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The Effects of Schizophrenia on the Brain

Adina Cazaban

Schizophrenia is a severe mental illness that affects one to two percent of people worldwide. Thedisorder can develop as early as the age of five, though it is very rare at such an early age. (3))Most men become ill between the ages of ! and "# whereas most women become ill betweenthe ages of "# and 3$. %ven though there are differences in the age of development between these&es, men and women are e'ually at ris for schizophrenia. ( ) There is of yet no definitiveanswer as to what causes the disorder. *t is believed to be a combination of factors includinggenetic ma e+up, pre+natal viruses, and early brain damage which cause neurotransmitter

problems in the brain. (3)

These problems cause the symptoms of schizophrenia, which include hallucinations, delusions,disordered thin ing, and unusual speech or behavior. o -cure- has yet been discovered,although many different methods have been tried. %ven in these modern times, only one in fiveaffected people fully recovers. ( ) The most common treatment is the administration ofantipsychotic drugs. ther treatments that were previously used, and are occasionally still givenare electro+convulsive therapy, which runs a small amount of electric current through the brainand causes seizures, and large doses of /itamin 0. (3)

1ue to neurological studies of the brain, antipsychotic drugs have become the most widely usedtreatments. These studies show that there are widespread abnormalities in the structuralconnectivity of the brains of affected people. (") *t was noticed that in brains affected withschizophrenia, far more neurotransmitters are released between neurons, which is what causesthe symptoms. 2t first, researchers thought that the problem was solely caused by e&cesses ofdopamine in the brain. owever, newer studies indicate that the neurotransmitter serotonin also

plays a role in causing the symptoms. This was discovered when tests indicated that many patients better results with medications that affect the serotonin as well as the dopaminetransmissions in the brain. (!)

ew test and machines also enabled researchers to study the structure of schizophrenic brainsusing Magnetic 4esonance *magery (M4*) and Magnetic 4esonance Spectroscopy (M4S). Thedifferent lobes of affected brains were e&amined and compared to those of normal brains,showing several structural differences. The most common finding was the enlargement of thelateral ventricles, which are the fluid+filled sacs that surround the brain. The other differences,however, are not nearly as universal, though they are significant. There is some evidence that thevolume of the brain is reduced and that the cerebral corte& is smaller. (")

Tests showed that blood flow was lower in frontal regions in afflicted people when compared tonon+afflicted people. This condition has become nown as hypofrontality. ther studies illustratethat people with schizophrenia often show reduced activation in frontal regions of the brainduring tas s nown to normally activate them. ( ) %ven though many tests show that the frontallobe function performance is impaired and although there is evidence of reduced volume of somefrontal lobe regions, no consistent pattern of structural degradation has yet been found. (")

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There is, however, a great deal of evidence that shows that the temporal lobe structures inschizophrenic patients are smaller. Some studies have found the hippocampus and amygdala to

be reduced in volume. 2lso, components of the limbic system, which is involved in the controlof mood and emotion, and regions of the Superior Temporal 5yrus (ST5), which is a largecontributor in language function, have been notably smaller. The eschl6s 5yrus (which contains

the primary auditory corte&), and the 7lanum Temporale are diminished. The severity ofsymptoms such as auditory hallucinations has been found to be dependent upon the sizes of theselanguage areas. (")

2nother area of the brain that has been found to be severely affected is the prefrontal corte&. The prefrontal corte& is associated with memory, which would e&plain the disordered thought processes found in schizophrenics. Test done on humans and animals in which the prefrontalcorte& has been damaged showed similar cognitive problems as those seen in schizophrenic

patients. The prefrontal corte& has one of the highest concentrations of nerve fibers with theneurotransmitter dopamine and scientists have learned that the relatively new antipsychotic drug,which increases the amount of dopamine released in the prefrontal corte&, often improves

cognitive symptoms. They also found that the prefrontal corte& contains a high concentration ofdopamine receptors that interact with glutamate receptors to enable neurons to form memories.This means that dopamine receptors may be especially important for reducing cognitivesymptoms. (#)

8hile these drugs do help control the symptoms of schizophrenia, they do not get rid of thedisorder. *t is becoming clearer ever day, 9ust what damage schizophrenia is doing to the brain,

but researchers are nowhere near to finding all of the answers. 1ifferent researchers are stillarguing over the conclusiveness of the data that does e&ist. ther scientists are trying to discoverthe cause of schizophrenia. *s it caused by various genes, by a virus, or from trauma: This too isstill a mystery. The only thing that is truly nown is that the disorder is debilitating and that it

affects nearly every portion of the brain. bviously, much more research still needs to be done tohelp those who suffer from it.

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Schizophrenia

Highlights

Causes of Schizophrenia

The causes of schizophrenia are un nown. Multiple factors may play a role such as genetics and brain chemistry.

Risk Factors for Schizophrenia

4is factors for schizophrenia include;

Age . Schizophrenia can occur at any age, but it tends to first develop (or at leastbecome evident) between adolescence and young adulthood.

Gender. Schizophrenia affects both men and women, although males tend to develop itat a slightly younger age (teens and 20s) than females (20s and 30s).

Family History . Schizophrenia often runs in families. lder paternal age is also beinginvestigated as a ris! factor for schizophrenia.

Complications of Schizophrenia

Schizophrenia can have a devastating impact on patients and their families. 7atients withschizophrenia have increased ris for self+destructive behaviors and suicide. The antipsychoticdrugs used to treat schizophrenia can have severe side effects, including increasing the ris ofobesity and diabetes.

Medications

Schizophrenia is a chronic condition, which is usually treated with antipsychotic medication.There are two main classes of these drugs;

"ypical antipsychotics include haloperidol (#aldol), chlorpromazine ("horazine),perphenazine ("rilafon), thioridazine ($ellaril), mesoridazine (Serentil), trifluoperazine(Stelazine), and fluphenazine (%roli&in). Side effects involving the nerves and musclemovement and coordination occur in up to '0 of patients. "ypical antipsychotics aresometimes referred to as first generation to distinguish them from newer secondgeneration atypical antipsychotics.

*typical antipsychotics include clozapine (+lozaril), risperidone ( isperdal), olanzapine(-ypre&a), uetiapine (Sero uel), ziprasidone (/eodon), aripiprazole (*bilify), andpalperidone ( nvega). "hese newer drugs may produce fewer unpleasant symptomsthan the older antipsychotics but new research shows they pose a similar ris! of adverseeffects on the heart, which may include sudden death. n addition, recent researchindicates that these drugs are no more effective than typical antipsychotics in treatingsome types of schizophrenia.

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ntroduction

Schizophrenia is a group of psychotic disorders that interfere with thin ing and mental oremotional responsiveness. *t is a disease of the brain. The term schizophrenia, which means-split mind,- was first used in < by Swiss psychiatrist %ugen 0leuler to categorize patients

whose thought processes and emotional responses seemed disconnected. 1espite its name, thecondition does not cause a split personality.

Schizophrenia is a group of psychotic disorders characterized by disturbances in perception,behavior, and communication that last longer than 1 months. ("his includes psychotic behavior.)* person with schizophrenia has deteriorated occupational, interpersonal, and self supportiveabilities.

Schizophrenia is characterized by the following symptoms; elusions #allucinations

isordered thin!ing

motional unresponsiveness

0ecause symptoms of schizophrenia arise from various physical processes and responddifferently to treatments, some doctors recommend classifying the disease based on the presenceof the following symptom groups;

4egative symptoms (including apathy and social withdrawal) %sychotic symptoms

isordered thin!ing

Some psychiatrists group psychotic and disordered thin ing into a single category called positive symptoms .

The disease is complicated by the fact that although a schizophrenic patient may have more thanone symptom, the patient rarely has all of them. Symptoms also often go into remission.

Causes

o single cause can account for schizophrenia. 4ather, it appears to be the result of multiplecauses such as genetic factors, environmental and psychological assaults, and possible hormonalchanges that alter the brain6s chemistry.

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Abnormalities in Brain Structure, Circuitry, and Chemicals

0rain scans using magnetic resonance imaging (M4*) have shown a number of abnormalities inthe brain6s structure associated with schizophrenia. Such problems can cause nerve damage anddisconnections in the pathways that carry brain chemicals.

0ecause these problems tend to show up on brain scans of people with chronic schizophreniarather than newly diagnosed patients, some doctors believe they may be a result of the diseaseand its treatments rather than a cause. (Medications used for schizophrenia can also cause brainshrin age over time.)

Abnormal Brain Chemicals. Schizophrenia is associated with an unusual imbalance ofneurotransmitters (chemical messengers between nerve cells) and other brain chemicals, such asdopamine overactivity, glutamate, reelin, and others. 8hether any changes in these chemicals inthe brain is a cause or a conse'uence of schizophrenia remains unclear.

Abnormal Circuitry. 2bnormalities in brain structure are also reflected in the disruptedconnections between nerve cells that are observed in schizophrenia. Such miswiring could impairinformation processing and coordination of mental functions. =or e&ample, auditoryhallucinations may be due to miswiring in the circuits that govern speech processing. Strongevidence suggests that schizophrenia involves decreased communication between the left andright sides of the brain.

Genetic Factors

Schizophrenia undoubtedly has a genetic component. The ris for inheriting schizophrenia is$> in those who have one immediate family member with the disease and about $> if the

disease affects both parents or an identical twin. =amily members of patients also appear to havehigher ris s for the specific symptoms (negative or positive) of the relative with schizophrenia.

4esearchers are see ing the specific genetic factors that may be responsible for schizophrenia insuch cases. ?urrent evidence suggests that there are a multitude of genetic abnormalitiesinvolved in schizophrenia, possibly originating from one or two changes in genetic e&pression.Scientists are beginning to discover the ways in which specific genes affect particular brainfunctions and cause specific symptoms. 5enes that have been studied include the neuregulin+gene, the @*5" gene, and the ? MT gene.

eredity does not e&plain all cases of the disease. 2bout !$> of people with schizophrenia have

no close relatives with the illness.

Infectious Factors

The case for viruses as a cause of schizophrenia rests mainly on circumstantial evidence, such asliving in crowded conditions. The ris is higher for people who are born in cities than in thecountry. The longer one lives in the city, the higher the ris . The following are some studiessuggesting an association;

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5inter and Spring 6irths. "he ris! for schizophrenia worldwide is 7 8 higher for thoseborn during winter and spring, when colds and viruses are more prevalent.

9arge :amilies. "he ris! for schizophrenia is also greater in large families in which thereare short intervals between siblings (2 or fewer years). Such observations suggest thate&posure to infection early in infancy may help set the stage for later development of thedisease.

%regnant $other;s &posure to

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$en tend to develop schizophrenia between the ages of =7 2>. %aranoid schizophreniamay be more common in men, and symptoms tend to be more severe.

"he onset in women is usually slightly later, between ages 27 3>, and the symptomstend to be less severe. "he earlier a girl starts menstruation, the longer she is protectedagainst schizophrenia. Schizophrenia is more severe during a woman;s menstrual cycle

when estrogen levels are low. Such findings and other evidence suggest that estrogenmay have nerve protecting properties. :or e&ample, the higher the estrogen levels infemale patients with schizophrenia, the better their mental functions.

Intelligence

7eople with schizophrenia span the full range of intelligence. *n fact, one study reported that ahigher than e&pected number of people who develop schizophrenia had been intellectually giftedchildren. 4esearch suggests, however, that a decline in *A scores during childhood may be a signof potential psychotic symptoms in adults.

Cultural and Geographic Factors

o cultural or geographic group is immune from schizophrenia, although the course of thedisease seems to be more severe in developed countries. owever, the content of delusions mayvary depending on a person6s culture. 2ccording to one study, %uropean patients were more aptto have delusions of poisoning or religious guilt while in Bapan the delusions were most oftenrelated to being slandered.

Socioeconomic Factors

Schizophrenia occurs twice as often in unmarried and divorced people as in married or widowedindividuals. =urthermore, people with schizophrenia are eight times more li ely to be in thelowest socioeconomic groups. owever, these findings are li ely to be a result of schizophreniarather than a cause. evertheless, low income and poverty increases the ris for delayeddiagnosis and treatment, and such delays could lead to more severe disease in patients with fewerresources.

Famine and Malnutrition

7renatal malnutrition may also play a role in the development of schizophrenia. Some studieshave found that people who are born during times of famine are more than twice as li ely todevelop schizophrenia as those born during years of ade'uate food. The association betweenfamine and schizophrenia illustrates how environmental and biologic factors are connected. =ore&ample, scientists thin that malnourished mothers may not get enough folate in their diet.=olate is a micronutrient important for genetic processes. =olate deficiencies may cause geneticmutations in the developing fetus that can lead to schizophrenia.

Other Factors Associated ith Schi!ophrenia

Being Left- or Mixed-Handed. The rate of left+handedness or mi&ed+handedness is significantlyhigher among patients with schizophrenia than the general population. This suggests that some

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neurologic pattern that may be responsible for each. (2 large minority of the population is non+right handed, and very few of these people develop schizophrenia.)

bsessive-Compulsive !isorder. bsessive compulsive disorder ( ?1) affects a significantnumber of schizophrenic patients. ?1 is an an&iety disorder mar ed by obsessions (recurrent

or persistent mental images, thoughts, or ideas) that may result in compulsive behaviors,repetitive, rigid, and self+prescribed routines that are intended to prevent the manifestation of theobsession. Some doctors believe the behaviors e&hibited in the disorder may actually be

protective in people with schizophrenia in early stages.

Behavioral and Motor "roblems in Childhood. ?hildren who later develop schizophrenia oftensuffer from the following certain problems, including e&cessive shyness or minor early physicaland motor+control problems. Such problems are so common, however, that their presencewithout any other ris factors is no cause for concern.

#athers Age. 2ccording to some studies, the older a father is when a child is born, the greater the

ris is for schizophrenia in his offspring, perhaps because of a greater chance of geneticmutations in the sperm that can be passed on. *n one study, children of fathers who were #$ yearsold or more faced a three+fold ris for schizophrenia compared to children of fathers who were"# or younger.

$pilepsy . 2 family history of epilepsy increases the chance for developing schizophrenia orsimilar psychosis. Scientists thin that epilepsy and schizophrenia may share similar genetic orenvironmental factors.

Complications

Schizophrenia has a devastating effect on all aspects of human thought, emotion, and e&pression.nly about "$> of patients reach full recovery after a first episode, but new drugs are offeringsignificant hope for improving 'uality of life.

Medical Illnesses

Studies have reported that people with severe mental illnesses suffer more from serious health problems than those without mental disorders, and they are less li ely to receive medical help.Substance abuse is a significant factor in this higher ris .

4esearch has suggested an increased ris of diabetes among people with schizophrenia. *n

addition, many new antipsychotic medications can elevate blood sugar levels. 7atients ta ingatypical antipsychotics drugs ++ such as clozapine, olanzapine, risperidone, aripiprazole,'uetiapine fumarate, and ziprasidone ++ should receive a baseline blood sugar level reading and

be monitored for any increases in blood sugar levels. (See !iabetes %is& and Atypical Antipsychotics in Medications section.)

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"epression

1epression is common later in adulthood. 2lthough this mood disorder can certainly be a resultof the negative social impact of schizophrenia, some doctors believe that depression is part of thedisease process itself.

#ffect on Social Status

Studies indicate that after "$ + 3$ years, half of patients are able to care for themselves, wor ,and participate socially. Support services and appropriate housing improve this outcome.Cnsurprisingly, the decline in status, including the inability to earn a living, is less steep whenthere are more financial resources and fewer emotional disorders at the outset of symptoms.2lso, on average, the later the onset of the disease, the milder the social impact. The long+termeffects on wor and relationships, however, are usually severe and difficult to repair, even ifsymptoms improve.

#ffect on Intelligence

*n one study, about half of patients e&perienced some decline in *A ( $ points or more), butintelligence scores remained the same in the other half. 4esearchers believe that a decline in *Areflects early nerve damage but that it is not an inevitable conse'uence of the disease process.

Suicide

*n spite of the sometimes frightening behavior, people with schizophrenia are no more li ely to behave violently than are those in the general population. *n fact, these patients are more apt towithdraw from others or to harm themselves.

'uicide. 0etween "$ + #$> of patients with schizophrenia attempt suicide, and an estimated < +3> commit suicide.

The general ris for suicide is higher at certain times in the course of the disease;

5ithin the first 7 years of onset of the disease uring the first 1 months after hospitalization

:ollowing an acute psychotic episode

The widespread use of antipsychotic drugs over the past decade does not appear to have hadmuch effect on suicide rates. *n fact, evidence suggests that the use of these drugs as a way ofreducing hospitalization time is increasing the incidence of suicide. 1epression, not delusions,appears to be the most important motive for suicide in these patients. Suicide ris is alsoassociated with prior suicide attempts, drug abuse, agitation, poor treatment compliance, fear ofmental deterioration, and personal loss.

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Self$"estructi%e Beha%iors

'mo&ing and ther Addictions. Most people with schizophrenia abuse nicotine, alcohol, andother substances. Substance abuse, in addition to its other adverse effects, increases non+compliance with antipsychotic drugs in the schizophrenic patient and may worsen symptoms.

Smo ing is of special interest. 2ccording to one study, up to DD> of schizophrenic patients arenicotine dependent. 0iologic and genetic factors may be partially responsible for the addiction inthis particular group. icotine helps reduce psychotic symptoms and impulsivity, perhaps byinhibiting the activity of a protein called monoamine o&idase 0 (M2 + 0), which is lin ed toimproved mood and possibly to nerve protection. Smo ing for schizophrenics, then, may be aform of self+medication.

besity and !iabetes. besity is very common in patients with schizophrenia. =actors thatcontribute to obesity and diabetes in these patients include unstable lifestyle, low socialeconomic status, and side effects of any antipsychotic medications. 7atients should be monitored

closely for onset diabetes.

#ffect on Family Members

=amily members suffer from grief, long+term guilt, and many emotional issues when faced witha schizophrenic loved one. *f these patients commit suicide, the effects can be devastating.

&ac' of Social and Go%ernment Support

*n the of all long+termhospitalization days. More than half of patients with schizophrenia re'uire public assistancewithin a year of their reentry into the community.

S!mptoms

4esearch indicates that symptoms in childhood strongly predict disease in adulthood. *n onelong+term study, over $> of people with schizophrenia who developed the disease in youngadulthood had reported psychotic symptoms by age . =or children with a family history ofschizophrenia, the following inherited traits may be warning signs;

eficits in wor!ing (short term) and verbal memory mpairments in gross motor s!ills (the child;s ability to control different parts of the body)

*ttention deficits

* decline in verbal memory, ?, and other mental functions

2ny signs of hallucinations or delusions must be differentiated from normal childhood fantasies.

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Most often, early warning signs go unnoticed, and schizophrenia usually becomes evident for thefirst time in late adolescence or early adulthood. Schizophrenia that starts in childhood oradolescence tends to be severe. *t should be strongly noted that the traits discussed above, evencombinations of them, can be present without schizophrenia.

(egati%e Symptoms

2 person with schizophrenia may have the following negative symptoms;

9ac! of self confidence 9ac! of emotions

+olorless spea!ing tones

nappropriate reactions to events (such as laughing hysterically over a loss)

* general loss of interest in life and the ability to e&perience pleasure

@ac of responsiveness and poor sociability often appear in childhood as the first indications ofschizophrenia. ?ertain imaging techni'ues suggest that these findings are based on biologicchanges in specific parts of the brain. *n many patients, however, negative symptoms do notappear until after positive symptoms develop. egative symptoms tend to be more common than

positive symptoms in older patients and typically persist after positive symptoms have beentreated.

Psychotic Symptoms

7sychotic symptoms, particularly delusions and hallucinations, are the most widely recognized

manifestations of schizophrenia. Hallucinations . * hallucination is the e&perience of seeing, hearing, tasting, smelling, or

feeling something that doesn;t really e&ist. *uditory hallucinations are false senses ofsound such as hearing voices that go unheard by others. "hey are the most commonpsychotic symptoms, affecting about '0 of patients.

Delusions . * delusion is a fi&ed, false belief. t can be bizarre (such as invisible alienshave entered the room through an electric soc!et) or nonbizarre (such as unwarranted

@ealousy or the paranoid belief in being persecuted or watched).

7sychotic symptoms usually occur every now and then, alternating with periods of remission.They typically occur in men ages E + 3$ and in women ages "$ + $.

Cogniti%e Impairment )"isordered *hin'ing+

The symptoms of cognitive impairment and disordered thin ing may occur before othersymptoms of schizophrenia. They include;

* lac! of attention.

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mpaired information processing and an aberrant association between words and ideas.Sometimes this condition is so e&treme that speech becomes incoherent and is referredto as Aword salad.A %atients may connect words because of similarity of sound, ratherthan by meaning, a condition !nown as Aclang associations.A

$emory impairment. n !eeping with other aspects of disordered thin!ing, memory

impairment in schizophrenia is li!ely to involve the inability to connect an event with itssource into a complete and whole memory. :or instance, a patient may recall and evenfeel a familiarity with a specific event but be unable to remember where, when, or how ittoo! place.

6ac!ward mas!ing dysfunction. "his is a trait in which a distraction causes a person toforget a preceding event. t might be an important symptom and a mar!er ofschizophrenia even in people with normal wor!ing memories.

7eople with schizophrenia do poorly on mental tas s re'uiring conscious awareness, such asverbal fluency, short+term and wor ing memory, and processing speed. owever, they are noworse than the general population in underlying (implicit) learning, such as grammar s ills,vocabulary, and spatial s ills (such as map reading). Some e&perts believe that impaired verbalmemory in schizophrenia is a conse'uence of depression and slowness, but not a result of thedisease process.

Other Symptoms

7eople with schizophrenia may e&perience other symptoms, such as intolerance of heat (oftenassociated with antipsychotic medications) and a reduced sense of smell.

Symptoms of Progression to Full$Blo n Schi!ophrenia

The course of the disease varies from one patient to the ne&t. Symptoms of psychosis can become gradually or suddenly evident.

n up to a third of patients, the disease is unrelenting and progresses from the firstepisode onward.

n others, schizophrenia follows a fluctuating course with psychotic flare ups, followed byremissions.

n one study, a third of patients e&perienced a complete remission of symptoms within 3years after one or more episodes. 5omen are more li!ely to go into remission, possiblybecause of some protective effect of estrogen on the brain.

Typically, patients develop considerable cognitive dysfunction (disordered thin ing) within thefirst + # years of the onset of psychotic symptoms. Some evidence indicates that the physicaldisease process in schizophrenia is progressive, as with 2lzheimer6s and 7ar inson6s disease.

owever, schizophrenia does not progress in the same way as those two diseases. Cnli e7ar inson6s and 2lzheimer6s, cognitive function usually eventually stabilizes. 7sychosis,disorganized thought, and negative symptoms often improve over time, although, even in such

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cases, deficits in verbal memory usually persist. (Thought disorder often improves along withimprovements in negative symptoms.)

"iagnosis

The doctor will use one or more verbal screening tests to help determine whether a patient6ssymptoms meet the criteria for schizophrenia. 0ecause no single symptom is specific toschizophrenia, a diagnosis may be made when one or more of the following conditions is

present;

f a patient has at least one active flare up lasting a month or more. "he flare up consistsof at least two characteristic symptoms (such as hallucinations, delusions, evidence ofdisorganized thin!ing, and emotional unresponsiveness with a flat spea!ing tone).

f the patient has particularly bizarre delusions or hallucinations, even in the absence ofother characteristic symptoms.

f certain symptoms are present for at least 1 months, even in the absence of activeflare ups. Such symptoms include mar!ed social withdrawal, peculiar behavior (tal!ing tooneself, severe superstitiousness), vague and incoherent speech, or other indications ofdisturbed thin!ing. "he patient;s social and personal relationships would also havedeteriorated since the onset of symptoms.

uling Out Other Conditions

The common hallmar s of schizophrenia are also symptoms that can occur in dozens of other psychologic and medical conditions, as well as with certain medications. Shared symptomsinclude delusions, hallucinations, disorganized and incoherent speech, a flat tone of voice, and

bizarrely disorganized or catatonic behavior (such as lac of speech, muscular rigidity, and

unresponsiveness).

2mong the conditions that may resemble schizophrenia are the following;

Depression. elusions that focus on a physical abnormality or disease that isn;t real,!nown as somatic delusions, sometimes occur in people with depression.

Bipolar Disorder . %aranoia and delusions of grandeur (the belief that one has a specialpower or mission) can occur in people with bipolar disorder during the manic phase.Sometimes it is difficult even for doctors to differentiate between these two disorders.

vidence suggests that they may share certain genetic factors that ma!e some familiesvulnerable to either one.

Schizophrenia-Li e !sychoses. Several other conditions e&hibit schizophrenia li!epsychoses but do not meet the diagnostic criteria for schizophrenia. Such conditionsmay be variations of entirely different diseases and are classified as schizoaffectivedisorder, schizophreniform psychosis, and atypical and brief reactive schizophrenia.

Alcohol and Drug Abuse. ither substance abuse itself or withdrawal from drugs oralcohol can trigger psychosis. 6ecause of the high ris! for substance abuse amongpeople with schizophrenia, it is important that the health professional distinguishpsychosis triggered by drugs or alcohol from a schizophrenic episode. Bsually, the

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diagnosis is confirmed if the psychosis ends after withdrawal from drugs or alcohol, andreturns if the patient returns to alcohol or substance abuse.

"edical #llnesses. ther causes of psychotic symptoms include cancer in the centralnervous system, encephalitis, neurosyphilis, thyroid disorders, *lzheimer;s disease,epilepsy, #untington;s disease, multiple sclerosis, stro!e, 5ilson;s disease, some

vitamin 6 deficiencies, and systemic lupus erythematosus. "edication $eactions. $any medications may induce psychosis as a side effect, and

some can precipitate delusions and severe confusion. Such medication inducedsymptoms are most often observed in elderly patients.

Imaging *echni-ues

Many brain imaging techni'ues can detect changes in the brain structure that relate to specificsets of symptoms in schizophrenia. These imaging techni'ues include magnetic resonanceimaging (M4*), single photon emission computed tomography (S7%?T), and positron emissiontomography (7%T). Such techni'ues are used as research tools. owever, research continues inevaluating whether they may be useful for identifying candidates for early treatment amonghigh+ris young people with early warnings signs of schizophrenia and brain damage.

Treatment

Schizophrenia is categorized as a brain disease, not a psychological disorder, and drug treatmentis the primary therapy. Studies indicate, however, that an integrated approach better preventsrelapses than routine care (medication, monitoring, and access to rehabilitation programs).

(ntegrated Approach. 2n integrated approach, which may help to ease psychotic symptoms, may

include; $otivational interviewing to encourage the patient;s commitment to change Bse of antipsychotic medications (generally atypical or novel antipsychotics) with

monitoring

+ommunity based rehabilitation and social s!ills training

:amily psychotherapy

+ognitive behavioral therapy to reduce delusions and hallucinations

Treatment of schizophrenia has traditionally focused on decreasing patients negative symptoms.Today, an important shift is now ta ing place. 1octors are now emphasizing patients ability tofunction ++ shop, eat, coo , clean, do laundry, and in some cases, wor independently.

$arly )reatment. The earlier schizophrenia is detected and treated, the better the outcome.7atients who receive antipsychotic drugs and other treatments during their first episode areadmitted to the hospital less often during the following # years and may re'uire less time tocontrol symptoms than those who do not see help as 'uic ly. *n spite of strong evidence for the

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positive effects of early treatment, patients usually do not receive treatment until after $ monthsof serious symptoms.

Classes of "rugs .sed for Schi!ophrenia

Most drugs that treat schizophrenia wor by bloc ing receptors of the neurotransmitterdopamine. 1opamine is thought to play a ma9or role in psychotic symptoms. 2lthough the drugsused to treat schizophrenia have important benefits, they may also cause side effects. The mostdisturbing and common side effects are those nown as extrapyramidal symptoms, whichinvolve the nerves and muscles controlling movement and coordination.

The following drug classes are generally used for schizophrenia;

%ypical antipsychotics . Bntil recently, these drugs were the mainstay treatments forschizophrenia. "hey include haloperidol (#aldol), chlorpromazine ("horazine),perphenazine ("rilafon), thioridazine ($ellaril), mesoridazine (Serentil), trifluoperazine(Stelazine), and fluphenazine (%roli&in). Side effects involving the nerves and musclemovement and coordination occur in up to '0 of patients. "ypical antipsychotics aresometimes referred to as first generation to distinguish them from newer secondgeneration atypical antipsychotics.

Atypical antipsychotics . "hese newer drugs may be better tolerated than the olderantipsychotics but new research contradicts the belief that they are safer for the heart."hey include clozapine (+lozaril), risperidone ( isperdal), olanzapine (-ypre&a),

uetiapine (Sero uel), ziprasidone (/eodon), aripiprazole (*bilify), and palperidone( nvega).

*hich )ype of !rug to Choose. 1octors have debated whether newer atypical antipsychoticscarry a treatment advantage over the older typical antipsychotics, which are much less e&pensive.

Most practicing psychiatrists feel that atypical antipsychotics may wor better than the olderdrugs. owever, the additional benefits may be modest for most patients. @arge, high+'ualitystudies have compared newer and older drugs and generally found that newer atypicalantipsychotics wor no better than older typical antipsychotics such as haloperidol, at least forinitial treatment of first+episode schizophrenia Similarly, for treatment of children andadolescents with schizophrenia, both atypical and typical antipsychotics appear to be e'uallyeffective, but atypical antipsychotics carry a higher ris for metabolic side effects.

Side effect profiles between typical and atypical antipsychotics are different. 0oth groups causee&trapyramidal side effects, (including muscle stiffness, tremors, and abnormal movements), but

the newer atypical drugs do not seem to cause them as often. owever, the atypicalantipsychotics pose a higher ris for weight gain, which can lead to diabetes as well as heartdisease.

ne problem with most of the studies that evaluate these medications is that often more than halfthe patients discontinue the drugs either because of side effects or because they do not feel themedications are helping them.

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*n "$$E, risperidone and aripiprazole became the first atypical antipsychotics approved fortreatment of schizophrenia in adolescents (ages 3 + E years). 1octors caution that moreresearch is needed to determine the long+term safety and efficacy of these drugs for pediatric

patients.

*reating an Acute or Initial Phase

=or the severe, active phase of schizophrenia, in9ections of an antipsychotic drug are typicallygiven every few hours until the patient is calm. 2nti+an&iety drugs are also often administered atthe same time. Some of the newer atypical drugs, such as olanzapine or risperidone, may proveto be as effective as the older antipsychotics with significantly fewer severe side effects. *n

patients who are being treated for the first time, improvement in psychotic symptoms may beevident within + " days of treatment, although the full benefit of the drug usually manifestsover about ! + D wee s. Thought disturbances tend to abate more gradually.

Maintenance

To reduce the ris of relapse, many doctors recommend that drugs be given daily for at least year. 2typical drugs are increasingly being used as maintenance for those with new+onset

psychosis, although the choice of the drug depends on many factors. Side effects andeffectiveness vary from individual to individual. Some trial and error ad9ustments may benecessary when prescribing dosage amounts so that the benefits of treatment outweigh the sideeffects of the therapy. The doctor must monitor the drug effects carefully.

Feeping patients on maintenance therapy, however, is very difficult, and many patients stop theirmedication. =actors that may contribute to poor compliance include;

9ower occupational status * history of alcohol or drugs abuse

elusions of persecution

* history of stopping medications within the first 1 months after diagnosis

Stopping Medications

early all patients e&perience some relapse or worsening of symptoms within " years of stoppingmaintenance medication. 4ecognizing signs of relapse and starting medications immediately canhelp prevent rehospitalization for these patients.

Supporti%e "rugs

2ntidepressants and anti+an&iety drugs may also play an important role in treating the patientwith schizophrenia, particularly given the role of depression in the high rates of suicide amongthese patients.

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2typical antipsychotics have some significant limitations and complications, and their benefitscompared to each other and to other antipsychotics are not always clear+cut. *n+depthcomparative studies are needed to determine which specific drugs are more effective and havefewer side effects than others.

'ide $ffects of Atypical Antipsychotics. 4asal congestion or runny nose rooling

izziness

#eadache

rowsiness although, sometimes the drugs may cause restlessness and insomnia

+onstipation

apid heart beat ifficulty urinating

S!in rash

ncreased body temperature

+onfusion, short term memory problems, disorientation, and impaired attention

The following are more severe side effects or complications that may occur with these drugs;

iabetes 5eight gain and metabolic problems. "he ris! is highest for olanzapine, and lowest foraripiprazole and ziprasidone.

Bnhealthy cholesterol levels. %articularly with olanzapine, increased ris! for high levelsof trigylcerides and total cholesterol.

Seizures.

&treme and very serious increases in body temperature.

Sudden drop in blood pressure (hypotension).

* significant drop in white blood cell count (neutropenia), which can be severe, occurs in= or more of patients, generally in the first 1 months after starting treatment. %atientsshould have their white blood count and absolute neutrophil count regularly monitored ifthey ta!e clozapine.

&trapyramidal side effects

+ataracts and worsening of any e&isting glaucoma.

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ncreased prolactin levels prolactin is a hormone associated with infertility andimpotence. #igh levels can cause menstrual abnormalities and may increase the ris! forosteoporosis and possibly breast cancer.

#eart problems, including sudden death.

"iabetes is' and Atypical Antipsychotics

2ll atypical antipsychotic drugs carry a blac bo& warning on their prescribing labels advisingthat these drugs can increase the ris of high blood sugar (hyperglycemia) and diabetes.( lanzapine is more li ely to cause high blood sugar levels than other atypical antipsychoticmedicines.) The C.S. =ood and 1rug 2dministration (=12) recommends that;

%atients with an established diagnosis of diabetes who begin atypical antipsychotictreatment should be regularly monitored for worsening of blood sugar control.

%atients with ris! factors for diabetes (obesity, family history of diabetes) should undergofasting blood sugar testing at the beginning of atypical antipsychotic treatment and

periodically during treatment. *ll patients treated with atypical antipsychotics should be monitored for high blood sugar

(hyperglycemia) symptoms.

%atients who develop hyperglycemia symptoms should undergo fasting blood sugartesting.

There may also be an increased bac ground ris of diabetes in patients with schizophrenia. 2s a precaution, many doctors advise that all patients treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levelsduring drug treatment. 7atients should also have their lipid and cholesterol levels monitored. H=or

more information, see (n-!epth %eport I!$; 1iabetes + type " .J

*ypical Antipsychotic "rugs

The standard typical antipsychotic drug used for schizophrenia is haloperidol ( aldol). thersinclude;

+hlorpromazine ("horazine) %erphenazine ("rilafon)

"hioridazine ($ellaril)

$esoridazine (Serentil)

"rifluoperazine (Stelazine)

:luphenazine (%roli&in)

Studies have not shown any significant difference in benefits among these drugs.

http://adam.about.net/reports/Diabetes-type-2.htmhttp://adam.about.net/reports/Diabetes-type-2.htm

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The beneficial impact of these drugs is greatest on psychotic symptoms, particularlyhallucinations and delusions in the early and midterm stages of the disorder. They are not verysuccessful in reducing negative symptoms. 0ecause of their significant side effects, many

patient6s stop ta ing the drug.

1epot therapy (long+lasting monthly in9ections, usually of haloperidol or fluphenazine) has beenused with success in people who have difficulty complying with a daily regimen of these drugs.4esearchers are studying low+dose regimens to discover if they can be effective and cause fewerside effects.

'ide $ffects of )ypical Antipsychotics. These drugs can have adverse side effects related to manyorgans and systems in the body. These drugs are also nown as neuroleptics , a name that comesfrom the severe neurological side effects that these medications can cause. Side effects include;

&trapyramidal symptoms Sleepiness and lethargy common in the beginning but usually decreases over time

nsomnia and agitation in some cases

ulling of the mind

4ausea, vomiting, diarrhea, constipation, and heartburn

ry mouth and blurred vision

*llergic reactions

Se&ual dysfunction a common reason why patients stop ta!ing the drugC amantadinemay help offset this side effect

4euroleptic malignant syndrome rare, but can be fatal without prompt treatment

ncreased prolactin levels prolactin is a hormone associated with infertility andimpotence. #igh levels can cause menstrual abnormalities and may increase the ris! forosteoporosis and possibly breast cancer

* sudden drop in blood pressure (hypotension)

*n increased ris! of sudden cardiac death

*n general, higher potency drugs cause less drowsiness and drops in blood pressure but pose ahigher ris for e&trapyramidal side effects. @ower+potency drugs (such as chlorpromazine,

thioridazine) are more sedating and have milder side effects.

#/trapyramidal Symptoms

early every drug used to date for schizophrenia can cause e&trapyramidal side effects to somedegree. These side effects involve the nerves and muscles controlling movement andcoordination.

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!escription of $xtrapyramidal 'ide $ffects. These effects resemble some of the symptoms of7ar inson6s disease and include the following conditions;

%ardi&e dys inesia is the most serious e&trapyramidal side effect. t often manifests itselfby repetitive and involuntary movements, or tics, most often of the mouth, lips, or of thelegs, arms, or trun!. Symptoms range from mild to severe, and sometimes interfere witheating and wal!ing. "hey may appear months or even years after ta!ing the drugs. *fterthe drug is stopped, symptoms can sometimes persist for wee!s or months and may bepermanent. Some people are more li!ely to develop these symptoms, including olderpatients, women, smo!ers, people with diabetes, and patients with movement disorders.

Acute dystonia typically develops shortly after ta!ing an antipsychotic drug. "hissyndrome includes abnormal muscle spasms, particularly sustained contortions of thenec!, @aw, trun!, and eye muscles.

ther e(trapyramidal symptoms. ther effects are agitation, slow speech, tremor, andretarded movement. t should be noted that sometimes these symptoms mimicschizophrenia itself. n response, the doctor may be tempted erroneously to increase thedosage.

)reatment of $xtrapyramidal 'ide $ffects. *n general, if e&trapyramidal side effects occur fromneuroleptic drugs, the doctor may first try to reduce the dosage or switch to an atypical drug.

ther approaches to reduce these symptoms include;

*nti par!insonism drugs !nown as anticholinergics increase dopamine levels and help torestore balance. *mong the anticholinergics sometimes used are trihe&yphenidyl(*rtane, "rihe&y) and benztropine (+ogentin). "hey are not helpful for tardive dys!inesia,however. Some of these drugs may also help in managing negative symptoms ofschizophrenia. "he use of these drugs, however, adds to the cost and complicatesmanagement. "hese medicines also have their own, sometimes serious, side effects.

$ost doctors recommend them only for patients who cannot be monitored regularly,need very high doses of powerful antipsychotic drugs, and are at ris! for severe sideeffects. "hey should be stopped after 3 or > months, if possible. f symptoms recur, thedrugs can be reinstituted. 5ithdrawal from anticholinergics can cause depression thatcan worsen schizophrenia.

6enzodiazepines may also alleviate these symptoms.

Supporti%e Add$On "rugs

Antidepressants. 2ntidepressants are recommended along with antipsychotics to alleviate thedepression that is so common in people with schizophrenia. ne study indicated that ta ingantidepressants may even help prevent relapse. *n spite of their benefits, fewer than half of all

patients ta e these medications.

Anti-Anxiety !rugs. 0enzodiazepines are drugs normally used to treat an&iety. They also havesome modest effect on psychotic symptoms. They may be useful in the early stages of a

psychotic relapse for preventing a full attac . They also are sometimes used to treat therestlessness and agitation that can occur with the use of neuroleptics. Severe side effects,including respiratory arrest, very low blood pressure, and loss of consciousness, have beenreported in a few people ta ing anti+an&iety medication and clozapine. There is no evidence,

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however, of a clear danger associated with the use of these two drugs. *n any case, prolonged useof anti+an&iety drugs is generally not recommended in schizophrenia. 8ithdrawal from thesedrugs should occur gradually.

Lithium. @ithium, ordinarily used for bipolar disorder, is useful for some schizophrenic patients.

*t appears to help those with fewer negative symptoms and without a family history ofschizophrenia. owever, there are no reliable criteria to predict who will benefit.

Anti-$pileptic !rugs. 1rugs ordinarily prescribed for epilepsy ++ such as carbamazepine(Tegretol), gabapentin ( eurontin), lamotrigine (@amictal), or others ++ are occasionally used incombination with antipsychotic drugs for patients who do not respond to standard drugs.

$strogen %eplacement in *omen. %strogen may be nerve+protective. Some investigators have proposed using estrogen therapy to help with cognitive impairment. owever, evidence is wea ,and cancer and cardiovascular ris s of estrogen therapy must be considered.

#s!chotherap!

ne+fifth to one+third of all patients with schizophrenia do not respond ade'uately to drugtreatment. Many patients who have been successfully treated with medications e&perience the-awa enings- phenomena, which are painful reactions that are manifested as inner emotions andthe recognition of real losses. The effects of the disease, in any case, are profoundly emotional.2s a result, psychological therapies can be helpful for many patients.

Cogniti%e$Beha%ioral and Other Psychosocial *herapies

The use of cognitive+behavioral therapy is showing particular promise for improvement in both

positive and negative symptoms in some patients, and the benefits may persist after treatment hasstopped. This approach attempts to strengthen the patient6s capacity for normal thin ing, usingmental e&ercises and self+observation. More evidence is showing that improving patients6 abilityto learn, remember, and pay attention allows them to better cope with ongoing positivesymptoms and lead independent lives. 7atients with schizophrenia are taught to critically analyzehallucinations and e&amine underlying beliefs in them.

Family and Outside Support Structures

7ositive social interaction is e&tremely important for people with schizophrenia and may helpreduce symptoms, including the number of delusional moments.

#amily 'upport. *t is deeply painful for anyone to interact with a loved one whose behavior isdetermined by a mysterious internal mechanism that has gone awry. 5iven support and direction,however, families or other caregivers can be very helpful in a number of ways;

"hey can encourage patients to comply with drug treatments and to recognize earlysigns of serious treatment side effects.

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"hey can be taught to recognize impending symptoms of relapse and help the patientavoid situations that might trigger them. (Symptoms for an impending relapse afterremission may include feeling distant from family and friends, being increasinglybothered by persistent thoughts, and having an increased interest in religion.)

Cnfortunately, the family6s own mental health is often threatened. 2s a result, careta ers alsoneed help. umerous studies have shown that patients with schizophrenia do worse in familieswho are too emotional, hostile, critical, or even overly involved. The problem is an emotionalloop;

5hen affection and reason have failed to bring a loved one bac! to reality, overly criticalor emotional family members typically react with anger and frustration.

"his generates an&iety and depression in patients.

"he subse uent e&pression of these emotions by the patient triggers yet more criticismor acting out. So the cycle continues.

ventually, out of despair and fear, the family may re@ect the patient completely.

Studies indicate that once the patient receives appropriate treatment and support, the family6sover+emotional state also recedes. Some studies have reported that when families receive help forthemselves (group support or cognitive therapy) the relapse rates for the related patients aresignificantly lower than for patients whose families did not see help. Still, only a small numberof families of patients with schizophrenia receive the support and education needed not only forthe patient but also for themselves.

Community )reatment "rograms. ?ommunity treatment programs, in which a team of professional caregivers provides treatment and support for patients in their homes, is highly beneficial and cost effective (compared to fre'uent hospitalization). 2t this time, however, only asmall percentage of patients participate in such programs.

+ocational %ehabilitation. 7aid wor may help the mental health of the patient. ne studyreported that after year, $> of wor ers with schizophrenia who were paid for their laborreported much improvement in all symptoms, and #$> reported much improvement in positivesymptoms. Those who were not paid for their wor did considerably less well. (The arts andcrafts activities that are often used to enhance self+esteem in rehabilitation programs offer fewreal benefits to the patient.)

Cnfortunately, at this time, few patients with schizophrenia are in programs that help them findand eep 9obs, and up to of patients with severe mental problems are unemployed.

$ther Treatments

%lectroconvulsive therapy (%?T), often called shoc treatment, has received bad press since itwas introduced in the < $s. owever, refined techni'ues have revived its use, particularly forthose with severe depression. *maging studies have not found that current %?T techni'ues causeany damage to the brain6s structure, and some doctors feel it is safer than drug therapy. 2 recent

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review of many clinical trials indicated that %?T combined with antipsychotic medication can provide rapid improvements for patients who are suicidal or severely psychotic. The reviewfound that the combined treatment wor ed better than antipsychotics alone for these patients.%?T treatments are usually given " + 3 times a wee , for a total of D + " sessions.

*ranscranial Magnetic Stimulation

*nvestigators are testing a procedure called slow repetitive transcranial magnetic stimulation(rTMS), which affects brain activity in the cerebral corte&. The procedure uses an electromagnet

placed on the scalp to administer magnetic stimulation to the brains cerebral corte&. This regionof the brain appears to be associated with auditory hallucinations. 2 review of # clinical trialsindicated that rTMS may be an effective treatment for auditory hallucinations. =urther research isunderway.