Neonatal Developmental Neuroplasticity:
A Critical Contribution from Environment
Robert M. Post
Hubel and Wiesel won the Nobel Prize for medicine with their elegant dissection of the impact of visual deprivation on the biochemistry, physiology and microstructure of the ocular dominance columns in the visual cortex (Hubel and Wiesel, 1979). They elucidated a gradient of progressively more profound and irreversible effects in the normal development of visual pathways and processing as a function of depriving environmental input by reducing visual input in one eye to virtually zero by suturing it shut. Not only was there dysfunction and atrophy of the ocular dominance columns related to the deprived eye, but a compensatory increase in those columns synaptically related to the eye that continued to have normal visual stimulation (Wiesel and Hubel, 1965; Hubel and Wiesel, 1979, 1998).
Similar, and perhaps even more complex, interactions appear to be occurring in diencephalic, paralimbic and cortical circuits involved in mediating the normal processes of maternal infant nurturing and bonding. The lack of normal developmental trajectories in this domain have been repeatedly linked to vulnerability to depression in adults later in life (Emde et al, 1965; Powell et al, 1967; Brown et al, 1973a, b; Breier et al, 1988). Thus, the neuropsychobiology of such early environmental insults is of particular interest to the topic of this chapter, and re-emphasizes a role for environmental contingencies as well as genetic inheritance in vulnerability to affective illness.
The work of Kendler and associates provides a particularly cogent set of examples of both gene and environmental effects. As illustrated in Figure XVIII–11.1, a variety of early environmental losses or adversities are risk factors for subsequent depressions (Kendler et al, 1993). In addition, concurrent stresses and losses interact with these earlier vulnerabilities in the precipitation of affective episodes. Moreover, minor or neurotic depressions are precursors to more major depressions, and major depressions are a key risk factor for subsequent major depressive recurrences, all within the background of genetic vulnerability to the recurrent affective disorders. Whether such dual contributions would meet the more formal criteria enunciated earlier by Boomstra and Martin for gene-environment interactions remains to be delineated, and in this chapter we will use the term interactions loosely only to imply that effects of both inherited and environmental domains can be discernible.
A similar interactive schema is evident in the risk factors for suicidality in patients with bipolar disorder (Leverich et al, 2002a, b). A family history of severe suicides attempted or completed, as well as a family history of substance abuse, interacts with a variety of environmental experiential variables as precursors of suicide attempts (Figure XVIII-11.2). An increased incidence of suicide attempts is affected by genetics, course of illness variables, psychiatric Axis I and Axis II comorbidities, medical comorbidities, and a history of early extreme stressors and environmental adversities (physical or sexual abuse in childhood or adolescence), as well as more proximal stressors such as loss of significant others and lack of adequate access to mental and medical health care.
Thus, paradigms in unipolar depression and in suicidality in patients with bipolar illness both indicate powerful interactions of genetic and environmental variables. On the experiential side, both paradigms suggest components of episode sensitization and stress sensitization.
Perhaps the best clinical evidence for the occurrence of episode sensitization is the study of Kessing et al (1998) of more than 20 000 patients hospitalized for depression or mania. These investigators found that for both unipolar and bipolar patients, the best predictor of incidence and time to relapse was the number of prior episodes, supporting the hypothesis that episodes beget episodes. However, one has to caution that it is possible that those patients who are most vulnerable to recurrence were preselected and one may have a poor prognosis subgroup in those who have the most prior episodes and subsequent recurrences. Kessing and associates present statistical reasons to suggest that this is not the case (Kessing, 1998; Kessing et al, 1998), but such a proposition could only be resolved with a randomized prospective study of adequate versus inadequate long-term prophylaxis to see whether the intervening occurrence of episodes did change the future course; this study is not really possible given the ethical constraints against inadequate prophylaxis.
The studies of Brown and colleagues (Harris et al, 1986, 1987; Bifulco et al, 1987) are among the most elegant in demonstrating the interaction of proximal and distal stressors in the occurrence of depression. Brown and colleagues found that a variety of risk factors in single mothers appeared to be associated with the occurrence of depression upon the occurrence of a proximal stressor. One of these factors, again related to loss of a significant other (in this case loss of one's mother in childhood), could act as a predictor of subsequent depression. This occurred with a variety of other modulating variables including lack of a confidant, having more than four children at home to care for, and lack of employment. The study of Breier et al (1988) is particularly revealing in terms of the potential lasting effects of early