BackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25 years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression.

Background Modulation of nicotinic acetylcholine receptors (nAChRs), specifically α4β2 subunit containing nAChRs, may be effective in the treatment of patients with major depressive disorder (MDD). Using [123I] 5-I-A-85380 single photon emission computed tomography (SPECT), we studied β2 subunit containing nAChR (β2*-nAChR) availability in patients with MDD. In order to understand the molecular basis of the change in receptor availability, we also studied β2*-nAChR binding in postmortem samples of human brains of MDD subjects. Methods 23 medication-free, early-onset, non-smoking subjects with familial MDD (8 acutely depressed (aMDD), 15 euthymic, recovered MDD subjects (rMDD)), and 23 age- and gender-matched, non-smoking controls had one [123I] 5-I-A-85380 SPECT scan and a magnetic resonance imaging (MRI) scan. β2*-nAChR availability was quantified as VT/fP. β2*-nAChR binding was analyzed in postmortem samples of the prefrontal cortex in 14 subjects with MDD and age-matched controls with [125I] 5-I-A-85380. Results β2*-nAChR availability in aMDD and rMDD subjects was significantly lower across all brain regions than in respective controls and lower in aMDD subjects than in rMDD subjects. MDD patients showed significant correlations between β2*-nAChR availability and lifetime number of depressive episodes, trauma and anxiety scores. There were no differences in β2*-nAChR number between groups in the human postmortem study. Conclusion β2*-nAChR availability is decreased in patients with MDD. The difference between β2*-nAChR availability in vivo and in postmortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability; lower receptor availability for the SPECT ligand could be caused by increased endogenous acetylcholine.

Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.