Increased densities of T and B lymphocytes indicate neuroinflammation in subgroups of schizophrenia and mood disorder patients

An increasing number of clinical, epidemiological and genetic studies as well as investigations of CSF and blood suggests that neuroinflammation plays an essential role in the etiology of schizophrenia and mood disorders. However, direct neuropathological evidence of inflammation within the brain tissue remains sparse and the regional distribution of lymphocytes as surrogate markers of blood-brain barrier (BBB) impairment has not yet been investigated in this context. Densities of T and B lymphocytes were assessed in coronal whole brain sections of 22 patients with schizophrenia and 20 patients suffering from major depression or bipolar disorder, compared to 20 individuals without neuropsychiatric disorders from the Magdeburg Brain Collection. Cell densities were determined by immunohistochemical staining (anti-CD3 for T cells, anti-CD20 for B cells), followed by automated microscopic image acquisition and analysis. Hierarchical clustering and detailed cluster analysis were performed to detect possible subgroups of patients. Regional distribution was assessed by analysis of color coded mappings based on microsopic scans. Elevated lymphocyte density was found in 7 out of 20 mood disorder patients (adj. p = 0.022; Fisher's exact test, FET), 9 out of 22 schizophrenic patients (adj. p = 0.014; FET) and in 1 of 20 controls (p < 0.005; FET). Several cases showed different patterns of infiltration affecting cortical regions or subcortical white matter, while some presented diffuse infiltration. In two thirds of patients, no increased lymphocyte density could be found. The current findings indicate that lymphocyte infiltration occurs in a greater proportion of schizophrenia and mood disorder patients as compared to healthy controls. Under healthy conditions lymphocytes rarely cross the BBB. Thus, higher densities are considered indicators of neuroinflammation associated with an impairment of the BBB.