Science does not describe and explain nature, rather, nature as exposed to our method of questioning -- Werner Heisenberg

Our brain, as our psyche, is custom made for us by our genes in non-linear dynamic, emergent relation with our unique environments and, importantly, how our experience is interpreted (by ourselves, others and our particular culture) and reacted to. Neurodiversity should not be a reason for social stigma, alienation or exclusion. As in ethnic or sexual diversity, neurodiversity can be a significant enriching experience for a particular culture, if the ‘boundaries’ of the latter are not excessively rigid and calcified, but simultaneously remain in a position of openness as well as continuity.

In graduate school in the 1970’s, we were taught that unlike bone marrow, skin, and intestines, etc., the CNS does not have a continuous renewal process. Pasko Rakic, in his neurobiology lectures at Yale, would say, “with respect to my skin, I am a new man every year.” As in much of science, previously espoused doctrines, have given way to cumulative challenging evidence to the contrary, e.g., neurogenetic reductionism and the theory/dogma of ‘no new neurons.’ For most of the history of neurobiology, the adult human brain was considered to be non-neurogenic, i.e., no new neurons are generated. However, now it is an established fact, that the adult human brain does precisely what tissue engineers intend to do in stem cell-based therapies for the brain: it creates new neurons. It is the stem cells of the adult brain which drives adult neurogenesis. And as I pointed out in a previous posting, this is also a ‘gift’ from the fetus to her or his mother. Fetal cells cross the maternal blood brain barrier, emerge as neurons, glial and immune cells and respond to maternal molecular distress signals (what a beautiful metaphor for therapeutic symbiosis!).

Gerd Kempermann (2006, Adult Neurogenesis: Stem Cells and Neuronal Development in the Adult Brain published by Oxford University Press) noted:

“The fundamental change that modern stem cell biology has introduced to science is similar to the paradigm shift caused by the sequencing of the genome: our view has changed from a deductive perspective, which we have become accustomed to in science, to an essentially open situation. Genes and stem cells are to a large degree characterized by their potential. This causes a reversed perspective that is much more difficult to deal with than the classical method, working backwards along a chain of causes...High-dimensional regulatory networks with seemingly fuzzy or chaotic properties within a cell and on a systems level have always made it impossible to speak in a strict and simple sense of causes. Therefore, what on the surface we perceive as a paradigm shift is actually a shift in perception itself and in awareness” (pp. 3-4).

Neurogenesis is the production of new neurons in the adult brain. It is much more a process than an event. It is much more than the division of a precursor cell. It involves multilevel molecular decisions, including securing the survival of the daughter cells. It entails also sending out the cellular processes of dendrites and axons which form synapses with other cells (some neurobiologists, like New York University’s Joseph LeDoux in his 2002 volume Synaptic Self,: How Our Brains Make Us Who We Are, “attempt to reduce the self neurobiologically to processes occurring and emerging from the synapses, even though our focus has moved to the intricate intracellular signaling transduction processes which lead to gene transcription and translation). A brain region which we call ‘neurogenic,’ can generate new neurons. Neurogenic implies two events: the presence of immature precursor cells from which new neurons can develop, and, a microenvironment that is permissive for neurogenesis to occur. In the adult mammalian brain there are two known neurogenic regions: the hippocampus (which is a key area in schizophrenia research) and the olfactory system. There are numerous anecdotal reports of neurogenesis occurring in other regions (e.g., the prefrontal cortex), but these have not passed the stage of being anecdotal.

Stress/fear/anxiety may be the most salient negative regulator of adult hippocampal neurogenesis. Research has demonstrated that stress downregulates cell proliferation in the hippocampal dentate gyrus and in the consecutive stages of neuronal development. Prenatal stress has been demonstrated to exert long-lasting negative effects on adult neurogenesis and appears to reduce the baseline level of adult hippocampal neurogenesis. It is also known (Heine et al 2004), that the negative effects of even prolonged stress on adult hippocampal neurogenesis are reversible. I theorized, in the past, that this may be an important factor in explaining the neuroimaging data in outcomes of schizophrenia: with successful treatment, ventriculomegaly (enlarged ventricles, presumed to be the result of atrophic processes in surrounding neural tissue, particularly the hippocampus and prefrontal regions) can be reversed.

In short, as persons recover, their brains recover from atrophic processes secondary to the cascading effects of stress, e.g., excessive glutamate, calcium, cortisol, etc. Psychosocial stress and social isolation (significantly contributing to the ‘negative’ symptoms in severe mental illness? -- the kind, I believe, is most salient in severe mental illness) has been demonstrated to decrease cell proliferation in the hippocampus, particularly in the dentate gyrus. Enriched environments and physical exercise (I believe secure attachments as well) increase neurogenesis. It may be, that the relation between stress and neurogenesis, follows an inverted U curve, i.e., low stress causing neurogenesis, and high levels, inhibiting neurogenesis. Glucocorticoids, i.e., cortisol, are regulators of neurogenesis.

Depression is associated with disturbed regulation of cortisol (as is bipolar disorder and schizophrenia). Depression can be ‘caused’ by prolonged anxiety/stress/fear (see the excellent volume Stress, the Brain and Depression by Herman van Praag, an early biological psychiatrist who is lately pointing out the significant limitations of reductionism, Ron de Kloet and Jim van Os, an excellent schizophrenia researcher whose research has demonstrated the significant role of psychosocial risk factors, not in the course and outcome, but in the initiation itself of the schizophrenias-published by Cambridge University Press in 2004). Stress also affects the number of sphere-forming cells that that can be derived from the brain, which serves as an estimate of the number of neural precursor cells in the subventricular zone (SVZ).

Postnatal handling, calming affectionate contact (perhaps a good case for adjunctive therapeutic massages in our socially isolated patients), reversed the inhibitory effects of prenatal stress on neurogenesis, i.e., increasing the number of sphere-forming cells. In recent research, which I have previously posted, oxytocin, which helps to consolidate bonding and affectionate ties between caregivers and offspring, is anxiolytic in its effects (therefore, another potential candidate for increasing neurogenesis and counteracting the atrophic processes associated with chronic stress). Nature constantly reveals a wisdom, conserved across generations, which has alerted us to the fundamental neurobiological basis of the importance of affectionate contact, secure attachments, compassion, etc.

Brian Koehler PhD
Postdoctoral Faculty of New York University
80 East 11th Street #339
New York NY 10003
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brian_koehler@psychoanalysis.net