INTRODUCTION: Depression is a heterogeneous disorder with diverse clinical presentations and etiological underpinnings, necessitating the identification of distinct subtypes to enhance targeted interventions. Dissociative symptoms, commonly observed in major depressive disorder (MDD) and linked to early life trauma, may represent a unique clinical dimension associated with specific neurocognitive deficits. Although emerging research has begun to explore the role of dissociation in depression, most studies have provided only descriptive analyses, leaving the mechanistic interplay between these phenomena underexplored. The primary objective of this study is to determine whether MDD patients with prominent dissociative symptoms differ from those without such symptoms in clinical presentation, neurocognitive performance, and markers of functional connectivity. This investigation will be the first to integrate comprehensive clinical evaluations, advanced neurocognitive testing, and high-resolution brain imaging to delineate the contribution of dissociative symptoms in MDD. METHODS: We will recruit fifty participants for each of three groups: (1) depressive patients with dissociative symptoms, (2) depressive patients without dissociative symptoms, and (3) healthy controls. Diagnostic assessments will be performed using the Structured Clinical Interview for DSM-5 (SCID) alongside standardized scales for depression severity, dissociation, and childhood trauma. Neurocognitive performance will be evaluated through a battery of tests assessing memory, attention, executive function, and processing speed. Structural and functional magnetic resonance imaging (MRI) will be conducted on a 3 Tesla scanner, focusing on the connectivity of the Default Mode Network with key regions such as the orbitofrontal cortex, insula, and posterior cingulate cortex. Data analyses will employ SPM-12 and Matlab-based CONN and PRONTO tools, with multiclass Gaussian process classification applied to differentiate the three groups based on clinical, cognitive, and imaging data. DISCUSSION: The results of this study will introduce a novel perspective on understanding the connection between major depressive disorder and dissociation. It could also aid in pinpointing a distinct form of depression associated with dissociative symptoms and early childhood stressors. CONCLUSION: Future research, aiming to forecast the response to biological and psychological interventions for depression, anticipates this subtype and provides insights.