Abstract
As the debate on classification of psychiatric disorders intensifies [1–7], a number of seminal articles, that would once have been the domain of neuropsychiatry, have been appearing in the general psychiatry literature [9–12]. These and other articles focus on the interaction between the human organism (and more specifically the nervous system) and the environment [9–18]. This integrated psychobiological approach will hopefully put an end to the outdated nature versus nurture argument (couched in our more sophisticated terms as genetic versus environmental). It will also hopefully ensure that our understanding of the patient will integrate beyond the more concrete biological and/or psychological and/or social approach, when taking into account the factors which contribute to the clinical presentation of mental illness.
If we conceptualise mental health as the ability of the brain to cope with the environment, then by definition, it follows that mental illness is the inability of the brain to cope with the environment. In the clinical setting, it is our role as psychiatrists to try to uncover the reasons why a particular brain cannot cope with a particular environment at a particular time in a particular person's life. In order to do this effectively, it is my contention that we, as psychiatrists, need to have a more sophisticated understanding of the neurobiological underpinnings of the functioning of the mind.
Essentially the mammalian nervous system can be seen as a series of increasingly complex reflex arcs. From the basic tendon reflex, to the reflexes of an emotionally coloured intellectual response to the proposal of a new hypothesis, the same three essential processes occur. The stimulus or affector, the integrator or processor, and the response or effector.
The stimulus is invariably environmental. However, it is often up to us as psychiatrists in the clinical setting, to decide whether this arises from the internal environment of the patient, or from the surrounding external environment. Not infrequently it is a combination of both internal and external stimuli which trigger the particular presentation.
For instance, we may be faced with an 18-year-old female who is complaining of symptoms suggestive of severe mixed anxiety and depression. On taking her history we discover that, in addition to being the recipient of inconsistent parenting, she also suffered a series of traumatic events, including childhood sexual and physical abuse. If we have an understanding of integrated psychobiology, this may lead us to speculate that these events may have affected the transcription of genetic material, laying down various traumatic memories in her medial temporal lobe, diencephalon, and striatum. The inconsistent and difficult behaviour of her 9-month-old son, triggers increased firing of these memory cells. This simultaneously leads to stimulation of the nearby amygdaloid complex, and our patient experiences increasing feelings of anxiety. At first she is unable to understand why she is feeling this particular emotion so strongly at this particular time. This, in turn, generates further anxiety as the usual feedback loops of the frontal lobes essential for cortical control of these temporolimbically based emotions are unable to exert an inhibitory influence on the now active hippocampal-amygdaloid complex. The firing of this temporolimbic area has in the meantime, via its projections to the hypothalamus and brainstem, set off a cascade of autonomic activity, stimulating our patient's heart rate, stimulating bowel motility, decreasing her appetite and wreaking havoc with her diurnal rhythms. Her frontal lobe biogenic amine systems, which are intimately related to reward-driven behaviour, become depleted of their amine precursors, and a profound depression results.
In order to grasp the concepts underpinning the above, it is essential that we, as psychiatrists, understand the genetic plasticity of the brain, and its constant interaction with the environment. Kandel [9], in his seminal article, is able to impart how genes may be viewed as the interactive basis of human response to social demands. Genes, in their plasticity, respond to environmental stimuli, and neuronal genetic material is altered by environmental input. This genetic material thus not only plays a role in determining how we respond to the environment, but is also altered by the manner in which we respond.
Take, for instance, the fascinating work done by Teicher and his group [19,20], in which they propose that early childhood abuse alters limbic and cortical functioning. A human is born with his or her biological substrate, which has developed in utero as a combination of inherited genetic material (the gene template) combined with the environmental influences occurring during gestation which lead to the alteration of genetic material. This malleable genetic material is, for the rest of the life of the organism, going to be involved in a dynamic interaction with the environment. What, I feel, we often fail to grasp, is the true dynamic interaction which is occurring.
A baby, let us for argument's sake say, a male, is born. It happens that this male baby's mother (our patient), during her childhood, suffered both physical and sexual abuse. It may be postulated that stability of personality development is to some extent dependent on environmental consistency. What can be more inconsistent than a supposedly trusted caregiver violating the trust of a dependent child? No wonder that brain may respond by continuing its development in a less than orderly fashion. At the age of 16 our patient met her boyfriend, and left home. Within a year she was pregnant, and her baby was born. The abuse which our patient suffered during her childhood, if the work of Teicher and his colleagues is to be accepted, led to an alteration of genetic expression, especially in the limbic system, of the mother. Our patient's baby may have inherited some of this altered genetic material, and may be born with a less than optimal genetic template. Unless he is lucky enough to be born into an exceptionally stable and consistent environment, and unless he is lucky enough that the genetic material he has inherited is malleable enough to respond to this environmental stability, the chances are highly likely that this inherited brain instability will help create an environmental climate conducive to the development of further brain instability. This baby, with his unstable genetic substrate, may respond to the caregiving attempts of his mother in a manner so inconsistent that she is unable to control her frustration. Our patient, already damaged by the experiences of her past, unfortunately no longer has the brain stability (supposing she actually had it at one time) to be able to respond to the inconsistent demands of her baby in a consistent fashion. This vicious interaction between genetic and environmental events not only contributes to the profound depression of our patient, but also paves the way for the later development of clinically overt psychopathology in her son.
For us then, as psychiatrists, to be expected to make a decision as to whether the subsequent presentation of psychosis/anxiety/depression in the baby when he becomes an adolescent is environmentally or genetically determined, in this context, makes no clinical sense. Clearly, the interaction of each individual in this system affects and is affected by the inherited and transcripted genetic material, as well as the manner in which the environment responds.
Let us take another example, the example of what is occurring as we read this article. If we integrate the models proposed by Barr and Kiernan [21], Kandel et al. [22], Othmer et al. [10] and Pearlson [23], the following formulation may apply.
The contents of this page enter our nervous system as light waves. These light waves stimulate the photoreceptor cells of our eyes where they are converted to electrical energy. Action potentials generated in these cells are transmitted via bipolar cells to ganglion cells in our retina. The axons of these ganglion cells then transmit what is now an electrochemically driven impulse, to the lateral geniculate body of the thalamus via our optic nerves and optic tracts. Fibres from the lateral geniculate nucleus in turn transmit impulses via the geniculocalcarine tract, some of which branch off over the temporal horn of the lateral ventricle, passing through the temporal lobes as Meyer's loop. All these fibres project to various parts of the primary visual cortex in the occipital lobe. In addition, some fibres from the retina terminate in various parts of the midbrain, the thalamus, and the hypothalamus.
At the level of the primary visual cortex, the brain is able to register that something formed has been seen.
Surrounding the primary visual cortex is the visual association cortex, which is involved in the recognition of objects, depth and colour perception, and other complex aspects of vision. It is in these posterior association areas that the brain reassembles what is being perceived. This is integrated as the written word. The physical context in which this material is presented is also integrated at this level. The further the impulse moves away from the primary cortical areas, the greater is the parallel input from neighbouring modalities. These areas are known as the heteromodal association cortex, and found in the temporal, parietal and frontal lobes.
The heteromodal association cortex receives data from multiple sensory modalities and transmits data to multiple secondary motor cortices. It has multiple connections with the limbic system, and is critically important in coordinating many sensory, motor and behavioural activities, and integrating them with drive and mood. Using knowledge of prior events to guide current behaviour, the heteromodal association cortex plays a key role in the mediation of complex cognitive tasks. At this point, we begin to integrate and process what we are reading within the framework of the intellectual and emotional context of our lives.
As these fibres from the visual association cortex are interacting with the heteromodal association cortex, fibres descending from the frontal eye fields anterior to the motor cortex, as well as fibres returning directly from the occipital cortex, project impulses via the superior colliculus, and other pathways, to converge in the medial longitudinal fasciculus. The axons of the medial longitudinal fasciculus also transmit impulses from the vestibular nuclei allowing for coordinated head and eye movement. Via a number of parallel reverberating feedback modulatory loops, such as projections back to the lateral geniculate nucleus, the input of this sensory information is modulated, allowing us not to become overwhelmed by different components of what is visually perceived.
It can thus be seen (literally) that, a complex mixture of intrinsic parallel processing excitatory, modulatory and inhibitory fibres, and interhemispheric, association, commissural and projection fibres, communicate with other areas of the cortex, and subcortical areas such as the thalamus, the amygdaloid-hippocampal complex, and the hypothalamus. It is through these complex interactions and feedback loops that the information being read is filtered, processed, understood and integrated and either accepted or rejected. The acceptance or rejection as well as the intellectual and emotional impact of this written material will depend on the context in which it is received, which in turn, is dependent on the context in which the brain of the individual reader or perceiver of this information has developed in the context of his or her particular background and genetic make-up.
Thus, some of you will read the above with an increasing level of excitement and recognition and feel this makes good sense; while others may knowingly shake your heads at what you perceive to be a sad attempt at the justification of biological reductionism.
How we react, and our conceptual understanding, will be dependent on the sophistication of our respective heteromodal association cortices, and how and why they have developed as they have.
While the basic substrate necessary for the receiving, filtering, processing, integrating of and reacting to the information is a functioning brain, the way in which our individual brains react is highly dependent not only on their basic genetic make-up, but on how the expression of the genes has been affected by our environmental backgrounds, and how our brains have, in turn, decided to respond to and attempt to alter this environment. Thus, some readers, suitably enthused by this material, will pore through the references in order to further your understanding of the material, and, in this way alter the genetic pathways which your brains may follow. Other readers, on the other hand, may choose to reject this explanation of the development of psychopathology, and resist the challenge of coping with the genetic transcription the further investigation of these concepts will pose.
As specialists in psychiatry, our conceptual understanding of these processes, and our clinical ability to predict their sophistication in our patients, will allow us to formulate individualised management plans. Our more integrated and sophisticated understanding of neurobiology will allow us to understand the brain changes we hope to achieve with our therapies, whether these therapies be pharmacologically or psychologically based. This may allow us, at the level of the individual patient, to tailor this plan to suit the abilities and needs of that patient.
It is through the movement away from the Cartesian notion of the ‘disembodied mind’ as Damasio [24] terms it, that we can begin to understand the complexly multifaceted inter-connections of the brain and nervous system with the rest of the physical organism. Hopefully, then, we can move away from the notion of equating psychological with something ephemeral or inexplicable, merely because we cannot grasp that such an intangible notion may have a physical basis.
As psychiatrists, with our medical and psychological training, we are placed in the unique position where we have not only to decide whether the interaction of a person's brain with the environment falls within the realms of normal; but we are also placed in a position in which we are allowed to prescribe therapies (pharmacological or psychological) which can potentially alter the way in which that brain reacts with the environment. If we are to do this, does it not behove us to have a specialist understanding of how this organ functions?
When a patient presents to us, will it remain acceptable in the new millennium, that as specialists in the field of psychiatry, we can continue to rely on attractive but unproven theories of psychodynamic explanations for why this person is unable to cope with the demands of his or her life at this particular time? Or will it be expected of us that we will be able to formulate an explanation based on our knowledge of neuroanatomy, neurophysiology and neurochemistry, integrated with our understanding of the interactions of the nervous system with the environment, from a phylogenetic, ontogenetic, and psychodynamic point of view?
By incorporating the integrated psychobiological approach into the clinical practice of psychiatry, I believe we can begin to approach a truly holistic understanding of the development and presentation of the individual patient's psychopathology.