Faculty Bibliography

OBJECTIVE: The aim of this study was to meta-analyze the prevalence of symptoms before an initial mood episode of bipolar disorder (BD) and the prevalence of subthreshold symptoms before a BD mood episode recurrence, to facilitate early identification and prevention. METHOD: Systematic literature reviews were conducted in PsycINFO and PubMed for prospective or retrospective studies reporting on the prevalence and longest duration of symptoms before an initial or recurrent mood episode of BD. Random effects meta-regression explored whether geographic location, age, percentage of female individuals, and study quality moderated the overall prevalence. RESULTS: In 11 studies (n = 1,078), the prodrome preceding an initial mood episode lasted 27.1 +/- 23.1 months (range, 4.6-130 months). In 10 studies (n = 1,000), the subthreshold symptoms preceding a recurrent mood episode lasted 1.0 +/- 0.9 months (range, 0.5-1.3 months). The most common symptoms were largely consistent with diagnostic criteria symptoms associated with the subsequent mood polarity for both the initial prodrome and the period prior to a recurrent mood episode. Few moderators of symptom prevalences emerged, and significant heterogeneity remained. CONCLUSION: The initial prodromal period is sufficiently long and characterized by symptoms of the subsequent mood episode to make early identification and intervention programs feasible. Conversely, the period of subthreshold symptoms before a recurrent mood episode is short, mandating adequate psychoeducation of patients and families, monitoring of changes in sleep and activity, plus sufficiently frequent follow-up visits to identify patients before a mood episode recurrence. Future prospective investigations, designed to address the identified shortcomings in the extant literature, are needed to identify more clinically applicable information.

This register-based cohort study investigated whether paternal occupational exposure to inorganic lead was related to offspring risk for schizophrenia spectrum disorder (SSD). Exposed men (n=11,863) were identified from blood lead measurements taken at the Finnish Institute of Occupational Health in 1973-1983. Data on mothers and their offspring born from 1972-1984 were obtained from the national Population Information System. Two population comparison offspring for each exposed offspring were matched on date of birth, sex and area (n=23,720). SSD cases were identified from The Finnish Hospital Discharge Register. Hazard ratios of SSD between exposed groups were analyzed using conditional proportional hazards regression, adjusted for parental history of psychoses, parental ages, language of offspring, father's employment, and father's self-employment. After 26-38years of follow up, there were no significant differences in the incidence of schizophrenia, either between the offspring of exposed (188/11,863; 1.6%) and unexposed fathers (347/23,720; 1.5%) or based on blood lead levels (adjusted hazard ratios (aHR): 0.97, CI 0.52-1.83, 1.25, CI 0.85-1.82, 0.90, CI 0.54-1.49, and 1.38, CI 0.65-2.92 for lead categories <0.5, 0.5-0.9, 1.0-1.4, and >/=1.5mumol/L, respectively, as compared to population comparison). Parental psychosis, paternal age and offspring language were associated with offspring risk. The findings suggest that paternal exposure to lead is not a risk factor for schizophrenia in offspring. However, the majority of exposed fathers had low-level exposure, and we cannot exclude the possibility of an effect for higher exposures to lead.

A major component of perception is hedonic valence: perceiving stimuli as pleasant or unpleasant. Here, we used early olfactory experiences that shape odor preferences and aversions to explore developmental plasticity in circuits mediating odor hedonics. We used 2-deoxyglucose autoradiographic mapping of neural activity to identify circuits differentially activated by biologically relevant preferred and avoided odors across rat development. We then further probed this system by increasing or decreasing hedonic value. Using both region of interest and functional connectivity analyses, we identified regions within primary olfactory, amygdala/hippocampal, and prefrontal cortical networks that were activated differentially by maternal and male odors. Although some activated regions remained stable across development (postnatal days 7-23), there was a developmental emergence of others that resulted in an age-dependent elaboration of hedonic-response-specific circuitry despite stable behavioral responses (approach/avoidance) to the odors across age. Hedonic responses to these biologically important odors were modified through diet suppression of the maternal odor and co-rearing with a male. This allowed assessment of hedonic circuits in isolation of the specific odor quality and/or intensity. Early experience significantly modified odor-evoked circuitry in an age-dependent manner. For example, co-rearing with a male, which induced pup attraction to male odor, reduced activity in amygdala regions normally activated by the unfamiliar avoided male odor, making this region more consistent with maternal odor. Understanding the development of odor hedonics, particularly within the context of altered early life experience, provides insight into the development of sensory processes, food preferences, and the formation of social affiliations, among other behaviors. SIGNIFICANCE STATEMENT: Odor hedonic valence controls approach-avoidance behaviors, but also modulates ongoing behaviors ranging from food preferences and social affiliation with the caregiver to avoidance of predator odors. Experiences can shape hedonic valence. This study explored brain circuitry involved in odor hedonic encoding throughout development using maternal and predator odors and assessed the effects of early life experience on odor hedonic encoding by increasing/decreasing the hedonic value of these odors. Understanding the role of changing brain circuitry during development and its impact on behavioral function is critical for understanding sensory processing across development. These data converge with exciting literature on the brain's hedonic network and highlight the significant role of early life experience in shaping the neural networks of highly biologically relevant stimuli.

Introduction: Delayed sleep and meal timing promote metabolic dysregulation and obesity. Altered coordination of sleep and eating may impact food reward valuation in the brain; yet the independent and collective contribution of sleep and meal times remains unknown. This pilot, randomized crossover study manipulates both sleep and meal times while preserving normal sleep duration (8 h time in bed for 5 nights) to test how misalignment of sleeping and eating behaviors affects intrinsic functional connectivity (iFC) across reward and interoception-related brain circuitry. Methods: Resting state functional MRI scans (3T Siemens Skyra; TR = 2.5s; 2 x ~5-minute runs) were obtained for 4 participants (3 males; 25.3 +/- 4.6 years) who completed all 4 phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; late sleep/late meal). Normal meal times were 1, 5, 11, and 12.5 h after awakening and late meal times were 4.5, 8.5, 14.5 and 16 h after awakening. For a priori selected regions-of-interest (seeds) relevant to food reward and interoception, each seed's iFC was calculated as the correlation between its time-series and that of every voxel, and then contrasted between conditions. Standard preprocessing and seed-based correlations used the Configurable Pipeline for the Analysis of Connectomes v0.3.9. Results: Statistically significant (p late) additionally significantly modulated iFC between left ventral striatum and precuneus. Other significant iFC modulations of components of reward and interoception circuitry will also be presented. Conclusion: These pilot findings provide support that misalignment of sleep and food timing alters iFC in regions relevant to food reward and interoception, motivating examination in a larger sample