What we teach today is part biology and part history… but we don't always know where one ends and the other begins.
In 2010, Dante Cicchetti emphasized that the abnormalities in the broad domains of genetics, neurobiology, cognition, emotion, and interpersonal relationships in severe mental disorders do not exist in isolation. He encouraged researchers to strive to comprehend the interrelationships between the biological, psychological, and social in these disorders.
Canadian psychologist Donald Hebb was asked the question: “Which contributes more to personality, nature or nurture?” Hebb's reply was to ask which contributes more to the area of a rectangle, the width or length? Social neuroscientists John Cacioppo and William Patrick, in commenting on this question, emphasized neither nature nor nurture (nor both), rather, dynamic gene-environment interactions which regulate gene suppression or expression. Gene-environment interactions directly relevant to psychotic disorders can be observed in the research of Pekka Tienari and colleagues.
In Finland, Tienari and colleagues demonstrated that in the adopted-away children of a biological mother with schizophrenia, adoptive-family rearing behavior is predictive of the later development of a schizophrenia spectrum disorder. Tienari and colleagues also found a significant association between communication deviance in adoptive parents and thought disorder in those children thought to be at genetic risk for a schizophrenia spectrum disorder but not in low-genetic-risk adoptees. These results are consistent with either genetic control of sensitivity to the environment or environmental control of gene expression. Importantly, there was no difference in the presence of communication deviance in the adoptive parents of high-risk versus low-risk adoptees, thus suggesting that the adoptees at high risk did not have a special impact on increasing the communication deviance in their adoptive parents. From the perspective of Tienari and colleagues, diseases will tend to cluster in families not because of a direct genetic effect, but because relatives are more vulnerable to the risk increasing effects of a particular environmental factor.
In reviewing recent research on structural brain imaging in schizophrenia, Christos Pantellis noted: “It is beyond doubt that there are gross neuroanatomical changes in patients with schizophrenia, but these are probably non-specific, weakly related to the cardinal manifestations of the disorder, and of largely unknown cause.” Paul Harrison and colleagues point out that the neuropathological findings in schizophrenia are not diagnostically specific and there are few established clinicopathological correlations. Patrick Sullivan and colleagues emphasized that the “pathogenesis of schizophrenia is unknown, and no compelling biological markers of sufficient sensitivity and specificity exist.” Daniel Weinberger and Pat Levitt went so far as suggesting:
Schizophrenia, of course, is not something someone has; it is a diagnosis someone is given. It is worth considering that the syndrome of schizophrenia is not a disease at all, but a state of brain function based on an altered developmental trajectory from early programming with changing repercussions throughout life…That there appear to be numerous genetic and environmental factors that can contribute in various combinations to this recognizable state of altered brain function further suggest that what we call schizophrenia may represent “not the result of a discrete event or illness process at all, but rather one end of the developmental spectrum that for genetic and other reasons approximately 0.5 percent of the population will fall into.”
The term “neuroplasticity” refers to the capacity of the nervous system to exhibit structural and functional adaptations to impinging stimuli. One important molecular biological basis for neuroplasticity is the
Brian Koehler, Ph.D., is adjunct professor in the Departments of Social Work and the Postdoctoral Program in Psychotherapy and Psychoanalysis at NYU, and at the CUNY graduate psychology department. He has a private practice in Westchester and Manhattan.
transcriptional function of genes. The transcriptional function of genes, and therefore neuronal functioning, is responsive to social and environmental factors. Stress-induced neuroplastic changes may be observed in persons with schizophrenia. Ralph Hoffman suggested that social deafferentation-induced neuroplasticity plays a role in schizophrenia. He noted: “…it is at least plausible that severe social withdrawal in humans during critical developmental periods induces deafferentation-like reorganization in regions of association cortex underlying social cognition that consequently produces spurious experiences with social meaning (e.g., hallucinations, delusions).”
Genes do not code for psychosis per se, e.g., hallucinations or delusions, rather, they sometimes code for proteins. They can code for proteins which may increase or decrease certain vulnerabilities, which in interaction with high-risk environmental factors (e.g., urban birth/living, migration), may or may not cross the threshold into clinical psychosis. Weinberger and Gregor Berger reminded us that “genes do not encode for psychopathology per se, and that the human genome did not evolve with the intention of reifying the DSM-IV criteria.”
Social psychiatrist Leon Eisenberg concluded that “genes set the boundaries of the possible; environments parse out the actual.”
We must not ignore or minimize the significant role of the social-psychological environment on genetic and epigenetic function. Social psychiatrist Leon Eisenberg concluded that “genes set the boundaries of the possible; environments parse out the actual.” It is also not possible to reduce everything to the molecular level or to physicochemical processes without vital information being lost. According to Derek Bolton and Jonathan Hill, intentional causal processes, e.g., subjective and sociocultural meanings, pervade biological systems to the level of DNA. Psychogenic and environmental stress has been shown to be genotoxic in various body cells by Harlow Fischman, Ronald Pero, and Dennis Kelly and to contribute to premature cell aging by Elissa Epel.
According to Ruth Lanius, Eric Vermetten, and Clare Pain, early life trauma such as physical, emotional, or sexual abuse, as well as neglect, bullying, and social isolation are correlated with pervasive neural alterations in both gray and white matter, e.g., atrophy and dysmyelination, respectively. In 1997, at an international conference on schizophrenia in London, I proposed that the neuroscience of the severe mental disorders overlaps with the neuroscience of chronic and profound stress, trauma, social isolation, extreme loneliness, and social defeat. Fourteen years later, I am even more convinced that this might be so for many persons diagnosed with a severe mental disorder. The role of various kinds of traumas in psychotic disorders is being increasingly recognized as seen in the work of Warren Larkin and Anthony Morrison; the catastrophic interaction hypothesis involving stress, trauma, emotion, and information processing abnormalities described by David Fowler; and theories linking cognition, emotion, and the social world by Paul Bebbington. Social isolation and loneliness can, among other things, undermine our capacity to think clearly and regulate our emotions, as well as increase our paranoid experience of others as described by Cacioppo and Patrick. In humans, loneliness, which is associated with higher rates of mortality and morbidity for every cause of death, has been demonstrated to predict the progression of neurodegenerative disease as well as to alter DNA transcription in the cells of our immune system. In addition to the consequences of cardiometabolic disease secondary to the use of second generation antipsychotic agents, I suggest that trauma, social isolation/defeat, loneliness and states of nonrelatedness (i.e., social disconnection) may be partly responsible for the reduced longevity in persons diagnosed with severe mental disorders reported by NIMH director Thomas Insel.
According to Richard Francis, it is the field of epigenetics that extends our understanding of genes from one to three dimensional processes. Art Petronis offered a succinct definition of epigenetics: “…epigenetics refers to regulation of gene expressions that are controlled by heritable but potentially reversible changes in DNA methylation and/or chromatin structure.” A large number of genes demonstrate an inverse relationship between the degree of DNA methylation and gene expression. Social and psychological experience can epigenetically alter gene expression. Some epigenetic “marks,” i.e., specific chemical attachments such as a methyl group, can be transgenerationally transmitted. This adds to the complexities of psychoanalytic models on the transgenerational transmission of trauma in psychosis as described by Francoise Davoine and Jean-Max Gaudilliere. Petronis proposed that epigenetic factors may help to explain the significant lack of full concordance for schizophrenia in monozygotic twins.
Petronis suggested that because of its complexity, the brain is likely to be vulnerable to even mild epigenetic malfunction which might lead to a diversity of small morphological and functional changes. The neural morphological aberrations observed in schizophrenia, according to Petronis, “are more likely to be just reporters of mild deviation in the developmental program rather than factors causing or predisposing to schizophrenia.” More recently, Petronis identified several dozen loci in the genome where epigenetic differences between people diagnosed with schizophrenia and controls emerged.
From a sociocultural framework, the following factors have been demonstrated in epidemiological research to be associated with the initiation, course, and outcome of severe mental disorders: urban birth/urban living, socioeconomic status, migration, reduced social support and networks, social isolation, social defeat and marginalization, childhood adversity, expressed emotion (particularly hostile criticism) in caregivers, stigma and discrimination, ethnic density, marital status, relative inequality, and others. A viable and coherent model of the schizophrenias would have to be able to explain the neuroscience and clinical findings, as well as the epidemiological research on social factors, including recovery research and the findings of the WHO studies in which Kim Hopper demonstrated better recoveries in developing countries as opposed to the developed nations. Hopper and colleagues challenged the premise that a deteriorating course is a significant feature of schizophrenia, a viewpoint which has accompanied us since the early taxonomic efforts of Emil Kraepelin. Hopper and colleagues proposed: “As the earlier WHO studies had suggested and others since have corroborated, the course of schizophrenia is not ‘hard-wired’ into the diagnosis itself; rather, it is a developmental product of continuing interaction of disease process, treatment, local environment, and the active agency of the person.”