Faculty Bibliography

Emotion regulation (ER) difficulties are ubiquitous among individuals with schizophrenia and have been hypothesized to contribute to stress sensitivity and exacerbation of psychotic symptoms in this population. However, the evidence supporting this link is equivocal, potentially due to previous studies' reliance on retrospective assessments of ER and psychosis, as well as lack of consideration of putative moderators such as emotion awareness. To address these limitations, we employed experience sampling method using mobile electronic devices to investigate the links between momentary in vivo use of ER strategies (_mER), emotion awareness, and psychotic symptoms during daily functioning. Fifty-four individuals with schizophrenia completed assessment of _mER and psychotic symptoms, along with traditional retrospective measures of ER and symptoms. Use of _mER suppression predicted significant increases in momentary experiences of thought insertion, mind reading, auditory and visual hallucinations. Use of _mER reappraisal predicted significant increases in momentary experiences of suspiciousness, thought insertion, and mind reading. Emotion awareness, driven primarily by difficulties identifying feelings, moderated the impact of ER on psychotic symptoms. There were no associations between retrospective measures of ER and symptoms. Our results indicate that, among individuals with schizophrenia, emotion awareness significantly impacts the relationship between use of ER and exacerbations in psychotic symptoms during the course of daily functioning. Our results highlight the need to incorporate emotion awareness and regulation difficulties into the development of treatment models and interventions for psychosis. In addition, our results underscore the need to employ in vivo, high time-resolution assessment methods to study dynamic clinical phenomena such as ER and psychotic symptoms.

BACKGROUND:Previous studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic load, and intakes of specific types of carbohydrates. OBJECTIVE:We hypothesized that higher GI and glycemic load would be associated with greater odds of insomnia prevalence and incidence. METHODS:This was a prospective cohort study with postmenopausal women who participated in the Women's Health Initiative Observational Study, investigating the relations of GI, glycemic load, other carbohydrate measures (added sugars, starch, total carbohydrate), dietary fiber, and specific carbohydrate-containing foods (whole grains, nonwhole/refined grains, nonjuice fruits, vegetables, dairy products) with odds of insomnia at baseline (between 1994 and 1998; n = 77,860) and after 3 y of follow-up (between 1997 and 2001; n = 53,069). RESULTS:In cross-sectional and longitudinal analyses, higher dietary GI was associated with increasing odds of prevalent (fifth compared with first quintile OR: 1.11; CI: 1.05, 1.16; P-trend = 0.0014) and incident (fifth compared with first quintile OR: 1.16; CI: 1.08, 1.25; P-trend < 0.0001) insomnia in fully adjusted models. Higher intakes of dietary added sugars, starch, and nonwhole/refined grains were each associated with higher odds of incident insomnia. By contrast, higher nonjuice fruit and vegetable intakes were significantly associated with lower odds of incident insomnia. Also, higher intakes of dietary fiber, whole grains, nonjuice fruit, and vegetables were significantly associated with lower odds of prevalent insomnia. CONCLUSIONS:The results suggest that high-GI diets could be a risk factor for insomnia in postmenopausal women. Substitution of high-GI foods with minimally processed, whole, fiber-rich carbohydrates should be evaluated as potential treatments of, and primary preventive measures for, insomnia in postmenopausal women.

Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypothalamus, pituitary, and adrenal glands, needs to be updated. Research in the last two decades shows that important bidirectional signaling between the HPA axis and intestinal mucosa modulates brain function and neurochemistry, including effects on glucocorticoid hormones and brain-derived neurotrophic factor (BDNF). The intestinal microbiome in earliest life, which is seeded by the vaginal microbiome during delivery, programs the development of the HPA axis in a critical developmental window, determining stress sensitivity and HPA function as well as immune system development. The crosstalk between the HPA and the Microbiome Gut Brain Axis (MGBA) is particularly high in the hippocampus, the most consistently disrupted neural region in persons with schizophrenia. Animal models suggest that the MGBA remains influential on behavior and physiology across developmental stages, including the perinatal window, early childhood, adolescence, and young adulthood. Understanding the role of the microbiome on critical risk related stressors may enhance or transform of understanding of the origins of schizophrenia and offer new approaches to increase resilience against stress effects for preventing and treating schizophrenia.

OBJECTIVE:Eating disorders (ED) and schizophrenia are frequently comorbid and schizophrenia shares genetic susceptibility with anorexia. Many factors associated with schizophrenia can disrupt eating, but ED can present years before schizophrenia. If premorbid ED distinguishes a particular subtype of schizophrenia, then phenotypic features may differ between schizophrenia cases with and without premorbid ED. METHOD/METHODS:This secondary analysis used data from an inpatient schizophrenia research study that comprehensively assessed life course psychiatric disorders (DIGS interview), intelligence (WAIS), global assessments of function (GAF) and assessed symptoms during medication-free and fixed dose neuroleptic phases (PANSS). RESULTS:(17.9, P < .0001). Only the premorbid ED group had gustatory hallucinations. They also demonstrated significantly more severe psychotic and disorganization symptoms during medication-free and fixed dose treatment phases, despite similar negative symptoms and GAF scores, as other cases. The premorbid ED group had significantly better cognition overall, but relatively lower nonverbal than verbal intelligence. DISCUSSION/CONCLUSIONS:Premorbid ED may define a specific subtype of schizophrenia that is common in females. Their more severe psychotic symptoms and better IQ, despite similarly impaired function and negative symptoms as other cases, suggests a distinct pathophysiology. Premorbid ED should be considered in evaluating risk states for schizophrenia, and as a relevant phenotype for treatment resistant schizophrenia.

BACKGROUND:Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood. METHODS:Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis. RESULTS:). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden. CONCLUSIONS:CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage.

This study used machine-learning algorithms to make unbiased estimates of the relative importance of various multilevel data for classifying cases with schizophrenia (n = 60), schizoaffective disorder (n = 19), bipolar disorder (n = 20), unipolar depression (n = 14), and healthy controls (n = 51) into psychiatric diagnostic categories. The Random Forest machine learning algorithm, which showed best efficacy (92.9% SD: 0.06), was used to generate variable importance ranking of positive, negative, and general psychopathology symptoms, cognitive indexes, global assessment of function (GAF), and parental ages at birth for sorting participants into diagnostic categories. Symptoms were ranked most influential for separating cases from healthy controls, followed by cognition and maternal age. To separate schizophrenia/schizoaffective disorder from bipolar/unipolar depression, GAF was most influential, followed by cognition and paternal age. For classifying schizophrenia from all other psychiatric disorders, low GAF and paternal age were similarly important, followed by cognition, psychopathology and maternal age. Controls misclassified as schizophrenia cases showed lower nonverbal abilities, mild negative and general psychopathology symptoms, and younger maternal or older paternal age. The importance of symptoms for classification of cases and lower GAF for diagnosing schizophrenia, notably more important and distinct from cognition and symptoms, concurs with current practices. The high importance of parental ages is noteworthy and merits further study.

The association of early trauma exposure with current cognition was examined in a research series of 56 schizophrenia cases with respect to the BDNF Val66Met polymorphism (rs6265, Val66Val, Val66Met, Met66Met), as met allele carriers have reduced neurotrophic activity. The Perceptual Organization Index had a significant negative correlation with trauma exposures only in met carriers, including early physical abuse, general trauma after age 18 years, and physical abuse. Within the Val66Val subgroup, there were no significant correlations between WAIS indices and traumatic experiences.