Schizoaffective Disorder

Etiology

The term schizoaffective disorder first appeared as a subtype of schizophrenia in the first edition of the DSM. It eventually became its own diagnosis despite a lack of evidence for unique differences in etiology or pathophysiology. Therefore, there have been no conclusive studies on the etiology of the disorder. However, investigating the potential causes of mood disorders and schizophrenia as individual disorders allows for further discussion.

Some studies show that as high as 50% of people with schizophrenia also have comorbid depression.[3] The pathogenesis of both mood disorders and schizophrenia is multifactorial and covers a range of risk factors, including genetics, social factors, trauma, and stress.[4] Among people with schizophrenia, there is a possible increased risk for first-degree relatives for schizoaffective disorder and vice-versa; there may be increased risk among individuals for schizoaffective disorder who have a first-degree relative with bipolar disorder schizophrenia, or schizoaffective disorder.[5]

Epidemiology

The diagnostic criteria for schizoaffective disorder have been reworded and addended since its inclusion in the DSM, making it difficult to subsequently conduct appropriate epidemiological studies. Thus, there have been no large-scale studies on the epidemiology, incidence, or prevalence of schizoaffective disorder. Research shows that 30% of cases occur between the ages of 25 and 35, and it occurs more frequently in women.[6][7] Schizoaffective disorder occurs about one-third as frequently as schizophrenia, and the lifetime prevalence appears to be around 0.3%.[5] Estimates are that schizoaffective disorder comprises 10 to 30% of inpatient admissions for psychosis.[8]

Pathophysiology

The exact pathophysiology of schizoaffective disorder is currently unknown. Some studies have shown that abnormalities in dopamine, norepinephrine, and serotonin may play a role.[9] Also, white matter abnormalities in multiple areas of the brain, particularly the right lentiform nucleus, left temporal gyrus, and right precuneus, are associated with schizophrenia and schizoaffective disorder.[10] Researchers have also found reduced hippocampal volumes and distinct deformations in the medial and lateral thalamic regions in those with schizoaffective disorder in comparison to controls.[11][12]

History and Physical

The first step in evaluation is obtaining a complete medical history while focusing on the diagnostic criteria for schizoaffective disorder. 

The specific DSM-5 criteria for schizoaffective disorder are as follows[1]:

A. An uninterrupted duration of illness during which there is a major mood episode (manic or depressive) in addition to criterion A for schizophrenia; the major depressive episode must include depressed mood.

Criterion A for schizophrenia is as follows[13]:

Two or more of the following presentations, each present for a significant amount of time during a 1-month period (or less if successfully treated). At least one of these must be from the first three below.

1. Delusions
2. Hallucinations
3. Disorganized speech (e.g., frequent derailment or incoherence).
4. Grossly disorganized or catatonic behavior
5. Negative symptoms (i.e., diminished emotional expression or avolition.)

B. Hallucinations and delusions for two or more weeks in the absence of a major mood episode (manic or depressive) during the entire lifetime duration of the illness.

C. Symptoms that meet the criteria for a major mood episode are present for most of the total duration of both the active and residual portions of the illness.

D. The disturbance is not the result of the effects of a substance (e.g., a drug of misuse or a medication) or another underlying medical condition.

The following are specifiers based on the primary mood episode as part of the presentation.

Bipolar type: includes episodes of mania and sometimes major depression.

Depressive type: includes only major depressive episodes.

Please note the patient must meet the criteria for A-D above to be diagnosed with schizoaffective disorder. It is not enough to symptoms of schizophrenia while meeting the criteria for a major mood episode. Please see the differential diagnoses and pearls sections below for more information.

The next step of evaluation is the objective and physical portion. A thorough mental status examination (MSE), physical examination, and neurologic examination should be completed to help rule out other differential diagnoses.

Evaluation

The following workup is optional and typically not needed to make the diagnosis. The history and physical are the mainstays of diagnosis. However, some elect to include additional tests or imaging to aid in the diagnosis, such as MRI (magnetic resonance imaging), EEG (electroencephalography), or CT (computed tomography).

Laboratory studies are tailored to the patient’s history, especially for those who have an atypical presentation.

• Complete blood count (CBC)
• Lipid panel
• Urine drug screen
• Urine pregnancy test
• Urinalysis
• Thyroid-stimulating hormone (TSH) level
• Rapid plasma reagent
• HIV test

If the patient's neurologic exam is found to be aberrant, performing a brain MRI or CT to rule out any suspected intracranial abnormalities may be considered.

Treatment / Management

The treatment of schizoaffective disorder typically involves both pharmacotherapy and psychotherapy. The mainstay of most treatment regimens should include an antipsychotic, but the choice of treatment should be tailored to the individual.[14] A study that reported obtained data on treatment regimens for schizoaffective showed that 93% of patients received an antipsychotic. 20% of patients received a mood-stabilizer in addition to an antipsychotic, while 19% received an antidepressant along with an antipsychotic.[15] Prior to initiating treatment, if a patient with schizoaffective disorder is a danger to themselves or others, inpatient hospitalization should be considered; this includes patients who are neglecting activities of daily living or those who are disabled well below their baseline in terms of functioning.

Pharmacotherapy

Antipsychotics: Used to target psychosis and aggressive behavior in schizoaffective disorder. Other symptoms include delusions, hallucinations, negative symptoms, disorganized speech, and behavior. Most first and second-generation antipsychotics block dopamine receptors. While second-generation antipsychotics have further actions on serotonin receptors. Antipsychotics include but are not limited to paliperidone (FDA approved for schizoaffective disorder), risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol.[16][17][18][19][20] Clozapine is a consideration for refractory cases, much like in schizophrenia.[18](A1)

Mood-stabilizers: Patients who have periods of distractibility, indiscretion, grandiosity, a flight of ideas, increased goal-directed activity, decreased need for sleep, and who are hyper-verbal fall under the bipolar-specifier for schizoaffective disorder. Consider the use of mood-stabilizers if the patient has a history of manic or hypomanic symptoms. These include medications such as lithium, valproic acid, carbamazepine, oxcarbazepine, and lamotrigine which target mood dysregulation.[21][22][23][24](A1)

Antidepressants: Used to target depressive symptoms in schizoaffective disorder. Selective-serotonin reuptake inhibitors (SSRIs) are preferred due to lower risk for adverse drug effects and tolerability when compared to tricyclic antidepressants and selective norepinephrine reuptake inhibitors.[25] SSRIs include fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine. It is vital to rule out bipolar disorder before starting an antidepressant due to the risk of exacerbating a manic episode.[26] 

Psychotherapy

Patients who have schizoaffective disorder can benefit from psychotherapy, as is the case with most mental disorders.

Treatment plans should incorporate individual therapy, family therapy, and psychoeducational programs. The aim is to develop their social skills and improve cognitive functioning to prevent relapse and possible rehospitalization.[27] This treatment plan includes education about the disorder, etiology, and treatment. (B2)

Individual therapy: This type of treatment aims to normalize thought processes and better help the patient understand the disorder and reduce symptoms. Sessions focus on everyday goals, social interactions, and conflict; this includes social skills training and vocational training.

Family and/or group therapy: Family involvement is crucial in the treatment of this schizoaffective disorder.[28] Family education aids in compliance with medications and appointments and helps provide structure throughout the patient's life, given the dynamic nature of the schizoaffective disorder. Supportive group programs can also help if the patient has been in social isolation and provides a sense of shared experiences among participants.(A1)

ECT (Electroconvulsive Therapy)

ECT is usually a last resort treatment. However, not only has it been used in urgent cases and treatment resistance, but it should also merit consideration in augmentation of current pharmacotherapy.[29] The most common indicated symptoms are catatonia and aggression. ECT is safe and effective for most chronically hospitalized patients.[30]

Differential Diagnosis

Because of criteria that encompass both psychotic and mood symptoms, schizoaffective disorder is easy to mistake for other mental disorders. Disorders that must be ruled out during the workup of schizoaffective disorder include:

• Schizophrenia
• Major depressive disorder with psychotic features
• Bipolar disorder

Schizophrenia and Schizoaffective Disorder: There has to be a definite period of at least two weeks in which there are only psychotic symptoms (delusions and hallucinations) without mood symptoms to diagnose schizoaffective disorder. However, a major mood episode (depression or mania) is present for the majority of the total duration of the illness. Once the psychotic symptoms predominate the majority of the total duration of the illness, the diagnosis leans towards schizophrenia. Also, schizophrenia requires 6 months of prodromal or residual symptoms; schizoaffective disorder does not require this criterion.

Major Depressive Disorder Psychotic Features and Schizoaffective Disorder: Patients with major depression with psychotic features (MDD with PF) only experience psychotic features during their mood episodes. In contrast, schizoaffective requires at least 2 weeks in which there are only psychotic symptoms (delusions and hallucinations) without mood symptoms. Patients with MDD with PF do not meet criterion A of schizoaffective disorder.

Bipolar Disorder and Schizoaffective Disorder: Similar to the contrasts of MDD w/ PF, patients with bipolar disorder with psychotic features only experience psychotic features (delusions and hallucinations) during a manic episode. Again, schizoaffective requires a period of at least 2 weeks in which there are only psychotic symptoms without mood symptoms. Psychotic features in bipolar disorder do not meet criterion A of schizoaffective disorder.

Prognosis

Given that the diagnostic criteria of schizoaffective disorder change periodically, prognostic studies have been challenging to conduct. However, a study by Harrison et al., 2001 on the overall prognosis of those with psychotic illness showed that 50% of cases showed favorable outcomes.[31] The defined favorable as minimal or no symptoms and/or employment. These outcomes were highly reliant on the early initiation of treatment and optimized treatment regimens as outlined above.

Complications

Left untreated, schizoaffective disorder has many ramifications in both social functioning and activities of daily living. These include unemployment, isolation, impaired ability to care for self, etc. Untreated mental disorders have more than just social and functional consequences. Some studies show that as many as 5% of people with a psychotic illness will commit suicide over their lifetime.[32] Research has shown that among all completed suicides, ten percent are attributable to those with a psychotic illness.[33]