Klempan, Muglia and Kennedy (200-in their “Genes and brain development” in Neurodevelopment and schizophrenia edited by Matcheri Keshavan, James Kennedy & Robin Murray for Cambridge University Press) noted:
“A neurodevelopmental etiology of schizophrenia is suggested by neuroimaging and postmortem studies revealing significant and replicated lateral ventricular enlargement, hippocampal and gray matter deficits, and cellular disarray, independent of duration of illness and antipsychotic treatment” (p. 3).
The above research findings need to be qualified. First, importantly, they are non-specific to schizophrenia. Secondly, the researchers have failed to point out other cogent explanations, particularly that these findings could very well be the downstream consequences of chronic and intense activation of the fear/anxiety neural pathways. Thirdly, there is research demonstrating the dynamicity of even such structural measures as ventriculomegaly in the disorder, e.g., as patients are successfully treated you can see a reversal of ventriculomegaly. It is extremely important to communicate to patients that their illness, as is the neuron and entire brain, is highly dynamic and plastic. Research has consistently demonstrated the multiplicity of courses and outcomes within the human disorders we have called the schizophrenias. Neurogenesis, neurotrophic factors, environmental regulation of gene expression, genetic control of sensitivity to the environment, epigenetic processes, compensatory neural plasticity and adaptations, sociocultural differences in course and outcomes, etc., all make for a much more interesting picture than the empty signifiers of schizophrenia as a “neurobiological brain disease” or chemical imbalances in the dopaminergic pathways.
McDonald and Murray (2004 - ”Can structural magnetic resonance imaging provide an alternative phenotype for genetic studies of schizophrenia?” in Neurodevelopment and schizophrenia, edited by Matcheri Keshavan, James Kennedy & Robin Murray for Cambridge University Press) stated:
“The relative lack of success in identifying genes of major effect for the illness, combined with the pattern of inheritance of schizophrenia, has led many researchers to favor a multifactorial model for susceptibility, whereby liability is continuous within the population and multiple genes interact with environmental stressors to propel the individual over a threshold for illness expression. Unlike other multifactorial diseases, such as diabetes mellitus and coronary heart disease, genetic research into schizophrenia suffers from the added disadvantage of having an uncertain phenotype with as yet no validating biological test, even at postmortem, and environmental factors that are unknown or of minor effect” (p. 138).
I disagree with their conclusions about the unknown environmental factors or characterizing them as having minor effect. I have recently posted to this listserve a recent review of updated research demonstrating a multiplicity of environmental factors putatively involved in the initiation, not just course, of the schizophrenias. In contrast to the viewpoint of McDonald and Murray (2004), Mortensen and colleagues demonstrated stronger and much larger effects for urban birth than for having a parent affected with schizophrenia.
In keeping with my emphasis on affective neuroscience and understanding severe mental disorders as largely disorders of affective-cognitive functioning (with a strong emphasis on affective functioning and sense of self-other relatedness), phenomenological description of such key processes as the self, intentionality, agency, consciousness, etc. is vital to any valid model of the schizophrenias. For the latter I would recommend the phenomenological research of Louis Sass and Josef Parnas (their work is included in Kircher, T. & David, A. (2003) (eds.).The Self in Neuroscience and Psychiatry. Cambridge , UK : Cambridge University Press). Also, Giovanni Stranghellini’s work is eminently worthwhile (Stanghellini, Giovanni (2004). Disembodied Spirits and Deanimated Bodies: The Psychopathology of Common Sense. Oxford University Press). Larry Davidson’s ( Yale University ) phenomenological research on recovery is quite significant (Davidson, L. (2003). Living Outside Mental Illness: Qualitative Studies of Recovery in Schizophrenia. NY: New York University Press).
I would like to present some contemporary neural research which, in my view, justifies an understanding of the schizophrenias as highly stress/fear/anxiety-driven disorders. As a caveat, by no means do I believe this is the whole story. Elsewhere I have written about the importance of identity formation and security of attachments in our understanding of the severe mental disorders. Being affectively attuned to the vulnerability and nature of the self processes, anxieties surrounding relatedness and isolation (a sense of personal non-existence), are crucial to our being effective therapists to persons with a psychotic disorder. We should also be attuned to our own vulnerabilities, countertransference hate and anxieties, as well as the therapeutic strivings on the part of the patient.
Francine Benes (2004-”The development of “mis-wired” limbic lobe circuitry in schizophrenia and bipolar disorder” in Neurodevelopment and schizophrenia edited by Matcheri Keshavan, James Kennedy & Robin Murray for Cambridge University Press) focuses on GABA (gamma-aminobutyric acid) and DA (dopamine) in her research on severe mental illnesses. GABA is an important inhibitory neurotransmitter in the brain and recent research has implicated it in bipolar and schizophrenic disorders. A preferential decrease in the density of non-pyramidal cells (these are interneurons which are largely GABAergic in nature) have been found in the anterior cingulate cortex (ACC) and prefrontal cortex (PFC). Benes (2004) reported dopamine (DA exerts an inhibitory effect on GABA interneurons) inputs to GABAergic interneurons in layer II of the anterior cingulate cortex have been increased, a shift away from pyramidal cells to interneurons, possibly related to pre- and postnatal stress. The net effect would be inhibition of inhibitory GABAergic interneurons (leading to greater activation). Excitatory fibers from the basolateral subdivision of the amygdala to the anterior cingulate cortex and the hippocampus (sectors CA2/3) would add to the decompensation of GABA cells. GABAergic cell development in the anterior cingulate is probably complete by early adolescence, while dopamine fibers and amygdalar projections continues into late adolescence and early adulthood (the critical time in which schizophrenic disorders often appear). As I have demonstrated in many previous postings, individuals exposed to early developmental stress (e.g., traumatic separations, abuse, neglect, etc.), may be overly sensitized to the effects of stress later in life (e.g., greater LHPA activation). During adolescence the stressed neural circuits could develop excessive dopaminergic and amygdalar inputs. Such changes, in addition to a host of others involving other neural pathways, could be associated with decompensation of the circuit if GABAergic cells are unable to provide sufficient inhibitory modulation. Therefore pyramidal cells would fire excessively and possibly result in oxidative stress to these cells and/or GABA neurons and lead to further dysfunction and even decompensation of the circuit.
Benes (2004) noted:
“Overall, the studies...have suggested the importance of viewing psychotic disorders from the standpoint of the development of integrated circuitry involving the amygdala, anterior cingulate cortex, and hippocampus. Changes in the activity level of convergent inputs to GABA cells in one or all of these regions during adolescence may serve as triggers for the onset of psychosis in susceptible individuals” (p. 305).
However, this model is significantly incomplete. One could not understand the symptomatology and phenomenology of the schizophrenias if one were to remain at the level of neural activity occurring within the isolated individual. The very personal sense of a threatened loss of self secondary to relational overwhelm or absence, excessive annihilatory shame, traumatic and shattering events, etc., is not to be found in our most sophisticated neuroimaging techniques. It is to be registered, understood, contained and therapeutically transformed within a relationship reliable, patient and strong enough to provide a safe home for the beleaguered and fragile self of the psychotic individual. A relationship which could patiently withstand the kill-or-be-killed emotional atmosphere (significant feelings in both members of the therapeutic dyad) which holds sway in the room for years. It is crucial that the therapist is neither killed off emotionally, nor resorts to talionic attempts to kill off the patient (e.g., through emotional abandonment, over interpretation which interferes with the growing therapeutic symbiosis, blaming the patient for impasse, excessive use of theory, etc.). The neural-stress theory of the schizophrenias needs to be understood within the superordinate need of the individual to safely exist within the minds of others.
Brian Koehler PhD
New York University
80 East 11th Street #339
New York NY 10003
212.533.5687
brian_koehler@psychoanalysis.net
