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A proportion of patients with major depressive disorder (MDD) show cognitive impairment that is associated with treatment nonresponse and poorer functional recovery. A broader range of cognitive dysfunction has been found to be associated with treatment-resistant depression (TRD) and with the presence of psychotic symptoms. Thus far, the effects of psychotic symptoms on the neuropsychological profile of patients with treatment-resistant MDD have not been investigated.In the present study, 44 treatment-resistant MDD patients with (n = 12) or without (n = 32) psychotic symptoms—based on the Structured Clinical Interview (SCID I)—were compared with regard to their clinical status and performance in a neuropsychological test battery. The neuropsychological test battery assessed verbal skills, processing speed, executive functions and memory functions.Patients with psychotic TRD displayed lower performance in processing speed than non-psychotic patients. The group differences were not associated with the severity or pervasiveness of depressive symptoms. The duration of depression (from the onset of depressive symptoms) was longer in the group of non-psychotic TRD patients, but no other group differences with respect to sociodemographic characteristics, age at the onset of symptoms or symptom severity were found.The results imply that among individuals suffering from MDD, patients with the psychotic subtype who are unresponsive to standard pharmacological and psychosocial treatments have an increased vulnerability to cognitive dysfunction in the area of processing speed. Further research with larger sample size is warranted to determine whether these group differences persist after remission.