Psihoze

[Bred]

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. Vi¹e od 100 000 hospitalizovanih.

Pozitivni Simptomi
Vi¹ak, prekomernost, ili distorzija (+). Disorganizovan govor - Ukazuje na poremeæaj mi¹ljenja (labava povezanost reèi do “salate u govoru”). Halucinacije - Sensorni do¾ivljaj bez spolja¹nje stimulacije (èesto auditivne, vidne, mirisne, taktilne). Deluzije - Ubedjenja suprotna realnosti, Èesto deluzije proganjanja, Ponekad deluzije velièine

Negativni Simptomi
Karakteri¹u se deficitima u pona¹anju (–). Adinamija - nedostatak energije & nemoguænost obavljanja svakodnevnih aktivnosti. Alogija (siroma¹tvo govora)- redukcija kolièine i sadr¾aja govora. Ahedonija - nemoguænost do¾ivljavanja zadovoljstva. Asociajlnost - te¹ki poremeæaji 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 pona¹anje, 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, èesto neadekvatno pona¹anje, ali ne zadovoljava kriterijume za katatoni tip. Katatoni tip - motorna imobilnost, katalepsija, stupor (vo¹tana nefleksibilnost). Ekscesna, besciljna motorna aktivnost. Ekstremni negativizam ili mutizam. Bizarni pokreti, stereotipija, bizarni manirizam ili grimase, eholalia ili ehopraksija

Etiologija ©izofrenije
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 ¹izofrenije

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 znaèenje =  nervnu transmisiju. U praksi, ovi termini oznaèavaju lekove koji se koriste za leèenje SCH. Postoji ¹irok spektar off-label applications. Neadekvatno se oznaèavaju kao "major tranquilizers". Ne¾eljeni efekti: Parkinsonizam; Distonija – abnormalni pokreti lica i tela movements; Akatizija (nemir); Tardivna diskinezija (long term) - Ekzacerebracija - drug holiday regime, èe¹æe se vidja u ¾ena,   Pogor¹ava se pri smanjenju doze, Ireversibilna (denervacijska superosteljivost). Mnogi ne¾eljeni efekti (mpr., konstipacija i metabolièki sindrom)

Antagonisti DA

Hlorpromazin, SmithKlineFrench, 1950. Thorazine - Derivat fenotiazina  (anti-emetik), Sna¾an sedativni efekat, brzo se razvija toleranca, Ima i  anti-holinergijsku aktivnost, Aktivno se metaboli¹e (polu¾ivot 30h). Ne¾eljeni efeki: Haloperidol (Haldol) - dugo se zadr¾ava u organizmu (samo se 60% ekskretuju tokom 1. nedelje.); Depresiv. Fluphenazine (Permitil & Prolixin) - manje sedativno

Noviji lekovi

Dibenzodiazapininski derivati. Utièu i na + i na – simptome. Neki daju manje izrene ne¾eljene efekte. Neki su toksièni za jetru. Skupi. Clozapine (Clozaril) - tretira + i – simptome, polu¾ivot 12 h, Limitirana upotreba (rezistentni pacijenti), Visok rizik od napada, Antiholinergijska, adrenolitièka, antihistaminska i antiserotoninska aktivnost. Risperdone (Risperdal) - Blokiras DA i 5-HT receptore. Dozno zavisni blag parkinsonizam mo¾e da dovede do hipotenzije. Olanzapine (Zyprexa) - vezuje se za DA i 5-HT receptore, ↓ rizik od Tardativne diskinezije, ↓ rizik od od napada.

POREMEÆAJI RASPOLO®ENJA

Karakteri¹u se poremeæajima raspolo¾enja, pona¹anja i afekata. Dele se na
•   depresivne poremeæaje,
•   bipolarne poremeæaje
•   depresije povezane sa medicinskom bole¹æu  ili zloupotrebom alkohola i lekova.



Bipolarna psihoza

Karakteri¹e se nepredvidivim oscilacijama raspolo¾enja od manije (ili hipomanije) do depresije. U nekih pacijenata se javljaju samo rekurentni napadi manije, koju, u èistom obliku, karakteri¹e ↑ psihomotorna aktivnost; ekscesna socijalna ekstravernost; ↓ potreba za snom; Impulsivno i poremeæeno rasudjivanje. U te¹koj maniji javljaju se deluzije i paranoidni naèin mi¹ljenja, slièno kao u SCH. U 50% obolelih javlja se kombinacija psihomotorne agitiranosti  i aktiviranosti sa anksiozno¹æu i iritabilno¹æu (tako da se nekada te¹ko razlikuje od agitirane depresije).

U nekim oblicima (bipolar II disorder), nisu prisutni svi elementi manije, i u tom sluèaju, potrebno je da postoje   rekurentne epizode depresije izmedju kojih se javljaju periodi blage aktivacije i ↑ energije (hipomania). U  ciklotimiènim poremeæajima, postoje brojni hipomanièni periodi, obièno kratkog trajanja, koji se smenjuju sa periodima u kojima se javlaju depresivni simptomi koji, prema te¾ini i du¾ini, ne mogu biti oznaèeni kao prava depresije (major depression). (Fluktuacije raspolo¾enja su hroniène i treba da budu prisutne najmanje dve godine da bi se postavila dijagnoza.)

Prava depresija (major depression)
Epizode  prave depresije karakteri¹e tuga, indiferentnost, apatija ili iritabilnost  + poremeæajritma spavanja, i apetita, gubitak te¾ine; motorna  agitacija ili retardacija; zamor; gubitak koncentracije, nemoguænost dono¹enja odluka; oseæej stida ili krivice; razmi¹ljanja o smrti i umiranju, gubitak sposobnosti u¾ivanja, rano budjenje, diurinalne varijacije raspolo¾enja (raspolo¾enje gore u jutarnjim èasovima), 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 (podlo¾nost):
•    poligenska (vi¹e gena)

b. Sredinskih faktora (okidaèi, engl. triggers):
•    te¹ko vreme/stres
•    alkohol i lekovi
•    veliki izazovi
•    lo¹a ishrana


Znaèajna genetska predispozicija. Javlja se u 80% sluèajeva u oba monozigotna blizanca. Nasledjuje se autozomno dominantno. Mnogi geni se povezuju sa ovim poremeæajem, sa najèvr¹æim dokazima za lokuse na hromozo¬mi¬ma 18p, 18q, 4p, 4q, 5q, 8p, 21q. Patogeneza jo¹ uvek nerazja¹njena. Neuroimaging pokazao promene volumenu amigdala, kao i promene u beloj mo¾danoj masi. Ispitivanja na celularnom nivou su ukazala da bi poremeæaji aktivnosti membranske  Na+/ K+- zavisne ATPaze i poremeæaji u transdukciji signala fosfoinoziolskim putem i posredstvom GTP-vezujuæih proteina mogli biti od znaèaja za nastanak poremeæaja. Neurofiziolo¹ke studije ukazuju da ovih osoba dolazi do poremeæaja cirkadijarnih ritmova (Litijum dovodi do terapijskih efekata resihhronizacijom intriziènih ritmova vezanih za dnevno/noæni ciklus.)

Postmortem ispitivanja pacijenata sa unilateralnom depresijom su pokazala. Izmenjenu noradrenergièku aktivnost, ukljuèujuæi smanjen broj noradrenergièkih neurona u lokusu ceruleusi i smanjeno vezivanje za adrenergièke receptore u cerebralnom korteksu. ↓nivoa triptofana u plazmi i koncentracije 5-hidroksiindolsiræetne 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 uspe¹no leèeni). Medjutim, buduæi da su promene raspolo¾enja u netretiranih pacijenata mnogo manje izra¾ene to se pretpostavlja da, iako postoji presinaptoèka serotoninska disfunkcija u depresiji, da ona samo doprinosi, a da nije glavni uzrok nastanka poremeæaja).

Unilateralna depresija
Neuroendokrine abnormalnosti - sekrecija kortizola i CRH, ↑ velièina adrenalne ¾lezde, ↓ inhibitorni odgovor glukokortikoida na davanje deksametazona, ↓ nivi TSH u odgovoru na infuziju TRH. Antidepresivi normalizuju ove poremeæaje. 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.