Schizophrenie ist eine psychische Störung[13] gekennzeichnet durch kontinuierliche oder wiederkehrende Episoden einer Psychose.[5] Zu den Hauptsymptomen gehören Halluzinationen (Normalerweise hört man Stimmen), Wahnvorstellungen, und desorganisiertes Denken.[7] Weitere Symptome sind sozialer Rückzug, verminderter emotionaler Ausdruck, und Apathie.[5][14] Die Symptome treten typischerweise schleichend auf, beginnen im jungen Erwachsenenalter, und lösen sich in vielen Fällen nie auf.[3][7] Es gibt keinen objektiven diagnostischen Test; Mit der Diagnose wird beobachtetes Verhalten beschrieben, das auf zahlreiche verschiedene Ursachen zurückzuführen sein kann. Neben beobachtetem Verhalten, Ärzte werden auch eine Anamnese erstellen, die die von der Person berichteten Erfahrungen enthält, und Berichte von anderen, die mit der Person vertraut sind, bei der Diagnosestellung.[7] Jemanden mit Schizophrenie diagnostizieren, Der Arzt soll bestätigen, dass die Symptome und die Funktionseinschränkung sechs Monate lang bestehen (DSM-5) oder einen Monat (ICD-11).[7][11] Viele Menschen mit Schizophrenie haben andere psychische Störungen, insbesondere Substanzstörungen, depressive Störungen, Angststörungen, und Zwangsstörung.[7][15][16][17]
Um 0.3% Zu 0.7% der Menschen erkranken im Laufe ihres Lebens an Schizophrenie.[18] In 2017, Es gab eine Schätzung 1.1 Millionen neue Fälle und in 2019 insgesamt 20 Millionen Fälle weltweit.[2][19] Männer sind häufiger betroffen und treten im Durchschnitt früher auf,[2] obwohl einige große Übersichten keine geschlechtsspezifischen Unterschiede in der Prävalenz der Störung festgestellt haben.[20][21] Zu den wahrscheinlichen Ursachen für Schizophrenie gehören genetische und umweltbedingte Faktoren.[5] Zu den genetischen Faktoren zählen eine Vielzahl häufiger und seltener genetischer Varianten.[22] Zu den möglichen Umweltfaktoren gehört das Aufwachsen in einer Stadt, Cannabiskonsum im Jugendalter, Infektionen, das Alter der Mutter oder des Vaters einer Person, und schlechte Ernährung während der Schwangerschaft.[5][23]
Bei etwa der Hälfte der mit Schizophrenie diagnostizierten Patienten kommt es langfristig zu einer deutlichen Besserung, ohne dass es zu weiteren Rückfällen kommt, und ein kleiner Teil davon wird sich vollständig erholen.[7][24] Die andere Hälfte wird eine lebenslange Beeinträchtigung haben.[25] In einigen Fällen kann es sein, dass Menschen wiederholt in Krankenhäuser eingeliefert werden.[24] Soziale Probleme wie Langzeitarbeitslosigkeit, Armut, Obdachlosigkeit, Ausbeutung, und Viktimisierung stehen häufig im Zusammenhang mit Schizophrenie.[26][27] Im Vergleich zur Gesamtbevölkerung, Menschen mit Schizophrenie haben eine höhere Selbstmordrate (um 5% gesamt) und mehr körperliche Gesundheitsprobleme,[28][29] was zu einem durchschnittlichen Rückgang der Lebenserwartung um führt 20 Jahre.[10] In 2015, eine Schätzung 17,000 Todesfälle wurden mit Schizophrenie in Verbindung gebracht.[12]
Die Haupttherapie besteht aus antipsychotischen Medikamenten, nebst Beratung, Berufsausbildung, und soziale Rehabilitation.[5] Bis zu einem Drittel der Menschen reagieren nicht auf anfängliche Antipsychotika, In diesem Fall kann das Antipsychotikum Clozapin verwendet werden.[30] In Situationen, in denen Ärzte die Gefahr einer Selbst- oder Verletzungsgefahr für andere einschätzen, Sie können einen kurzen unfreiwilligen Krankenhausaufenthalt verhängen.[31] Bei einer kleinen Anzahl von Menschen mit schwerer Schizophrenie kommt eine Langzeit-Krankenhauseinweisung in Betracht.[32] In einigen Ländern sind unterstützende Dienste begrenzt oder nicht verfügbar, Langzeitaufenthalte im Krankenhaus kommen häufiger vor.[33]
Anzeichen und Symptome
Meine Augen im Moment der Erscheinungen des deutschen Künstlers August Natterer, der an Schizophrenie litt
Schizophrenie ist eine psychische Störung, die durch erhebliche Veränderungen der Wahrnehmung gekennzeichnet ist, Gedanken, Stimmung, und Verhalten.[34] Die Symptome werden positiv beschrieben, und negativ, und kognitive Symptome.[3][35] Die positiven Symptome einer Schizophrenie sind bei jeder Psychose gleich und werden manchmal als psychotische Symptome bezeichnet. Diese können bei jeder der verschiedenen Psychosen vorhanden sein, und sind oft vorübergehender Natur, was eine frühzeitige Diagnose einer Schizophrenie problematisch macht. Eine Psychose, die zum ersten Mal bei einer Person auftritt, bei der später eine Schizophrenie diagnostiziert wird, wird als Erstepisodenpsychose bezeichnet (FEP).[36][37]
Positive Symptome
Positivsymptome sind Symptome, die normalerweise nicht auftreten, sind aber bei Menschen während einer psychotischen Episode bei Schizophrenie vorhanden. Dazu gehören Wahnvorstellungen, Halluzinationen, und desorganisierte Gedanken und Sprache, werden typischerweise als Manifestationen einer Psychose angesehen.[36] Halluzinationen betreffen am häufigsten den Hörsinn als Stimmenhörer, manchmal können aber auch andere Geschmackssinne betroffen sein, Sicht, Geruch, und berühren.[38] Sie hängen typischerweise auch mit dem Inhalt des Wahnthemas zusammen.[39] Wahnvorstellungen sind bizarrer oder verfolgender Natur. Verzerrungen der Selbsterfahrung, etwa das Gefühl, dass die eigenen Gedanken oder Gefühle nicht wirklich die eigenen sind, zu glauben, dass Gedanken in den eigenen Geist eingefügt werden, manchmal auch als Passivitätsphänomene bezeichnet, kommen auch häufig vor.[40] Denkstörungen können Denkblockaden umfassen, und desorganisierte Sprache – Sprache, die nicht verständlich ist, wird als Wortsalat bezeichnet.[3][41] Positive Symptome sprechen im Allgemeinen gut auf Medikamente an,[5] und nehmen im Krankheitsverlauf ab, möglicherweise im Zusammenhang mit dem altersbedingten Rückgang der Dopaminaktivität.[7]
Negative Symptome
Negativsymptome sind Defizite normaler emotionaler Reaktionen, oder anderer Denkprozesse. Die fünf anerkannten Bereiche negativer Symptome sind:: abgestumpfter Affekt – flacher Ausdruck oder wenig Emotionen; alogia – eine Spracharmut; Anhedonie – Unfähigkeit, Freude zu empfinden; Asozialität – der Mangel an Lust, Beziehungen aufzubauen, und Willenskraft – mangelnde Motivation und Apathie.[42][43] Avolition und Anhedonie werden als Motivationsdefizite angesehen, die aus einer beeinträchtigten Belohnungsverarbeitung resultieren.[44][45] Belohnung ist der Haupttreiber der Motivation und wird hauptsächlich durch Dopamin vermittelt.[45] Es wurde vermutet, dass negative Symptome mehrdimensional sind und sie wurden in zwei Unterbereiche eingeteilt: Apathie oder mangelnde Motivation, und verminderter Ausdruck.[42][46] Apathie schließt Willensfreiheit ein, Anhedonie, und sozialer Rückzug; Ein verminderter Ausdruck schließt einen stumpfen Affekt mit ein, und Alogie.[47] Manchmal wird verminderter Ausdruck sowohl als verbal als auch als nonverbal behandelt.[48]
Apathie macht etwa aus 50 Prozent der am häufigsten festgestellten negativen Symptome und beeinträchtigt das funktionelle Ergebnis und die anschließende Lebensqualität. Apathie hängt mit einer gestörten kognitiven Verarbeitung zusammen, die sich auf das Gedächtnis und die Planung einschließlich zielgerichteten Verhaltens auswirkt.[49] Die beiden Teilbereiche haben die Notwendigkeit getrennter Behandlungsansätze nahegelegt.[50] Ein weiteres bekanntes negatives Symptom ist der Mangel an Stress – verbunden mit einem verminderten Erleben von Depressionen und Angstzuständen.[51] Häufig wird zwischen den Negativsymptomen unterschieden, die der Schizophrenie innewohnen, als primär bezeichnet; und solche, die aus positiven Symptomen resultieren, vor den Nebenwirkungen von Antipsychotika, Substanzgebrauchsstörung, und soziale Deprivation – sogenannte sekundäre Negativsymptome.[52] Negativsymptome reagieren weniger gut auf Medikamente und sind am schwierigsten zu behandeln.[50] Allerdings bei richtiger Einschätzung, Sekundäre Negativsymptome sind einer Behandlung zugänglich.[46]
Skalen zur gezielten Beurteilung des Vorliegens von Negativsymptomen, und zur Messung ihrer Schwere, und ihre Änderungen wurden seit den früheren Skalen wie der PANNS eingeführt, die sich mit allen Arten von Symptomen befasst.[50] Bei diesen Skalen handelt es sich um das klinische Beurteilungsgespräch für negative Symptome (KAINS), und die Skala für kurze negative Symptome (BNSS) auch Waagen der zweiten Generation genannt.[50][51][53] In 2020, zehn Jahre nach seiner Einführung, Eine interkulturelle Studie zum Einsatz von BNSS ergab kulturübergreifend gültige und zuverlässige psychometrische Beweise für die Fünf-Domänen-Struktur.[51] The BNSS is designed to assess both the presence and severity and change of negative symptoms of the five recognised domains, and the additional item of reduced normal distress.[51] BNSS can register changes in negative symptoms concerning psychosocial and pharmacological intervention trials. BNSS has also been used to study a proposed non-D2 treatment called SEP-363856. Findings supported the favouring of five domains over the two-dimensional proposition.[51]
Cognitive symptoms
See also: Visual processing abnormalities in schizophrenia
Cognitive deficits are the earliest and most constantly found symptoms in schizophrenia. They are often evident long before the onset of illness in the prodromal stage, and may be present in early adolescence, or childhood.[54][55] They are a core feature but not considered to be core symptoms, ebenso wie Positiv- und Negativsymptome.[56][57] Jedoch, Ihr Vorhandensein und der Grad der Funktionsstörung gelten als besserer Indikator für die Funktionalität als die Darstellung der Kernsymptome.[54] Kognitive Defizite verschlimmern sich in der ersten Psychoseepisode, kehren dann aber wieder zum Ausgangswert zurück, und bleiben im Krankheitsverlauf einigermaßen stabil.[58][59]
Es wird angenommen, dass kognitive Defizite die negativen psychosozialen Folgen bei Schizophrenie auslösen, und es wird behauptet, dass sie einer möglichen Verringerung des IQ gegenüber der Norm gleichkommen 100 bis 70–85.[60][61] Kognitive Defizite können neurokognitiver Natur sein (unsozial) oder der sozialen Erkenntnis.[62] Neurokognition ist die Fähigkeit, Informationen zu empfangen und sich daran zu erinnern, und beinhaltet verbale Gewandtheit, Erinnerung, Argumentation, Problemlösung, Geschwindigkeit der Bearbeitung, und auditive und visuelle Wahrnehmung.[59] Es wird festgestellt, dass das verbale Gedächtnis und die Aufmerksamkeit am stärksten beeinträchtigt sind.[61][63] Eine Beeinträchtigung des verbalen Gedächtnisses geht mit einer verminderten semantischen Verarbeitung einher (die Bedeutung von Wörtern in Beziehung setzen).[64] Eine weitere Gedächtnisstörung ist die des episodischen Gedächtnisses.[65] Eine bei Schizophrenie häufig auftretende Beeinträchtigung der visuellen Wahrnehmung ist die visuelle Rückwärtsmaskierung.[59] Zu den Beeinträchtigungen der visuellen Verarbeitung gehört die Unfähigkeit, komplexe visuelle Illusionen wahrzunehmen.[66] Die soziale Kognition befasst sich mit den mentalen Operationen, die zur Interpretation erforderlich sind, und das Selbst und andere in der sozialen Welt verstehen.[59][62] Auch hier handelt es sich um eine damit verbundene Beeinträchtigung, und die Wahrnehmung von Gesichtsemotionen wird oft als schwierig empfunden.[67][68] Die Gesichtswahrnehmung ist für die normale soziale Interaktion von entscheidender Bedeutung.[69] Kognitive Beeinträchtigungen reagieren normalerweise nicht auf Antipsychotika, und es gibt eine Reihe von Interventionen, mit denen versucht wird, sie zu verbessern; Besonders hilfreich ist die kognitive Remediationstherapie.[57]
Beginn
Weitere Informationen: Grundsymptome der Schizophrenie
See also: Schizophrenie im Kindesalter und Jugend § Veränderungen im Gehirn
Der Beginn liegt typischerweise im späten Teenager- und frühen 30. Lebensjahr, Die höchste Inzidenz trat bei Männern in den frühen bis mittleren Zwanzigern auf, und bei Frauen in den späten Zwanzigern.[3][7][11] Beginn vor dem Alter von 17 wird als Frühbeginn bezeichnet,[70] und vor dem Alter von 13, wie es manchmal passieren kann, wird als Schizophrenie im Kindesalter oder als sehr früh einsetzende Schizophrenie bezeichnet.[7][71] Ein späteres Stadium des Beginns kann im Alter zwischen 10 und 15 Jahren auftreten 40 Und 60, bekannt als Spätschizophrenie.[62] Ein späteres Auftreten im Alter von 60, die möglicherweise schwer als Schizophrenie zu unterscheiden ist, ist als sehr spät einsetzende schizophrenieähnliche Psychose bekannt.[62] Es hat sich gezeigt, dass bei spätem Auftreten häufiger Frauen betroffen sind; they have less severe symptoms and need lower doses of antipsychotics.[62] The tendency for earlier onset in males is later seen to be balanced by a post-menopausal increase in the development in females. Estrogen produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload.[72] There has been a dramatic increase in the numbers of older adults with schizophrenia.[73] An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early onset and late-onset illness.[62][74]
Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the prodromal stage.[7] Up to 75% of those with schizophrenia go through a prodromal stage.[75] The negative and cognitive symptoms in the prodrome stage can precede FEP by many months and up to five years.[58][76] The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis.[59] Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of at risk mental state.[59] Cognitive dysfunction at an early age impact a young person’s usual cognitive development.[77] Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies.[58][76] Es wird vermutet, dass die Verwendung entzündungshemmender Verbindungen wie D-Serin den Übergang zur Schizophrenie verhindern kann.[58] Kognitive Symptome sind nicht sekundär zu positiven Symptomen oder den Nebenwirkungen von Antipsychotika.[59]
Kognitive Beeinträchtigungen im Prodromalstadium verschlimmern sich nach der ersten Episode einer Psychose (Danach kehren sie zum Ausgangswert zurück und bleiben dann einigermaßen stabil), Es ist von größter Bedeutung, frühzeitig einzugreifen, um einen solchen Übergang zu verhindern.[58] Eine frühzeitige Behandlung mit kognitiven Verhaltenstherapien ist der Goldstandard.[76] Bei Schizophrenie treten häufig neurologische leichte Anzeichen von Ungeschicklichkeit und Verlust der Feinmotorik auf, Dies kann durch eine wirksame Behandlung von FEP behoben werden.[11][78]
Risikofaktoren
Hauptartikel: Risikofaktoren für Schizophrenie
See also: Entwicklungspsychobiologie
Schizophrenia is described as a neurodevelopmental disorder with no precise boundary, or single cause, and is thought to develop from gene–environment interactions with involved vulnerability factors.[5][79][80] The interactions of these risk factors are complex, as numerous and diverse insults from conception to adulthood can be involved.[80] A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.[80][81] The genetic component means that prenatally brain development is disturbed, and environmental influence affects the postnatal development of the brain.[82] Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.[82]
Genetic
Estimates of the heritability of schizophrenia are between 70% Und 80%, was das impliziert 70% Zu 80% Die individuellen Unterschiede im Risiko für Schizophrenie hängen mit der Genetik zusammen.[22][83] Diese Schätzungen variieren aufgrund der Schwierigkeit, genetische und umweltbedingte Einflüsse zu trennen, und ihre Genauigkeit wurde in Frage gestellt.[84][85] Der größte Risikofaktor für die Entwicklung einer Schizophrenie besteht darin, einen Verwandten ersten Grades mit der Krankheit zu haben (Risiko ist 6.5%); mehr als 40% Eineiige Zwillinge von Schizophreniekranken sind ebenfalls betroffen.[86] Wenn ein Elternteil betroffen ist, beträgt das Risiko ca 13% und wenn beide betroffen sind, ist das Risiko nahezu groß 50%.[83] Jedoch, DSM-5 weist darauf hin, dass die meisten Menschen mit Schizophrenie keine familiäre Vorgeschichte von Psychosen haben.[7] In den Ergebnissen von Kandidatengenstudien zur Schizophrenie konnten im Allgemeinen keine konsistenten Zusammenhänge festgestellt werden,[87] und die genetischen Loci, die durch genomweite Assoziationsstudien identifiziert wurden, erklären nur einen kleinen Teil der Variation der Krankheit.[88]
Es ist bekannt, dass viele Gene an Schizophrenie beteiligt sind, jeweils mit geringer Wirkung und unbekannter Übertragung und Ausdruck.[22][89][90] Die Summierung dieser Effektgrößen zu einem polygenen Risikoscore kann dies zumindest erklären 7% der Variabilität der Haftung für Schizophrenie.[91] Um 5% der Fälle von Schizophrenie sind vermutlich zumindest teilweise auf seltene Variationen in der Kopienzahl zurückzuführen (CNVs); Diese strukturellen Variationen sind mit bekannten genomischen Störungen verbunden, die Deletionen bei 22q11.2 beinhalten (DiGeorge-Syndrom) und 17q12 (17q12-Mikrodeletionssyndrom), Vervielfältigungen bei 16p11.2 (am häufigsten gefunden) und Löschungen bei 15q11.2 (Burnside-Butler-Syndrom).[92] Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.[92]
The genes CRHR1 and CRHBP are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the HPA axis, and their interaction can affect this axis. Response to stress can cause lasting changes in the function of the HPA axis possibly disrupting the negative feedback mechanism, homeostasis, and the regulation of emotion leading to altered behaviors.[81]
The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. Es wird erwartet, dass genetische Varianten, die das Risiko einer Schizophrenie erhöhen, aufgrund ihrer negativen Auswirkungen auf die Fortpflanzungsfähigkeit selektiert werden. Es wurden eine Reihe möglicher Erklärungen vorgeschlagen, einschließlich der Tatsache, dass Allele, die mit dem Schizophrenierisiko verbunden sind, nicht betroffenen Personen einen Fitnessvorteil verleihen.[93][94] Obwohl einige Beweise diese Idee nicht stützen,[85] andere schlagen vor, dass eine große Anzahl von Allelen, von denen jedes einen kleinen Beitrag leistet, bestehen bleiben kann.[95]
Umweltfreundlich
Weitere Informationen: Ernährung vor der Geburt, Vorgeburtlicher Stress, und neuroplastische Auswirkungen der Umweltverschmutzung
Umweltfaktoren, Zu den Erkrankungen, die jeweils mit einem geringen Risiko für die Entwicklung einer Schizophrenie im späteren Leben verbunden sind, gehört Sauerstoffmangel, Infektion, vorgeburtlicher mütterlicher Stress, und Unterernährung der Mutter während der pränatalen Entwicklung.[96] Ein Risiko ist auch mit mütterlicher Fettleibigkeit verbunden, bei zunehmendem oxidativem Stress, und Fehlregulierung der Dopamin- und Serotoninwege.[97] Es wurde gezeigt, dass sowohl mütterlicher Stress als auch Infektionen die fetale Neuroentwicklung durch einen Anstieg entzündungsfördernder Zytokine verändern.[98] Bei einer Geburt im Winter oder Frühling besteht ein geringeres Risiko, möglicherweise aufgrund eines Vitamin-D-Mangels[99] oder eine vorgeburtliche Virusinfektion.[86] Andere Infektionen während der Schwangerschaft oder rund um die Geburt, die mit einem erhöhten Risiko verbunden sind, umfassen Infektionen durch Toxoplasma gondii und Chlamydien.[100] Das erhöhte Risiko liegt bei etwa fünf bis acht Prozent.[101] Virusinfektionen des Gehirns im Kindesalter sind auch mit dem Risiko einer Schizophrenie im Erwachsenenalter verbunden.[102]
Negative Kindheitserlebnisse (Asse), schwere Formen davon werden als Kindheitstraumata eingestuft, range from being bullied or abused, to the death of a parent.[103] Many adverse childhood experiences can cause toxic stress and increase the risk of psychosis.[103][104][105] Chronic trauma can promote lasting inflammatory dysregulation throughout the nervous system.[106] It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system.[106] Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.[107]
Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two,[28][108] even after taking into account drug use, ethnic group, and size of social group.[109] A possible link between the urban environment and pollution has been suggested to be the cause of the elevated risk of schizophrenia.[110]
Other risk factors of importance include social isolation, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.[86][111] Having a father older than 40 Jahre, or parents younger than 20 years are also associated with schizophrenia.[5][112] It has been suggested that apart from gene-environment interactions, environment-environment interactions also be taken into account as each environmental risk factor on its own is not enough.[96]
Substance use
Weitere Informationen: Risk factors of schizophrenia § Substance use
About half of those with schizophrenia use recreational drugs, including cannabis, tobacco, and alcohol excessively.[113][114] Der Konsum von Stimulanzien wie Amphetamin und Kokain kann zu einer vorübergehenden Stimulanzienpsychose führen, die der Schizophrenie sehr ähnlich ist. Selten, Auch Alkoholkonsum kann zu einer ähnlichen alkoholbedingten Psychose führen.[86][115] Medikamente können von Menschen mit Schizophrenie auch als Bewältigungsmechanismus eingesetzt werden, um mit Depressionen umzugehen, Angst, Langeweile, und Einsamkeit.[113][116] Der Konsum von Cannabis und Tabak ist nicht mit der Entwicklung kognitiver Defizite verbunden, und manchmal wird ein umgekehrter Zusammenhang gefunden, wenn ihre Anwendung diese Symptome verbessert.[57] Jedoch, Substanzgebrauchsstörungen gehen mit einem erhöhten Suizidrisiko einher, und ein schlechtes Ansprechen auf die Behandlung.[117]
Cannabiskonsum kann ein Faktor sein, der zur Entwicklung einer Schizophrenie beiträgt, möglicherweise das Krankheitsrisiko bei bereits gefährdeten Personen erhöhen.[23] Das erhöhte Risiko erfordert möglicherweise das Vorhandensein bestimmter Gene in einem Individuum.[23] Sein Einsatz ist mit einer Verdoppelung des Tarifs verbunden.[118] Die Verwendung wirksamerer Cannabissorten mit einem hohen Anteil des Wirkstoffs Tetrahydrocannabinol (THC), erhöht das Risiko weiter. Eine dieser Sorten ist als Skunk bekannt.[119][120]
Mechanismen
Hauptartikel: Mechanismen der Schizophrenie
See also: Aberrante Salienz
Die Diagnose einer Schizophrenie wird nicht durch einen objektiven diagnostischen Test gestellt; Vielmehr wird die Diagnose verwendet, um beobachtetes Verhalten zu beschreiben, das auf zahlreiche verschiedene Ursachen zurückzuführen ist. Es wurden eine Reihe von Modellen vorgeschlagen, um Zusammenhänge zwischen veränderter Gehirnfunktion und Schizophrenie zu erklären.[28] Das vorherrschende Modell der Schizophrenie ist das einer neurologischen Entwicklungsstörung, und die zugrunde liegenden Veränderungen, die auftreten, bevor Symptome sichtbar werden, werden als Folge der Interaktion zwischen Genen und der Umwelt angesehen.[121] Umfangreiche Studien stützen dieses Modell.[75] Mütterliche Infektionen, Mangelernährung und Komplikationen während der Schwangerschaft und Geburt sind bekannte Risikofaktoren für die Entwicklung einer Schizophrenie, die normalerweise zwischen dem Alter auftritt 18-25 ein Zeitraum, der sich mit bestimmten Stadien der neurologischen Entwicklung überschneidet.[122] Gen-Umwelt-Interaktionen führen zu Defiziten in den neuronalen Schaltkreisen, die sich auf sensorische und kognitive Funktionen auswirken.[75]
Die vorgeschlagenen gängigen Dopamin- und Glutamat-Modelle schließen sich nicht gegenseitig aus; Jedem wird eine Rolle in der Neurobiologie der Schizophrenie zugeschrieben.[123] Das am häufigsten vorgeschlagene Modell war die Dopamin-Hypothese der Schizophrenie, which attributes psychosis to the mind’s faulty interpretation of the misfiring of dopaminergic neurons.[124] This has been directly related to the symptoms of delusions and hallucinations.[125][126][127] Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis.[128][129] A decrease in D1 receptors in the dorsolateral prefrontal cortex may also be responsible for deficits in working memory.[130][131]
The glutamate hypothesis of schizophrenia links alterations between glutamatergic neurotransmission and the neural oscillations that affect connections between the thalamus and the cortex.[132] Studies have shown that a reduced expression of a glutamate receptor – NMDA receptor, and glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with schizophrenia.[132][133][134] Post-mortem studies consistently find that a subset of these neurons fail to express GAD67 (GAD1),[135] in addition to abnormalities in brain morphometry. The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as gamma waves that have a frequency of between 30 Und 80 hertz. Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality.[135][136][137][138] An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of astrocytes. Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia.[139] Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of EAAT2 a glutamate transporter in astrocytes; supporting the glutamate hypothesis.[139]
Deficits in executive functions, such as planning, inhibition, and working memory, are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to utilize this to direct cognition and behavior.[140][141] Diese Beeinträchtigungen wurden mit einer Reihe von Neuroimaging- und neuropathologischen Anomalien in Verbindung gebracht. Zum Beispiel, Funktionelle Neuroimaging-Studien berichten über Hinweise auf eine verminderte neuronale Verarbeitungseffizienz, Dabei wird der dorsolaterale präfrontale Kortex stärker aktiviert, um im Vergleich zur Steuerung von Arbeitsgedächtnisaufgaben ein bestimmtes Leistungsniveau zu erreichen. Diese Anomalien können mit dem konsistenten Obduktionsbefund eines reduzierten Neuropils zusammenhängen, Dies wird durch eine erhöhte Dichte der Pyramidenzellen und eine verringerte Dichte der dendritischen Stacheln nachgewiesen. Diese zellulären und funktionellen Anomalien können sich auch in strukturellen Neuroimaging-Studien widerspiegeln, die ein verringertes Volumen der grauen Substanz im Zusammenhang mit Defiziten bei Arbeitsgedächtnisaufgaben feststellen.[142]
Positive Symptome wurden mit einer kortikalen Ausdünnung im Gyrus temporalis superior in Verbindung gebracht.[143] Severity of negative symptoms has been linked to reduced thickness in the left medial orbitofrontal cortex.[144] Anhedonia, traditionally defined as a reduced capacity to experience pleasure, is frequently reported in schizophrenia. Jedoch, a large body of evidence suggests that hedonic responses are intact in schizophrenia,[145] and that what is reported to be anhedonia is a reflection of dysfunction in other processes related to reward.[146] Gesamt, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.[147]
It has been hypothesized that in some people, development of schizophrenia is related to intestinal tract dysfunction such as seen with non-celiac gluten sensitivity or abnormalities in the gut microbiota.[148] A subgroup of persons with schizophrenia present an immune response to gluten differently from that found in people with celiac, with elevated levels of certain serum biomarkers of gluten sensitivity such as anti-gliadin IgG or anti-gliadin IgA antibodies.[149]
Another theory links abnormal brain lateralization to the development of being left-handed which is significantly more common in those with schizophrenia.[150] This abnormal development of hemispheric asymmetry is noted in schizophrenia.[151] Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.[150][152]
Bayesian models of brain functioning have been utilized to link abnormalities in cellular functioning to symptoms.[153][154] Both hallucinations and delusions have been suggested to reflect improper encoding of prior expectations, thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of circuits that mediate predictive coding, reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.[155][156][157]
Diagnosis
Hauptartikel: Diagnosis of schizophrenia
There is no objective test or biomarker to confirm the diagnosis. Psychoses can occur in several conditions and are often transient making early diagnosis of schizophrenia difficult. Psychosis noted for the first time in a person that is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).
Criteria
Schizophrenie wird anhand der Kriterien des Diagnose- und Statistikhandbuchs für psychische Störungen diagnostiziert (DSM) veröffentlicht von der American Psychiatric Association oder der International Statistical Classification of Diseases and Related Health Problems (ICD) herausgegeben von der Weltgesundheitsorganisation. Diese Kriterien nutzen die selbstberichteten Erfahrungen der Person und gemeldete Verhaltensauffälligkeiten, gefolgt von einer psychiatrischen Begutachtung. Die Untersuchung des psychischen Zustands ist ein wichtiger Teil der Beurteilung.[158] Ein etabliertes Instrument zur Beurteilung der Schwere positiver und negativer Symptome ist die Positive and Negative Syndrome Scale (PFANNEN).[159] Dabei wurden Mängel im Zusammenhang mit Negativsymptomen festgestellt, und andere Skalen – das klinische Beurteilungsgespräch für negative Symptome (KAINS), and the Brief Negative Symptoms Scale (BNSS) have been introduced.[50] The DSM-5, veröffentlicht in 2013, gives a Scale to Assess the Severity of Symptom Dimensions outlining eight dimensions of symptoms.[56]
DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, Halluzinationen, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or catatonic behaviour.[7] A different diagnosis of schizophreniform disorder can be made before the six months needed for the diagnosis of schizophrenia.[7]
In Australia the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning.[160] In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, Studie, or to carry on ordinary daily living, and with other similar conditions ruled out.[161]
The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high.[162] The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom.[40]
A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.[56]
Changes made
Both manuals have adopted the chapter heading of Schizophrenia spectrum and other psychotic disorders; ICD modifying this as Schizophrenia spectrum and other primary psychotic disorders.[56] The definition of schizophrenia remains essentially the same as that specified by the 2000 text revised DSM-IV (DSM-IV-TR). Jedoch, with the publication of DSM-5, the APA removed all sub-classifications of schizophrenia.[56] ICD-11 has also removed subtypes. The removed subtype from both, of catatonic has been relisted in ICD-11 as a psychomotor disturbance that may be present in schizophrenia.[56]
Another major change was to remove the importance previously given to Schneider’s first-rank symptoms.[163] DSM-5 still uses the listing of schizophreniform disorder but ICD-11 no longer includes it.[56] DSM-5 also recommends that a better distinction be made between a current condition of schizophrenia and its historical progress, to achieve a clearer overall characterization.[163]
A dimensional assessment has been included in DSM-5 covering eight dimensions of symptoms to be rated (using the Scale to Assess the Severity of Symptom Dimensions) – these include the five diagnostic criteria plus cognitive impairments, mania, and depression.[56] This can add relevant information for the individual in regard to treatment, prognosis, and functional outcome; it also enables the response to treatment to be more accurately described.[56][164]
Two of the negative symptoms – avolition and diminished emotional expression, have been given more prominence in both manuals.[56]
Comorbidities
Many people with schizophrenia may have one or more other mental disorders, such as panic disorder, obsessive–compulsive disorder, or substance use disorder. These are separate disorders that require treatment.[7] When comorbid with schizophrenia, substance use disorder and antisocial personality disorder both increase the risk for violence.[165] Comorbid substance use disorder also increases risk for suicide.[117]
Sleep disorders often co-occur with schizophrenia, and may be an early sign of relapse.[166] Sleep disorders are linked with positive symptoms such as disorganized thinking and can adversely affect cortical plasticity and cognition.[166] The consolidation of memories is disrupted in sleep disorders.[167] They are associated with severity of illness, a poor prognosis, and poor quality of life.[168][169] Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.[168] Genetic variations have been found associated with these conditions involving the circadian rhythm, dopamine and histamine metabolism, and signal transduction.[170] Limited positive evidence has been found for the use of acupuncture as an add-on.[171]
Differential diagnosis
See also: Dual diagnosis and Comparison of bipolar disorder and schizophrenia
To make a diagnosis of schizophrenia other possible causes of psychosis need to be excluded.[172] Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, or as schizophreniform disorder. Psychosis is noted in Other specified schizophrenia spectrum and other psychotic disorders as a DSM-5 category. Schizoaffective disorder is diagnosed if symptoms of mood disorder are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.[7]
Psychotic symptoms may be present in several other conditions, including bipolar disorder,[8] borderline personality disorder,[9] substance intoxication, substance-induced psychosis, and a number of drug withdrawal syndromes. Non-bizarre delusions are also present in delusional disorder, and social withdrawal in social anxiety disorder, avoidant personality disorder and schizotypal personality disorder. Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia.[7] Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia.[173] There can be considerable overlap with the symptoms of post-traumatic stress disorder.[174]
A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as metabolic disturbance, systemic infection, syphilis, HIV-associated neurocognitive disorder, Epilepsie, limbic encephalitis, and brain lesions. Schlaganfall, Multiple Sklerose, hyperthyroidism, hypothyroidism, and dementias such as Alzheimer’s disease, Huntington-Krankheit, frontotemporal dementia, and the Lewy body dementias may also be associated with schizophrenia-like psychotic symptoms.[175] It may be necessary to rule out a delirium, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific medical indication or possible adverse effects from antipsychotic medication. In children hallucinations must be separated from typical childhood fantasies.[7] It is difficult to distinguish childhood schizophrenia from autism.[71]
Prevention
Prevention of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.[176] There is tentative though inconclusive evidence for the effectiveness of early intervention to prevent schizophrenia in the prodrome phase.[177] There is some evidence that early intervention in those with first-episode psychosis may improve short-term outcomes, but there is little benefit from these measures after five years.[28] Cognitive behavioral therapy may reduce the risk of psychosis in those at high risk after a year[178] and is recommended in this group, by the National Institute for Health and Care Excellence (NICE).[34] Another preventive measure is to avoid drugs that have been associated with development of the disorder, including cannabis, cocaine, and amphetamines.[86]
Antipsychotics are prescribed following a first-episode psychosis, and following remission a preventive maintenance use is continued to avoid relapse. Jedoch, it is recognised that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.[179]
Management
Hauptartikel: Management of schizophrenia
The primary treatment of schizophrenia is the use of antipsychotic medications, often in combination with psychosocial interventions and social supports.[28][180] Community support services including drop-in centers, visits by members of a community mental health team, supported employment,[181] and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) is associated with a poorer outcome in both the short term and the long term.[182]
Voluntary or involuntary admittance to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery.[26] This process was known as deinstitutionalization, and community and supportive services were developed in order to support this change. Many other countries followed suit with the US starting in the 60s.[183] There still remain a smaller group of people who doctors and courts do not agree to discharge.[26][32] In some countries that lack the necessary supportive and social services, Längere Krankenhausaufenthalte sind häufiger.[33]
Medikamente
Risperidon (Handelsname Risperdal) ist ein häufiges atypisches Antipsychotikum.
Die Erstbehandlung bei Schizophrenie ist ein Antipsychotikum. Die Antipsychotika der ersten Generation, heute typische Antipsychotika genannt, sind Dopaminantagonisten, die D2-Rezeptoren blockieren, und beeinflussen die Neurotransmission von Dopamin. Die wurden später herausgebracht, die Antipsychotika der zweiten Generation, die als atypische Antipsychotika bekannt sind, kann auch Auswirkungen auf einen anderen Neurotransmitter haben, Serotonin. Antipsychotika können die Angstsymptome innerhalb weniger Stunden nach ihrer Anwendung lindern, bei anderen Symptomen kann es jedoch mehrere Tage oder Wochen dauern, bis sie ihre volle Wirkung entfalten.[36][184] Sie haben wenig Einfluss auf negative und kognitive Symptome, was durch zusätzliche Psychotherapien und Medikamente unterstützt werden kann.[185] There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people.[186] Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.[187][188]
Tobacco smoking increases the metabolism of some antipsychotics, by strongly activitating CYP1A2, the enzyme that breaks them down, and a significant difference is found in these levels between smokers and non-smokers.[189][190][191] It is recommended that the dosage for those smokers on clozapine be increased by 50%, and for those on olanzapine by 30%.[190] Die Folge einer Raucherentwöhnung kann zu einer erhöhten Konzentration des Antipsychotikums und damit zu einer Toxizität führen, Daher müsste eine Überwachung der Wirkung im Hinblick auf eine Verringerung der Dosierung erfolgen; Viele Symptome können sich spürbar verschlimmern, und extreme Müdigkeit, Auch Krampfanfälle mit Rückfallgefahr sind möglich. Ebenso kann es sein, dass bei Personen, die wieder mit dem Rauchen beginnen, die Dosierung entsprechend angepasst werden muss.[189][192] Die verändernden Wirkungen sind auf Verbindungen im Tabakrauch und nicht auf Nikotin zurückzuführen; Der Einsatz einer Nikotinersatztherapie hat daher die gleiche Wirkung wie eine Raucherentwöhnung, und es wäre weiterhin eine Überwachung erforderlich.[189]
Um 30 Zu 50 Prozent der Menschen mit Schizophrenie akzeptieren nicht, dass sie eine Krankheit haben oder halten sich nicht an die empfohlene Behandlung.[193] For those who are unwilling or unable to take medication regularly, long-acting injections of antipsychotics may be used,[194] which reduce the risk of relapse to a greater degree than oral medications.[195] When used in combination with psychosocial interventions, they may improve long-term adherence to treatment.[196]
Research findings suggested that other neurotransmission systems, including serotonin, glutamate, GABA, and acetycholine, were implicated in the development of schizophrenia, and that a more inclusive medication was needed.[191] A new first-in-class antipsychotic that targets multiple neurotransmitter systems called lumateperone (ITI-007), was trialed and approved by the FDA in December 2019 for the treatment of schizophrenia in adults.[191][197][198] Lumateperone is a small molecule agent that shows improved safety, and tolerance. It interacts with dopamine, Serotonin, and glutamate in a complex, uniquely selective manner, and is seen to improve negative and positive symptoms, and social functioning.[199] Lumateperone was also found to reduce potential metabolic dysfunction, have lower rates of movement disorders, and have lower cardiovascular side effects such as a fast heart rate.[191]
Side effects
Typical antipsychotics are associated with a higher rate of movement disorders including akathisia. Some atypicals are associated with considerable weight gain, diabetes and the risk of metabolic syndrome.[200] Risperidon (atypical) has a similar rate of extrapyramidal symptoms to haloperidol (typical).[200] A rare but potentially lethal condition of neuroleptic malignant syndrome (NMS) has been associated with the use of antipsychotics. Through its early recognition, and timely intervention rates have declined. Jedoch, an awareness of the syndrome is advised to enable intervention.[201] Another less rare condition of tardive dyskinesia can occur due to long-term use of antipsychotics, developing after many months or years of use. It is more often reported with use of typical antipsychotics.[202]
Clozapine is associated with side effects that include weight gain, tiredness, and hypersalivation. More serious adverse effects include seizures, NMS, neutropenia, and agranulocytosis (lowered white blood cell count) and its use needs careful monitoring.[203][204] Studies have found that antipsychotic treatment following NMS and neutropenia may sometimes be successfully rechallenged (restarted) with clozapine.[205][206]
Clozapine is also associated with thromboembolism (including pulmonary embolism), Myokarditis, and cardiomyopathy.[207][208] A systematic review of clozapine-associated pulmonary embolism indicates that this adverse effect can often be fatal, and that it has an early onset, and is dose-dependent. The findings advised the consideration of using a prevention therapy for venous thromboembolism after starting treatment with clozapine, and continuing this for six months.[208] Constipation is three times more likely to occur with the use of clozapine, and severe cases can lead to ileus and bowel ischemia resulting in many fatalities.[203]
Jedoch, the risk of serious adverse effects from clozapine is low, and there are the beneficial effects to be gained of a reduced risk of suicide, and aggression.[209][210] Typical antipsychotics and atypical risperidone can have a side effect of sexual dysfunction.[86] Clozapine, olanzapine, and quetiapine are associated with beneficial effects on sexual functioning helped by various psychotherapies.[211] Unwanted side effects cause people to stop treatment, resulting in relapses.[212]
Treatment resistant schizophrenia
About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.[213] Jedoch, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment resistant schizophrenia (TRS), and clozapine will be offered.[214][30] Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.[28][86][215] Zwischen 12 Und 20 per cent will not respond to clozapine and this group is said to have ultra treatment resistant schizophrenia.[214][216] ECT may be offered to treat TRS as an add-on therapy, and is shown to sometimes be of benefit.[216] A review concluded that this use only has an effect on medium-term TRS and that there is not enough evidence to support its use other than for this group.[217]
TRS is often accompanied by a low quality of life, and greater social dysfunction.[218] TRS may be the result of inadequate rather than inefficient treatment; it also may be a false label due to medication not being taken regularly, or at all.[210] Um 16 per cent of people who had initially been responsive to treatment later develop resistance. This could relate to the length of time on APs, with treatment becoming less responsive.[219] This finding also supports the involvement of dopamine in the development of schizophrenia.[210] Studies suggest that TRS may be a more heritable form.[220]
TRS may be evident from first episode psychosis, or from a relapse. It can vary in its intensity and response to other therapies.[218] This variation is seen to possibly indicate an underlying neurobiology such as dopamine supersensitivity (DSS), glutamate or serotonin dysfunction, inflammation and oxidative stress.[214] Studies have found that dopamine supersensitivity is found in up to 70% of those with TRS.[221] The variation has led to the suggestion that treatment responsive and treatment resistant schizophrenia be considered as two different subtypes.[214][220] It is further suggested that if the subtypes could be distinguished at an early stage significant implications could follow for treatment considerations, and for research.[216] Neuroimaging studies have found a significant decrease in the volume of grey matter in those with TRS with no such change seen in those who are treatment responsive.[216] In those with ultra treatment resistance the decrease in grey matter volume was larger.[214][216]
A link has been made between the gut microbiota and the development of TRS. The most prevalent cause put forward for TRS is that of mutation in the genes responsible for drug effectiveness. These include liver enzyme genes that control the availability of a drug to brain targets, and genes responsible for the structure and function of these targets. In the colon the bacteria encode a hundred times more genes than exist in the human genome. Only a fraction of ingested drugs reach the colon, having been already exposed to small intestinal bacteria, and absorbed in the portal circulation. This small fraction is then subject to the metabolic action of many communities of bacteria. Activation of the drug depends on the composition and enzymes of the bacteria and of the specifics of the drug, and therefore a great deal of individual variation can affect both the usefulness of the drug and its tolerability. It is suggested that parenteral administration of antipsychotics would bypass the gut and be more successful in overcoming TRS. The composition of gut microbiota is variable between individuals, but they are seen to remain stable. Jedoch, phyla can change in response to many factors including ageing, diet, substance use, and medications – especially antibiotics, laxatives, and antipsychotics. In FEP, schizophrenia has been linked to significant changes in the gut microbiota that can predict response to treatment.[222]
Psychosocial interventions
Weitere Informationen: Management of schizophrenia § Psychosocial
A number of psychosocial interventions that include several types of psychotherapy may be useful in the treatment of schizophrenia such as: family therapy,[223] group therapy, cognitive remediation therapy,[224] cognitive behavioral therapy, and metacognitive training.[225] Skills training, and help with substance use, and weight management– often needed as a side effect of an antipsychotic, are also offered.[226] In the US, interventions for first episode psychosis have been brought together in an overall approach known as coordinated speciality care (CSC) and also includes support for education.[36] In the UK care across all phases is a similar approach that covers many of the treatment guidelines recommended.[34] The aim is to reduce the number of relapses and stays in hospital.[223]
Other support services for education, employment, and housing are usually offered. For people suffering from severe schizophrenia, and discharged from a stay in hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.[227][228] Another more intense approach is known as intensive care management (ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that ICM improves many of the relevant outcomes including social functioning.[229]
Some studies have shown little evidence for the effectiveness of cognitive behavioral therapy (CBT) in either reducing symptoms or preventing relapse.[230][231] Jedoch, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and has been recommended in Canada, but it has been seen here to have no effect on social function, relapse, or quality of life.[232] In the UK it is recommended as an add-on therapy in the treatment of schizophrenia, but is not supported for use in treatment resistant schizophrenia.[231][233] Arts therapies are seen to improve negative symptoms in some people, and are recommended by NICE in the UK.[184][234] This approach however, is criticised as having not been well-researched, and arts therapies are not recommended in Australian guidelines for example.[234][235][236] Peer support, in which people with personal experience of schizophrenia, provide help to each other, is of unclear benefit.[237]
Other
Exercise including aerobic exercise has been shown to improve positive and negative symptoms, Erkenntnis, working memory, and improve quality of life.[238][239] Exercise has also been shown to increase the volume of the hippocampus in those with schizophrenia. A decrease in hippocampal volume is one of the factors linked to the development of the disease.[238] Jedoch, there still remains the problem of increasing motivation for, and maintaining participation in physical activity.[240] Supervised sessions are recommended.[239] In the UK healthy eating advice is offered alongside exercise programs.[241]
An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of folate, and vitamin D are linked to the risk factors for the development of schizophrenia and for early death including heart disease.[242][243] Those with schizophrenia possibly have the worst diet of all the mental disorders. Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis.[242] The use of supplemental folate is recommended.[244] A zinc deficiency has also been noted.[245] Vitamin B12 is also often deficient and this is linked to worse symptoms. Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits.[242] It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of probiotics.[245]
Violence
Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators.[7] Schizophrenic people are commonly exploited and victimized by violent crime as part of a broader dynamic of social exclusion.[26][27] People diagnosed with schizophrenia are also subject to forced drug injections, seclusion and restraint, at high rates.[31][32]
The risk of violence by schizophrenic people is small. There are minor subgroups where the risk is high.[165] This risk is usually associated with a comorbid disorder such as a substance use disorder – in particular alcohol, or with antisocial personality disorder.[165] Substance use disorder is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in theory of mind impairments.[246][247] Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence.[248] These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence.[249][250]
A review in 2012 hat das gezeigt 6 percent of people convicted of homicide in Western countries had been diagnosed as schizophrenic.[249] Another wider review put the figure at between 5 Und 20 percent.[251] People convicted of homicide were found more likely to have committed it during first episode psychosis, and this accounted for 38.5 percent (of the 5 Zu 20 percent of perpetrators who were diagnosed schizophrenic, so 2 Zu 7.7 percent of perpetrators total.)[251] The association between schizophrenia and violence is complex. Homicide is linked with young age, male sex, a history of violence, and a stressful event in the preceding year. Clinical risk factors are severe untreated psychotic symptoms – untreated due to either not taking medication or to the condition being treatment resistant.[249] A comorbid substance use disorder or an antisocial personality disorder increases the risk for homicidal behaviour by 8-fold, in contrast to the 2-fold risk in those without the comorbid disorders.[165] Rates of homicide linked to psychosis are similar to those linked to substance misuse, and parallel the overall rate in a region.[252] What role schizophrenia has on violence independent of substance misuse is controversial, but certain aspects of individual histories or mental states may be factors.[253]
Hostility is anger felt and directed at a person or group and has related dimensions of impulsiveness and aggression. When this impulsive aggression is evident in schizophrenia neuroimaging has suggested the malfunctioning of a neural circuit that modulates hostile thoughts and behaviours that are linked with negative emotions in social interactions. This circuit includes the amygdala, Striatum, prefrontal cortex, anterior cingulate cortex, insula, and hippocampus. Hostility has been reported during acute psychosis, and following hospital discharge.[254] There is a known association between low cholesterol levels, und Impulsivität, and violence. A review finds that people with schizophrenia, and lower cholesterol levels are four times more likely to instigate violent acts. This association is also linked to the increased number of suicides in schizophrenia. It is suggested that cholesterol levels could serve as a biomarker for violent and suicidal tendencies.[255]
A review found that just under 10 percent of those with schizophrenia showed violent behaviour compared to 1.6 percent of the general population. An excessive risk of violence is associated with drugs or alcohol and increases the risk by as much as 4-fold. Violence often leads to imprisonment. Clozapine is an effective medication that can be used in penal settings such as prisons. Jedoch, a condition of benign ethnic neutropenia in many African-Americans excludes them from the use of clozapine the most effective medication. Cognitive deficits are recognised as playing an important part in the origin and maintenance of aggression, and cognitive remediation therapy may therefore help to prevent the risk of violence in schizophrenia.[248]
Prognosis
Schizophrenia has great human and economic costs.[5] It results in a decreased life expectancy of 20 Jahre.[4][10] This is primarily because of its association with obesity, poor diet, a sedentary lifestyle, and smoking, with an increased rate of suicide playing a lesser role.[10][256] Side effects of antipsychotics may also increase the risk.[10] These differences in life expectancy increased between the 1970s and 1990s.[257] An Australian study puts the rate of early death at 25 Jahre, and views the main cause to be related to heart disease.[207]
Several studies indicate that almost 40% of those with schizophrenia die from complications of cardiovascular disease including heart attacks, and sudden cardiac death which is seen to be increasingly associated.[243] An underlying factor of sudden cardiac death may be Brugada syndrome (BrS) – BrS mutations that overlap with those linked with schizophrenia are the calcium channel mutations.[243] BrS may also be drug-induced from certain antipsychotics and antidepressants.[243] Primary polydipsia, or excessive fluid intake, is relatively common in people with chronic schizophrenia.[258][259] This may lead to hyponatremia which can be life-threatening. Antipsychotics can lead to a dry mouth, but there are several other factors that may contribute to the disorder. It is suggested to lead to a reduction in life expectancy by 13 per cent.[259] A study has suggested that real barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, Stress, stigma, and medication side effects, and that these need to be changed.[260]
Schizophrenia is a major cause of disability. In 2016 it was classed as the 12th most disabling condition.[261] Etwa 75% of people with schizophrenia have ongoing disability with relapses[262] Und 16.7 million people globally are deemed to have moderate or severe disability from the condition.[263] Some people do recover completely and others function well in society.[264] Most people with schizophrenia live independently with community support.[28] Um 85% are unemployed.[5] In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.[265] Males are affected more often than females, and have a worse outcome.[266] But according to some reports, there is no difference in prevalence.[20][21] Outcomes for schizophrenia appear better in the developing than the developed world.[267] These conclusions have been questioned.[268] Social problems, such as long-term unemployment, Armut, Obdachlosigkeit, Ausbeutung, stigmatization and victimization are common consequences, and lead to social exclusion.[26][27]
There is a higher than average suicide rate associated with schizophrenia estimated at around 5% Zu 6%, most often occurring in the period following onset or first hospital admission.[11][29] Several times more (20 Zu 40%) attempt suicide at least once.[7][269] There are a variety of risk factors, including male gender, Depression, a high IQ,[269] heavy smoking,[270] and substance use.[117] Repeated relapse is linked to an increased risk of suicidal behavior.[179] The use of clozapine can reduce the risk of suicide and aggression.[210]
A strong association between schizophrenia and tobacco smoking has been shown in worldwide studies.[271][272] Smoking is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 Zu 90% being regular smokers, as compared to 20% of the general population.[272] Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content.[39] Some propose that this is in an effort to improve symptoms.[273] Among people with schizophrenia use of cannabis is also common.[117]
Epidemiology
Hauptartikel: Epidemiology of schizophrenia
In 2017, the Global Burden of Disease Study estimated there were 1.1 million new cases, and in 2019 WHO reported a total of 20 Millionen Fälle weltweit.[2][19] Schizophrenia affects around 0.3–0.7% of people at some point in their life.[18] It occurs 1.4 times more frequently in males than females and typically appears earlier in men[86] – the peak ages of onset are 25 years for males and 27 years for females.[274] Onset in childhood, vor dem Alter von 13 can sometimes occur.[7][71] Other reviews find no difference in the prevalence of schizophrenia between the sexes.[20][21] A later onset can occur between the ages of 40 Und 60, known as late onset, and also after 60 known as very late onset.[62]
Worldwide, schizophrenia is the most common psychotic disorder.[74] The frequency of schizophrenia varies across the world,[7][275] within countries,[276] and at the local and neighborhood level.[277] This variation has been estimated to be fivefold.[5] It causes approximately one percent of worldwide disability adjusted life years[86] and resulted in 17,000 deaths in 2015.[12]
In 2000, the World Health Organization found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.[278] Um 1.1% of adults have schizophrenia in the United States.[279] Jedoch, in areas of conflict this figure can rise to between 4.0 Und 6.5%.[280]
Geschichte
Der Begriff „schizophrenia“ was coined by Eugen Bleuler.
Accounts of a schizophrenia-like syndrome are rare in records before the 19th century. The earliest cases detailed were reported in 1797, Und 1809.[281] Dementia praecox, meaning premature dementia was used by German psychiatrist Heinrich Schüle in 1886, and then in 1891 by Arnold Pick in a case report of hebephrenia. In 1893 Emil Kraepelin used the term in making a distinction, known as the Kraepelinian dichotomy, between the two psychoses – dementia praecox, and manic depression (now called bipolar disorder).[10] Kraepelin believed that dementia praecox was probably caused by a systemic disease that affected many organs and nerves, affecting the brain after puberty in a final decisive cascade.[282] It was thought to be an early form of dementia, a degenerative disease.[10] When it became evident that the disorder was not degenerative it was renamed schizophrenia by Eugen Bleuler in 1908.[283]
The word schizophrenia translates as „splitting of the mind“ and is Modern Latin from the Greek roots schizein (σχίζειν, „to split“) and phrēn, (φρεν, „mind“)[284] Its use was intended to describe the separation of function between personality, thinking, Erinnerung, and perception.[283]
The term schizophrenia used to be associated with split personality by the general population but that usage went into decline when split personality became known as a separate disorder, first as multiple identity disorder , and later as dissociative identity disorder.[285] In 2002 in Japan the name was changed to integration disorder, and in 2012 in South Korea, the name was changed to attunement disorder.[28][286][287]
A molecule of chlorpromazine, the first antipsychotic developed in the 1950s.
In the early 20th century, the psychiatrist Kurt Schneider listed the psychotic symptoms of schizophrenia into two groups of hallucinations, and delusions. The hallucinations were listed as specific to auditory, and the delusional included thought disorders. These were seen as the symptoms of first-rank importance and were termed first-rank symptoms. Whilst these were also sometimes seen to be relevant to the psychosis in manic-depression, they were highly suggestive of schizophrenia and typically referred to as first-rank symptoms of schizophrenia. The most common first-rank symptom was found to belong to thought disorders.[288][289] In 2013 the first-rank symptoms were excluded from the DSM-5 criteria.[163] First-rank symptoms are seen to be of limited use in detecting schizophrenia but may be of help in differential diagnosis.[290]
Before the 1960s, doctors in America primarily diagnosed nonviolent petty criminals and women with schizophrenia, categorizing the latter as ill for not performing their duties within patriarchy as wives and mothers. Official descriptions emphasized the „calm“ nature of such persons. Jedoch, in the mid-to-late 1960s, psychiatrists began diagnosing black men as schizophrenic at much higher rates, often citing their civil rights and Black Power activism as delusions, and categorizing them as „hostile and aggressive.“[291][292]
From the 1960s until 1989, psychiatrists in the USSR and Eastern Bloc diagnosed thousands of people with sluggish schizophrenia,[293][294][295] based on „the assumption that symptoms would later appear,“[296] weil der Entzug der gesetzlichen Rechte behinderter Menschen es zu einer bequemen Möglichkeit machte, politische Dissidenten einzusperren.[297] Die träge Schizophrenie-Diagnose wurde diskreditiert und international verurteilt.[298]
Psychiater führten bei vielen der ersten Menschen, bei denen sie eine Schizophrenie diagnostizierten, psychochirurgische Eingriffe durch. Hierbei handelte es sich insbesondere um Frontallobotomien, die in den 1930er bis 1970er Jahren in den Vereinigten Staaten durchgeführt wurden, und bis in die 1980er Jahre in Frankreich, Dazu gehört entweder die Entfernung von Hirngewebe aus verschiedenen Regionen oder die Durchtrennung von Leitungsbahnen,[299] mittlerweile weithin als schwerwiegende Menschenrechtsverletzung anerkannt.[299][300] In den 1930er Jahren wurden eine Reihe von Schockbehandlungen eingeführt, die Anfälle auslösten (Krämpfe) oder Komas.[301] Bei der Insulinschocktherapie wurden große Dosen Insulin gespritzt, um ein Koma auszulösen, which in turn produced hypoglycemia and convulsions.[301][300] The use of electricity to induce seizures was developed, and in use as electroconvulsive therapy (ECT) von 1938.[302] Stereotactic surgeries were developed in the 1940s.[302] In the mid-1950s scientists developed and introduced the first typical antipsychotic, chlorpromazine.[303] In the 1970s the first atypical antipsychotic clozapine, was introduced followed by the introduction of others.[304]
In the early 1970s in the US, the diagnostic model used for schizophrenia was broad and clinically based using DSM II. It had been noted that schizophrenia was diagnosed far more in the US than in Europe which had been using the ICD-9 criteria. The US model was criticised for failing to demarcate clearly those people with a mental illness, and those without. In 1980 DSM III was published and showed a shift in focus from the clinically-based biopsychosocial model to a reason-based medical model.[305] DSM IV showed an increased focus to an evidence-based medical model.[306]
Subtypes of schizophrenia classified as paranoid, disorganized, catatonic, undifferentiated, and residual type were difficult to distinguish between and are no longer recognized as separate conditions by DSM-5 (2013)[307] or ICD-11.[308][309][310]
Society and culture
John Nash, an American mathematician and joint recipient of the 1994 Nobel Memorial Prize in Economic Sciences, der an Schizophrenie litt. His life was the subject of the 1998 book, A Beautiful Mind by Sylvia Nasar.
In 2002, the term for schizophrenia in Japan was changed from seishin-bunretsu-byō (精神分裂病, lit. „mind-split disease“) to tōgō-shitchō-shō (統合失調症, lit. „integration-dysregulation syndrome“) to reduce stigma.[311] The new name also interpreted as „integration disorder“ was inspired by the biopsychosocial model; it increased the percentage of people who were informed of the diagnosis from 37 Zu 70% over three years.[286] A similar change was made in South Korea in 2012 to attunement disorder.[287] A professor of psychiatry, Jim van Os, has proposed changing the English term to psychosis spectrum syndrome.[312] In 2013 with the reviewed DSM-5, the DSM-5 committee was in favor of giving a new name to schizophrenia but they referred this to WHO.[313]
In the United States, the cost of schizophrenia – including direct costs (outpatient, inpatient, Drogen, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated to be $62.7 billion in 2002.[314] In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital and social care, and treatment.[5]
The book A Beautiful Mind chronicled the life of John Forbes Nash who had been diagnosed with schizophrenia and went on to win the Nobel Memorial Prize in Economic Sciences. This was later made into the film with the same name. An earlier documentary was made with the title A Brilliant Madness.
In 1964 a lengthy case study of three males diagnosed with schizophrenia who each had the delusional belief that they were Jesus Christ was published as a book. This has the title of The Three Christs of Ypsilanti, and a film with the title Three Christs was released in 2020. Such religious delusions are a fairly common feature in psychoses including schizophrenia.[315][316]
Media coverage relating to violent acts by people with schizophrenia reinforces public perception of an association between schizophrenia and violence.[317] Such sensationalist reporting stigmatizes schizophrenia more than any other mental illness.[318] In the UK guidelines are given for the reporting of different conditions. Its campaigns have shown a reduction in negative reporting.[318][319]
Research directions
A 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).[321] Most studies focus on transcranial direct-current stimulation (tDCM), and repetitive transcranial magnetic stimulation (rTMS).[322] Techniques based on focused ultrasound for deep brain stimulation could provide insight for the treatment of AVHs.[322]
An active area of research as of 2020 is the study of potential biomarkers that would help in diagnosis and treatment of schizophrenia. Possible biomarkers include markers of inflammation,[323] neuroimaging,[324] brain-derived neurotrophic factor (BDNF),[325] and speech analysis. Some inflammatory markers such as C-reactive protein are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.[326] Deficits in sleep spindles in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.[167] MicroRNAs are highly influential in early neuronal development, and their disruption is implicated in several CNS disorders; circulating microRNAs (cimiRNAs) are found in body fluids such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.[327][328]
