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Nicotine dependence and major depressive disorder (MDD) are highly comorbid, yet causal links between these prevalent disorders are unclear. One possible mechanism is that nicotine ameliorates MDD-related neurobiological dysfunction in specific networks. For instance, cortico-striatal circuitry is enhanced by nicotine, and such paths are disrupted in individuals with MDD. Specifically, MDD has been associated with reduced connectivity between the nucleus accumbens (NAc) and rostral anterior cingulate cortex (rACC) but enhanced connectivity between the dorsal striatum (DS) and dorsolateral prefrontal cortex (DLPFC). Determining whether nicotine normalizes these circuits in non-smokers with MDD may elucidate mechanisms underlying links between disorders. This was tested by administering placebo and a 2-mg dose of nicotine to unmedicated non-smokers with and without MDD prior to collecting resting-state functional magnetic imaging data using a cross-over design. On placebo, individuals with MDD showed significantly reduced NAc-rACC and a trend for enhanced DS-DLPFC functional connectivity relative to healthy controls. In MDD, acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. Nicotine's effects on NAc-rACC connectivity was influenced by anhedonia, consistent with the role of this network in reward and nicotine's ability to enhance reward deficiencies in MDD. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD. Nicotine's influence on these circuitries highlights a possible mechanism whereby individuals with MDD are more vulnerable to develop nicotine dependence. Findings suggest that nicotinic agents may have therapeutic effects on disrupted cortico-striatal connectivity.

Objective: Persons in psychiatric inpatient hospitals represent a unique population with high rates of suicidal ideation and behavior as well as childhood maltreatment. Lower levels of perceived distress tolerance (DT) are associated with a history of childhood maltreatment and suicidal ideation and behavior in adulthood. Our study examined the association of childhood maltreatment severity with self-report and behavioral indices of suicide through perceived DT in a sample of adults in an acute-care psychiatric inpatient unit. We hypothesized that lower levels of perceived DT would account for the association between (a) childhood maltreatment severity and suicidal ideation severity and (b) childhood maltreatment severity and prehospitalization suicidality. Method: The sample was composed of 94 trauma-exposed adults (60% men; Mage = 33.43; SD = 12.06) admitted to a psychiatric acute-care inpatient hospital in a large metropolitan area in the southern United States. Approximately 55% of the sample were hospitalized due to suicidality, with an average number of 1.28 (SD = 2.42) prior suicide attempts; 3% of patients exhibited suicidality during their hospitalization. All patients reported experiencing at least one type of childhood maltreatment, with varying degrees of exposure. We conducted indirect effects analyses using PROCESS Macro for SPSS. Results: Childhood maltreatment severity was indirectly associated with both suicidal ideation severity and prehospitalization suicidality through DT. Conclusions: Findings advance our understanding of the association between childhood maltreatment and increased risk for suicidal ideation and behavior in adulthood, specifically among the psychiatric inpatient population.