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Psihoze
« on: 15-12-2006, 09:57:18 »

Shizofenija (SCH)

Cause is unknown. Affect 1 out of 100 people. Often begins ages 16-30. More hospital beds than any other. Medical illnes. 2.5% of total U.S. healthcare budget. Often chronic. Occurs in .2% to 1.5% population. Affect men and woman equally. Age of onset varies across time. Lower life expectancy. Increased risk of suicide. People with schizophrenia have "split personalities". People with schizophrenia are intellectualy disabled? People with schizophrenia are dangerous? People with schizophrenia are addicted to their drugs? Schizophrenia is not caused by bad parenting or unhappy childhood. Schizophrenia is notdue to a weaknesss in character. Schizophrenia is not due to a negative social label. Schizophrenia is not a hopeless situation.

Schizophrenia is to psychiatry what cancer is to medicine: a sentence as well as a diagnosis. 2 miliona obolelih i USA. Vi筫 od 100 000 hospitalizovanih.

Pozitivni Simptomi
Vi筧k, prekomernost, ili distorzija (+). Disorganizovan govor - Ukazuje na poreme鎍j mi筶jenja (labava povezanost re鑙 do “salate u govoru”). Halucinacije - Sensorni do緄vljaj bez spolja筺je stimulacije (鑕sto auditivne, vidne, mirisne, taktilne). Deluzije - Ubedjenja suprotna realnosti, 萫sto deluzije proganjanja, Ponekad deluzije veli鑙ne

Negativni Simptomi
Karakteri箄 se deficitima u pona筧nju (–). Adinamija - nedostatak energije & nemogu鎛ost obavljanja svakodnevnih aktivnosti. Alogija (siroma箃vo govora)- redukcija koli鑙ne i sadr綼ja govora. Ahedonija - nemogu鎛ost do緄vljavanja zadovoljstva. Asociajlnost - te筴i poreme鎍ji socijalne komunikacije. Nedostatak emocija ili neadekvatni afekti - izostanak ili neadekvatna ekspresija emocija.

SIMPTOMI tip I vs. tip II

 
Shizofrenija - kriterijumi
1.   Najmanje 2 od dole nabrojanih, kada se pacijent prati tokom 1 meseca: deluzije, halucinacije, disorganizacija govora, disorganizovano ili katatono pona筧nje, negativni simptomi.
2.   Trajanje simptoma  6 meseci
3.   Da nisu izazvani lekovima (npr. amfentaminska psihoza)

Tri tipa shizofrenije
Paranoidni tip - Deluzije i halucinacije. Nema disorganizovanog govora, katatonije ili nedostatka afekata. Disorganizovani tip - Disorganizovan govor, 鑕sto neadekvatno pona筧nje, ali ne zadovoljava kriterijume za katatoni tip. Katatoni tip - motorna imobilnost, katalepsija, stupor (vo箃ana nefleksibilnost). Ekscesna, besciljna motorna aktivnost. Ekstremni negativizam ili mutizam. Bizarni pokreti, stereotipija, bizarni manirizam ili grimase, eholalia ili ehopraksija

Etiologija ﹊zofrenije
Genetic studies using twin, family and adoption techniques reveal that a predisposition for schizophrenia is transmitted genetically. Brain pathology, possibily including damage to the fetal brain from virus-like diseases, are likely biological vulnerabilities for schizophrenia (diathesis).

The causes of schizophrenia
Genetic influences – runs in families, increased risk based on genetic relatedness, search for marker genes. Smooth pursuit eye tracking.

Brain pathology in schizophrenia
Brain of schizophrenic patientes show reduce volume of temporal and frontal cortex; enlarged ventricels (reflecting loss of brain cells) – for 12 of 15 twins, the schizophrenic twin could be identified by enlarged ventricels; reduced metabolic activity within prefrontal cortex (frontal hypoactivation). Neurobiological influenses. Exces dopamine (D2 receptors) – antagonists: neurpleptics, drugs that reduce dopamine, negative side effects, L-DOPA (agonist), amphetamines. Genetic influences.

Biochemistry of schizophrenia
Dopamine theory holds that the positive symptoms of schizophrenia result from excessive activity of dopamine in brain. Antischizophrenia drugs block dopamine receptors. The Antischizophrenia drugs take several weeks to act clinically, yet rapidliy block dopamine receptors. Ungestion of amphetamine can induce psychosis; amphetamine causes the release of dopamine from neurons.

Slika!


Dopamin
Smatra se da SCH nastaje zbog prekomerne aktivnosti DA sistema u CNS-u. Samo blokiranjem delovanja DA deluje se na pozitivne simptome. Nije cela slika (tj. glutamat, 5-HT) #

 
Terapija 筰zofrenije

Biological treatments – electroconvulsive and insulin coma shock treatments were minimally effective; psychosurgery is the international destruction of brain tissue to alter behavior; prefrontal lobotomy was used to treat SCH. Drug therapies supplanted psychosurgery – use of neuroleptic medications to treat positive symptoms of SCH. Chlorpromasine was introduced in US in 1954.

Neuroleptici ili Antipsihotici

Bukvalno zna鑕nje =  nervnu transmisiju. U praksi, ovi termini ozna鑑vaju lekove koji se koriste za le鑕nje SCH. Postoji 筰rok spektar off-label applications. Neadekvatno se ozna鑑vaju kao "major tranquilizers". Ne緀ljeni efekti: Parkinsonizam; Distonija – abnormalni pokreti lica i tela movements; Akatizija (nemir); Tardivna diskinezija (long term) - Ekzacerebracija - drug holiday regime, 鑕规e se vidja u 緀na,   Pogor筧va se pri smanjenju doze, Ireversibilna (denervacijska superosteljivost). Mnogi ne緀ljeni efekti (mpr., konstipacija i metaboli鑛i sindrom)

Antagonisti DA

Hlorpromazin, SmithKlineFrench, 1950. Thorazine - Derivat fenotiazina  (anti-emetik), Sna綼n sedativni efekat, brzo se razvija toleranca, Ima i  anti-holinergijsku aktivnost, Aktivno se metaboli筫 (polu緄vot 30h). Ne緀ljeni efeki: Haloperidol (Haldol) - dugo se zadr綼va u organizmu (samo se 60% ekskretuju tokom 1. nedelje.); Depresiv. Fluphenazine (Permitil & Prolixin) - manje sedativno

Noviji lekovi

Dibenzodiazapininski derivati. Uti鑥 i na + i na – simptome. Neki daju manje izrene ne緀ljene efekte. Neki su toksi鑞i za jetru. Skupi. Clozapine (Clozaril) - tretira + i – simptome, polu緄vot 12 h, Limitirana upotreba (rezistentni pacijenti), Visok rizik od napada, Antiholinergijska, adrenoliti鑛a, antihistaminska i antiserotoninska aktivnost. Risperdone (Risperdal) - Blokiras DA i 5-HT receptore. Dozno zavisni blag parkinsonizam mo緀 da dovede do hipotenzije. Olanzapine (Zyprexa) - vezuje se za DA i 5-HT receptore, ↓ rizik od Tardativne diskinezije, ↓ rizik od od napada.

POREME艫JI RASPOLO瓻NJA

Karakteri箄 se poreme鎍jima raspolo緀nja, pona筧nja i afekata. Dele se na
•   depresivne poreme鎍je,
•   bipolarne poreme鎍je
•   depresije povezane sa medicinskom bole规u  ili zloupotrebom alkohola i lekova.


 
Bipolarna psihoza

Karakteri筫 se nepredvidivim oscilacijama raspolo緀nja od manije (ili hipomanije) do depresije. U nekih pacijenata se javljaju samo rekurentni napadi manije, koju, u 鑙stom obliku, karakteri筫 ↑ psihomotorna aktivnost; ekscesna socijalna ekstravernost; ↓ potreba za snom; Impulsivno i poreme鎒no rasudjivanje. U te筴oj maniji javljaju se deluzije i paranoidni na鑙n mi筶jenja, sli鑞o kao u SCH. U 50% obolelih javlja se kombinacija psihomotorne agitiranosti  i aktiviranosti sa anksiozno规u i iritabilno规u (tako da se nekada te筴o razlikuje od agitirane depresije).

U nekim oblicima (bipolar II disorder), nisu prisutni svi elementi manije, i u tom slu鑑ju, potrebno je da postoje   rekurentne epizode depresije izmedju kojih se javljaju periodi blage aktivacije i ↑ energije (hipomania). U  ciklotimi鑞im poreme鎍jima, postoje brojni hipomani鑞i periodi, obi鑞o kratkog trajanja, koji se smenjuju sa periodima u kojima se javlaju depresivni simptomi koji, prema te緄ni i du緄ni, ne mogu biti ozna鑕ni kao prava depresije (major depression). (Fluktuacije raspolo緀nja su hroni鑞e i treba da budu prisutne najmanje dve godine da bi se postavila dijagnoza.)

Prava depresija (major depression)
Epizode  prave depresije karakteri筫 tuga, indiferentnost, apatija ili iritabilnost  + poreme鎍jritma spavanja, i apetita, gubitak te緄ne; motorna  agitacija ili retardacija; zamor; gubitak koncentracije, nemogu鎛ost dono筫nja odluka; ose鎒j stida ili krivice; razmi筶janja o smrti i umiranju, gubitak sposobnosti u緄vanja, rano budjenje, diurinalne varijacije raspolo緀nja (raspolo緀nje gore u jutarnjim 鑑sovima), Disforija (kvalitativno se razlikuje od tuge)

Simptomi manije i depresije

CRITERIA FOR MANIC EPISODE:
At least three of the following symptoms must be present with the “elevated, expansive, or irritable” mood; if the mood is only irritable, four symptoms must be present.
1.inflated self-esteem or grandiosity
2.decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
3.more talkative than usual or pressure to keep talking
4.flight of ideas or subjective experience that thoughts are racing
5.distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
6.increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
7.excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying spree, sexual indiscretions, or foolish business investments)

CRITERIA FOR MAJOR DEPRESSIVE EPISODE:
At least five of the following symptoms must be present for at least two weeks, and one of the symptoms must be either symptom 1 or symptom 2.
1.depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful) Note: In children and adolescents, can be irritable mood.
2.markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) 
3.significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: in children, consider failure to make expected weight gains. 
4.insomnia or hypersomnia nearly every day 
5.psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness of being slowed down)
6.fatigue or loss of energy nearly every day
7.feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
8.diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
9.recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

Diagnoze:

•   Bipolar I disorder - major depressive episodes & manic episodes
•   Bipolar II disorde - major depressive episodes & hypomanic episodes
•   Cyclothymia - milder depression & hypomanic episodes
•   Dysthymic disorder - milder depression
•   Major depressive disorder (unipolar) - major depressive episodes

Sub-categories:
•    rapid cycling
•    mixed episode

Fact Sheet:
•    About 2 million Americans are found to have bipolar in any given year – about 1% of the popul.
•    Approximately 1/2 of these people are not receiving any treatment for their illness at any given time.  Many such individuals are homeless or in jail.
•    This is a lethal disease left untreated: 10-15% of those with bipolar disorder commit suicide.
•    Men and women are equally susceptible to bipolar.
•    Blacks and whites are equally susceptible, whereas Latinos may have lower-than-average preva¬lence.
•    Bipolar disorder may be increasing in prevalence; may have been much less common prior to 19th century.
•    The total annual cost of bipolar disorder in the U.S. has been estimated at approx. $45 billion.

Kombinacija…
 
a. Genetskih faktora (podlo緉ost):
•    poligenska (vi筫 gena)
 
b. Sredinskih faktora (okida鑙, engl. triggers):
•    te筴o vreme/stres
•    alkohol i lekovi
•    veliki izazovi
•    lo筧 ishrana
 
 
Zna鑑jna genetska predispozicija. Javlja se u 80% slu鑑jeva u oba monozigotna blizanca. Nasledjuje se autozomno dominantno. Mnogi geni se povezuju sa ovim poreme鎍jem, sa naj鑦r规im dokazima za lokuse na hromozo¬mi¬ma 18p, 18q, 4p, 4q, 5q, 8p, 21q. Patogeneza jo uvek nerazja筺jena. Neuroimaging pokazao promene volumenu amigdala, kao i promene u beloj mo綿anoj masi. Ispitivanja na celularnom nivou su ukazala da bi poreme鎍ji aktivnosti membranske  Na+/ K+- zavisne ATPaze i poreme鎍ji u transdukciji signala fosfoinoziolskim putem i posredstvom GTP-vezuju鎖h proteina mogli biti od zna鑑ja za nastanak poreme鎍ja. Neurofiziolo筴e studije ukazuju da ovih osoba dolazi do poreme鎍ja cirkadijarnih ritmova (Litijum dovodi do terapijskih efekata resihhronizacijom intrizi鑞ih ritmova vezanih za dnevno/no鎛i ciklus.)

Postmortem ispitivanja pacijenata sa unilateralnom depresijom su pokazala. Izmenjenu noradrenergi鑛u aktivnost, uklju鑥ju鎖 smanjen broj noradrenergi鑛ih neurona u lokusu ceruleusi i smanjeno vezivanje za adrenergi鑛e receptore u cerebralnom korteksu. ↓nivoa triptofana u plazmi i koncentracije 5-hidroksiindolsir鎒tne kiseline (glavni metabolit serotonina u mozgu) u CST i ↓ vezivanje za trombocitni transporter za serotonin → ulogu serotoninskog sistema. (↑nivoa triptofana – prekursora serotonina u krvi, dovodi do reverzije antidepresivnih efekata u pacijenata koji su uspe筺o le鑕ni). Medjutim, budu鎖 da su promene raspolo緀nja u netretiranih pacijenata mnogo manje izra緀ne to se pretpostavlja da, iako postoji presinapto鑛a serotoninska disfunkcija u depresiji, da ona samo doprinosi, a da nije glavni uzrok nastanka poreme鎍ja).

Unilateralna depresija
Neuroendokrine abnormalnosti - sekrecija kortizola i CRH, ↑ veli鑙na adrenalne 緇ezde, ↓ inhibitorni odgovor glukokortikoida na davanje deksametazona, ↓ nivi TSH u odgovoru na infuziju TRH. Antidepresivi normalizuju ove poreme鎍je. Major depression povezana sa ushodnom regulacijom ekspresije proinflamacijskih citokina.


Bipolarna psihoza i kreativnost

Gene   Gene Effect   Just a little   Too much
A   Connect unrelated ideas   Creativity   Tangential, disorganized
B   Seek novelty   Fascinated by change, curious   Jumping from project to project
C   Be aware of others' opinions   Socially polished   Anxious, suspicious, paranoid
D   High energy level   Very productive   Can't stop, slow down, Racing thoughts, Unable to focus, Scattered activity
E   Take risks   Courageous   Bad judgment about harm

 
A few famous bipolars:
Jimi Hendrix, Patty Duke, Ted Turner, Jackson Pollack, Kurt Cobain, Jonathan Winters, Vincent van Gogh, Sylvia Plath, Ernest Hemingway,    Peter Gabriel, Virginia Woolf, Winston Churchill (unipolar)

from Jamison
KEY: H= Asylum or psychiatric hospital;    S= Suicide;    SA = Suicide Attempt 

Writers  Hans Christian Andersen, Honore de Balzac, James Barrie, William Faulkner (H), F. Scott Fitzgerald (H), Ernest Hemingway (H, S), Hermann Hesse (H, SA), Henrik Ibsen, Henry James, William James, Samuel Clemens (Mark Twain), Joseph Conrad (SA), Charles Dickens, Isak Dinesen (SA), Ralph Waldo Emerson, Herman Melville, Eugene O'Neill (H, SA), Mary Shelley, Robert Louis Stevenson, Leo Tolstoy, Tennessee Williams (H), Mary Wollstonecraft (SA), Virginia Woolf (H, S) 

Composers  Hector Berlioz (SA), Anton Bruckner (H), George Frederic Handel, Gustav Holst, Charles Ives, Gustav Mahler, Modest Mussorgsky, Sergey Rachmaninoff, Giocchino Rossini, Robert Schumann (H, SA), Alexander Scriabin, Peter Tchaikovsky 

Nonclassical composers and musicians  Irving Berlin (H), Noel Coward, Stephen Foster, Charles Mingus (H), Charles Parker (H, SA), Cole Porter (H) 

Poets  William Blake, Robert Burns, George Gordon, Lord Byron, Samuel Taylor Coleridge, Hart Crane (S) , Emily Dickinson, T.S. Eliot (H), Oliver Goldsmith, Gerard Manley Hopkins, Victor Hugo, Samuel Johnson, John Keats, Vachel Lindsay (S), James Russell Lowell, Robert Lowell (H), Edna St. Vincent Millay (H), Boris Pasternak (H), Sylvia Plath (H, S), Edgar Allan Poe (SA), Ezra Pound (H), Anne Sexton (H, S), Percy Bysshe Shelley (SA), Alfred, Lord Tennyson, Dylan Thomas, Walt Whitman 

Artists  Richard Dadd (H), Thomas Eakins, Paul Gauguin (SA), Vincent van Gogh (H, S), Ernst Ludwig Kirchner (H, S), Edward Lear, Michelangelo, Edvard Meunch (H), Georgia O'Keeffe (H), George Romney, Dante Gabriel Rossetti (SA) 



Popular Medications

Mood stabilizers: Lithium, Depakote, Atretol and Tegretol
Anti-Depressants: Wellbutrin, Prozac, Zoloft, Paxil
Anti-Psychotics: Haldol, Trilafon, Thorazine, Mellaril, Clozapine
Benzodiazepines (for anxiety & insomnia): Valium, Xanax

Nutrition (Omega-3 fatty acids)

There is no cure for bipolar disorder – it must be treated over a lifetime.


 

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