Insight Matters
Fall, 2003

Resculpting the Brain: Psychiatric Treatments and Brain Repair
by Henry A. Nasrallah, M.D., Editor

Recent neuroscience research has been producing some fascinating revelations for psychiatry: both pharmacotherapy and psychotherapy appear to exert their beneficial effects by generating new brain tissue: neurons, glia, axons, dendrites, dendritic spines and synapses. It is the dawn of a new era where effective psychotropics and psychotherapies appear to act as "neuroplasticity enhancers" and thereby gradually re-engineer the structure of the brain to mend and heal psychiatric brain disorders.

It began with the worrisome discovery over the past decade that psychotic episodes were associated with progressive and extensive loss of brain tissue in schizophrenia as measured on follow-up MRI brain scans. Subsequently, similar adverse neuroplastic changes were observed in other psychiatric disorders such as bipolar disorder, major depression and post-traumatic stress disorder. The volume of the hippocampus, a critical brain structure for cognition and information processing, was found to be reduced by up to 30% in psychotic and mood disorders. The frontal and temporal cortices also showed progressive tissue loss in schizophrenia. This initially was suspected to be "neurodegeneration" or "neurotoxicity" resulting from repetitive psychotic or depressive episodes. However, research points to multiple possible mechanisms such as apoptosis, hypercortisolemia, inflammation or excessive free radical formation.

Then in the late 1990's, a long-standing dogma about the brain was shattered. Contrary to the rigid long-standing belief that brain cells that are lost for any reason are never replaced, it was discovered that neurogenesis is an ongoing process in several brain regions (hippocampus, periventricular area and olfactory tubercle). However, unless neuroprotective factors are in place, only a small proportion of these progenitor brain cells survive and differentiate into neurons or glia that get consolidated into existing brain tissue.

In tandem with the above, a series of surprising findings emerged about psychotropic medications: lithium, valproate and SSRI's were found to enhance neurogenesis. Then, atypical antipsychotics, but not haloperidol, were found to stimulate neurotropic factors , tipping the balance in favor of cell survival after they are generated. Thus,mood stabilizers, antidepressants and atypical antipsychotics appear to have neuroprotective properties that gradually help replenish brain tissue by enhancing the survival and reducing the apoptotic resorption of newly created progenitor brain cells. Furthermore, atypical antipsychotics
have been reported to modulate the immune response and consequently decrease the inflammatory response.

The resulting epiphany is that psychopharmacology may work by repairing the structure of the brain, not just by correcting a "chemical imbalance". The full therapeutic/neuroprotective effects become more evident with uninterrupted long-term use[ probably 6-12 months or longer]. The possibility that a steady stream of new neurons and glia can form, migrate and establish connections with existing brain tissue raises the possibility that clinical recovery and concomitant neuroanatomical recovery may be possible in schizophrenia in the context of effective relapse prevention.

The effects of psychotherapy can be no less impressive in terms of structural brain changes. Talking, listening, expressing feelings, gaining insights, forming memories and connecting the conceptual dots between behaviors and experiences, are all neurobiological processes that trigger neuroplasticity. With every psychotherapeutic process, dendritic spines and inter-neuronal circuitry are created, gradual modifying the structural connectivity of the brain.

Thus, whether we psychiatrists conduct a psychotherapeutic session or administer a medication, we may be, in fact, reshaping and remolding our patient's brain structure! Who would have thought that biopsychosocial treatment is a process of therapeutic neuroanatomical resculpting that can rejuvenate and heal ailing brains.

Why do they call us shrinks? Neuroplastic surgeons seems more appropriate!

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