Inflammatory shift in long-standing bipolar disorder

By Eleanor McDermid, Senior medwireNews Reporter

Patients with chronic bipolar disorder, but not those with schizophrenia, have a shift towards an M1 rather than an M2 macrophage response, research suggests.

M1 macrophages are “regarded as pro-inflammatory, phagocytic, potentially tissue damaging”, explain the researchers, whereas M2 macrophages are “immunomodulatory, tissue remodeling and pro-reparative.”

Paolo Brambilla (University of Udine, Italy) and co-workers measured messenger (m)RNA levels of various inflammatory and immune cell markers in peripheral blood mononuclear cells obtained from 20 patients with bipolar disorder and 20 with schizophrenia (both groups had been ill for a median of 14 years) and 20 mentally healthy controls.

As reported in Translational Psychiatry, they found that mRNA levels of the M1 monocyte markers interleukin (IL)-6 and CC chemokine ligand (CCL)-3 were significantly increased in the bipolar disorder patients relative to both schizophrenia patients and controls.

Conversely, mRNA levels of the M2 markers, CCL-1, CCL-22 and IL-10 were significantly lower in the bipolar patients than in the other two groups. Neither M1 nor M2 monocyte markers differed between the schizophrenia patients and controls.

The finding of a shift towards M1 monocytes in bipolar patients supports a previous study “and strengthens the case for the identification of a subgroup of [bipolar disorder] patients who may benefit by anti-inflammatory therapies”, say the researchers.

They caution, however, that it is not yet clear whether the shift is a cause or consequence of bipolar disorder. “In the latter case, anti-inflammatory therapeutic strategies would be less relevant”, they note. “If, however, this monocyte modulation precedes disease onset, it is most likely connected to its etiology, and its therapeutic targeting may be extremely efficacious.”

The team also found some evidence for changes in T-helper cell (Th) responses in bipolar disorder patients, although the direction of change was less clear. mRNA levels of the Th1 marker C–C chemokine receptor (CCR)-5 were significantly reduced in patients with bipolar disorder relative to controls but not when compared with levels in the schizophrenia patients.

However, mRNA levels of the Th2 marker CCL-2 were also reduced in bipolar patients versus schizophrenia patients and controls, while levels of another Th2 marker – IL-4 – were significantly increased relative to levels in controls but not schizophrenia patients.

Finally, and in line with previous research, patients with bipolar disorder had significantly reduced mRNA levels of the T-regulatory cell marker transforming growth factor β relative to schizophrenia patients and controls.

As this is “considered a potent anti-inflammatory mediator” its downregulation may therefore “expose the brain of subjects with [bipolar disorder] to an increased susceptibility to neurotoxicity”, says the team.

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