Individuals in a major depressive episode often display impairment in cognitive control, and this impairment exists outside of the acute phase of illness. Impairment in cognitive control also has been associated with exposure to childhood adversity (CA). The current study examined whether exposure to CA can explain variance in a component of cognitive control—inhibitory control—independent of diagnostic status in young adults with and without a history of depression. Healthy control individuals (n = 40) and individuals with remitted major depressive disorder (n = 53) completed a task measuring inhibitory control, reported level of CA and completed a scanning session to assess gray matter volume and resting state connectivity in regions associated with cognitive control. The results demonstrate that higher levels of CA were associated with poorer inhibitory control, reduced right middle frontal gyrus gray matter, decreased connectivity of salience and emotion networks and increased connectivity in cognitive control networks, even after controlling for diagnostic status, residual depression symptoms and current stressors. Together, the results suggest that inhibitory control impairment and intrinsic connectivity changes may be characterized as developmental sequelae of early stress exposure.

Recent work showed that unsupervised learning of a complex environment activates synaptic proteins essential for the stabilization of long-term potentiation (LTP). The present study used automated methods to construct maps of excitatory synapses associated with high concentrations of one of these LTP-related proteins [CaMKII phosphorylated at T286/287, (pCaMKII)]. Labeling patterns across 42 sampling zones covering entire cross sections through rostral hippocampus were assessed for two groups of rats that explored a novel two-room arena for 30 min, with or without a response contingency involving mildly aversive cues. The number of pCaMKIIimmunopositive (ϩ) synapses was highly correlated between the two groups for the 21 sampling zones covering the dentate gyrus, CA3c/hilus, and apical dendrites of field CA1, but not for the remainder of the cross section. The distribution of pCaMKIIϩ synapses in the large uncorrelated segment differed markedly between the groups. Subtracting home-cage values removed high scores (i.e., sampling zones with a high percentage of pCaMKIIϩ contacts) in the negative contingency group, but not in the free-exploration animals. Three sites in the latter had values that were markedly elevated above other fields. These mapping results suggest that encoding of a form of memory that is dependent upon rostral hippocampus reliably occurs at high levels in discrete anatomical zones, and that this regionally differentiated response is blocked when animals are inhibited from freely exploring the environment by the introduction of a mildly aversive stimulus.

There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs.

The medial and orbitofrontal regions of prefrontal cortex (PFC) have been implicated in guiding optimal behavior and updating the economic value of rewards that result from choice behaviors. Both regions mature through adolescence into early adulthood and are thus vulnerable to exposure to neurotoxins, such as alcohol, during this critical developmental window. We sought to examine how voluntary alcohol consumption during adolescence would alter long-term PFC function and subsequent decision-making behavior in adulthood. Male and female rats were given adolescent intermittent ethanol (AIE) exposure to provide voluntary access to alcohol during the period of PFC maturation. In adulthood, we assessed the long-term effects on decision-making behavior using a risk task in adulthood, while concurrently recording neural activity in orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC). While control animals' preferences for risky rewards increased with the likelihood of their delivery, AIE animals showed an overall reduction in their preferences for the risky option with higher levels of alcohol consumption, suggesting reduced discriminability of uncertain rewards and a shift away from the potential for reward omission. During task performance, neurons in mPFC and OFC responded to events (lever press, reward delivery). In mPFC, neurons with phasic increases at the time of lever press showed a reversal from larger elevations for risky presses in control animals to larger elevations for certain presses as prior alcohol consumption increased. Neurons in mPFC generally showed less discrimination of reward outcome with increased alcohol consumption as well. In OFC, responses to lever press were largely unaffected by AIE exposure. However, encoding of reward size in OFC showed differential effects in males and females. With higher alcohol consumption in males, OFC neurons showed largest excursions from baseline activity in response to largest reward, and smallest excursions for reward omission. This discrimination was reduced as prior alcohol consumption increased. In females, neurons with increased reward-activity, showed an overall higher level of activity due to stronger responses to certain rewards that were selected more frequently. Collectively the results show diminished capacity of PFC to encode decision-related elements to guide adaptive behavior and further clarify the lasting impact of adolescent alcohol use on neural function and behavior, even in the absence of continued use.