Schizoaffective DisorderOver the decades, these patients were often classifi ed as havingatypical schizophrenia, good prognosis schizophrenia, remittingschizophrenia, or cycloid psychosis. Inherent within these diagnoseswas the implication that they shared similarities to schizophreniaand also appeared to have a relatively better course ofillness. With the advent of effective treatment of bipolar disorderwith lithium salts, some of these patients started respondingto lithium, and the term schizoaffective disorder gained furthermomentum and evolved in the direction of bipolar disorder. Unfortunately,this lack of diagnostic clarity has plagued the diagnosisof schizoaffective disorder such that there is much that isunknown about the illness.EpidemiologyThe diagnosis of schizoaffective disorder has undergone numerouschanges through the decades making it diffi cult to get reliableepidemiology information. When data was pooled togetherfrom various clinical studies, approximately 2 to 29% of thosepatients diagnosed to have mental illness at the time of the studywere suffering from schizoaffective disorder with women havinga higher prevalence (Keck et al., 2001). This could possiblybe explained by a higher rate of depression in women. Relativesof women suffering from schizoaffective disorder have a higherrate of schizophrenia and depressive disorders compared withrelatives of male schizoaffective subjects. The estimated lifetimeprevalence of schizoaffective disorder is possibly in the range of0.5 to 0.8%. In the inpatient settings of New York State psychiatrichospitals, approximately 19% of 6000 patients had a diagnosisof schizoaffective disorder (Levinson et al., 1999).Gender and AgeThe depressive type of schizoaffective disorder appears to bemore common in older people while the bipolar type probablyoccurs more commonly in younger adults. The higher prevalenceof the disorder in women appears to occur particularly amongstthose who are married. As in schizophrenia, the age of onset forwomen is later than that for men. Depression tends to occur morecommonly in women.EtiologyThe etiology of schizoaffective disorder is unknown. There is adearth of data relating to this illness. Studies involving families ofschizoaffective probands suggest that they have signifi cantly higherrates of relatives with mood disorder than families of schizophreniaprobands. It is possible that some of the same environmentaltheories that apply to schizophrenia and bipolar disorder may alsoapply to schizoaffective disorder. It is most likely that schizoaffectivedisorder is a heterogeneous condition. Thus, depending on thetype of schizoaffective disorder studied an increased prevalenceof either schizophrenia or mood disorders may be found in theirrelatives. As a group, patients with schizoaffective disorder have aprognosis intermediate between mood disorders and schizophrenia.Thus, on an average they have a better course than those sufferingfrom schizophrenia, respond to mood stabilizers more oftenand tend to have a relatively nondeteriorating course.DiagnosisSchizoaffective disorder criteria have evolved over the years andundergone major changes. According to the DSM-IV, a patientwith schizoaffective disorder must have an uninterrupted periodof illness during which, at some time, they meet the diagnosticcriteria for a major depressive episode, manic episode, or a mixedepisode concurrently with the diagnostic criteria for the activephase of schizophrenia (criteria A for schizophrenia). Additionally,“the patient must have had delusions or hallucinations for atleast 2 weeks in the absence of prominent mood disorder symptoms”during the same period of illness. The mood disorder symptomsmust be present for a substantial part of the active and residual

psychotic period. The essential features of schizoaffectivedisorder must occur within a single uninterrupted period of illnesswhere the “period of illness” refers to the period of active or residualsymptoms of psychotic illness and this can last for yearsand decades. The total duration of psychotic symptoms must be atleast 1 month to meet the criteria A for schizophrenia and thus, theminimum duration of a schizoaffective episode is also 1 month.The criteria for major depressive episode requires a minimumduration of 2 weeks of either depressed mood or markedlydiminished interest or pleasure. As the symptoms of loss of pleasureor interest commonly occur in nonaffective psychotic disorders,to meet the criteria for schizoaffective disorder criteria A,the major depressive episode must include pervasive depressedmood. Presence of markedly diminished interest or pleasureis not suffi cient to make a diagnosis as it is possible that thesesymptoms may occur with other conditions too.The DSM-IV diagnosis of schizoaffective disorder canbe further classifi ed as schizoaffective disorder bipolar type orschizoaffective disorder depressive type. For a person to be classified as having the bipolar subtype he/she must have a disorderthat includes a manic or mixed episode with or without a historyof major depressive episodes. Otherwise the person is classifi edas having depressive subtype having had symptoms that meet thecriteria for a major depressive episode with no history of havinghad mania or mixed state.Clinical FeaturesThe clinical signs and symptoms of schizoaffective disorderinclude all the signs and symptoms of schizophrenia, and a manic episode and/or a major depressive episode. The schizophreniaand mood symptoms may occur together or in an alternatesequence. The clinical course can vary from one ofexacerbations and remissions to that of a long-term deterioration.Presence of mood-incongruent psychotic features – wherethe psychotic content of hallucinations or delusions is not consistentwith the prevailing mood – more likely indicate a poorprognosis.Differential DiagnosisThe possible differential diagnosis consists of bipolar disorderwith psychotic features, major depressive disorder with psychoticfeatures and schizophrenia. Clearly, substance inducedstates and symptoms caused by coexisting medical conditionsshould be carefully ruled out. All conditions listed in differentialdiagnosis of schizophrenia, bipolar disorder and majordepressive disorder should be considered including but not limitedto those patients undergoing treatment with steroids, thoseabusing substances such as PCP and medical conditions such astemporal lobe epilepsy. In circumstances where there is ambiguity,it may be prudent to delay making a fi nal diagnosis untilthe most acute symptoms of psychosis have subsided and timeis allowed to establish a course of illness and collect collateralinformation.Course and PrognosisDue to the evolving nature of the diagnosis and limited studiesdone thus far much remains unknown. However, to the extentthat this illness has symptoms from both a major mood disorderand schizophrenia, theoretically one can confer a relatively betterprognosis then schizophrenia and a relatively poorer prognosisthen bipolar disorder, The following variables are harbingers ofa poor prognosis:1. a poor premorbid history;2. an insidious onset;3. absence of precipitating factors;4. a predominance of psychotic symptoms, especially defi cit ornegative ones;5. an early age of onset;

6. an unremitting course, and;7. a family history of schizophrenia.The corollary would be that the opposite of each of these characteristicswould suggest a better prognosis. Interestingly, the presenceor the absence of Schneiderian fi rst-rank symptoms doesnot seem to predict the course of illness. The incidence of suicidein patients with schizoaffective disorder is at least 10%. Somedata indicate that the suicidal behavior may be more common inwomen then men.In one study, 82% of those patients who were sufferingfrom a fi rst episode of schizoaffective disorder, and had recovered,experienced psychotic relapse within 5 years. These patientshad high rates of second and third relapses despite carefulmonitoring. Medication discontinuations in fi rst episode patientswho are stable for 1 year substantially increase relapse risks.Aside from medication status, premorbid social adjustment wasthe only predictor of relapse in their study. Poor adaptation toschool and premorbid social isolation predicted initial relapseindependent of medication status. Thus, like schizophrenia, therisk of relapse is diminished by antipsychotic maintenance treatment(Robinson et al., 1999).TreatmentWith the shifting defi nitions of schizoaffective disorder, evaluatingthe treatment of schizoaffective disorder is not easy. Moodstabilizers, antidepressants and antipsychotic medications clearlyhave a role in management of these patients. The presentingsymptoms, their duration and intensity, and patient choices needto be incorporated into deciding what treatment(s) to choose.Antipsychotic MedicationsAtypical antipsychotic medications are reported to be more effectivethan the typical ones in the treatment of schizoaffectivedisorder. They appear to have a more broad-spectrum effectsthen the typical agents. Optimizing antipsychotic treatment, especiallywith the novel agents, is more likely to be effective thanthe routine use of adjunctive antidepressants or mood stabilizers.However, when indicated, the use of antidepressants is well supportedin schizoaffective patients who present with a full depressivesyndrome after stabilization of psychosis.Olanzapine, ziprasidone and risperidone appear to be effectiveagainst symptoms of psychosis, mania and depression.Clozapine use may be benefi cial in the treatment of refractoryschizoaffective disorder as it has both mood stabilizing and antipsychoticproperties, a substantial advantage.Mood StabilizersA small number of studies suggest that valproic acid, lithium andlamotrigine are effective in treating the manic symptoms associatedwith schizoaffective disorder, bipolar type.Antidepressants The novel antipsychotic agents are often efficacious against depression in patients who suffer from both depressionand psychosis negating the need for routine use of antidepressants.However, there are patients who remain depressedeven with optimal antipsychotic and mood stabilizer treatment.SSRIs are widely used in patients who present with schizoaffectivedisorder with depression. If the SSRIs and newer antidepressantsdo not show effi cacy, tricyclic antidepressants do have a role.Interestingly, chlorpromazine in combination with amitriptylinewas reported to be as effective as chlorpromazine alone. Manystudies suggest that addition of antidepressants helps in effectivetreatment of depression in schizoaffective disorder. Occasionally,antidepressants may worsen the course. For patients sufferingfrom depression where they are not responding adequatelyand are at risk for suicide, ECT is an effective alternative.Psychosocial Treatment To the extent that schizoaffectivedisorder shares symptoms with schizophrenia, most of the psychosocialtreatments used in the treatment of schizophrenia are

likely to be useful in the treatment of schizoaffective disorder.Specifi cally, patients benefi t from individual supportive therapy,family therapy, group therapy, cognitive–behavioral therapy andsocial skills training. Many patients would be suitable candidatesfor assertive community therapy (ACT). Depending on the levelof recovery, some of the patients may need rehabilitation servicesto assist them with either developing skills for some form of employmentor assistance to maintain a job. Family members benefitfrom support groups such as NAMI or MDA groups.DSM-IV-TR Criteria 295.70Schizoaffective DisorderAn uninterrupted period ofA. illness during which, at some time, there is either amajor depressive episode, a manic episode, or a mixedepisode concurrent with symptoms that meet criterion Afor schizophrenia.Note: The major depressive episode must include criterionA1: depressed mood.B. During the same period of illness, there have beendelusions or hallucinations for at least 2 weeks in theabsence of prominent mood symptoms.C. Symptoms that meet criteria for a mood episode arepresent for a substantial portion of the total duration ofthe active and residual periods of the illness.D. The disturbance is not due to the direct physiologicaleffects of a substance (e.g., a drug of abuse, amedication) or a general medical condition.Specify type:Bipolar type: if the disturbance includes a manic or amixed episode (or a manic or a mixed episode and majordepressive episodes)Depressive type: if the disturbance only includes majordepressive episodes

Pathophysiology SchizophreniaNeurochemical Theories DopamineDopamine is the most extensively investigated neurotransmittersystem in schizophrenia. In 1973 it was proposed that schizophreniais related to hyperactivity of dopamine. This propositionbecame the dominant pathophysiological hypothesis for the next15 years. Its strongest support came from the fact that all commerciallyavailable antipsychotic agents have antagonistic effectson the dopamine D2 receptor in relation to their clinical potencies(Creese et al., 1975). In addition, dopamine agonists, such as amphetamineand methylphenidate, exacerbate psychotic symptomsin a subgroup of patients with schizophrenia. Moreover, as notedearlier, the most consistently reported postmortem fi nding in theliterature of schizophrenia is elevated D2 receptors in the striatum.SerotoninClozapine has a relatively high affi nity for specifi c serotonin (5-hydroxytryptamine [5-HT]) receptors (5-HT2A and 5-HT2C) andrisperidone, has even greater serotonin antagonistic properties.Clozapine, risperidone, olanzapine, quetiapine and ziprasidone,the novel antipsychotic agents, have a greater ratio of serotonin 5-HT2A to dopamine D2 binding affi nity. This has led to the hypothesisthat the balance between serotonin and dopamine may bealtered in schizophrenia. Serotonin 5-HT2A (and other serotonin)receptor occupancy by the antipsychotic drugs, depending on theareas of the brain involved, could be associated with improvementin cognition, depression and D2 receptor mediated EPS.There has been an explosion of new information about thestructure and function of 5-HT receptors. To date, 15 serotoninreceptor subtypes have been identifi ed. Two receptors, 5-HT6 and5-HT7, have been proposed as candidates for atypical drug action

and are therefore reasonable targets for pathophysiologicalstudies of schizophrenia. It is clear that the fi eld is in the earlystages of understanding the possible involvement of serotonin inschizophrenia.GABAGABA is the major inhibitory neurotransmitter in brain. Supportfor GABA’s involvement in schizophrenia comes from twolines of investigation. First, clinical trials have demonstratedthat benzodiazepines, administered both in conjunction withantipsychotic drugs and as the sole treatment, are effective atreducing symptoms in subgroups of schizophrenia patients.Benzodiazepines are agonists at GABAA receptors. Secondly,postmortem studies have found a defi cit in GABA interneuronsin the anterior cingulum and prefrontal cortex and decreasedGABA uptake sites in the hippocampus. GABAergic neuronsare especially vulnerable to glucocorticoid hormones and also toglutamatergic excitotoxicity.