Schizoaffective Disorder

Over the decades, these patients were often classifi ed as having atypical schizophrenia, good prognosis schizophrenia, remitting schizophrenia, or cycloid psychosis. Inherent within these diagnoses was the implication that they shared similarities to schizophrenia and also appeared to have a relatively better course of illness. With the advent of effective treatment of bipolar disorder with lithium salts, some of these patients started responding to lithium, and the term schizoaffective disorder gained further momentum and evolved in the direction of bipolar disorder. Unfortunately, this lack of diagnostic clarity has plagued the diagnosis of schizoaffective disorder such that there is much that is unknown about the illness.

Epidemiology
The diagnosis of schizoaffective disorder has undergone numerous changes through the decades making it diffi cult to get reliable epidemiology information. When data was pooled together from various clinical studies, approximately 2 to 29% of those patients diagnosed to have mental illness at the time of the study were suffering from schizoaffective disorder with women having a higher prevalence (Keck et al., 2001). This could possibly be explained by a higher rate of depression in women. Relatives of women suffering from schizoaffective disorder have a higher rate of schizophrenia and depressive disorders compared with relatives of male schizoaffective subjects. The estimated lifetime prevalence of schizoaffective disorder is possibly in the range of 0.5 to 0.8%. In the inpatient settings of New York State psychiatric hospitals, approximately 19% of 6000 patients had a diagnosis of schizoaffective disorder (Levinson et al., 1999).

Gender and Age

The depressive type of schizoaffective disorder appears to be more common in older people while the bipolar type probably occurs more commonly in younger adults. The higher prevalence of the disorder in women appears to occur particularly amongst those who are married. As in schizophrenia, the age of onset for women is later than that for men. Depression tends to occur more commonly in women.

Etiology
The etiology of schizoaffective disorder is unknown. There is a dearth of data relating to this illness. Studies involving families of schizoaffective probands suggest that they have signifi cantly higher rates of relatives with mood disorder than families of schizophrenia probands. It is possible that some of the same environmental theories that apply to schizophrenia and bipolar disorder may also apply to schizoaffective disorder. It is most likely that schizoaffective disorder is a heterogeneous condition. Thus, depending on the type of schizoaffective disorder studied an increased prevalence of either schizophrenia or mood disorders may be found in their relatives. As a group, patients with schizoaffective disorder have a prognosis intermediate between mood disorders and schizophrenia. Thus, on an average they have a better course than those suffering from schizophrenia, respond to mood stabilizers more often and tend to have a relatively nondeteriorating course.

Diagnosis
Schizoaffective disorder criteria have evolved over the years and undergone major changes. According to the DSM-IV, a patient with schizoaffective disorder must have an uninterrupted period of illness during which, at some time, they meet the diagnostic criteria for a major depressive episode, manic episode, or a mixed episode concurrently with the diagnostic criteria for the active phase of schizophrenia (criteria A for schizophrenia). Additionally, the patient must have had delusions or hallucinations for at least 2 weeks in the absence of prominent mood disorder symptoms during the same period of illness. The mood disorder symptoms must be present for a substantial part of the active and residual psychotic period. The essential features of schizoaffective

disorder must occur within a single uninterrupted period of illness where the period of illness refers to the period of active or residual symptoms of psychotic illness and this can last for years and decades. The total duration of psychotic symptoms must be at least 1 month to meet the criteria A for schizophrenia and thus, the minimum duration of a schizoaffective episode is also 1 month. The criteria for major depressive episode requires a minimum duration of 2 weeks of either depressed mood or markedly diminished interest or pleasure. As the symptoms of loss of pleasure or interest commonly occur in nonaffective psychotic disorders, to meet the criteria for schizoaffective disorder criteria A, the major depressive episode must include pervasive depressed mood. Presence of markedly diminished interest or pleasure is not suffi cient to make a diagnosis as it is possible that these symptoms may occur with other conditions too. The DSM-IV diagnosis of schizoaffective disorder can be further classifi ed as schizoaffective disorder bipolar type or schizoaffective disorder depressive type. For a person to be classifi ed as having the bipolar subtype he/she must have a disorder that includes a manic or mixed episode with or without a history of major depressive episodes. Otherwise the person is classifi ed as having depressive subtype having had symptoms that meet the criteria for a major depressive episode with no history of having had mania or mixed state.

Clinical Features
The clinical signs and symptoms of schizoaffective disorder include all the signs and symptoms of schizophrenia, and a manic episode and/or a major depressive episode. The schizophrenia and mood symptoms may occur together or in an alternate sequence. The clinical course can vary from one of exacerbations and remissions to that of a long-term deterioration. Presence of mood-incongruent psychotic features where the psychotic content of hallucinations or delusions is not consistent with the prevailing mood more likely indicate a poor prognosis.

Differential Diagnosis
The possible differential diagnosis consists of bipolar disorder with psychotic features, major depressive disorder with psychotic features and schizophrenia. Clearly, substance induced states and symptoms caused by coexisting medical conditions should be carefully ruled out. All conditions listed in differential diagnosis of schizophrenia, bipolar disorder and major depressive disorder should be considered including but not limited to those patients undergoing treatment with steroids, those abusing substances such as PCP and medical conditions such as temporal lobe epilepsy. In circumstances where there is ambiguity, it may be prudent to delay making a fi nal diagnosis until the most acute symptoms of psychosis have subsided and time is allowed to establish a course of illness and collect collateral information.

Course and Prognosis

Due to the evolving nature of the diagnosis and limited studies done thus far much remains unknown. However, to the extent that this illness has symptoms from both a major mood disorder and schizophrenia, theoretically one can confer a relatively better prognosis then schizophrenia and a relatively poorer prognosis then bipolar disorder, The following variables are harbingers of a 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 or negative 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 characteristics would suggest a better prognosis. Interestingly, the presence or the absence of Schneiderian fi rst-rank symptoms does not seem to predict the course of illness. The incidence of suicide in patients with schizoaffective disorder is at least 10%. Some data indicate that the suicidal behavior may be more common in women then men. In one study, 82% of those patients who were suffering from a fi rst episode of schizoaffective disorder, and had recovered, experienced psychotic relapse within 5 years. These patients had high rates of second and third relapses despite careful monitoring. Medication discontinuations in fi rst episode patients who are stable for 1 year substantially increase relapse risks. Aside from medication status, premorbid social adjustment was the only predictor of relapse in their study. Poor adaptation to school and premorbid social isolation predicted initial relapse independent of medication status. Thus, like schizophrenia, the risk of relapse is diminished by antipsychotic maintenance treatment (Robinson et al., 1999).

Treatment
With the shifting defi nitions of schizoaffective disorder, evaluating the treatment of schizoaffective disorder is not easy. Mood stabilizers, antidepressants and antipsychotic medications clearly have a role in management of these patients. The presenting symptoms, their duration and intensity, and patient choices need to be incorporated into deciding what treatment(s) to choose.

Antipsychotic Medications
Atypical antipsychotic medications are reported to be more effective than the typical ones in the treatment of schizoaffective disorder. They appear to have a more broad-spectrum effects then the typical agents. Optimizing antipsychotic treatment, especially with the novel agents, is more likely to be effective than the routine use of adjunctive antidepressants or mood stabilizers. However, when indicated, the use of antidepressants is well supported in schizoaffective patients who present with a full depressive syndrome after stabilization of psychosis. Olanzapine, ziprasidone and risperidone appear to be effective against symptoms of psychosis, mania and depression. Clozapine use may be benefi cial in the treatment of refractory schizoaffective disorder as it has both mood stabilizing and antipsychotic properties, a substantial advantage.

Mood Stabilizers
A small number of studies suggest that valproic acid, lithium and lamotrigine are effective in treating the manic symptoms associated with schizoaffective disorder, bipolar type. Antidepressants The novel antipsychotic agents are often effi cacious against depression in patients who suffer from both depression and psychosis negating the need for routine use of antidepressants. However, there are patients who remain depressed even with optimal antipsychotic and mood stabilizer treatment. SSRIs are widely used in patients who present with schizoaffective disorder with depression. If the SSRIs and newer antidepressants do not show effi cacy, tricyclic antidepressants do have a role. Interestingly, chlorpromazine in combination with amitriptyline was reported to be as effective as chlorpromazine alone. Many studies suggest that addition of antidepressants helps in effective treatment of depression in schizoaffective disorder. Occasionally, antidepressants may worsen the course. For patients suffering from depression where they are not responding adequately and are at risk for suicide, ECT is an effective alternative. Psychosocial Treatment To the extent that schizoaffective disorder shares symptoms with schizophrenia, most of the psychosocial treatments 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, cognitivebehavioral therapy and

social skills training. Many patients would be suitable candidates for assertive community therapy (ACT). Depending on the level of recovery, some of the patients may need rehabilitation services to assist them with either developing skills for some form of employment or assistance to maintain a job. Family members benefit from support groups such as NAMI or MDA groups.

DSM-IV-TR Criteria 295.70

Schizoaffective Disorder An uninterrupted period of A. illness during which, at some time, there is either a major depressive episode, a manic episode, or a mixed episode concurrent with symptoms that meet criterion A for schizophrenia. Note: The major depressive episode must include criterion A1: depressed mood. B. During the same period of illness, there have been delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms. C. Symptoms that meet criteria for a mood episode are present for a substantial portion of the total duration of the active and residual periods of the illness. D. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition. Specify type: Bipolar type: if the disturbance includes a manic or a mixed episode (or a manic or a mixed episode and major depressive episodes) Depressive type: if the disturbance only includes major depressive episodes

Pathophysiology Schizophrenia Neurochemical Theories Dopamine

Dopamine is the most extensively investigated neurotransmitter system in schizophrenia. In 1973 it was proposed that schizophrenia is related to hyperactivity of dopamine. This proposition became the dominant pathophysiological hypothesis for the next 15 years. Its strongest support came from the fact that all commercially available antipsychotic agents have antagonistic effects on the dopamine D2 receptor in relation to their clinical potencies (Creese et al., 1975). In addition, dopamine agonists, such as amphetamine and methylphenidate, exacerbate psychotic symptoms in a subgroup of patients with schizophrenia. Moreover, as noted earlier, the most consistently reported postmortem fi nding in the literature of schizophrenia is elevated D2 receptors in the striatum.

Serotonin
Clozapine has a relatively high affi nity for specifi c serotonin (5hydroxytryptamine [5-HT]) receptors (5-HT2A and 5-HT2C) and risperidone, has even greater serotonin antagonistic properties. Clozapine, risperidone, olanzapine, quetiapine and ziprasidone, the novel antipsychotic agents, have a greater ratio of serotonin 5HT2A to dopamine D2 binding affi nity. This has led to the hypothesis that the balance between serotonin and dopamine may be altered in schizophrenia. Serotonin 5-HT2A (and other serotonin) receptor occupancy by the antipsychotic drugs, depending on the areas of the brain involved, could be associated with improvement in cognition, depression and D2 receptor mediated EPS. There has been an explosion of new information about the structure and function of 5-HT receptors. To date, 15 serotonin receptor subtypes have been identifi ed. Two receptors, 5-HT6 and 5-HT7, have been proposed as candidates for atypical drug action and are therefore reasonable targets for pathophysiological studies of schizophrenia. It is clear that the fi eld is in the early stages of understanding the possible involvement of serotonin in schizophrenia.

GABA
GABA is the major inhibitory neurotransmitter in brain. Support for GABAs involvement in schizophrenia comes from two lines of investigation. First, clinical trials have demonstrated that benzodiazepines, administered both in conjunction with antipsychotic drugs and as the sole treatment, are effective at reducing symptoms in subgroups of schizophrenia patients. Benzodiazepines are agonists at GABAA receptors. Secondly, postmortem studies have found a defi cit in GABA interneurons in the anterior cingulum and prefrontal cortex and decreased GABA uptake sites in the hippocampus. GABAergic neurons are especially vulnerable to glucocorticoid hormones and also to glutamatergic excitotoxicity.