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Il disturbo Schizoaffettivo implicazioni cliniche trattamento

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									Il disturbo Schizoaffettivo:
         criteri diagnostici e
                  trattamento
           Prof. Mauro Mauri
            Clinica Psichiatrica
            Università di Pisa
Doschizoaffective disorders
exist all?
   More than 100 years ago Kraepelin proposed a very
    pratical and persuasive solution to a longstanding
    problem in clinical psychiatry.
   To reduce heterogeneity by splitting the perplexing
    variety of psychopatological signs and symptoms, of
    patterns of deviant behavior and experiences, of short-
    and long-term course and outcome of functional
    disturbances into two major groups:
        Dementia Praecox
        Manic-depressive illness

                          Acta Psychiatr Scand 2006: 13:369-371. Editorial
   In this way, he created the so-called
    ‘Kraepelinian dichotomy’, which turned out to
    be clinically useful for subsequent decades.
   However,       he    himself   got    skeptical
    subsequently if this simplistic solution really
    worked in pratice as the number of ‘cases
    in-between’ were too numerous.


Do schizoaffective disorders exist all? Acta Psychiatr Scand 2006: 13:369-371. Editorial
Schizoaffective Disorders

   In 1933, Kasanin first coined this
    term…




Do schizoaffective disorders exist all? Acta Psychiatr Scand 2006: 13:369-371. Editorial
   About 70 years ago, the concept of
    schizoaffective disorders emerged
    from difficulties in practicing
    Kraepelin’s dichotomy by separating
    schizophrenia and affective
    disorders.



Do schizoaffective disorders exist all? Acta Psychiatr Scand 2006: 13:369-371. Editorial
 Schizoaffective Disorders
 Although originally related to ‘reactive
  psychoses’ in the Scandinavian tradition, the
  term became transformed to indicate the
  intraindividual co-occurrence of both severe
  affective as well as severe psychotic
  syndromes, which did not fit in either of
  Kraepelin’s categories.



Langfeldt G. The prognosis in schizophrenia and the factors influencing the course of
the disease. Acta Psychiatr Neurol Scand 1937; Suppl. 13:1–228.
    Schizoaffective Disorders

   The widespread use of this term reflected
    the clinical need to consider border-cases
    separately.
   Many clinicians are probably motivated to
    use this category because of implications
    on the course of Illness.




Do schizoaffective disorders exist all? Acta Psychiatr Scand 2006: 13:369-371. Editorial
Orientamenti attuali
Le evidenze empiriche attualmente
 disponibili sembrano indicare che i disturbi
 schizoaffettivi costituiscono un gruppo
 eterogeneo di condizioni morbose.

Non ha senso affermare che essi, nel loro
 complesso, rappresentino sempre delle
 varianti della schizofrenia, oppure delle
 varianti dei disturbi affettivi maggiori,
 oppure una terza psicosi.
   Definizione

L’espressione ―disturbo schizoaffettivo‖(1) può essere usata
  per identificare l’una e/o l’altra delle seguenti situazioni
  cliniche:
 Comparsa successiva e indipendente di una sindrome
  affettiva e di una schizofrenica (dist. schizoaffettivo tipo I)
 Comparsa contemporanea, nel medesimo episodio, di una
  sintomatologia di tipo affettivo e una di tipo schizofrenico
  (dist. schizoaffettivo tipo II).



                                         Maj e Perris, 1985
I Disturbi Schizoaffettivi:
Modelli Teorici
1.Varietà atipiche della schizofrenia
2.Varietà atipiche dei disturbi
  affettivi maggiori
3.Terza Psicosi
4.Continuum Psicotico
5.Manifestarsi contemporaneo di
  schizofrenia e di un disturbo
  affettivo maggiore.
Modelli interpretativi dei Disturbi
Schizoaffettivi
Modello Binario o   I disturbi schizoaffettivi sono sempre
dicotomico neo-       varietà atipiche della schizofrenia o
 kraepeliniano           dei disturbi affettivi maggiori


  Modello della        Almeno una parte dei disturbi
  terza psicosi      schizoaffettivi costituisce un’entità
                    nosografica distinta dalla schizofrenia
                       e dai disturbi affettivi maggiori

  Modello del        I disturbi schizoaffettivi occupano la
  continuum         parte intermedia di uno spettro ai cui
   psicotico        estremi si pongono le forme tipiche di
                       schizofrenia e di disturbo affettivo
                                    maggiore
 Ilproblema della natura dei
  disturbi schizoaffettivi e dei loro
  rapporti con la schizofrenia e
  con i disturbi affettivi maggiori è
  tuttora controverso.
Schizophrenia Spectrum
…Schizophrenia Spectrum almost
certainly includes schizoaffective
disorders (and) should probably
also include at least the psychotic
forms of mania and depression.

                           (Andreasen, 1995)
I sistemi nosografici hanno
proposto nel tempo criteri ora
rigidi e restrittivi, ora ampi e
comprensivi, senza raggiungere
una delimitazione accettabile sul
piano psicopatologico e clinico.
                          (TSUANG e LOYD, 1986)
Seppure gli estensori delle varie
edizioni del DSM abbiano inteso
segnare confini netti tra psicosi
bipolare e schizofrenica, il
problema rimane irrisolto con le
sue caratteristiche storiche.
Spectrum of Endogenous
Psychoses
                    Endogenous Psychoses




     Affective         Schizoaffective     Schizophrenia
    Psychoses             Disorder




  Bipolar Psychotic Bipolar   Depressive Depressive Negative
  Disorder Depression Type      Type      Episodes    Sxs




                                                    After Kraepelin E, 1921
              Schizophrenia with
               Bipolar Spectrum




             Bipolar Spectrum with
               Psychotic Features

Schizophrenia Spectrum (H.Y. Meltzer, 1995)
Schizophrenia Spectrum
   Schizophrenia
   Schizoaffective Disorder
   Bipolar Psychotic Disorder
   Psychotic Depression
   Schizophreniform Disorder
   Schizotypal Personality Disorder
   Schizoid Personality Disorder
   Paranoid Personality Disorder
                                       Meltzer, 1996
     Bipolar-Schizophrenia continuum
     Manic-depression and schizophrenia are 2 distinct
      disorders. (Kraepelin’s)
     Proponents of the bipolar continuum theory support the
      concept of an expanded psychiatric continuum ranging
      from unipolar to bipolar disorder, to schizoaffective
      psychosis, all the way to schizophrenia.
     Much of the evidence supporting the continuum
      concept is based upon genetic, biochemical, and
      pharmacologic findings.

Hans-Jürgen Möller, M.D Bipolar Disorder and Schizophrenia: Distinct Illnesses or
a Continuum? (J Clin Psychiatry 2003;64[suppl 6]:23–27)
Continuum Psicotico


Il tentativo di tracciare una linea di
demarcazione genetica tra disturbi
schizofrenici e disturbi affettivi è
fallito.


                               Crow, 1990
Family linkage studies

•Clinical, familial, and, more recently,
 genetic linkage studies suggest that
 overlapping genetic susceptibility might
 contribute to both schizophrenia and
 bipolar disorder.

Franck Schürhoff, M.D. et al.,Familial Aggregation of Delusional Proneness in Schizophrenia
and Bipolar Pedigrees (Am J Psychiatry 2003; 160:1313–1319)
Family linkage studies

• Overlap between bipolar disorder and schizophrenia has long been noted
  clinically. About 9% of people with schizophrenia have manic syndromes and
  25% have depressive syndromes psychotic symptoms—hallucinations and
  delusions—occur in 58% of people with bipolar I disorder. The existence of a
  diagnostic category incorporating elements of mood disorder and
  schizophrenia—schizoaffective disorder—reflects the difficulty that occasionally
  arises in distinguishing the two illnesses. Evidence for overlapping heritability of
  bipolar disorder and schizophrenia has emerged from genetic epidemiologic
  studies



James B. Potash, Suggestive Linkage to Chromosomal Regions 13q31and 22q12 in Families With
Psychotic Bipolar Disorder (Am J Psychiatry 2003; 160:680–686)
…la mappatura di regioni “sospette” evidenzia una
sovrapposizione     delle   regioni   di    linkage   per     la
Schizofrenia e i Disturbi Affettivi… questi risultati fanno
ipotizzare l’esistenza di geni condivisi da entrambi i
disturbi e la possibilità che questi geni possano
contribuire alle basi molecolari delle psicosi funzionali.



                                           Wildenauer, 1999
This notion is supported by various independent findings.

High degree of genetic transmissibility.Gene mapping for both
diseases is in its early stages, but certain susceptibility markers
appear to be located on the same chromosomes.

Bipolar disorder and schizophrenia also             demonstrate       some
similarities in neurotransmitter dysfunction.

As further indirect evidence of a possible association, many newer
atypical antipsychotic agents approved for the treatment of
schizophrenia are also proving useful for bipolar disorder.

Hans-Jürgen Möller, M.D Bipolar Disorder and Schizophrenia: Distinct
Illnesses or a Continuum? (J Clin Psychiatry 2003;64[suppl 6]:23–27)
Neuroanatomy
Various structural abnormalities have been found in imaging studies of
patients with bipolar disorder or schizophrenia, although none has yet
provided any clear answers regarding a possible relationship between the 2
disorders.
Ventricular enlargment
Prefrontal atrophy
Disgenesy of hippocampal structure
Glycocorticoid hypersecretion
Muscle-scheletal anomalies
Riduction of number of 5-HT 2 receptors
Altered eye movements
Cognitive deficits
…nonostante una ampia sovrapposizione delle anomalie
 strutturali nelle cosiddette psicosi endogene, la corteccia
 associativa, il sistema limbico e le strutture asimmetriche
 sono maggiormente coinvolte nella Schizofrenia, mentre
 lievi anomalie strutturali nei nuclei della base, specie nel
 nucleo accumbens e nell’area ipotalamica, potrebbero
 avere un ruolo cruciale nei Disturbi dell’Umore.


                                             Baumann, 1999
La diagnosi di schizofrenia
basata solo sui sintomi è
spesso erronea.


                     Pope & Lipinsky, 1978
Sebbene gli aspetti sintomatologici della
schizofrenia si collochino in primo piano
rispetto ad altre manifestazioni nell'esame del
quadro clinico globale, non emergono, alla luce
dei     più     recenti   contributi,    sintomi
patognomonici o combinazioni di sintomi in
grado di differenziare la malattia da altre
patologie di confine.
                                  (Clayton, 1986)
I confini della schizofrenia e
dei disturbi bipolari


'I sintomi della mania o degli stati
misti sono spesso simili a quelli
della schizofrenia; si tratta di
un'ampia zona di confine in cui la
diagnosi diviene incerta...'

                      Cassano & Mauri, 1990
    Sintomi Psicotici nella Mania

• Deliri             • Allucinazioni
   Grandiosità         Uditive
   Riferimento         Visive
   Persecuzione        Olfattive
   Somatici            Tattili
   Nichilistici
   Bizzarri         • Disturbi formali del pensiero
   Sistematizzati   • Sintomi di primo rango
                     • Catatonia
                                       (McElroy, 1995)
Episodi maniacali e sintomi
psicotici


   50% con almeno un delirio

   15% con almeno una allucinazione

   20% con     disturbi   formali   del
    pensiero

                    Goodwin and Jamison, 1990
Altrettanto erronea può essere
la diagnosi fondata sull'epoca,
sulla modalità di esordio,
sull'evoluzione sugli esiti.
 Number of Psychotic Symptoms as a function
 of Age at onset in Bipolar Patients

100
                                           >3 psychotic
80                                         symptoms

60                                         1-2 psychotic
                                           symptoms
40
                                           No psychotic
20                                         symptoms

0
      <20   20-29   30-39 =/>40   Age at onset of Bipolar Illness
                                            Rosen et al., 1993
Atypical and subthreshold forms                                       of
bipolarity in relation to age at onset
                                Ebephrenia like mania
Early Onset                     Abrupt & temporary psychomotor
(in childhood & adolescence)     agitation
                                Pseudo-conduct disorder mania



                                  Mild elation
                                  Marked exhaustibility of the
Late Onset                         manifestations
(in elderly)                      Partial symptomatology
                                  Prevalence of dysphoria over euphoria
                                  Paranoid content
Enduring deficit syndrome

Le modificazioni di personalità, il decorso
subcronico, la patologia intercritica persistente, il
decadimento       della   performance       sociale,
rappresentano aspetti comuni a disturbi mentali
diversi. Pertanto anche la specificità del criterio
centrato sulla sindrome deficitaria persistente, è
in discussione.
Patologia affettiva e Schizofrenia

…la patologia affettiva è esclusa dalla
 schizofrenia sulla base di un arbitrario
 approccio gerarchico; gli aspetti di
 decorso e di durata sono stabiliti in
 modo del tutto convenzionale.

                                CARSON, 1984
Settanta anni dopo Bleuler siamo ancora
incapaci di affermare con sicurezza che
la schizofrenia rappresenta un'entità
unitaria, o più precisamente che i
comportamenti convenzionalmente
associati con questo termine derivano da
un unico nucleo o deficit.

                                 Carson, 1984
Rapporti tra diagnosi e trattamento

 L’ impiego di una categoria
  diagnostica è in rapporto alla
  disponibilità di trattamenti efficaci.
 L’area di un disturbo mentale tende
  pertanto ad espandersi o a ridursi.
   Due disturbi distinti ?


Due aspetti sindromici dello
     stesso disturbo?
   On a clinical level the overlap between
    the sindromes of schizophrenia and
    affective disorders are too broad to be
    captured by the intermediate diagnosis of
    schizoaffective disorders.


                    Acta Psychiatr Scand 2006: 13:369-371. Editorial
   In contrast to its clinical popularity, research
    investigations in this diagnostic category -
    although operational definitions became
    available - remained relatively rare as it
    becomes from a PubMed search (search terms
    in titles: schizoaffective disorder =230 citations;
    schizophrenia =13.297; bipolar disorder =2.355;
    during a 10-year period 1995-2005).


                          Acta Psychiatr Scand 2006: 13:369-371. Editorial
   The diagnosis ‘schizoaffective disorder’
    has not yet been unequivocally defined
    after more than 70 years.




                    Acta Psychiatr Scand 2006: 13:369-371. Editorial
   It is more appropriate to integrate
    categorical diagnostic concepts with
    dimensions: a psychotic, a manic
    and a depressive one, which allows
    graduations and overlaps.



                     Acta Psychiatr Scand 2006: 13:369-371. Editorial
    Treatment of schizoaffective
    disorders
                     Condition                                                             Treatment
                  Acute Episodes
    Mainly affective episodes
    Schizomanic (-bipolar)                                  Li, antipsychotics (when highly excited)
    Schizodepressive                                        Antidepressants, Antipsychotics (Olz, Ris, Zip.)
    Mainly schizophrenic
    Schizomanic                                             Antipsychotics
    Schizodepressive                                        Antipsychotics, ECT
             Long-Term Treatment
    Mainly affective
    Schizobipolar                                           Li, Carbamazepine
    Schizodepressive                                        Carbamazepine, Li
    Mainly schizophrenic
    Schizobipolar                                           Antipsychotics (Olz)
    Schizodepressive                                        Antipsychotics
Maj M, Perris C. Patterns of course in patients with a cross-sectional diagnosis of schizoaffective disorder. J Affect Disord. 1990 Oct;20(2):71-7.
    Treatment of schizoaffective
    disorders: Acute Episodes
 For mainly affective schizomanic
  episodes lithium and antipsychotics are
  the best evaluated medications and
  should be the first line treatment. In highly
  excited schizomanic syndromes
  antipsychotics are superior to lithium.
 In mainly schizophrenic schizomania
  antipsychotics are probably the best
  choice, although there are only few data.
    Treatment of schizoaffective
    disorders: Acute Episodes
   A difficult to treat condition is the schizodepressed
    syndrome. Predominantly affective schizodepressed
    episodes might benefit from treatment with
    antidepressant or antipsychotics.
   Olanzapine, risperidone and ziprasidone promising
    results with regards to schizodepression have to be
    viewed as preliminary with regard to schizoaffective
    disorder.
   Electroconvulsive therapy has not been sufficiently
    studied in this sub-group. However, given its efficacy in
    major depression and in schizophrenia it might be a
    promising treatment option.
    Treatment of schizoaffective
    disorders: long-term treatment
   First choice for predominantly affective schizobipolar patients is
    lithium. Carbamazepine was as effective as lithium in one RCT but
    is less well studied.
   From one RCT, however, it appears that carbamazepine might be
    superior to lithium in the sub-group of mainly affective
    schizodepressive patients.
   A family history of bipolar disorder and pronounced suicidality also
    supports lithium. This, however, is an analogy to bipolar disorder
    and has not been shown for SAD.
   In pts with mainly schizophrenic SAD antipsychotics are the long-
    term treatment of choice and, in the absence of sufficient data,
    treatment decision have to be made in analogy to schizphrenia.
         Treatment of schizoaffective
         disorders: long-term treatment
        For SAD, olanzapine is the only drug has been tested in a RCT in
         long-term treatment. From observational studies there are
         encouraging results for the use of clozapine in SAD long-term
         treatment.
        Combination treatment is increasingly common (1). However, it has
         not been well studied (2). For SAD, therefore, combination should
         be deployed only after monoterapy fails.
        Combination of lithium and haloperidol(3) as well as lithium and
         carbamazepine(4) have been reported to be safe and affective.

    1)     Kupfer et al. Demographic and clinical characteristics of individuals in a bipolar disorder case
           registry. J Clin Psychiatry. 2002 Nov;63(11):1045-6
    2)     Baethge C et al. Long-term combination therapy versus monotherapy with lithium and
           carbamazepine in 46 bipolar I patients.J Clin Psychiatry. 2005 Feb;66(2):174-82
    3)     Lowe MR and Batchelor DH. Lithium and neuroleptics in the management of manic depressive
           psychosisHuman psychopharmacology, 5, 267-74
    4)     Bocchetta A.Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective study
           on long-term prophlyactic effectiveness. Clin Psychopharmacol. 1997 Apr;17(2):92-6.
Conclusion
   … ‘patients with schizoaffective disorders in
    their majority have in fact a different social
    adaption, a different symptomatology, and a
    different prognosis than pure schizophrenic
    patients. It is useful for the physician and it is a
    hope for the patient to know that. A useful
    clinical diagnosis which concerns millions of
    people can not be abandoned in favour of
    permanently changing theoretical concepts’.

        A. Marneros: Letters to the Editor. Acta Psychiatr Scand 2007: 115: 162–165

								
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