ABSTRACT
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.
Subject(s)
Brain/diagnostic imaging , Cognition/physiology , Depressive Disorder, Major/diagnostic imaging , Executive Function/physiology , Gray Matter/diagnostic imaging , Adolescent , Depressive Disorder, Major/psychology , Emotions , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Young AdultABSTRACT
BACKGROUND: Major depressive disorder (MDD) and anxiety disorders are highly comorbid, sharing many similar symptoms, including impairments in cognitive control. Deficits in cognitive control could be a potential mechanism underlying impaired emotion regulation in mood disorders. METHODS: Participants were 44 individuals with no history of mental illness (healthy controls, HC), 31 individuals in the remitted state of MDD (rMDD), and 18 individuals who met lifetime DSM-IV-TR criteria for rMDD and an anxiety disorder in remission (Comorbid). Participants completed a Parametric Go/No-Go (PGNG) test during fMRI. Event-related analyses modeled activity for cognitive control successes (Hits for Targets, Rejections for Lures) and failures (Commissions on Lures) on the PGNG task. RESULTS: The rMDD group showed significantly reduced activity within the cognitive control network (CCN) during Commission errors, including the middle frontal gyrus and inferior parietal lobule (IPL). The Comorbid group showed significantly reduced activity in several clusters within the CCN during correct Rejections, including the left IPL and right inferior frontal gyrus and greater subgenual cingulate. Notably, during correct Rejections, 60% of activation for the Comorbid group was within the Salience and Emotion Network (SEN), with 0% within the CCN. LIMITATIONS: The size of the Comorbid subgroup was modest, preventing subanalysis of the different AD subtypes. CONCLUSIONS: 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.
Subject(s)
Anxiety Disorders/physiopathology , Cognition/physiology , Depressive Disorder, Major/physiopathology , Gyrus Cinguli/physiology , Adolescent , Brain Mapping , Comorbidity , Emotions/physiology , Executive Function , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Young AdultABSTRACT
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 pCaMKII-immunopositive (+) 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 pCaMKII+ 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 pCaMKII+ 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.
