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Behavioral Genetics: Challenges and Opportunities

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Behavioral Genetics: Challenges and Opportunities

Mark R. Zuccolo

What is the mind and how it functions remains a mystery. Various psychological theories give us sometimes conflicting taxonomies. Philosophy and religion offer their interpretation. In many ways, we remain unable to define with certainty this object of investigation. When pathologists dissect cadavers they do not find in any part of body evidence of thoughts, emotions, conflicts, intelligence, the ego, superego, or id. These remain theoretical constructs that do not materialize into some stable and measurable physical entity. For some scientists this means that we must try harder to find an organic explanation for the mind’s existence. Notable among these are Sir John Eccles (1991), who won the 1963 Nobel Prize for his research on the synapse, and the equally famous physiologist Sir Charles Sherrington (F. C. Rose, 2001). Others support the idea that the mind is a completely immaterial entity and thus resort to esoteric concepts such as the spirit or the soul (Sabaawi, 2004). 

As is commonly accepted that a spiritual entity cannot become physically ill, the precise nature of an illness that affects the intangible mind remains today an unsolved problem and matter for debate. While the expression “mental disorder” is commonly used in its metaphorical sense, biopsychology is seeking to erase the difference between mind and body, dealing with the mind as if it were an organ of the human body that can become ill just like any other, and that therefore can and must be cured with medical interventions (Andreasen, 1997). Even if we accept the idea that the mind has some physical attributes represented by its alleged inhabiting of the brain and the nervous system, it appears questionable that it would possess the same concreteness as other organs of the human body. The fact that some manifestations of mental illness are caused by organic pathologies do not appear to legitimate a biological explanation of mental disorders, but simply that there may be a correlation without implying causation (Badaracco, 2006). The same psychiatric manifestations are in fact present in individuals who do not suffer from these same physical pathologies. All that might be concluded in this respect is that the mind can respond in the same way to a variety of physical and psychological stressors (Columbus, 2001).   

The concept of mental illness is part of the medical model of psychological disorders, which presupposes that biological causes are preeminent and most relevant in diagnosis. In this view symptoms do not have meaning, a history or a context; the disturbance is explained by the equation symptom equals disorder, and disorder equals deviation from the norm (Engel, 1977). The supporters of this model are fully aware of the biopsychosocial causality model, but they support the supremacy of biological causes, relegating psychosocial factors to the role of concomitant causes or simple indicators that provide evidence for the onset at various developmental stages of pathologies that were hard-coded in an individual’s genes (Keefe, Abernethy, & Campbell, 2005). They support the necessity of “medical cures” and give lesser importance to psychotherapies and to social support systems. Some of these biological approaches, such as nutritional modifications and orthomolecular psychiatry, are not necessarily reductionistic but they may conceptually minimize the value and the role of psychosocial factors in the genesis of mental disorder, reaffirming the supremacy of traditional medicine. 

Psychiatrists often refrain from dialoguing with their patients outside the scope of their clinical investigation, preferring to focus their attention on neurotransmitters, vitamin deficiencies, shortfall of certain chemicals and every other thing that is not the mind (Pert, 2002). The scientific contradictions of the concept of mental disease have been brilliantly discussed by the psychiatrist Thomas Szasz, professor emeritus at the State University of New York, Syracuse, in his now famously controversial book “The Myth of Mental Illness” in which he unequivocally states that mental illness in a modern invention that dates no further back than the 19th century (Szasz, 1974).   I too found this book to be very interesting!

Modern medicine considers causes, symptoms and clinical signs as conceptually discernable entities (Melmed, 2003). The cause is defined as the pathogenic agent and its elimination is the main objective of the cure; the symptoms are the visible expression of the pathogen, which in part we may be able to see and in part is subjectively reported by the patient; the clinical signs are objective measurement made with medical instruments and laboratory analyses. There are physical pathologies that are classified as such purely on the basis of visible or self-reported symptoms, for which no organic cause can be found (Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002). This apparent weakness of the medical model cannot be used to legitimate mental illness when there are no obvious pathogens and no objective measurements can be taken. 

Today, all the mental disturbances are considered disorders, and the expression “mental disorder” is synonymous with “mental illness“. To this date, no mental disorder has been conclusively demonstrated to have a purely biological etiology and their diagnoses is not carried out with objective measurements or laboratory test as for all other diseases, but exclusively with behavioral observation and testing. The diagnostic handbook of mental disorders classifies them on the basis of their symptoms and not of the causes that may have produced these symptoms or on the observable clinical signs (APA, 2000). It classifies behaviors (motor or verbal) and not physiopathological neurochemical, genetic or phenotypic alterations. For this reason it is not suitable to empirical scrutiny and mental diseases must be demonstrated to exist without the assistance of diagnostic instrumentation. To diagnose a depression by counting the symptoms listed in the handbook and then saying that they determine the existence of depression is like measuring an individual’s fever and then saying that the fever exists because his or her bodily temperature is elevated (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961; T. W. Miller, 1996). 

To this must also be added the very diverse interpretation that various schools of thought attribute to a disorder such as depression. It is perhaps too facile to seek in genetics and biology that which is not conceptually clear in our logical evaluation. There is overwhelming evidence that indicates purely psychological factors as the likely cause of most mental disorders. Many psychological theories support this hypothesis, even if their use of medical terminology may confuse more than clarify the matter (Yager, 2005). Mental disorders are made of thoughts, emotions and behaviors, much like every other activity of human beings. A significant portion of our emotions is nothing more than the product of our thoughts, as recognized by the cognitive-behaviorist Albert Ellis, who stated that “A large part of what we call emotion, in other words, is nothing more or less than a certain kind - a biased, prejudiced, or strongly evaluative kind - of thinking” (1958, p. 38). Thoughts, behaviors and emotions cannot become ill, they can only be dysfunctional, that is, maladaptive for the person and detrimental to his or her social interactions. 

Nature gives us in dowry many useful tools that are necessary to survive and to thrive, and which appear to be genetically determined. It is open to debate whether these genetic blueprints have the force and the importance that is currently attributed to them. A classic example is imprinting, an instinctive behavior first studied by the ethologist Konrad Lorenz (1997). Each higher-order animal is born with the predisposition to establish a close relationship with whoever first interacts with it. Something of a genetic nature tells it that its survival depends on this bonding. This genetic program does not have a corrective feedback; therefore the animal can mistake for a parent a human being or even an artificial creation such as a puppet. Rather than interpreting a precise genetic program, the animal seems to respond in a purely automatic way to the first stimulus that comes in focus, a reflex that urges it to begin a social interaction that forms the basis of what we call imprinting. Lorenz’s goose Martina was not capable of being with the other geese without showing great agitation that only her human trainer could assuage (Harre, 1981). Today, a psychiatrist may say that she suffered from a mental disorder, probably genetic in nature, with imbalances in the levels of certain brain neurotransmitters. The truth may be that the genes having done their part, the environment did not prove to be conducive to good mental health. It is probable that many mental problems depend on these incongruences. 

Arguably, human beings commit more errors in constructing their life than Mother Nature commits in their genetic make-up and these errors are the prevailing cause of many mental disorders. Today, there is a tendency to underestimate the influence of the mind on an individual’s biological status.  In their book “The Invisible Plague: The Rise of Mental Illness from 1750 to the Present”, Torrey and Miller (2002) assert that before the advent of industrialization incidence of schizophrenia was of 1 per 2,000 population. 

Industrialization has been accompanied by a dramatic increase of this disorder. In England, Canada and the USA there has been an increase in the incidence of schizophrenia by a factor of seven and in Ireland by a factor of 16 between the 18th and 20th century. Autism has gone from 1 in thousands to 1 in less than 200. The increase is observable also in underdeveloped nations and a difference of incidence is notable between urban and rural residents. Today, in industrialized societies the incidence of schizophrenia is of 1-2%. Even though this correlation has been interpreted in sometimes conflicting ways, it is hard not to notice the role played by the environment (Kremen, 2005; Moritz & Woodward, 2006; Strous & Cowan, 1995). 

Psychosomatic medicine has long been a discipline that studies how the psyche may influence the body and contribute to the onset and maintenance of organic pathologies that need medical attention (Alexander, 1941). Behavioral genetics studies the behavioral phenotypes of major genetic syndromes and seeks to examine their genetic etiology, genetic counseling, physical features, medical problems, cognitive and behavioral profile, and psychopathology. The speculated correlation between the identified gene and the pathophysiology of the cognitive and behavioral features is also being investigated. Updated knowledge of behavioral phenotypes may help mental health practitioners identify these conditions, refer the patient and his/her family for genetic diagnosis and counseling, make specific treatment recommendations, and contribute to research and syndrome delineation (Moldavsky, Lev, & Lerman-Sagie, 2001).

The perception of one’s own inability to face life’s challenges creates stress and depression with an attending reduction of immune defenses (Bakács, Mehrishi, Szabados, Varga, & Tusnády, 2001; Goodnow, 2001). The greater the depression, the weaker appear the individual’s defenses against viral and bacterial attacks. Stress is therefore correlated to an increase in infectious diseases, to the development of malignant neoplasia, to the faster growth of cancerous cells, and heart disease (G. E. Miller, Freedland, Carney, Stetler, & Banks, 2003). The list of organic pathologies that have been directly ascribed, in toto or in part, to psychological causes is growing longer, so much so that the risk of runaway generalization has been noted. 

To avoid the facile equation unhappiness = disease, it is necessary to apply scientific criteria that may be used to establish when the normal pathos of daily life may become clinical pathology. As early as 1945, René Spitz inquired on the effects of the separation of children from their parents within the first few months of life and their institutionalization in orphanages (APP, 2003). The children showed immediate signs of distress manifested by crying, loss of weight, insomnia, progressive shut down of communication with adults, increased vulnerability to disease, generalized motor retardation, facial rigidity with loss of the ability to smile, lethargy, depression, inability or refusal to eat unassisted. The majority of these symptoms disappeared if within four months the children were adopted. If the adoption did not take place at least within the first year of life the children’s clinical situation would worsen and often become irreversible. Mortality among these orphans was as high as 30% up to the age of two years. At four years of age many were generally incapable to stand on their own, to walk and to speak. Over 20% of them were still institutionalized after 40 years (Spitz, 1945). Subsequent research conducted by the World Health Organization has confirmed the presence of these pathologies in institutionalized children in many countries (Brown, Cueto, & Fee, 2006; Houweling, Kunst, & Mackenbach, 2001; McGregor, 1992).  

The results of research on genetic ancestry that seeks to identify psychopathologies running in families across multiple generations have been criticized as underestimating learning and environmental variables. In most cases behaviors are learned from a prolonged contact with one’s parents, who are for children the most powerful of models. The underestimation of the learning that takes place by imitation and through operant conditioning is one of the criticisms most often leveled at behavioral genetics. J. B. Watson (1913), founder of the behavioral school, asserted that mental diseases do not exist, and that the behaviors ascribed to mental illness were in effect learned in unfavorable situations of life (Watson, 1928). Research on how genes affect behavior and on how genetic effects are modulated across life spans of environmental interactions seeks to counter this criticism. For example, studies that investigate general and specific cognitive abilities, reading disability, fragile-X syndrome, and triplet repeats look at their impact on cognitive ability and disability. Personality, sexual orientation, and health habits such as smoking and drinking are currently being studied in view of possible genetic predispositions. Also researched are specific psychopathologies and neurological disorders, such as Huntington's disease, alcoholism, Alzheimer's disease, schizophrenias, affective disorders, and aggression (Kremen, 2005; R. J. Rose, 1995).

Studies conducted on twins, the mainstay of behavioral genetics research, have yet to determine the location of any gene responsible for mental disorders. In nature no two individuals have been shown to be genetically identical, not even monozygotic twins. Their life experiences, even in the same household, cannot be identical. A critical analysis of the methodological deficiencies of twin research has been offered by Joseph (1998), who focused attention on the pitfalls of the “equal environment assumption” in the classical approach to twin health research. The most sensible approach appears to be a compromise between assuming direct genetic causality and the many environmental factors that influence the process. Actually, a lot of twin studies look at twins separated at birth and note their similarities in behavior.  The neuron-centric hypothesis, that seeks the cause of mental disorders in chemical imbalances in the levels of certain neurotransmitters in the synaptic cleft of cerebral cells, is for the time being only inconclusively supported by empirical evidence (Kandel & Squire, 2000; Valenstein, 1998). 

As of today, no phenotype has been demonstrated to be a valid biological marker of the presumed genetic causes of any mental disorder (Potash, 2006). Currently, no mental disorder can be diagnosed with medical instrumentation, not even the most studied of all, schizophrenia (Hanson, 2004; Weiser, Van Os, & Davidson, 2005). There is no scientific test that can prove the link between genes and mental disorders. A genetic factor that may predispose the individual to certain mental disorders, in some cases alleged with the presumed location of specific genes, has not been offered as an empirically demonstrable cause but at best as a statistical projection (Heinssen, Cuthbert, Breiling, Colpe, & Dolan-Sewell, 2003). Genetic science, unlike the diagnostic handbook of mental disorders, deals with quantities and not with categories (Yager, 2005). Its fundamental assumption, valid until proven otherwise, is that all humans have the same genes. Any variation has been attributed to simple mutations that render certain individuals more vulnerable than others. 

To further complicate the matter, the criterion used to establish whether a gene is to be considered abnormal or normal still eludes genetic researchers. It appears extremely difficult, for example, to address racial differences in the human genome, or even to agree on what constitutes a genome that is truly representative of all human beings. The so-called standard genome does not correspond to any real person and it has, for the time being, only a theoretical function. Advances in model fitting are addressing this issue, with an emphasis on the development of an approach to compares heritability of dimensions and disorders, thus directly confronting the question of the etiological association between normal and abnormal (M. Neiss & Almeida, 2004). Studies have been under way since at least 1991 concerning what behavioral genetics may tell us about environmental effects and what molecular genetics can tell us about behavior. Other issues being explored include the theory of quantitative genetics, the importance of non-shared environment and the genetic influence on environmental measures (Moffitt, 2005; Plomin & Rende, 1991).

Can an individual’s double helix of DNA become the new diagnostic handbook for mental disorders?  Doing so, beyond present scientific challenges, may run the risk of transferring to behavioral genetics the psychiatric bias that classifies individuals into having a normal or an abnormal psychology (Yager, 2005). In fact, the scientific approach to this question that is being taken by genetic researchers does necessarily divide the genes, and the individuals who carry them, in two groups, abnormal or normal. The equation single gene = single protein = single function = specific disease, may amount to short-sighted biological determinism that understates environment and learning. 

Little it is known about how genes work. Every gene appears to have multiple functions and can codify many different proteins (Brain & Cox, 2006). Each of these proteins can have multiple functions and perform in the cell many different roles. DNA is among the more inert and less reactive molecules of the human body, it does not produce anything, it does not react with anything, and it does not even have the ability to reproduce itself without the contribution of external agents (Goodnow, 2001; Kalat, 2004). Still in its infancy, modern biological research has succeeded in mapping the human genome but has offered precious little help in understanding physical diseases and even less in understanding mental illness. It has not taught us much more than what we already knew about human beings, and it is so far somewhat of a disappointment, unless we settle for knowing that we have 25% more genes than a head of lettuce (Kalat, 2004).

Recent research has uncovered the startling fact that genes do not determine the composition of proteins and that the complex composition of proteins and their activity within and without the cell is what we must study (Brain & Cox, 2006; Modlin, Brightbill, & Godowski, 1999). This is the new science of proteomics, whose aim is to determine which proteins the genes encode and to decipher how these proteins function to direct the behavior of a cell or organ, and what role they may play in the onset and maintenance of disease (Lundblad, 2005).   

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