![]() ![]() Imaging studies using single photon emission computed tomography (SPECT) (Vogeley et al., 2001b), positron emission tomography (PET) (Happe et al., 1996) or fMRI (Gallagher et al., 2000) have utilized different ToM paradigms (Stuss et al., 2001 Vogeley et al., 2001a) with mixed results. The interest in mirror neurons (Rizzolatti and Fabbri-Destro, 2008) provides a potential neural basis for intent prediction of others. Lower social function is associated with higher risks for symptom recurrence 1 year after recovering from a major depressive episode (Uekermann et al., 2008). The failure to evolve mentalization partially explains pervasive developmental disorders (Ozonoff et al., 1991 Happe, 1994 Happe et al., 1996), schizophrenia (Pilowsky et al., 2000) and reduced social interactions in depression (Uekermann et al., 2008). Mentalization is a higher order capacity, either deficient in clinical populations or progressively enhanced with better caretaking and affective attunement. Theory of mind (ToM) is a research and conceptual rubric of an “imagined involvement” that was derived from studies of autism. Functional neuroimaging studies consistently find abnormal ventral limbic and paralimbic activity in depression (Price and Drevets, 2009) – the very same regions implicated in the mediation of social relatedness and mentalization (Choi-Kain and Gunderson, 2008 Hartmann, 2009). Also, critical social events marked with insecure attachment or losses of significant others often precipitate depressive symptoms (Anisman, 1984). Conversely, low levels of oxytocin have been linked to depression (Bell, 2006), with patients experiencing and observed to possess “dis-affiliation” with others. It is increasingly released in affectively rich dyadic settings such a when social attunement occurs between mother and infant, in breastfeeding, early skin to skin contact, and later in sexual intercourse and climax (Nelson and Panksepp, 1998 Uvnas-Moberg, 1998). It begins in infancy and is facilitated by positive social interactions (Fonagy and Target, 2007) and early attachment experiences (Meins et al., 2002).Īlthough little is known about the neurophysiology of such experiences, there is evidence that oxytocin, a neuropeptide, promotes positive social interactions and preferences (Hurlemann et al., 2010), Winslow and Insel, 2004 Zak et al., 2005), enhances socially reinforced learning and faces recognition (Marsh et al., 2010), Guastella et al., 2008), exerts anxiolytic effects and is a key modulator of early mother-infant bonding and maternal caretaking (Panksepp, 2005). Mentalization allows individuals to estimate others’ states of mind, and one's reactions and reflections upon that approximation represent an advantageous ability given that humans need good social bonds for maximum health, adaptation, and richer relationships. Mentalization, a developmentally derived ability to affectively and cognitively infer the mental state of others is crucial to sociality and is enhanced by propitious genetics and secure attachments (Choi-Kain and Gunderson, 2008 Hartmann, 2009). Further studies are needed to explore long-term exposure to pro-social neuropeptides on mood in depressed populations and assess their clinical relevance. Conclusion: Depression is associated with increased paralimbic activity during emotional mental attribution of others, appearing to be distinctly modulated by oxytocin when compared to healthy controls. Oxytocin also led to inverse effects in reaction times on attribution task between groups, with controls getting faster and depressed individuals slower to respond. Compared to placebo, oxytocin in depressed subjects showed increased activity in the superior middle frontal gyrus and insula, while controls exhibited more activity in ventral regions. Depressed subjects showed increased anterior ventral activation for the RMET minus gender identification contrast whereas matched controls showed increased dorsal and frontal activity. Results: Before oxytocin administration, RMET engaged the medial and lateral prefrontal cortex, amygdala, insula and associative areas. Each subject performed reading the mind in the eyes task (RMET) before and after inhalation of oxytocin or placebo control for a total of 80 scans. Method: We enrolled 10 unmedicated depressed adults and 10 matched healthy controls in a crossover, double blind placebo controlled fMRI 40 i.u. To date, no study has looked at the effects of oxytocin in modulating brain activity in depressed individuals nor attempted to correlate this activity with attribution of mental activity in others. Background: Oxytocin is a stress-attenuating and pro-social neuropeptide. ![]()
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