Research is revealing the specific microcomponents of family and
environmental stress that interact continually over time with a biologically
compromised brain to produce schizophrenia.
That was the message psychiatrist William McFarlane, M.D., brought to APA's
2007 Institute on Psychiatric Services in New Orleans in October.
McFarlane described a large and growing body of research that has
elucidated the specific nonbiological stressors that impact a compromised
neurobiology—not just periodically in "large hits," but
continually across childhood and adolescence, like a steady drizzle with a
cascading effect toward psychosis. This burgeoning literature provides the
theoretical foundation for the efficacy of psychosocial interventions,
especially multifamily psychoeducational groups whose purpose and function
McFarlane also described at the meeting.
William McFarlane, M.D., was presented the APA/American Psychiatric
Foundation Alexander Gralnick Award for Research in Schizophrenia at APA's
fall institute. With him are Paul Burke (left), executive director of the
foundation, and Thomas McGlashan, M.D., chair of the Gralnick award
Credit: Ellen Dallager
McFarlane is a professor of psychiatry at the University of Vermont and
director of the Center for Psychiatric Research at Maine Medical Center and
Spring Harbor Hospital. He delivered his lecture, "Biosocial Treatment
of Schizophrenia," after being awarded the APA/American Psychiatric
Foundation 2007 Alexander Gralnick Award for Research in Schizophrenia.
He stressed that a decade's worth of research on microcomponents of
environmental stress affirms the genetic nature of schizophrenia and does
nothing to revive long-discredited theories blaming families or"
schizophrenogenic" mothers. Time and again research has shown
that family and environmental stressors—encompassing very subtle
interactions common to many families—work only in tandem with biological
determinants to produce psychosis.
"Patients' symptoms seem to elicit certain kinds of rejecting or
anxious responses, which in themselves elicit more symptoms," McFarlane
said. "Who do you blame? It's really a no-fault situation—the
family is doing something, but they are only responding to the disorder. The
negativity is reciprocal.
"These young people may deteriorate very slowly in function, which
can make family members anxious, angry, or depressed. And in many of the
families that have had a history of schizophrenia or psychotic disorders, the
anxiety level can begin to rise to astronomical levels. It can be extremely
scary if they have some idea of what this might mean."
McFarlane is also director of the National Program Office of the Robert
Wood Johnson (RWJ) Foundation for its Early Detection and Intervention for the
Prevention of Psychosis Program and the Portland Early Identification and
Referral (PIER) Program. The PIER program is the model for a fivesite program
dedicated to prevention of schizophrenia that has been awarded a grant of
$14.8 million from RWJ.
McFarlane said the theoretical justification for psychosocial treatment of
schizophrenia is founded on the late George Engel's"
biopsychosocial" model of disease progression now well known
among contemporary psychiatrists. But the most recent research on
schizophrenia has revealed an important nuance: where once environmental
influences were considered to be intermittent, occurring in large discrete"
hits" on the biological mechanism, it now appears that some of
these influences are continuous, dynamic, and interactive.
"There are big hits but also microhits that evoke changes at the
biological and social levels in interaction with each other over time,"
he said. "The best way to conceive of this is as a kind of helix
interacting systematically between those two elements."
He cited a model first put forward by Barbara Cornblatt, Ph.D., of Albert
Einstein College of Medicine, in which insults to the brain occurring in utero
lead to a chain of events beginning with cognitive deficits, affective
symptoms, social isolation, and school failure.
"At some point in the progression of negative symptoms and
disability, we have the superimposition of positive symptoms and the emergence
of a diagnosis," McFarlane said. "Our conception is that these
social and environmental factors are operating continuously."
And they are operating on a biologically based sensitivity to sensory
stimulation, prolonged stress and strenuous demands, rapid change, complexity,
social disruption, illicit drugs and alcohol, and negative emotional
McFarlane also showed a brief computer video, produced by Paul Thompson,
M.D., Judith Rappoport, M.D., and colleagues, showing the loss of cortical
volume between the ages of 14 and 19 in children who go on to develop
schizophrenia. That progressive loss of cortical volume would seem to present
a hopeless case for schizophrenia, without a genetic cure.
"But Rappoport and Thompson themselves said that even though the
progression of this process is genetically controlled, the initiation of it is
not," McFarlane said. "Can we stop that progression? I don't know,
but the biosocial model suggests we should look at the interaction between
those social triggers and the biological process."
Of all the biologically determined psychosocial sensitivities believed to
precipitate psychosis, the most subtle are negative emotional experiences.
But paradoxically it is this factor— especially high family"
expressed emotion"—for which there is the most accumulated
data. High expressed emotion refers to the rejection, criticism, and anxious
overinvolvement that patients are liable to elicit from parents and other
One of the most conclusive studies documenting the role of high exppressed
emotion in the risk for schizophrenia is a 2004 study by Pekka Tienari, Ph.D.,
and colleagues published in the March 2004 British Journal of
In that study, a Finnish national sample of adoptees whose birth mothers
had a schizophrenia-spectrum disorder was compared blindly with adoptees
without this genetic risk. Adoptive rearing was assessed using family rating
scales that looked at expressed emotion and other family relating patterns,
based upon extended family observations at initial assessment. Adoptees were
independently rediagnosed after a median interval of 12 years.
Tienari and colleagues found that family ratings were a significant
predictor of schizophrenia-spectrum disorders in adoptees at high genetic risk
of schizophrenia, but not in those at low genetic risk. They concluded that
adoptees at high genetic risk are significantly more sensitive to adverse
versus "healthy" rearing patterns than are adoptees at low genetic
McFarlane emphasized that study rules out the possibility of family
relating patterns having any effect on schizophrenia in the absence of a
genetic risk. "But the only group that has a high risk are those that
have a genetic risk and family dysfunction," he said. "Both are
necessary, but neither alone is sufficient."
He added that Tienari's families were drawn from a random sample, so they
could not be said to represent unusually dysfunctional families.
McFarlane also described his own work elucidating components of expressed
emotion—warmth, protectiveness, rejection, and fusion—in the early
and late prodromal phases. And he described a theoretical model of social
performance deficits combined with perceptual distortions and pervasive
anxiety eliciting criticism and anxiety from family members in the early
prodrome; this in turn results in withdrawal, feelings of"
oddness," and further functional deterioration.
The work of Tienari, McFarlane, and others has laid the groundwork for
psychosocial interventions, especially the use of multifamily
psychoeducational groups. These groups are designed to empower family members
with information about the disease and the kind of social interactions that
can exacerbate symptoms in the affected family member.
In highly structured sessions, multifamily groups are taught specific
strategies for lowering anxiety, conflict, and expressed emotion. These
strategies are expressed with such simple, nonclinical tags as "go
slow," "give 'em space," "set limits,""
keep it simple," "lower expectations," and"
solve problems step by step."
McFarlane said a substantial body of literature has established the
efficacy of such groups on measures such as improved family-member well-being,
increased patient participation in rehabilitation, substantially increased
employment rates, decreased psychiatric symptoms, improved social functioning,
and decreased family distress.
"One of the interesting things about family psychoeducation is that a
lot of clinical goals are achievable without the patient's
participation," McFarlane said. "They have to give consent, but if
they decide not to show up for the group, the family can be taught to alter
the psychosocial environment to serve their needs even when the patient is not
An asbstract of "Genotype-Environment Interaction in
Schizophrenia-Spectrum Disorder" is posted at<http://bjp.rcpsych.org/cgi/content/abstract/184/3/216>.▪