Psychiatrists diagnose and treat a variety of forms of mental illness. For many years now, we have used the Diagnostic and Statistical Manual (DSM) prepared by the American Psychiatric Association as our guide in diagnosing mental illness. Underlying the previous DSM III and the current DSM IV (and it now looks almost a certainty that it will also underly the upcoming DSM V) is the assumption that meaningful distinctions can be made between different mental "disorders" based on psychiatric symptoms (experienced by the patient and communicated by him to the clinician) and signs (behaviors observed by the clinician, including occasionally performance on psychological or neuropsychological tests). This assumption is generally amplified in the minds of most psychiatrists to the point that different disorders, such as Major Depressive Disorder, Bipolar Affective Disorder, and Schizophrenia, are considered separate illnesses or diseases, whose distinct pathophysiologies are just waiting to be more fully elucidated.
This assumption, that psychiatric symptomatology can be used as a basis for diagnosing different mental illnesses, is generally considered to be so obvious and basic to psychiatric practice, as well as to research, that it is rarely discussed. However, the assumption is not only completely unfounded; it is actually on its face implausible and even preposterous. It likely will turn out to be one of the biggest red herrings in the history of modern medicine.
Advances in recent decades in knowledge of neurochemistry and neuropharmacology have fostered a casual conception of the brain as a collection of a relatively small number of neurotransmitter "systems." Such a view may be part of what has led researchers and other leaders in psychiatry astray. In contrast, if one keeps in mind that the brain is first and foremost a vast and complex array of communicating circuit elements, one is quickly drawn to the conclusion that all psychiatric symptoms are likely to be non-specific.
Neurologists, who have strayed much less from a view of the brain as circuitry, have always known that neurological conditions generally are not diagnosable on the basis of symptoms alone. A lesion may produce a set of signs or symptoms, and on the basis of that symptomatology, the location of the lesion may be determined. But the history of the illness as well as other information the neurologist may obtain (blood tests, spinal taps, MRI's, etc.) may reveal a variety of different types of disease processes: for example infections, tumors, strokes, or traumatic injuries. There is little specificity in either direction: a particular type of insult may cause a variety of different symptoms or signs, and a particular symptom or sign may result from a variety of types of insult.
Why on earth should anyone assume that psychiatric symptoms, which reflect pathological functioning of brain systems that are generally larger, more diffusely organized (or widely distributed), more complex, and more subject to individual variation than those involved in neurological conditions, would be any more specific with regard to the underlying disease process? We already know, for example, that cases of mental illness symptomatically resembling schizophrenia or bipolar disorder have resulted from traumatic brain injuries. (Like neurologists, psychiatrists do obtain histories to attempt to discover a physical cause of illness. But unlike neurologists, psychiatrists are faced, in the majority of cases, with no physical explanation for illness. They tend to assume in each such case that the unknown pathophysiological mechanism is specific to the category of mental illness that the case best fits according to its signs and symptoms.)
It is much more reasonable to suspect that different types of permanent and temporary brain lesions, and very likely with many possible locations or distributions, can result in similar pathological mental states and behaviors. Conversely, a particular insult, for example a bad gene, an infectious agent, or a psychosocial stressor, likely may manifest itself in several possible pathological brain states and symptomatologies depending on interactions with other factors. In other words, there is probably little specificity, in either direction, between different forms of mental illness and their causes.
We also know that psychiatric diagnoses are often inconsistent over time. A patient may get a diagnosis of major depression, then later have a manic episode and get a diagnosis of bipolar disorder, and then later develop fairly chronic psychotic symptoms and get a diagnosis of schizoaffective disorder. At each new diagnosis, the clinician is likely to assume that the earlier diagnoses were wrong; symptoms were latent, or possibly missed by the clinician. However, If one has the view that all psychiatric symptoms are non-specific, then one is much less surprised if symptoms develop or disappear with time.
We do of course have to keep in mind a psychiatric patient's history when treating symptoms. Most notably, we need to treat a patient with depressive symptoms differently if she has a history of manic episodes. But it is a big step from acknowledging the need for such considerations to presuming that there is a disease called bipolar disorder that is pathophysiologically distinct from purely depressive illness. The data from family studies are consistent with genetic factors being at least somewhat non-specific; family members of patients with bipolar disorder have an increased likelihood not only of having bipolar disorder, but also of having unipolar depression. Such studies may have shown no increased likelihood of mood disorders among family members of patients with schizophrenia. However, there appears to be an increased risk of both schizophrenia and bipolar disorder, as well as depression and schizoaffective disorder, among family members of patients with schizoaffective disorder. The data are consistent with the idea that some genotypes tend to predispose strongly towards mental illness manifesting with psychosis, others towards mental illness manifesting with mood episodes, and others towards severe mental illness with less specificity.
Researchers studying possible genetic factors and other possible causal or predisposing factors need to give more consideration to the possibility that many of these factors are likely to have low specificity with regard to symptomatology or manifestations of mental illness, especially of severe forms. (In less severe cases of anxiety or depressive illness, there naturally will be relatively high specificity for the effects of certain types of environmental stressors. For example, loss of a loved one will tend to precipitate depressive symptoms more often than anxiety symptoms.) Toxoplasmosis was recently shown to be likely to be a causative factor for some cases of schizophrenia (Niebuhr DW 2008 Selected infectious agents and risk of schizophrenia among US military personnel Am J Psychiat 165:99-106), but it may turn out to be causative for some cases of other forms of mental illness as well. It already appears, for example, that alleles of the serotonin transporter gene that result in high rates of transcription of the gene are associated with major depression, bipolar disorder, and schizophrenia (studies cited in Kohen R et al 2008 Association of serotonin transporter gene polymorphisms with poststroke depression Arch Gen Psychiat 65:1296-1302).
Pathophysiological mechanisms mediate the effects of genes and other predisposing factors, as well as of precipitating factors, that cause mental illness. It is reasonable to presume that in the forward direction (from causes to effects) there is fairly high specificity going from ultimate causes to pathophysiological mechanisms (a particular gene or a particular infectious agent may always predispose to, or trigger, the same pathophysiological process), but little specificity in going from pathophysiological mechanisms to behavioral signs and subjective symptoms, such as thoughts and emotions (a particular pathophysiological mechanism may cause a variety of possible manifestations of mental illness, depending on where it starts and where it spreads in the brain, as well as on individual differences in the organization and structure of neural, vascular, and other brain components).
The most common pathophysiological mechanisms may turn out to be very few in number compared to the variety of manifestations of mental illness, as well as compared to the probably large number of predisposing genotypes and other causal factors. The pathophysiologies of mental illness could then be thought of as a sort of bottleneck: a small number of routes connecting a large number of causative factors on one side with a large number of symptomatologies on the other.
Not only can particular kinds of insults to the brain result in different forms of mental illness; they can cause cognitive deficits as well. Persons with mental retardation are at higher risk of developing schizophrenia. Persons with autism are at high risk of having mental retardation. Schizophrenia is almost always associated with cognitive decline. Cognitive decline in dementia is often accompanied by psychotic symptoms. Confusional states in delirium are characterized typically by cognitive impairment and delusional thinking. A recent study (Gale, CR et al 2008 Cognitive ability in early adulthood and risk of 5 specific psychiatric disorders in middle age: the Vietnam experience study Arch Gen Psychiat 65:1410-1418) found an association between low cognitive ability and risk of several types of mental illness. None of these associations should be surprising if we recall that the various components of intelligence as well as the various components of mental health are all functions of the brain. We need an inclusive concept of “mental weakness,” or “brain insufficiency.” Then we can say that a particular kind of insult can cause brain insufficiency, which in turn can be manifest as any number of cognitive deficits and symptoms of mental illness alone or, as is almost always the case, in combination.
Rejecting the idea that there are many distinct mental illnesses distinguishable by symptomatology need not cause us to change too much how we treat patients, because our treatments are in any case for symptoms, not for disorders. However, it may save us time spent in silly pondering over why different DSM diagnoses were given at different times to a single patient, and it may make us more prepared to witness the appearance or disappearance of symptoms in a patient. In cardiovascular disease, physicians are ready to add pressors to the medication regimens of patients who have been treated for hypertension, but then develop heart failure. We need similar flexibility in our psychiatric treatments.
As in cardiovascular disease, most cases of mental illness are multi-factorial in their causes. There are multiple possible genetic susceptibilities, and multiple possible types of environmental insults and stresses. There are a variety of possible resulting pathological brain states manifesting with various symptomatologies. There do seem to be some particular genetic susceptibilities or environmental insults that tend to predispose to particular pathological states and symptomatologies, but to a large extent, the greater variety of possible symptoms in mental illness than in cardiovascular disease simply reflects the fact that the central nervous system is more complex than the cardiovascular system, and more diverse in its functions.