A deficit of oligodendrocytes has been reported in the prefrontal cortex (PFC) in schizophrenia (SCH), bipolar disorder (BPD) and major depression (MDD). Also, a decreased size of pyramidal neurons has been detected in layer III in SCH and in mood disorders. Since oligodendrocytes have a trophic influence on neurons, reduced neuronal size reported in these disorders might be associated with the deficit in subpopulation of perineuronal oligodendrocytes. We hypothesized that deficit of perineuronal oligodendrocytes might occur in SCH and mood disorders.We estimated the number of oligodendroglial satellites of pyramidal neurons and the size of pyramidal neurons in layer III (Brodmann's area 9) in Nissl stained sections in SCH, BPD, MDD and normal controls. The Stanley Foundation Neuropathology Consortium brain collection consisted of 15 cases in each of four groups was used.We detected a prominent and significant reduction in the number of perineuronal oligodendrocytes in the sublayers IIIa, IIIb and IIIc in SCH, BPD and MDD as compared to controls. The BPD group differed significantly from SCH group and from MDD group. There were no significant differences in somal sizes of pyramidal neurons in the sublayers IIIa, IIIb, IIIc between each of the psychiatric groups and the control group. Only BPD group showed significantly smaller neuronal size in sublayer IIIc as compared to controls.Our data provide evidence for a deficit of perineuronal oligodendrocytes in severe mental disorders that may play a key role in the pathophysiology of SCH, BPD and MDD.