Treating the Toughest Cases of Depression and Brain Illness

Inflammatory Aspects of Psychiatric Illness

There may be pharmacologic remedies that increase the likeliehood of preparing a person to regain or finally become resilient. In this regard, Miller & Raison remind us of the complex relationship of the immune system and neuropsychiatric wellness:

The role of inflammation as a common mechanism of disease including disorders such as cardiovascular dis- ease, diabetes, and cancer has been considered one of the major insights of the decade. The extension of this important revelation to neuropsychiatric disorders is now beginning to have a major impact in the disciplines of Psychiatry and Neurology, as researchers and clinicians alike are recognizing the importance of immune and inflammatory processes in neurodegenerative disorders, mood and anxiety disorders as well as schizophrenia. Probably, the greatest area of focus to date in Psychiatry has been on the potential role of the activated immune system in depression.

We know that systemic inflammation will commonly affect the brain through direct and less-direct means. Consequences include mild depression or depression-like illness. Hannestad comments:

“Systemic inflammation in humans causes an in- crease in depressive symptoms and concurrent changes in glucose metabolism in the insula and cingulate—brain regions that are involved in interoception, positive emotionality, and motivation. In fact at an extreme an immune dysbalance is a likely agent in the evolution of and maintenance of thereby chronic schizophrenia-spectrum illnesses.”

Of extreme interest is the opportunity for treatment of CNS inflammation by anti-inflammatory approaches. While relatively more ancient interventions have been noted to help in the occasional patient, some modern approaches are being refined. These include the occasional application of adjunctive treatment with COX-2 inhibitors for mood, schizophrenia-spectrum, and autism-spectrum conditions. Tobinick discovered a direct approach to CNS inflammation through a relatively non-invasive perispinal injection:

Etanercept is a potent antagonist of TNF, a pleotropic immune signaling molecule that is also a pivotal regulator of synaptic function. Excess TNF is centrally involved in the pathogenesis of a variety of inflammatory neurological disorders, including Alzheimer’s disease, sciatica, traumatic brain injury and spinal cord injury. Perispinal etanercept produces rapid improvement in both Alzheimer’s disease and sciatica and in other forms of disc-related pain. Basic research and the observed clinical effects suggest that etanercept has the surprising ability to penetrate into the cerebrospinal fluid after perispinal administration. Perispinal administration is a novel method of delivery designed to introduce this anti-TNF molecule into the bidirectional cerebrospinal venous system and the cerebrospinal fluid to facilitate its selective delivery to either spinal structures or the brain.