The field of schizophrenia research recently has seen remarkable progress in the understanding and treatment of this disabling condition, and this special report reflects such progress. Leading academic clinicians provide comprehensive overviews of the present state of knowledge on key aspects of the detection, course and treatment of schizophrenia.

Addressing the course of schizophrenia in late life, Dilip V. Jeste, M.D., and Elizabeth W. Twamley, Ph.D., carefully document the salient characteristics of late-onset schizophrenia. They thoughtfully assert that these observations may reflect differences in the neurobiology of schizophrenia when it emerges later in life. They also provide practical guidance on the treatment of psychosis in late life.

Perhaps the most pronounced advancement in schizophrenia research is the prodigious developments in the treatment of people with schizophrenia. In a very short period of time, the pharmacotherapy of schizophrenia has expanded in options, diversified in approaches and ultimately provided heightened optimism for superior clinical outcomes for patients suffering with this illness. However, while the advances in the pharmacotherapy can allow for more effective treatment without motor side effects, these new drugs also have their own adverse-effect profiles. Hua Jin, M.D., and Jonathan M. Meyer, M.D., carefully review the emerging issue of diabetes mellitus with atypical antipsychotic use. They highlight that glucose dysregulation poses significant challenges--and opportunities--for the comprehensive care of people with schizophrenia.

This special report synthesizes a wide array of new information. The efforts of the contributors to provide a scholarly account of the current "state-of-play" of these important aspects of the course and treatment of schizophrenia are much appreciated. 

 recognizes Dr. Buckley for his assistance in planning and reviewing this special report section. Dr. Buckley is professor and chair of the department of psychiatry and health behavior at the Medical College of Georgia. Within the field of schizophrenia, his research has focused on antipsychotic medications and brain imaging studies. He has also written and edited numerous books and articles on the topic.  

Articles

The field of schizophrenia recently has seen remarkable progress in the understanding and treatment of this disabling condition. Dr. Buckley provides highlights of this special report.

Addressing Challenges and Opportunities for Better Outcomes

He blocks the path between me and the door
with his body and the smell of gin,
his wife still dressed in a hospital johnny, 
charcoal crust caked on her lips.
Like a thunderhead on a stifling afternoon
his voice rises and I grow quiet,
sweat beading like rain under my arms.
He waves his fist at me for keeping her prisoner
in the hospital, then suddenly reaches
inside his jacket-I'm sure he's going for a gun.
I wish I could say I responded like a martial artist,
but I sat as still as a hijacked 	passenger 
imagining the perfect black circle 
pointed at my face, the explosion
of gray smoke, the smell of black powder
and I could see the sharp margins
of the entrance wound, gray matter
splashed on the wall, my blood pooled
on the floor. But his hand shoots out 
with a photo of them at the beach,
his nails clawing her sunburned shoulder:
She's coming home now. 

Intimidation

As part of its task to conduct a comprehensive study of the U.S. mental health care system, the President's New Freedom Commission on Mental Health held its second meeting last November to focus on the critical role that housing plays for people with mental illness.

Most discussions about housing focus on the public sector, where the majority of people with serious mental illness receive treatment and where the supply of safe and affordable housing is in short supply. 

Housing is also a concern for the private sector. Patients with serious mental illness who are seen in private practice settings are of a different socioeconomic status than those treated in the public sector, but they still run the risk of losing the supports that keep them from entering the public system--namely employment, insurance and housing.

People under psychiatric care who are in the middle- and upper-income brackets often have family support above and beyond what is available to individuals in the public sector, Darrel Regier, M.D., executive director of the American Psychiatric Institute for Research and Education at the American Psychiatric Association, told 

However, that support is not guaranteed for life. Housing concerns are especially severe for aging middle-class parents who are providing for an adult child with mental illness. Their support, at the very least, helps keep the person out of the hospital and, in other cases, allows the person to hold down a job and receive private insurance benefits.

"The main worry in their lives is when they die, who's going to take care of these kids, and are they going to have adequate services for chronic illness?" Regier explained.

Those services include housing, drop-in centers and case management for coordinating the full range of medical care and other supports. While some parents will leave a nest egg that will provide their child with housing, the majority of parents will have exhausted their reserves on long-term health care costs that exceeded their insurance. 

This is a generic problem for people who have severe disabilities, Regier said. It speaks to the need for affordable housing and better links between public and private systems. Sometimes the best services for people with serious mental illnesses are found in the public sector, but they cannot get to these services until they spend down their resources and become eligible for Medicaid.

Because people with mental illnesses who are covered by private health insurance are probably not receiving housing assistance from the federal government, their particular housing concerns are less likely to be addressed by mental health care advocates. 

With the federal budget in deficit, advocates are focused on preventing cuts to existing programs at the U.S. Department of Housing and Urban Development (HUD) that serve people in the most desperate straits. These include the Shelter Plus Care program for homeless people and rental assistance provided through the Section 8 and Section 811 programs. 

(Several nonprofit organizations are also trying to address housing concerns. For more information, please see the news brief on p51 in the printed version of this issue--Ed.)

"HUD programs are underfunded relative to the need of people out there with worst-case housing needs," Andrew Sperling, deputy executive director of policy at the National Alliance for the Mentally Ill (NAMI), told 

. "And they tend to be triaged in the sense of getting assistance to those most in need."

Members of NAMI consistently identify access to safe and affordable housing as one of the biggest concerns for families that are responsible for the care of a person with serious mental illness. A national survey of NAMI membership found that 42% of people with severe mental illness lived with their families and that 11.2% lived with other relatives. Only 14% live in supervised community housing.

"It is very clear that the evidence from these studies and surveys demonstrates an impending national crisis for people with serious brain disorders and their families," NAMI member Margaret Stout told a Senate committee in 1998. "The public system intended to meet the housing and community support needs of people with severe mental illnesses is simply not equipped to handle existing demands for services, much less the estimated infusion of seriously disabled adults when their parents die."

No significant policy changes have occurred to address the issue since that testimony, Sperling told 

. But the graying of NAMI members continues. The issue is becoming critical as a large number of baby-boom children with serious mental illness continue living with their parents. As these parents move into their 70s and 80s over the next decade, they will no longer be able to care for their children at home.

Sperling explained that the stable housing environments in their parents' homes have helped keep many people out of institutional care. However, there is not a lot of data on the phenomenon because it is a difficult trend to track.

A number of families have anticipated future problems by establishing a special needs trust. This type of trust, which holds the title for the house, allows the adult child with mental illness to continue living in the parental home without losing eligibility for Supplemental Security Income and Medicaid. On the other hand, many families have not prepared, Sperling said. In addition, other issues arise, such as whether the child can maintain the house and keep up on property taxes and other financial obligations.

If a person lives in substandard housing, whether it is the result of a low-paying job or being unemployed, chances are they won't be receiving ongoing services, according to Wendi Cook, program coordinator for adult mental health services at the National Mental Health Association. Most often, the person is more concerned with being safe in the community, or staying warm or having enough to eat.

Consequently, when the person does receive services, often they are the most expensive kind, such as emergency department visits and incarceration, Cook told 

. And, once they get into the health care system, they usually end up in psychiatric institutions. This dynamic puts a financial strain on the entire system, from publicly funded programs to the clinicians and facilities that care for the patient.

If someone lives in substandard housing and a crisis occurs, most likely the person will eventually lose their home and end up on the street. At that point, it becomes a much larger community problem.

People with mental illness who are employed and receive private insurance are not immune from this. Most people are two paychecks away from homelessness, Cook said. An increase in insurance premiums, a layoff or a long-term crisis that affects employment can quickly push a private-sector patient into the public sector.

Policy changes currently being debated in Washington, D.C., might make that transition even more difficult. Currently, HUD's budget is set up so that a portion of its money goes to housing and a portion goes to services, Cook said. The goal is to get people into services that help them maintain housing.

However, the Bush administration is seeking to channel most HUD money toward housing, rather than services. In theory, those services would be picked up by the U.S. Department of Health and Human Services (HHS), but that does not appear to be happening, Cook said. People will receive housing but not the services that help keep them housed unless this issue is addressed. As budget proposals for 2004 make their way through Congress, mental health care advocates will be pushing for HHS to designate services for people in low-income housing who otherwise would have received service supports through HUD.

Regier has a patient with schizoaffective disorder who he has followed for 20 years. The patient was lucky to have parents with enough money to set him up with a condominium that was completely paid for before they died. He also has a healthy sibling who keeps track of him.

The patient holds a job as a clerk typist in a federal government office. He is a smart man with a college education and the ability to speak three languages. Still, Regier has to see him once a week for 15 to 20 minutes to keep track of medications, side effects and his overall condition, which can include mania, depression or psychosis.

The patient has no housing problem because his family has been able to give him the support he needs. This, in turn, makes it easier for him to keep his job. And that allows him to enjoy federal insurance benefits. Those supports make it more likely that he will keep his house.

However, if a patient loses any one of the three--the job, the benefits or the house--things can quickly spiral out of control.

In the private sector, Regier said, there tends to be a focus on patients who walk through the door and can afford care, and not as much attention to the system as a whole, but the public safety net of housing and services is crucial.

"Once you lose that job, you're vulnerable, even as a middle-class person," Regier said. Usually, private practitioners become aware of this only if it happens within their own families or with long-term patients who have a sudden demise. At that point, the psychiatrist must decide whether to continue with the patient. If the resources just aren't there, the patient may very well be out of luck.

It is a problem that all private practitioners worry about to some degree, Regier said. If family support disappears and a patient loses housing or a job or both, what can the clinician do?

Once a patient winds up on Medicaid, they have to struggle with a public-sector system that is under its own financial pressures. In Montgomery County, Md., for example, Medicaid services are provided through a fee-for-service reimbursement model in which categorical programs have been increasingly defunded.

That's when people start falling through the cracks, Regier said. If you don't have the categorical funding for case management in a fee-for-service managed care model, you've got a real problem. People begin missing their appointments, and no one is there to help manage their money. They miss their rent payments and wind up on the street.

The New Freedom Commission is aware that housing and supportive services would go a long way toward preventing this cycle. "We need more housing, not just more Haldol [haloperidol]," said one patient, commenting on the commission's interim report.

Confirming what many already know, the report said that affordable, safe housing is difficult to come by in the public sector. The wait for subsidized housing is two years or longer. Transitional housing is lacking, forcing many people released from psychiatric institutions to live in the streets.

Tanya Tull, president and CEO of Los Angeles-based Beyond Shelter Inc., told participants at the commission's November forum that Americans have come to look on homelessness as an inevitable and acceptable problem. The country's patchwork of emergency shelters and transitional housing perpetuate homelessness, which can only be addressed with permanent housing.

Tull embraces a housing first philosophy. Getting homeless people into permanent housing should be a program's central goal, she said. Providing permanent housing assistance up front can significantly reduce the time people spend being homeless. Necessary services include crisis intervention and stabilization, intake and assessment, targeted assistance for moving into permanent housing, and home-based case management.

Studies have demonstrated that supportive housing produces a number of positive outcomes, Carol Wilkins, director of intergovernmental policy at the Oakland, Calif.-based Corporation for Supportive Housing, told the commission. 

Emergency department and hospital visits can drop by more than 50%, Wilkins said, and the use of primary care services to address substance abuse problems increases. Supportive housing also improves participation in work and employment services.

While housing problems for the mentally ill are usually associated with patients receiving public care, private patients also face obstacles over obtaining and keeping adequate housing. What are the issues, and what can agencies do to ensure all patients, regardless of socioeconomic status, have adequate housing?

Housing Concerns Loom Large for Patients

, a film made 35 years ago, is a text that might give Americans some perspective on our own situation today. As I watched the film again after so many years, I realized for the first time that Gillo Pontecorvo had achieved something beyond his conscious artistic and political intentions. Like Leo Tolstoy, who meant to show the evils of adultery in Anna Karenina but created a character that transcended his moralizing agenda, Pontecorvo's Algerians transcend his Marxist categories and labels. If Pontecorvo could now revisit his own film, even he might recognize that the march of history turned in a different direction; one that he did not predict and would not like. The historical turn has been to traditional Islam, not to the Marxist idea of dialectical progress. Film critic Pauline Kael was not wrong in describing Pontecorvo as a Marxist poet, but Pontecorvo's poetry was a celebration of humanity. He described himself as "someone who approached man and the human condition with a feeling of warmth and compassion." His film and his poetry were an attempt to connect himself and his Western audiences, through their common humanity, to the Arabs of the Casbah--to what, in academic jargon, we now call the "alien others." He embraced what is different in the Arabs of the Casbah, including their Islamic traditions, and made them fully human for us. Yes, there is tragic necessity, but Pontecorvo's inspiration is utopian. Revolution, even in the style of Frantz Fanon, held for him the promise of a universal community in which Pontecorvo and perhaps many European Marxists imagined themselves sharing.

Pontecorvo's classic film chronicles the French military efforts to put down the Algerian rebellion. Pontecorvo was a multitalented man who produced several memorable films, all of them with a Marxist message. Although he was inspired by Sergei M. Eisenstein, he worked in the tradition of Roberto Rossellini's version of Italian neorealism.

 in black and white, using lenses and camera angles that reproduced realistic images like those of the mass media. Pontecorvo succeeded so well that many in his audiences thought they were watching newsreel footage and a documentary of the National Liberation Front's (FLN) revolutionary struggle against their French colonial oppressors. And Pontecorvo succeeded on another political level: He convinced middle-class audiences that terrorism--the bombing of innocent people--might be necessary. This was Kael's judgment: she described the film as "the rape of the doubting intelligence." She dubbed Pontecorvo the most dangerous kind of Marxist, a "Marxist poet" who uses the power of the film medium to persuade his audience that terrorism is a tragic necessity.

Pontecorvo wanted to portray the Marxist understanding of the historical processes that "once begun cannot be stopped." In the film, it seems that the French paratroopers have broken the back of the secret revolutionary organization when their captured leader is paraded before a press conference and asked if the FLN is now defeated. The actor, who is in fact the man who led the FLN, replies, "In my opinion, the FLN has more chances of beating the French army than the French have of stopping history."

Pontecorvo wrote about that line, "Not only did we believe this to be right, but we really liked the idea that it was right." He believed history was moving "in a certain way," that the class struggle would continue in the Third World, with the lumpen-proletariat of the colonized people taking up arms against the colonists. It was this Fanonian psychiatric gloss on Marxism that Sartre had endorsed. The wretched of the earth, the black faces who had been condemned to wear white masks would assert their own identity through acts of violence--rising up against oppression even when it came from "super-civilized France." The French had been defeated by that march of history in Vietnam, and Pontecorvo wanted to depict the last futile stand of the French colonial empire in Algiers. Out of the Casbah would come the Viet Cong of Algeria. Pontecorvo claimed that the guiding principle of his filmmaking was the "Dictatorship of Truth," and his version of Truth certainly disturbed the super-civilized French, who banned his film. All over the world, critics recognized that The Battle of Algiers had the power of truth revealed or, like Kael, they worried that the film took audiences by storm, gave them no chance to think. It was not truth but ultimate propaganda; Kael described it as the left equivalent of Leni Riefenstahl's deification of Adolph Hitler in Triumph of the Will.

Pontecorvo's film no longer has the immediacy that it had in the late 1960s. We all experienced the enormity of Sept. 11 on television, and the moral imagination of Americans could not conceive of a Pontecorvo justification for such acts of terrorism. President Bush spoke for the passionate convictions of the American public when he promised a terrible and inescapable retribution. Overnight, even leftist doves turned into war hawks. Something had to be done, and in the mood of the country, it seemed more than reasonable to invade Afghanistan. A year and a half later--like Pontecorvo's French paratroopers who put down the insurrection in the Casbah--we seem to have achieved complete victory and our nation is ready for war with Iraq as Bush continues on the offensive designated "Operation Enduring Freedom."

Pontecorvo's film is perhaps most ironically instructive on that American rallying cry. His French paratroopers ignored all legal restraints and used torture to gain the information necessary to destroy the FLN and won the battle of Algiers; but, as we are shown, they lose the war to maintain the French colonial empire. Without warning, two years after the French victory comes the inevitable march of history as the entire Arab population swarms out of the Casbah to march on the French city of Algiers. The French respond to this unexpected crisis using every brutal technique of riot control at their disposal, including gas, machine gun fire and tanks, to drive the Arabs back toward the Casbah. There is a brief lull in the riot scripted by Pontecorvo. As night and fog fall over the city, a French police authority addresses the unseen mob through a megaphone. "What do you want?" he asks in bewilderment. In response, mobs of Arabs emerge from the fog demanding and celebrating their freedom. Pontecorvo had imagined this scene as an ecstatic ballet in which the camera would focus on an Arab woman who the French police would push down again and again, and each time, she would rise up in a dance of freedom. This was the revelation to Western audiences, that the Arab Muslims of the Casbah saw themselves as freedom fighters. It is a revelation to remember today.

Kael wrote in 1972 that Pontecorvo's historical-determinist message seeps right into your bones. But she assumed that what Pontecorvo's film showed us was how "the Algerian people were spontaneously turned into Marxist revolutionaries by historical events."

Pontecorvo and his writer Pier Franco Solinas created a screenplay out of a Marxist/Fanonian screed, and that is what audiences saw at the time. There can be no more powerful demonstration that meaning comes from the context in which a text is seen. In today's context, what one sees is that Pontecorvo's film shows not Marxist revolutionaries but Arab-Muslim fundamentalists mobilizing the people of the Casbah. The very first FLN communique to the people of Algiers in the film proclaims, "Our revolt is against colonialism, our goal to restore independent Algeria within the framework of Islamic principles." In fact, throughout 

, it is Islam, not Marxism that is the yeast of the revolutionary solidarity that rises in the Casbah. The screenplay was, as Solinas said, "An ideological debate in dramatic form," but the film portrays a cleansing of the Arab people by a return to Islamic principles and a puritanical Islam that blames the French colonizers for imposing European decadence on Algiers. It is the French who have made the Arabs their prostitutes; undermined the traditional authority of the Muslim family; and brought cigarette smoking, alcoholism and drug addiction to their community. Osama Bin Laden, the Taliban, the Ayatullah ul-Uzma Khamenei and many other Islamic fundamentalists would sign on to this argument.

The FLN begins its campaign for the good will of the Arabs of the Casbah not by teaching Marxism, but by preaching Islam. The FLN understands that its recruits have been drawn from marginalized outcasts with every reason to hate the French and nothing to lose. These recruits and the Arabs of the Casbah must be purified and ennobled before they can undertake guerilla warfare, and they will only achieve this through a return to Islamic traditions. Pontecorvo's example is the young Arab Ali La Pointe, who is an illiterate juvenile delinquent, a sometime boxer, grifter and street criminal. He is ready to join the FLN after he witnesses from his prison window the guillotining of a man who goes to his death chanting, "Tahia el Djez-air" (long live Algeria). In order to join the revolutionary underground, Ali must agree to kill a French policeman. His hatred of the police is fueled by all the resentments of his life. The FLN trick him with an unloaded gun, this test is only to prove that he is not a French double agent. His real rite of passage into the FLN will come when he kills a friend, an Arab pimp who controls a string of brothels. Ali la Pointe is first a servant of Islamic purification, only then can he become a revolutionary leader of the FLN.

This purification of the Arab people through violence in the name of Islam is a central theme in Pontecorvo's film. In an unforgettable scene, we are shown a derelict Arab alcoholic who is set upon by a baiting pack of young boys who symbolize the new Islamic order. All this is now so obvious and undeniable that it seems strange that 35 years ago even the clear-eyed Kael could not see it. And here is a more radical suggestion that Pontecorvo, the artist, created all this without appreciating what he was doing. Looking at 

 today, what is prophetic is his background local color theme of Islamic fundamentalism and what proved false was Pontecorvo's foreground depiction of "the world moving in a certain way," in the direction foretold by the Marxist dialectical vision.

How did so much Islamic fundamentalism find its way into Pontecorvo's film? I believe there are several answers, all of which have to do with how the film was actually made. Yacef Saadi, who had been the military head of the FLN in Algiers, came to Italy looking for a director to make a movie of the Algerian struggle from the Algerian point of view. The Algerians could not provide great financial resources, but they could give the filmmaker access to any site he wanted and they could put crowds of people at his disposal. And Pontecorvo made good use of what he was given. Crowds, not stars, were to be the protagonists of the film. Pontecorvo had been a journalist and a still photographer, and he decided with one notable exception not to use professional actors. With a photographer's eye he chose people like Brahim Haggiag, the young man who played Ali La Pointe. His method of casting meant that the faces in the film are visually arresting, that the actors--at least in appearance--are authentic, and that there is no Hollywood or studio gloss. But such actors cannot be expected to mouth Marxist slogans convincingly. The lines Pontecorvo gave them were natural to them, the product of long hours interviewing FLN members and French Algerians who had participated in the events that would be depicted. Reading Pontecorvo's description of his research methods, one could almost say he psychoanalyzed the participants on both sides and distilled their collective memories into his dialogue. When Pontecorvo began to film and edit, he kept adding touches to convey the particulars of Algerian life in the Casbah. His impulse was to capture "the feelings and the emotions shared by a multitude." And what his Algerian actors and extras shared was their Islamic tradition. Muslims are often shown at their prayers with their foreheads pressed to the ground in submission to their God. No such image appears in this film. There is a less familiar prayerful position in which they raise their head and hold out their cupped hands. To Western eyes, the latter is the much more acceptable picture of pious humility. It is only in that collective gesture that Pontecorvo's Muslims respond to the tragedies that befall them. In the final scene where the residents of the Casbah appear out of the night and fog and demand their freedom, Pontecorvo had intended to have all the extras chanting political slogans. But he felt it just did not work. Then he hit on the idea of having the Arab women erupt into their traditional ululation--rhythmic piercing cries. It has an awesome effect, but it asserts not the brotherhood of revolution but the unifying exotic claim of Arab identity. And Pontecorvo thought it worked so well he used it in an earlier moment of the film as the rallying cry of the Casbah.

There is another very important moment in the film when Pontecorvo's artistic imagination privileges Muslim tradition. One of the most striking contrasts in Algiers was the difference between the appearance of the French and the Muslim women. The French women wear stylish short dresses, dye and coif their hair, use lipstick, and emphasize their sexuality. The Arab women of the Casbah cover their long hair, use no cosmetics, and conceal their faces and their sexuality. There comes a moment in the escalating terrorism when the French police supervisor decides on an unofficial act of counterterrorism. He sets off some dynamite in the Casbah, destroying homes and killing innocent men, women and children. An FLN response is justified. Three Arab women are shown cutting their hair and putting on makeup and French-style dress. There can be no doubt that this is a ritual moment of Western degradation as these modest Muslim women are being transformed into sexual objects. To make this unmistakable, we are shown French soldiers and other men hitting on them as they deliver their hidden time bombs. Pontecorvo films each of these three women looking around the crowded places their bombs will destroy. One woman's gaze lingers over a small boy licking his ice cream cone before she leaves her bomb. Watching those women today, it seems clear that what made their terrorist mission sacred was Islamic faith, not revolutionary solidarity. Each woman fully appreciates that there will be innocent victims, but theirs is a holy cause. Pontecorvo also films a scene where FLN terrorists hijack an ambulance and drive down a street, machine-gunning the French people on the sidewalks. When they run out of ammunition they suicidally crash the ambulance into a crowd.

Pontecorvo thought that the French torture of their captives was worse than any Algerian terrorism, but what his artistry now reveals is that the uprising against the decadent West was not terrorism in the name of Marx, but tactics in a holy war where martyrs go to heaven. If in the 1960s Pontecorvo made the mistake of seeing 

 through a Marxist prism, today we may be making a similar mistake. America, as it searches for enduring freedom, sees itself as fighting for democracy against corrupt, if not crazed, dictators like Saddam Hussein and madmen like Bin Laden. But, as Pontecorvo shows us, the Islamic people on the other side have their own ideas about freedom, and for many of them, it will be a holy war in which terrorism is a sacred duty. If you have a "doubting intelligence," it is time to look at the lessons of history in Pontecorvo's The Battle of Algiers and think for yourself.

With the seemingly impending war with Iraq, Dr. Stone revisits the Marxist-based film The Battle of Algiers and is surprised to find Islamic fundamentalism prominently featured throughout. Looking back, he finds nothing in the director's or writer's notes, or in critics' writings on the film, to indicate they were aware of its presence-the film was viewed through the context of the time. Are we still making this deadly error in dealing with Muslim nations?

Commentary On the Prospect of War

Schizophrenia is a devastating psychiatric disorder that affects 1% of the population worldwide. Patients often suffer their first psychotic outbreak in their late teens or early 20s. Despite advances in neuroleptic drugs, many patients' symptoms remain refractory to treatment, with recurrent episodes of auditory and visual hallucinations, bizarre delusions, depression, and social withdrawal that can last an entire lifetime. Neuroimaging studies now suggest that schizophrenia is a disorder of brain development, with anatomic abnormalities present at disease onset. Teen-agers with a severe, early-onset form of schizophrenia also exhibit a dynamically spreading wave of cortical gray matter loss, detectable in sequential magnetic resonance imaging scans. The tissue loss begins in a small region of the parietal cortex and moves forward to engulf frontal and temporal systems. These deficits correlate with psychotic symptom severity and may link with cortical dopamine or serotonin dysfunction. The shifting pattern of deficits is distinct from the neurodegeneration observed in the dementias and may be an exaggeration or derailment of the neuronal remodeling that normally occurs in late teen-age brain development. Computerized tracking of these cortical deficits will help understand how neuroleptic drugs decelerate or block the disease process. Cortical deficits are also detectable in patients' first-degree relatives, who are at greatly increased genetic risk for schizophrenia (10% lifetime risk). In the future, these dynamic and genetic brain maps may predict imminent onset of the disease, identifying pre-symptomatic brain changes in family members who are candidates for early interventions. 

One of the greatest enigmas in contemporary psychiatry is why schizophrenia strikes in the late teen-age years or young adulthood, often without warning. With an average age of onset around 20 to 25 in men and 25 to 30 in women, psychotic outbreaks in schizophrenia may include delusions, hallucinations and bizarre thoughts (i.e., positive symptoms). Negative symptoms include chronic depression, flattened affect, poverty of speech, loss of motivation and social decline. If these symptoms are untreated, the active phase of florid psychotic symptoms may last forever; however, they may be controlled to a degree by antipsychotics. Even when medications are effective, psychotic outbreaks are often replaced by a residual phase of poverty of thought or blunted affect. Around 20% of patients have a single psychotic outbreak, and 35% have multiple episodes without severe functional or personality impairments (Green, 1999). The remainder of patients has relatively static (10%) or progressive (35%) functional impairments between psychotic episodes.  

Unlike Alzheimer's disease, where amyloid plaques, neurofibrillary tangles and neuronal loss are pervasive in the brain at autopsy, there are no widely accepted pathologic hallmarks of schizophrenia. This is frustrating, as a biochemical marker could provide the basis for a diagnostic test and a target for drug action or disease prevention. Nonetheless, multiple lines of evidence suggest that cortical neurotransmitter function is disturbed in schizophrenia. Abnormalities in cortical dopamine, serotonin, glutamate, 

-aminobutyric acid (GABA) and norepinephrine have been intensively investigated. Classical antipsychotics (e.g., haloperidol [Haldol]) alleviate positive symptoms by blocking dopamine (D

-type) receptors in the limbic and prefrontal cortices of the brain, systems that regulate emotion and executive function. Newer atypical antipsychotics, including clozapine (Clozaril) and olanzapine (Zyprexa), powerfully block the 5-HT

 dopamine receptors and tend to outperform haloperidol in reducing negative symptoms (Bilder et al., 2002). Intriguingly, genetic studies suggest that 2% of patients with schizophrenia exhibit a chromosomal deletion in region 22q11, which harbors the gene encoding catechol-O-methyltransferase (COMT), a powerful inactivator of dopamine. Mice with targeted deletion of this gene have excess dopamine in the prefrontal cortex. This is consistent with the notion that patients with this deletion (which confers a 25% to 30% lifetime risk of schizophrenia) may suffer from a functional excess of cortical dopamine, and this may be responsible for their positive symptoms. 

Advances in neuroimaging, and structural MRI in particular, have empowered the search for biological markers of schizophrenia. Reduced cortical and hippocampal volume are found consistently in patients with schizophrenia, and the ventricular and sulcal cerebral spinal fluid spaces are often enlarged. Diffuse gray matter deficits are observed on MRI even in first-episode patients, where the confounding effects of medication on brain structure are ruled out. There is great interest in identifying when these anatomical deficits first appear. If their origins were identified, it may be possible to pinpoint precisely where, and when, an active pathological process begins. This could allow earlier disease detection and targeted interventions. 

Over 20 years of studies suggest that the origins of schizophrenia, as well as multiple risk factors, may lie in childhood or embryonic brain development. Obstetric risk factors, which confer a later risk for schizophrenia, include fetal malnutrition, extreme prematurity, hypoxia and ischemia (Cannon et al., 2002b). People born in winter months (Kirch, 1993) or exposed to the influenza virus in the second trimester (Mednick et al., 1988) may also have an increased incidence of schizophrenia. Some studies have contested this association, but others suggest that early viral exposure may increase risk for other psychiatric disorders as well (Akil and Weinberger, 2000). Given the array of proposed risk factors, disrupted brain development may play a causative role in schizophrenia. If this is the case, a key puzzle is why there is a long gap between an early cerebral insult and the emergence of symptoms 20 or more years later. To explain this, some theorists favor a two-hit (or diathesis-stress) model, in which an early developmental or genetic anomaly must be compounded by psychological trauma, viral infection or some currently unknown trigger later in life for the disease to be expressed. 

Renewed interest in the developmental hypothesis comes from recent brain imaging studies. These identify a drastic remodeling of brain structure in the teen-age years and beyond. Well into adolescence, there are growth spurts in myelination (Thompson et al., 2000), and dramatic waves of gray matter loss (Giedd et al., 1999a; Sowell et al., 1999). In a landmark paper based on MRIs of healthy subjects, Giedd et al. (1999b) built quadratic growth curves between the ages of 4 and 20 for gray matter volumes in each lobe of the brain. Perhaps surprisingly, the overall volume of gray matter declined sharply after the age of 12, especially in frontal and parietal cortices. This process continued through adolescence and beyond, with the latest decrements occurring in the frontal cortex (Sowell et al., 1999). Since schizophrenia typically strikes at a time when these developmental changes are still occurring, an intriguing hypothesis is that a normal teen-age process of dendritic remodeling and synapse elimination (sometimes called pruning) may be accelerated or otherwise derailed in schizophrenia (Feinberg, 1982). This excessive pruning may reach a threshold level where cortical information processing is disrupted. It may also account for the increased neuronal packing density seen in some cortical layers in postmortem studies of patients with schizophrenia (Selemon et al., 1995).  

In a large-scale effort to map the trajectory of brain changes during development, Judith Rapoport, M.D., and her colleagues at the National Institute of Mental Health have scanned over 1,000 children and teen-agers with high-resolution MRIs (Rapoport et al., 1999). Most of these children have been scanned every two years since 1992, producing a remarkable time-lapse movie showing their brain development. Among those patients scanned at NIMH were 50 adolescents (30 boys, 20 girls) with early-onset schizophrenia (EOS). These patients satisfied DSM-III-R/DSM-IV criteria for diagnosis of schizophrenia before age 13. Rigorous clinical and cognitive evaluations revealed their symptoms were continuous with the adult disorder; many patients resemble poor-outcome adult cases (Rapoport and Inoff-Germain, 2000). 

My colleagues and I studied these brain scans in collaboration with the NIMH group. We developed computerized methods to pinpoint rates of brain growth and gray matter loss in individual children and teen-agers and visualized these patterns as color-coded three-dimensional maps. Combining data from multiple subjects, we compared the amount of gray matter in multiple cortical regions across subjects and across sequential scans. This analysis produced color-coded three-dimensional maps of the cortex showing loss rates and group differences, and highlighting regions where these changes link with outcome measures or symptom severity. The brain maps for patients with EOS, published in the Proceedings of the National Academy of Sciences (Thompson et al., 2001), revealed a surprisingly dynamic pattern of disease progression. At their first scan (mean age=13), patients showed a 10% gray matter deficit, which was confined to a small region of the parietal cortex involved in spatial association, compared to healthy controls. Over the five succeeding years, this brain tissue loss swept forward, like a forest fire, into frontal and temporal brain regions.

Male and female patients showed a similar, dynamically spreading pattern of deficits. The frontal eye fields lost tissue fastest (5% per year); frontal and temporal regions were spared initially, but were subsequently engulfed. By age 18, gray matter was reduced by up to 20% to 25% in some brain regions. 

The spreading deficits correlated, in some respects, with functional decline as well. Total frontal loss rates correlated with negative symptoms (total scores on the Scale for Assessing Negative Symptoms [SANS]) at final scan (p<0.038). This makes sense, as negative symptoms are thought to derive in part from reduced dopaminergic activity in frontal cortices. At an individual level, rates of temporal loss correlated strongly with Scale for Assessing Positive Symptoms (SAPS) total scores at final scan (p<0.015, left hemisphere; p<0.004, right hemisphere). Faster losses in both the superior temporal gyri and the entire temporal cortices were significantly associated with a more severe clinical profile of positive symptoms (e.g., hallucinations or delusions). While tissue loss rates were not significantly linked with the rate of change in SAPS scores from baseline (p>0.05), and SAPS scores were not linked with the amount of tissue at baseline (p>0.05), loss rates were a good predictor of positive symptoms at follow-up (i.e., the remaining symptoms that were refractory to medication). 

To rule out confounding medication effects, a second medication- and IQ-matched control group was also studied, consisting of patients diagnosed with psychosis not otherwise specified. These patients exhibited only mild tissue loss, essentially confined to superior frontal cortices in a highly circumscribed pattern. Importantly, the pervasive, unrelenting spread of tissue loss was specific to schizophrenia and was not medication induced (although its rate could well be modulated by medication). 

An exciting open question is how strongly different antipsychotic drugs combat this wave of loss. Clinical studies in adult patients, using MRI to assess cortical integrity, suggest that atypical drugs decelerate overall gray matter loss, while gray matter progressively declines in patients taking haloperidol alone (J. Lieberman, M.D., personal communication, 2001). In both teen-age- and adult-onset patients, these progressive losses appear to continue for a long period after diagnosis (here seven years), offering a window of opportunity for interventions. Dynamic brain maps, such as the ones shown here, may help evaluate the spatial selectivity of these medication responses when comparing different neuroleptics. Computational brain maps also make it easy to stratify cohorts into subgroups with different symptom profiles. Patterns of brain change in responders may, in the future, be compared with groups who remain refractory to treatment.   

A shifting pattern of deficits raises perplexing questions. Is the wave of gray matter loss an exaggeration of a "normal wave" of gray matter pruning? Or is it a separate process entirely that begins in the teen-age years? Could it be a neurodegenerative process, similar to the progressive wave of gray matter loss seen in Alzheimer's disease (Thompson et al., 2003)?  

The strongest evidence against extensive neuronal loss in schizophrenia is the lack of reactive gliosis. Glial cell swelling and proliferation is the brain's natural response to neuronal cell death, and it is strikingly absent in postmortem studies. Nonetheless, in vivo proton magnetic resonance spectroscopy studies show that frontal N-acetylaspartate is reduced, and this is a good marker of neuronal integrity. Positron emission tomography also shows reduced frontal lobe glucose metabolism in both early- and adult-onset patients. Impaired cortical activation is also seen in functional MRI studies of working memory and executive function. These deficits are clearest in tasks (e.g., Wisconsin Card Sorting) that place heavy demands on frontal systems. 

Rather than widespread cell loss (as in the dementias), it is more likely that neuronal shrinkage, reductions in dendritic complexity and synaptic loss, as well as vascular changes, may underlie the gray matter changes observed here in schizophrenia. An intriguing hypothesis is that schizophrenia patients may suffer an abnormal intensification of whatever regional gray matter loss occurs in healthy subjects at their specific age of onset. This idea may reconcile why deficits in EOS and adult-onset cases differ, somewhat, in their scope and severity. Predominantly frontal and temporal gray matter losses tend to be reported in adult-onset patients, while more pervasive losses are seen in early-onset studies. Frontal and temporal lobes are the last to show gray matter loss in healthy controls. These systems may be especially vulnerable if the disease begins in young adulthood, while they are being actively remodeled. Additional cortical systems may be vulnerable if the disease hits earlier, in the early teen-age years. 

Two final studies illustrate the usefulness of neuroimaging as a biomarker in schizophrenia. In a recent twin study (Cannon et al., 2002a), we detected frontal and temporal cortical deficits (around 5% to 8%) in healthy relatives of patients who are at increased genetic risk for developing the disease. These deficits were correlated with the degree of genetic affinity to a patient (i.e., worse deficits in identical twins of patients than fraternal twins, for example, as the latter share fewer genes with a patient). Patients' siblings and children have a 10% lifetime risk of developing schizophrenia, much greater than the 1% risk in the general population. 

Isolation of a brain deficit that is an index of liability for schizophrenia is important for two reasons. First, a heritable biomarker, found in at-risk relatives, can be used in genetic association and linkage studies. Differences between MRIs of relatives can be covaried with the number of alleles they share with a patient at a candidate marker locus, to see if particular genetic loci play a role in increasing liability. The notion of genetic linkage (which links trait variation with allelic variation at a marker locus) can be generalized to the notion of a brain map of linkage, showing brain deficits that are linked with allelic variations (e.g., Thompson et al., 2003). As neuroimaging and genetic databases increase in size and content, the merger of genetics and neuroimaging will empower the search for (and characterization of) susceptibility genes. This is likely to clarify their effects on brain phenotype and disease progression in human populations. 

Secondly, analysis of brain changes in those at genetic risk may help identify relatives who are in the prodromal (i.e., pre-symptomatic) phase of the disease. Since individual outcomes depend heavily on how early the disease process is detected, relatives with both genetic and neuroimaging risk markers may be able to use this information proactively. Armed with this knowledge, they may in the future opt for early interventions and drug treatment before the ravages of the disease have set in. 

Special thanks go to the members of the NIMH Child Psychiatry Branch, the University of California, Los Angeles, Laboratory of Neuroimaging, and the Queensland Center for Magnetic Resonance, for their key role in the studies summarized here.

 Akil M, Weinberger DR (2000), Neuropathology and the neurodevelopmental model. In: The Neuropathology of Schizophrenia: Progress and Interpretation, Harrison PJ, Roberts GW, eds. New York: Oxford University Press, pp189-212. 
 

 Bilder RM, Goldman RS, Volavka J et al. (2002), Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry 159(6):1018-1028 [see comment].
 

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Schizophrenia is a devastating psychiatric disorder that affects 1% of the population worldwide. Patients often suffer their first psychotic outbreak in their late teens or early 20s. Despite advances in neuroleptic drugs, many patients' symptoms remain refractory to treatment, with recurrent episodes of auditory and visual hallucinations, bizarre delusions, depression, and social withdrawal that can last an entire lifetime.

Brain Mapping in Adolescents With Very Early Onset Schizophrenia

Thus, insofar as it is possible--and all of us fail now and then when one of our private interests is touched upon--the psychiatrist remembers that his role is that of an expert.

On Oct. 20, 2000, the New York Academy of Medicine, the New York Medical College and the World Psychiatric Association jointly sponsored a conference titled "Psychiatry and Religion: Friends or Foes?" The conference was oversubscribed, with standing room only for some of the more than 150 people present. Three previous presidents of the American Psychiatric Association were in attendance; two were presenters. In the course of the daylong meeting, each speaker agreed that we have to carefully proscribe our interventions in areas outside our expertise and called on clergy to do the same. The details of where to place the boundaries were left open for discussion and are still ripe for research.

Little did any of us realize that less than a year later, expert dialogue between clinicians and clergy would be crucial in the aftermath of Sept. 11, 2001 (American Red Cross, 2002).

The need for research to determine the best mode of reciprocal collaboration between clergy and mental health care professionals was made dramatically apparent after the attack on the World Trade Center. Civic leaders called upon citizens to go to their houses of worship and to seek psychological counseling. In St. Paul's Chapel--an Episcopal church that was a main place of refuge for relief workers at Ground Zero--a handwritten sign near the entrance said, "Counselor available. Please ask" (Wakin, 2001).

For the past 10 years, I have studied the process of reciprocal collaboration between clergy and clinicians. In the last five years, I have implemented pilot projects designed to examine the complementarity of religion and mental health care within the contexts of professional and vocational specialization (Milstein et al., 1999).

Research has consistently shown that people with emotional problems most frequently turn to clergy for help (Chalfant et al., 1990; Gurin et al., 1960; Veroff et al., 1981) and that even people with serious mental illness are as likely to contact clergy as they are to contact mental health care professionals (Larson et al., 1988). In a survey conducted less than one month after Sept. 11, approximately 60% of all the respondents said they would likely seek help from a spiritual counselor, compared to 45% of all the respondents who would likely seek help from their physician and 40% who would seek help from a mental health care professional (American Red Cross, 2002).

People do not choose these patterns of help-seeking because they are unaware of mental health care resources. Rather, they do so because they are more familiar with clergy, clergy do not charge fees and there is less stigma involved in discussing one's personal problems with clergy (Chalfant et al., 1990; Schindler et al., 1987). It is estimated that 10% of people who go to clergy with psychological problems are then referred to mental health care professionals (Mollica et al., 1986). Few studies have examined circumstances wherein mental health care professionals have made referrals to or consulted with clergy (Weaver et al., 1998, 1997).

In order to collaborate, clergy and clinicians must be able to recognize those signs and symptoms that indicate a need for consultation or referral. The 

 introduced a new V code, religious or spiritual problem (V62.89), which the 

(Lu et al., 1997) describes as a category to employ in order to explicitly differentiate psychiatric mental disorders (e.g., schizophrenia, major depression) that require clinical attention from profound personal religious concerns that are not mental disorders but may be a focus of clinical attention because of difficulty integrating these experiences into the individual's social or emotional life (e.g., mystical experience, religious doubt). A third distinct category discussed in the sourcebook is labeled pure religious problems. These are described as emotional difficulties that people have within the context of organized religion and warrant neither clinical attention nor a 

 diagnosis (e.g., mourning rituals, religious doctrine).

An example of the first category (mental disorders that present with religious ideation) would be a young man with schizophrenia who has isolated himself in his room and reports seeing God talking with His angels. This person should be treated by a clinician and referred to a mental health care professional if first brought to clergy. A vignette study we conducted with rabbis and clinical psychologists found agreement on this course of action, with one rabbi exclaiming, "We go right to the emergency room!" (Milstein et al., 2000).

Examples of the second category of presenting problems consist of emotional difficulties resulting from strong religious experiences and may include mystical experiences or questions of personal faith that leave a person with troubling questions, emotional discomfort and a sense of isolation (Lu et al., 1997). Although these problems may be a focus of clinical attention, they are not mental disorders and could receive a 

diagnosis of religious or spiritual problem (V62.89). Expertise for this type of care may not belong only to psychiatry, and therefore a collaborative approach may be most appropriate.

Psychiatry has come to recognize the importance of culture as the interpretive system through which people seek answers to complex questions (Bruner, 1990; Gaw, 1993). Religion is a central aspect of nearly every culture, and clinicians need to be familiar with the "nuances of an individual's cultural frame of reference" or else they "may incorrectly judge as psychopathology those normal variations in behavior, belief, or experience that are particular to the individual's culture" (APA, 1994). Therefore, if people come for clinical care in response to emotional difficulty associated with a loss of faith or anger at God after Sept. 11, we are ethically obligated to understand their theological perspective from within the interpretive system of their religious beliefs and wisdom traditions (Hopkins et al., 1995). This understanding could be gained through consultation with the patients' own clergy or with another trusted clergy with knowledge of these faiths. With the patient's consent, the clinician and clergy could devise a treatment plan incorporating each profession's expertise.

Finally, the third category of pure religious problems would not receive a 

 diagnosis. This category includes normal bereavement, wherein the person is grieving but not depressed, and the mourner has many religious and philosophical questions. A large part of the professional role of clergy is guiding individuals and families through the rituals--as well as the emotional trauma--of death and burial. This is an area of psychological suffering with which clergy have expertise different from that of psychiatrists, and mental health care professionals could gain knowledge from them.

Once a differential diagnosis from within the three categories has been established, a subsequent psychiatric (or nonpsychiatric) response may be considered.

Some clinicians who are co-religionist with their patients might choose to work without consultation. Some may believe that doctors and their patients should engage in religious rituals together, as part of the healing process. Although such interventions could be personally gratifying, Harry Stack Sullivan reminded us nearly 50 years ago that we should not work outside our scope of expertise. I would instead propose that we develop collaborative relationships with clergy. They are the experts in matters of religion.

Trauma, depression, bereavement, anxiety and loss of religious faith have all arisen in the aftermath of Sept. 11. We know that more than a year later, some people are only now beginning to discuss the effects of the attack on their emotional well-being (Goode and Eakin, 2002). We expect that clergy are seeing some of these signs, hearing their parishioners' symptoms and could, therefore, serve as conduits to appropriate clinical care. There may also be times when it is appropriate for psychiatrists to serve as conduits to clerical care.

Since 1998, I have worked with the pastoral care and education department at the Westchester Division of the New York Hospital, Weill Cornell Medical Center, to develop outreach programs to community clergy. At the hospital, we hosted a breakfast presentation by clinicians. After telling the clergy of the different mental health care services we offered, we had them write down a paragraph describing one or more challenging congregants. Our chaplain suggested to the participants that these congregants could be found among the 2% of parishioners seeking help who use 80% of the clergy's counseling hours. 

We then organized several clergy case conferences based on the diagnostic similarity of the congregants described. The associate medical director presided over three separate meetings, and we were able to offer some specific suggestions to the clergy. At the same time they provided mutual comfort to one another through dialogue they initiated. Subsequent to this outreach, several clergy made referrals to our facility. We have also been able to engage clergy in the discharge planning of some patients who are active in their congregations.

Collaboration with clergy need not be limited to institutional outreach. Individual clinicians could begin their own network of collaboration through attending the interfaith clergy meetings that are common in most communities. The key to success is to develop ongoing reciprocal interaction. Clergy are disinclined to maintain contact with clinicians who treat them as a quiescent source of referrals (Meylink and Gorsuch, 1988). Two resources that have been very helpful in our outreach are the 

Mental Illnesses Awareness Guide for Clergy and Other Spiritual Leaders

, distributed at no cost (APA, 1997); and the Web site for Pathways to Promise, a nondenominational organization consisting of religious congregations who seek to increase awareness about mental illness <

Currently, at the Montefiore Medical Center Geriatric Psychiatry Clinic in the Bronx, I am the principal investigator of a study funded by the National Institute of Mental Health that explores geriatric psychiatry outpatients' opinions about collaboration between clergy and clinicians. The data from this study will help us develop Project C.O.P.E. (Clergy Outreach & Professional Engagement), a study designed to measure the salutary (or harmful) effects of interaction between patients' clinicians and their clergy. We hypothesize that the effects could include improved adherence to psychiatric care because of reduced stigma and improved clinical outcomes from increased social support.

Sept. 11 taught many lessons about how all of us are capable of working across social and professional boundaries to help the injured to heal. Research on the outcomes of reciprocal collaboration between psychiatrists and clergy is a project intended to bring disparate areas of expertise to the single goal of improved mental health.

American Red Cross (2002), The Lifecycle of a Disaster: Ritual and Practice: Understanding the Impact of the 9/11 Terrorist Attacks on Faith Communities and Their Leaders. New York: American Red Cross.
 

APA (1994), DSM-IV. Washington, D.C.: American Psychiatric Association, ppxxiv, 684-685.
 

APA (1997), Mental Illnesses Awareness Guide for Clergy and Other Spiritual Leaders. Washington, D.C.: American Psychiatric Association, Division of Public Affairs.
 

Bruner JS (1990), Acts of Meaning. Cambridge, Mass.: Harvard University Press.
 

Chalfant HP, Heller PL, Roberts AE et al. (1990), The clergy as a resource for those encountering psychological distress. Review of Religious Research 31(3):305-313.
 

Gaw AC (1993), Culture, Ethnicity, and Mental Illness. Washington, D.C.: American Psychiatric Press.
 

Goode E, Eakin E (2002), Mental health: the profession tests its limits. New York Times. Sept. 11.
 

Gurin G, Veroff J, Feld S (1960), Americans View Their Mental Health: A Nationwide Interview Survey. New York: Basic Books.
 

Hopkins E, Kelley R, Bentley K et al. (1995), Working With Groups on Spiritual Themes: Structured Exercises in Healing, Vol. 2. Duluth, Minn.: Whole Person Associates.
 

Larson DB, Hohmann AA, Kessler LG et al. (1988), The couch and the cloth: the need for linkage. Hosp Community Psychiatry 39(10):1064-1069.
 

Lu FG, Lukoff D, Turner R (1997), Religious or Spiritual Problems. In: DSM-IV Sourcebook, Vol. 3. Widiger TA, Frances AJ, Pincus HA et al., eds. Washington, D.C.: American Psychiatric Association, pp1001-1016.
 

Meylink WD, Gorsuch RL (1988), Relationship between clergy and psychologists: the empirical data. Journal of Psychology and Christianity 7(1):56-72.
 

Milstein G, Midlarsky E, Link BG et al. (2000), Assessing problems with religious content: a comparison of rabbis and psychologists. J Nerv Ment Dis 188(9):608-615.
 

Milstein G, Sims E, Liggins L (1999), Community outreach by a mental center: a dialogue with clergy. The Community Psychologist 32(1):49-51. 
 

Mollica RF, Streets FJ, Boscarino J, Redlich FC (1986), A community study of formal pastoral counseling activities of the clergy. Am J Psychiatry 143(3):323-328.
 

Schindler F, Berren MR, Hannah MT et al. (1987), How the public perceives psychiatrists, psychologists, nonpsychiatric physicians, and members of the clergy. Professional Psychology: Research and Practice 18(4):371-376.
 

Veroff J, Kulka RA, Douvan EAM (1981), Mental Health in America, 1957 to 1976. New York: Basic Books.
 

Wakin DJ (2001), Terror attacks could change paths of faith. New York Times. Sept. 30.
 

Weaver AJ, Samford JA, Kline AE et al. (1997), What do psychologists know about working with the clergy? An analysis of eight APA journals: 1991-1994. Professional Psychology: Research and Practice 28(5):471-474.
 

Weaver AJ, Samford JA, Larson DB et al. (1998), A systematic review of research on religion in four major psychiatric journals: 1991-1995. J Nerv Ment Dis 186(3):187-190.

The World Trade Center attack changed the face of the United States and of psychiatry. Men and women of the cloth and of the clinic came together to care for the stricken masses. Yet, members of the clergy do not always refer congregants who exhibit duress to the psychiatrist, nor do psychiatrists refer patients to the clergy. What keeps these two fields apart? What is best for your patient?

Clergy and Psychiatrists: Opportunities for Expert Dialogue

With the aging of the baby boomers, the number of people in the United States older than 65 is projected to double from about 35 million today to nearly 70 million by 2030. There will be a disproportionately greater increase in the number of elderly Americans who suffer from a mental illness--from approximately 6 million today to about 15 million by 2030 (Jeste et al., 1999a). Younger adults who have a serious mental illness, such as schizophrenia, currently have a significantly shorter life span than those without mental illness. The average life span of these patients is expected to increase, thanks to improved pharmacologic and other treatments, as well as general improvement in health and nutrition. In addition, as people in the general population live longer, the numbers of individuals who will develop psychotic disorders in later life will also grow.

One of the most disenfranchised groups in health care is older people with psychotic disorders. The health-related well-being of older patients with psychosis living in the community is comparable to (or even slightly worse than) that of outpatients with AIDS (Patterson et al., 1996). 

Acute psychotic symptoms in older people may reflect delirium or metabolic causes. Chronic and persistent psychotic symptoms belong to one of two groups: primary psychotic disorders (such as schizophrenia, delusional disorder, psychotic mood disorder) or psychosis secondary to dementia or other general medical conditions. Two important chronic psychotic disorders in older people that will be discussed in this article are schizophrenia in late life and psychosis of Alzheimer's disease (AD). Table 1 highlights the main differences between these two conditions (Jeste and Finkel, 2000). 

(Due to copyright concerns, this table cannot be reproduced online. Please see Table 1 on p19 of the print edition--Ed.)

Schizophrenia affects about 1% of the population and is arguably the most expensive mental illness in adults. Furthermore, the cost of health care tends to be highest for the oldest of these patients (Cuffel et al., 1996). Older adults with schizophrenia often live alone, in assisted-care facilities, in homeless shelters or on the street. The proportions of those living with family or in long-term institutional settings are relatively small. These patients are usually unable to work or interact with society in a productive manner. Nonetheless, research in late-life schizophrenia shows that the century-old Kraepelinian concept of "dementia praecox"--i.e., a disorder with onset restricted to adolescence or early adulthood with progressive downhill course--is not quite accurate. Schizophrenia can manifest for the first time in middle age or later, and the course of schizophrenia in old age is typically different from that of dementia (Jeste et al., 1997).

Of the older people with schizophrenia, nearly 25% have late-onset schizophrenia (with onset of illness usually in middle age), while the remaining 75% have had schizophrenia since adolescence or early adulthood. Middle-age-onset patients are similar to early-onset patients in terms of positive symptoms (paranoid delusions and auditory hallucinations), family history of the illness, pattern of cognitive impairment (deficits in learning and abstraction but not in delayed recall), nonspecific brain-imaging abnormalities such as mild ventricular enlargement and white matter hyperintensities, chronicity of illness, and higher mortality from suicide and other causes (Jeste et al., 1997). However, late-onset schizophrenia is characterized by less severe negative symptoms such as social withdrawal and blunting of emotions, less severe deficits in learning, need for and tolerance to lower doses of antipsychotic medications, and a much higher proportion of women than men. One possible explanation for this gender difference is related to a loss of estrogen with menopause in older women. The theory is that estrogen has a protective effect against schizophrenia, and when that protection diminishes, women who are vulnerable to develop schizophrenia begin to manifest symptoms of the illness (Seeman, 1997).

The course of early-onset schizophrenia in older age is relatively stable and non-deteriorating. Most elderly people with schizophrenia are symptomatic and disabled but not demented and are living in the community. Negative symptoms persist, whereas positive symptoms tend to show a modest improvement with aging (Cohen et al., 2000).

Can schizophrenia ever remit? Most people are now familiar with the story of John Forbes Nash, Ph.D., the Nobel Prize-winning mathematician whose remission of schizophrenia around the age of 60 was portrayed in the Academy Award-winning film, 

. Yet the concept of remission of schizophrenia continues to be controversial. One would not typically expect a person with schizophrenia in remission to display completely normal life functioning. The physical effects of aging, biopsychosocial stressors of old age, effects of having suffered from decades of severe psychiatric illness, side effects of treatments, social stigma and the typical history of suboptimal premorbid functioning interact to preclude such outcomes. It is worth stressing that schizophrenia is a neurodevelopmental disorder--i.e., people with schizophrenia usually have had somewhat impaired cognitive functioning since early childhood. 

Nonetheless, patients in persistent clinical remission should be free of positive and negative symptoms, have reasonably age-appropriate everyday functioning, and be without psychiatric hospitalization for the previous five years or longer. Such remission may occur in up to 20% of aging patients with schizophrenia. Better premorbid functioning, female gender, later age of symptom onset, shorter duration of illness, paranoid subtype, early initiation of treatment and psychosocial support have been reported to be associated with a greater likelihood of remission.

Treatment of schizophrenia in most cases involves a combination of antipsychotic medications and psychosocial therapy.

Psychosis of AD is a serious problem for caregivers and often results in institutionalization of the patient (Jeste and Finkel, 2000). Although estimates of the prevalence of psychotic symptoms in dementia vary, approximately 50% of patients experience delusions or hallucinations within the first three years after a clinical diagnosis of AD is made (Paulsen et al., 2000). The usual symptoms of psychosis of AD are simple paranoid delusions of stealing or hiding things, jealousy, or infidelity on the part of the spouse. Visual hallucinations are more frequent than auditory ones (Jeste and Finkel, 2000). Psychosis is more likely to present during intermediate stages of dementia than in very early or very late stages. Psychotic symptoms are rarely the initial manifestation of AD. As the severity of dementia increases, psychotic symptoms improve--it is unclear if this is true remission or merely a result of worsening cognition and speech making it difficult for the patient to express their delusions. 

The optimal treatment of psychosis in AD may include pharmacotherapy and/or psychosocial interventions. Pharmacotherapy is necessary when the psychotic symptoms are severe enough to cause distressing agitation or aggression or otherwise disrupt the patient's functioning. The doses of antipsychotics should be considerably lower in patients with dementia than in those with schizophrenia, as can be seen in Table 2 (Jeste et al., 1999b). Psychosocial approaches to treatment emphasize caregiver education and environmental modifications to increase patients' orientation and decrease confusion. Such interventions may include optimization of social contact, increase in structured activities, environmental enrichment, prevention of overstimulation and light therapy (Cohen-Mansfield, 2001).

Antipsychotic medications usually constitute the primary pharmacotherapy for psychotic disorders (Jeste et al., 1999b). Guidelines for the dosing of antipsychotic medications are presented in Table 2. In older people, the heightened risk of sedation, postural hypotension, anticholinergic side effects, extrapyramidal symptoms and, especially, tardive dyskinesia makes conventional antipsychotic medications less suitable in most cases. The atypical antipsychotics should usually be considered the first-line treatments because of their greater safety. Nonetheless, even with these medications, sedation, hypotension, weight gain, diabetes and cardiac conduction changes are causes for concerns. For older patients with schizophrenia or psychosis of AD, risperidone (Risperdal), olanzapine (Zyprexa) and quetiapine (Seroquel) are currently the three most frequently prescribed antipsychotics. Studies of ziprasidone (Geodon) in this population have not yet been published. Aripiprazole (Abilify) has recently been approved as an antipsychotic by the U.S. Food and Drug Administration.

Psychosocial treatments are essential for older people with psychoses. As mentioned previously, some nonpharmacologic interventions have empirical support for efficacy in psychosis of AD. For older patients with schizophrenia, a number of different individual and group therapies are beginning to be studied. In our center, we have focused on the following interventions (Granholm et al., 2002):

Cognitive-behavioral social skills training to target delusional thinking, social skills and coping strategies;

Medication adherence therapy to provide education and medication management skills to promote adherence to antipsychotic medication regimens;

Functional adaptation skills training, a group training program that teaches everyday living skills (e.g., financial management, use of transportation); 

Work rehabilitation, using a supported employment model.

There is still much work to be done in terms of optimizing treatment of psychotic symptoms while reducing side effects, increasing optimal health behaviors (e.g., medication adherence, smoking cessation, nutrition and exercise) and minimizing disparities in access to health care for older patients with psychoses. However, there are many reasons to be optimistic about future therapies for older patients with psychoses, as the numbers of clinicians and researchers in the field of geriatric psychiatry continue to grow.

Cohen CI, Cohen GD, Blank K et al. (2000), Schizophrenia and older adults. An overview: directions for research and policy. Am J Geriatr Psychiatry 8(1):19-28.
 

Cohen-Mansfield J (2001), Nonpharmacologic interventions for inappropriate behaviors in dementia: a review, summary, and critique. Am J Geriatr Psychiatry 9(4):361-381.
 

Cuffel BJ, Jeste DV, Halpain M et al. (1996), Treatment costs and use of community mental health services for schizophrenia by age cohorts. Am J Psychiatry 153(7):870-876.
 

Granholm E, McQuaid JR, McClure FS et al. (2002), A randomized controlled pilot study of cognitive behavioral social skills training for older patients with schizophrenia. Schizophr Res 53(1-2):167-169 [letter].
 

Jeste DV, Alexopoulos GS, Bartels SJ et al. (1999a), Consensus statement on the upcoming crisis in geriatric mental health. Research agenda for the next 2 decades. Arch Gen Psychiatry 56(9):848-853.
 

Jeste DV, Finkel SI (2000), Psychosis of Alzheimer's disease and related dementias. Diagnostic criteria for a distinct syndrome. Am J Geriatr Psychiatry 8(1):29-34 [see comment].
 

Jeste DV, Rockwell E, Harris MJ et al. (1999b), Conventional vs. newer antipsychotics in elderly patients. Am J Geriatr Psychiatry 7(1):70-76.
 

Jeste DV, Symonds LL, Harris MJ et al. (1997), Nondementia nonpraecox dementia praecox? Late-onset schizophrenia. Am J Geriatr Psychiatry 5(4):302-317 [see comment].
 

Patterson TL, Kaplan RM, Grant I et al. (1996), Quality of well-being in late-life psychosis. Psychiatry Res 63(2-3):169-181.
 

Paulsen JS, Salmon DP, Thal LJ et al. (2000), Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurology 54(10):1965-1971 [see comment].
 

Seeman MV (1997), Psychopathology in women and men: focus on female hormones. Am J Psychiatry 154(12):1641-1647 [see comment].

Although late-onset psychosis is not as common as the early-onset variety, it can still pose difficulties in diagnosing and treating patients. How are patients with late-onset psychosis different from those who have early-onset, and what sorts of issues should clinicians be aware of?

Understanding and Managing Psychosis in Late Life

Since their introduction, the atypical antipsychotics clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel) and ziprasidone (Geodon) have been widely prescribed for the management of patients with schizophrenia and other psychotic disorders or severe behavioral disturbances. This is, in part, due to emerging evidence suggesting beneficial effects on positive symptoms, negative symptoms and cognition in schizophrenia, combined with the lower propensity of the atypical antipsychotics for extrapyramidal symptoms or tardive dyskinesia than conventional antipsychotics. However, there have been case reports, retrospective studies and recently published epidemiological data suggesting that certain of these newer agents may be associated with metabolic abnormalities, including significant weight gain, hypertriglyceridemia, and new-onset type 2 diabetes mellitus (DM) or diabetic ketoacidosis (DKA). 

As the proportion of patients with psychosis and other disorders using atypical antipsychotics continues to grow, these potential metabolic adverse effects are a focus of interest, not only because of the resultant medical complications--including mortality--but also the greater cost of care exacted for the evaluation and treatment of metabolic complications and their sequelae. The concern about medication-related DM is heightened in patients with schizophrenia due to the twofold greater prevalence of type 2 DM in this group compared to the general population (Dixon et al., 2000). Moreover, the possibility that DKA may arise at times as the first presentation of DM is alarming, as this is a serious acute medical condition with significant morbidity and mortality. 

Since the first atypical antipsychotic was introduced in 1987, numerous single cases or case series have reported the potential association between atypical agents and new-onset DM or exacerbation of pre-existing DM. Early last year, we reported data based on an analysis of 45 published cases (clozapine [20 cases], olanzapine [19 cases], quetiapine [three cases] and risperidone [three cases]) with sufficient documentation to make an association between the use of an atypical antipsychotic and the development of new-onset DM (Jin et al., 2002). The mean age was 40.3 years (range=16 to 56), 87% were male, and 47% were African-American. At time of diagnosis, 63% had blood glucose values greater than 500 mg/dL, and 50% manifested no weight gain at time of presentation with DM. It should be noted that at baseline, 84% were >5% over ideal body weight, and 42% of these new-onset diabetes cases initially presented with DKA. The mean duration of atypical antipsychotic exposure prior to the development of DM or DKA was 19 weeks (range=two weeks to 124 weeks), with 14% developing DM or DKA within a month after starting the atypical antipsychotic.

Over the past two years, Elizabeth Koller, M.D., of the U.S. Food and Drug Administration, and colleagues have used data from the FDA MedWatch surveillance program pooled with published cases and abstracts to examine the association between atypical antipsychotic therapy and DM, hyperglycemia or DKA. The data for clozapine and olanzapine have been published (Koller and Doraiswamy, 2002; Koller et al., 2001), while preliminary findings for risperidone were presented at a meeting (Koller et al., 2002). Koller and colleagues identified 753 cases having DM, of which 384 cases were treated with clozapine, 237 with olanzapine and 132 with risperidone. Furthermore, among the new-onset DM patients, DKA was reported in 80 of both the olanzapine and clozapine cases and in 36 risperidone cases. Of particular concern were the reported deaths: 25 for clozapine, 15 for olanzapine and five for risperidone. Among patients who developed hyperglycemia or DM on clozapine or olanzapine, more than 60% of cases were noted within six months after starting atypical antipsychotic therapy. Although the number of individuals exposed to risperidone is significantly greater than those exposed to olanzapine, the retrospective and unsystematic nature of case reporting does not permit calculation of relative risk between agents.

Since 2001, several large retrospective studies have examined the relative risk of DM associated with different antipsychotics, primarily in patients with schizophrenia. Comparing 552 patients with schizophrenia on clozapine and 2,461 on typical agents in the Iowa Medicaid database, researchers found a relative risk of developing DM of 2.5 only among those on clozapine ages 20 to 34, but not for the cohort as a whole (Lund et al., 2001). A case control study of older diabetics (mean age=63.6 ±18.3) and controls (mean age=61.9 ±17.5) examined the odds of developing DM related to clozapine exposure (Wang et al., 2002). In this group of primarily nonpsychotic patients (only 40.3% had a psychotic disorder), neither clozapine dose nor duration of exposure (up to 176 days) was associated with increased odds of developing DM.

In 2002, three large comparative database studies were published examining DM prevalence and risk among several atypical agents and conventional antipsychotics. One analyzed health plan claims databases comprising 2.5 million individuals to report on the odds of developing DM during 12 months of exposure in psychotic patients (diagnosed by 

The atypical antipsychotics have become the treatment of choice for patients with psychotic and other behavioral disorders. However, case reports, retrospective studies and epidemiological data suggest that these medications may be associated with new-onset type 2 diabetes and diabetic ketoacidosis.

Psychiatric Times Vol 20 No 3