More evidence for an immune/inflammatory imbalance in both bipolar disorder and teenage suicide

Summary: Neuroinflammatory signaling molecules are elevated in bipolar disorder patients compared to controls. Marked increases in proinflammatory cytokines are also observed in the brains of teen suicide victims. Brain inflammation, immune system dysregulation and the loss of self-tolerance are key factors in the management of BP and major depression.A paper just published in the Journal of Psychiatric Research offers further evidence for the role of neuroinflammation resulting from immune system dysregulation in bipolar disorder. The authors state:

"Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls."

The authors measured plasma levels of adiponectin, resistin, leptin, TNF-α and TNF-α soluble receptors in thirty bipolar patients along with thirty controls matched by age, gender and body-mass index (BMI). The subjects were also assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales. What did the data show?

"BD patients presented increased plasma levels of adiponectin, leptin and sTNFR1."

This is but one drop in a sea of emerging evidence for the role of brain inflammation and immune dysregulation in neuropsychiatric disorders that clinicians should consider in comprehensive case management. The authors conclude:

"This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD."

Another study in the same journal documents a marked increase in proinflammatory cytokines in the frontal lobes of teenagers attempting suicide. The authors observe:

""Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims."

So they evaluated 24 teenage suicide victims and 24 matched normal control subjects for gene and protein expression levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tissue necrosis factor (TNF)-α in the prefrontal cortex (PFC). Again we see the markers for brain inflammation:

"Our results show that the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α were significantly increased in Brodmann area 10 (BA-10) of suicide victims compared with normal control subjects."

This is the deepest biological expression of the loss of self-tolerance in these disorders. Autoimmune inflammatory conditions require evaluation of all the known underlying causal factors that may contribute to the loss of self and chemical tolerance in order to design the most helpful treatment plan. The authors conclude:

"These results suggest an important role for IL-1β, IL-6, and TNF-α in the pathophysiology of suicidal behavior and that proinflammatory cytokines may be an appropriate target for developing therapeutic agents."