequency of depressive episodes during the menopausal transition in women with bipolar disorder: preliminary report

OBJECTIVE: Data are emerging in bipolar disorder regarding mood across phases of the female reproductive life, yet information about mood during the menopausal transition remains limited. The menopausal transition in women without mood disorders is associated with an increase in depression. This study assesses mood course during the menopausal transition in women with bipolar disorder. METHODS: We monitored mood episodes in 47 women with bipolar disorder ages 45-55 for 17.0+/-14.0 months with systematic treatment enhancement program for bipolar disorder (STEP-BD) standardized evaluations. Charts were additionally reviewed for menstrual status and menstrual history, as well as mood episode type, duration, frequency and history. RESULTS: During the menopausal transition 68% of women with bipolar disorder experienced at least one depressive episode. Depression (but not mood elevation) episode frequency significantly increased during the menopausal transition compared to reported frequency during patients\u27 reproductive years. History of pre-menstrual and or post-partum mood instability did not predict perimenopausal mood episodes. CONCLUSIONS: Women with bipolar disorder experience a high frequency of depressive episodes during perimenopausal years and this frequency appears greater than during prior reproductive years. Prospective controlled studies are needed to better understand the course of mood episodes and to enhance the effectiveness of managing bipolar disorder during the menopausal transition

Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study

A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted