Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD.

Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task.

The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall.

The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.

Individuals with major depressive disorder (MDD) tested in either the depressed (dMDD) or remitted phase (rMDD) recall fewer specific and more categorical autobiographical memories (AMs) compared to healthy controls (HCs). The current study aimed to replicate findings of AM overgenerality in dMDD or rMDD, and to elucidate differences in neurophysiological correlates of AM recall between these MDD samples and HCs.

Unmedicated participants who met criteria for the dMDD, rMDD or HC groups (n = 16/group) underwent functional magnetic resonance imaging (fMRI) while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from an assigned semantic category and counting the number of risers in a letter string.

The results showed fewer specific and more categorical AMs in both MDD samples versus HCs; dMDDs and rMDDs performed similarly on these measures. The neuroimaging results showed differences between groups in the dorsomedial prefrontal cortex (DMPFC), lateral orbitofrontal cortex (OFC), anterior insula, inferior temporal gyrus and parahippocampus/hippocampus during specific AM recall versus example generation. During specific AM recall cued by positively valenced words, group differences were evident in the DMPFC, middle temporal gyrus, parahippocampus/hippocampus and occipital gyrus, whereas differences during specific AM recall cued by negatively valenced words were evident in the DMPFC, superior temporal gyrus and hippocampus.

AM deficits exist in rMDDs, suggesting that these impairments constitute trait-like abnormalities in MDD. We also found distinct patterns of hemodynamic activity for each group as they recalled specific AMs, raising the possibility that each group used a partly unique strategy for self-referential focus during successful retrieval of specific memories.