A recent article by Lichtenstein et al. and an accompanying commentary by Owen & Craddock (both cited below) in the January 17, 2009, issue of the The Lancet bring up an ongoing controversy: Are schizophrenia and bipolar disorder much more biologically related to one another than current mental disorder classification schemes like DSM-IV would suggest? Do they share a similar genetic pathway that would ultimately make treatment for both more alike and more effective?
THE DIFFERING DIAGNOSTIC CRITERIA & CLINICAL CONCEPTUALIZATIONS
OF SCHIZOPHRENIA & BIPOLAR DISORDER
Schizophrenia tends to be categorized as a cognitive disorder where patients may have one or more of the following: strange thoughts, hearing voices when they’re not there, see things that are not there, erratic speech patterns ( sometimes wildly jumbled syntactically, sometimes lapsing into non-communicative catatonia), and especially a severe lack of logic in their cause-and-effect thinking, all to the degree that they significantly affect their life and relationships.
Bipolar disorder tends to be classified as a disturbance of mood levels. Moods swing way up and often then go way down. Generally, bipolar patients are observed to have abnormally heightened feelings about themselves that simply are not likely to be proportional with reality ( they believe that they can rule the world; they have I boundless energy; they’re think they’re tremendously productive or creative; they can go without sleep, sometimes for days at a time; they can spend money like it’s going out of style, feeling there’s not really any good reason to stop at the moment ; and often exhibit markedly increased libido).
These highs are followed by abnormally low feelings about themselves that are also not likely to be proportional (they are suddenly of no consequence to anyone; they have no energy at all; they can’t accomplish anything ever again ; they sleep all the time; they have no interest in pleasurable activities, including sex).
While there are certainly variations in the presence or absence of given symptoms, and even intermixing of up-and-down symptoms in some patients at the same time, bipolar disorder for the most part, is about the patient feeling ebullient at one point and then feeling totally flat at another, to such a degree that it impairs their ability to function in the real world.
THE SHARED CO-MORBIDITIES & REAL-LIFE CONSEQUENCES OF LIVING WITH THESE DISEASES WHEN THE PATIENT DOES NOT COMPLY WITH EFFECTIVE TREATMENT ARE NUMEROUS & PERHAPS NOT COINCIDENTAL
The idea that these mental illnesses may be closer than the way they are framed as distinct clinical entities, comes at least in part from shared maladaptive behaviors that are thought to be predisposing or concurrent to the long-term bad outcomes of letting either disease go without effective treatment.
Both schizophrenics and bipolars tend to abuse alcohol and drugs, and many times they are the same ones, although the dominant choice of substance differs somewhat by diagnosis. There is some evidence that in recent decades, schizophrenics have been significantly greater users of marijuana, while bipolar patients have favored methamphetamines, quite possibly because they can give a low mood state bipolar person a feeling of exhilaration and high energy, not unlike their high or manic moods.
A SMALL (& OFTEN MISTAKENLY EXAGGERATED) BUT NOT INSIGNIFICANT SHARED PROPENSITY FOR IRRATIONAL VIOLENCE
Likewise there are accounts that a small proportion of patients with either of these disorders (5%-10% depending on the study, but disproportionately reported as being commonplace in the popular press in any case), commits a violent act against innocent bystanders, caretakers or family members.
The truth is that most persons with serious mental disorders are not violent, and are more often the victims of violence themselves.
Nonetheless in studies of that small proportion of schizophrenics who commit acts of violence the cause is thought to be based on a typically bizarre belief that the victim of the assault was someone who somehow was mysteriously persecuting them, or monitoring or stealing their thoughts.
With bipolar patients, the victim is often a person who forcefully contradicts the bipolar patient’s assertions of the patient’s vast superiority, or who tries to intervene in a destructive behavior (such as a spending spree or drinking binge) or someone who reports to a rapidly speaking manic bipolar patient that they are simply not making any sense and cannot be understood, whereupon the manic person strikes out in frustration of the audience’s “slowness” of comprehension.
The underlying motive seems to be rage on the part of the bipolar perpetrator, that their particular view of the state of affairs or evaluation of their exalted status is just not being taken seriously by the rest of the world.
SHARED DISINTEGRATION OF FAMILIES, SCHOOLING & EMPLOYABILITY
There is also a commonality of familial, educational, and occupational breakdowns between poorly managed schizophrenics and bipolar patients. Marriages are often strained to the point of dissolution (and severe mental illness is grounds for a virtually automatic divorce in most states).
Likewise, students of high-school ( and even of college age), are not likely to have their odd and generally disruptive behaviors tolerated by their peers, even if under ADA, the school (or university) is required to make reasonable accommodation for the student if they are notified in advance officially by the student or their parent or guardian that they require special treatment.
While employers are now also under similar strictures, they are not required to keep on the payroll a patient who simply can no longer do the job or any available comparable work, or who cannot conform their behavior sufficiently to work alongside colleagues or with customers.
Often in either the educational or occupational setting, extended periods of unexplained or unexcused patient absenteeism is the reason for dismissal. There is some good news in that today Social Security disability is more readily attained by those with intractable mental disorders.
SHARED PROPENSITY FOR SHORTER LIFESPANS & SUICIDE
Unfortunately there is a shared prevalence of suicide (depending on the study in the teens of percentage), and an equally dramatic lifespan reduction of between 15-20 years on average, among noncompliant bipolars and schizophrenics. The lifespan reduction may well be tied to concurrent trend among schizophrenics and bipolars towards homelessness or living in single-room occupancy settings in marginal neighborhoods that are poorly served by any form of healthcare.
SHARED PROPENSITY FOR RESPONDING WELL TO THE SAME DRUGS & SHARED PROPENSITY FOR DOWNWARD SPIRALS WHEN THE PATIENTS STOP TAKING THEM
Still another commonality between bipolar patients and schizophrenics is their increasingly common pool of prescribed medications. Clozapine, olanzapine, risperidone, ziprasidone, and ariprazole which were once used primarily for psychotic episodes among schizophrenics, are now also being used for longer term bipolar patients with more severe symptoms, with a great deal of success.
The fact that these drugs work when they are taken religiously suggests that the diseases may operate via similar neurochemical pathways. Unfortunately, frequent noncompliance of both schizophrenics and bipolar with their medications, is another shared trait between the two patient populations. The frequency, speed and degree of symptomatic recurrence also appear to be about the same among bipolar and schizophrenics, and the untoward side-effects of the drugs also show a striking similarity.
IF MANY OF THE BEHAVIORS, OUTCOMES & EVEN SOME OF THE EFFECTIVE MEDICINES ARE THE SAME, MIGHT THERE BE A COMMON GENETIC BASIS?
While any one of these commonalities might be explained away individually, the common collective pattern between the two clinical groups increasingly suggests a common causation, probably at the molecular level, given the common effectiveness of the pharmacology.
In other words, a genetic load for either schizophrenia or bipolar disorder is said to be “prodromal,” meaning very highly predictive of development of the disease despite various educational or social interventions.
The first objection to this genetically prodromal argument is that it smacks to some civil liberties, educational association, and nonmedical therapist groups as “biological determinism” meaning that the patient is inevitably destined (or labelled as destined) to get the disease, no matter what else happened to the patient, and often despite all therapeutic interventions designed to avoid the development of the illnesses.
Some feel that too strong a genetic explanation underplays the role of bad environmental influences such as indifferent parenting, poor schooling, poverty, childhood trauma, malnutrition, the presence of drugs and alcohol in the environment, and even toxins in the food and water, or shared epidemic exposure to influenza or other infectious diseases that are known to cause cognitive damage to children and even to fetuses --------all of which have their scientific or social work adherents as agents of causation of one or the other of these mental illnesses.
But this can be answered by far more rigorous and empirical studies (particularly studies of twins reared apart, and adoption studies where the family environments & schooling are very different) that suggest that the causations proposed by classic psychoanalysis and social critics of psychiatry seem to account for very little that would deflect a straightforward genetic explanation. Most convincing is the opposite case: there are few large statistically reliable reports of a pattern of adopted kids from “normal” birth parent routinely developing bipolar disorder or schizophrenia, even when they are raised by adoptive parents who have one or the other disorder. The odds of seemingly normal adoptees developing these disorders later in life are vastly closer to that of the random population.
Nonetheless, even in the most deterministic genetic analyses, a few percentage points ( from 4.5%-7.4% for schizophrenia; 3.4%-6.2% for bipolar disorder)are allocated today towards “epigenetic” or environmental factors.
What makes the Lichetenstein et al. study cited below so important , and so very definitive, is that it involves an incredible 9,009, 202 individual studied from more than two million different families. The study of these very highly detailed and standardized government health insurance records turned up 35,985 clearly diagnosed schizophrenics and 40, 487 clearly diagnosed bipolars , which generated a follow-up examination of the same records for any patterns of mental health disorders among relatives of varying degrees of closeness, whether living together or living apart.
The statistical inheritability of schizophrenia was placed at 64% (versus 1% occurrence in the general population) and 59% for bipolars (versus 3% in the general population).
But what is even more striking is that in families where one sibling had bipolar disorder, not only did other siblings have an increased risk of bipolar disorder, but also of developing schizophrenia, or developing both bipolar disorder and schizophrenia.
This common biological-relatedness-propensity, or shared genetic load result even held up when a sibling with one or the other disorder was raised entirely apart from the birth family.
The scariest if entirely reasonable corollary of this study may be the that a parent from a family that seemingly has a genetic history of one mental illness that marries into another family with the other, appears to convey to their children, not just a propensity for one or the other illness as the same rate as their parent’s generation, but actually a higher rate of getting either or both.
This dangerous idea only makes sense only if the genes for one illness essentially pile on with the other, because it turns out that they are essentially the same genes that encode for the same structural (white matter) and metabolic (neurochemical) processes.
In other words, introducing more bad genes into a family clearly means more bad outcomes are likely in their children.
This starkly “eugenic” sounding formulation , if eventually proven true, however, has a really sympathetic and beneficial effect on the patients themselves: if the diseases are essentially the same and additively reinforcing in their genetic roots, and in subsequent brain structures and processes, then drugs treatments and future diagnostic procedures could one day be much more unified, and ultimately more beneficial to both variations of what, at its core, may be the same brain malfunction.
This is particularly important given that the Diagnostic & Statistical Manual V, the tool with which the vast majority of the mentally are diagnosed and treated, is just around the corner.
Tony Stankus, firstname.lastname@example.org Life Sciences Librarian & Professor
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