Disease State Diagnosis

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The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) category for the schizophrenic disease spectrum is designated as 295.xx, 'schizophrenia and other psychotic disorders'4 with the main subclasses being: paranoid type (295.30); disorganized type (295.10); catatonic type (295.10); undifferentiated type (295.90); and residual type (295.6) as well as schizophreniform disorder (295.40); schizoaffective disorder (295.70; including bipolar and depressive types); delusional disorder (297.1); brief psychotic disorder (298.8); and shared psychotic disorder (297.3).

The three main symptoms of schizophrenia are 'positive', 'negative' symptoms, and 'cognitive dysfunction.' Positive symptoms (although by no means positive to the patients) are defined as an excess or distortion of normal function and include: bizarre behavior, auditory, and, more rarely, visual hallucinations, paranoid and other types of delusions, and disorganized thought. Negative symptoms include a diminution or loss of normal function and include: affective flattening, anhedonia, social withdrawal, lack of motivation and spontaneity, and alogia and avolition - poverty of thought and speech. Cognitive impairment in schizophrenia begins before the onset of the psychosis and remains severe, with some worsening, throughout the illness. While the precise domains of cognitive dysfunction in patients with schizophrenia remain to be elucidated, schizophrenia is clearly associated with widespread, multifaceted impairments in cognitive function, including executive function, attention, processing, vigilance, verbal learning and memory, verbal and spatial working memory, semantic memory, and social cognition. Recent evidence suggests that cognitive impairment may be of equal or greater importance than positive or negative symptoms in predicting functional outcomes, such as work status, quality of life, and social problem solving.5 For example, cognitive dysfunction along with disorganization symptoms discriminates schizophrenic patients who are able to work from those who are not.

There are six diagnostic criteria for schizophrenia4: (1) characteristic symptoms, that include (i) delusions, (ii) hallucinations, (iii) disorganized speech, (iv) grossly disorganized or catatonic behavior, and (v) negative symptoms (affective flattening, alogia (poverty or absence of speech), avolition (lack of interest and drive)) - two or more of which are present for a significant duration over a 1 month period; (2) social/occupational dysfunction; (3) duration -continuous signs of the disturbance for at least 6 months (unless successfully treated after early diagnosis); (4) schizoaffective and mood disorder exclusion; (5) substance/general medical condition exclusion; (6) relationship to a pervasive developmental disorder, e.g., autistic disorder. While considerable research has been directed at the genetics of the disorder and significant advances have been made in the development of imaging tools and methods, there is currently no objective clinical test for diagnosis.

The importance of cognitive dysfunction has recently been highlighted by an initiative to define the guidelines for drug approval for this indication. A consortium6 headed by the National Institutes of Mental Health (NIMH) and including academic groups and representatives from the Food and Drug Administration (FDA) and industry is validating methods for evaluating drug effects on cognitive function in patients with schizophrenia, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative has been formed as an outgrowth of these interactions and this group has promulgated a cognitive testing battery that currently is undergoing validation studies in patients.

More recently, it has been argued that comorbid mood disorders are sufficiently common in schizophrenic patients to justify a fourth set of characteristic symptoms. Depression and bipolar disorder are highly comorbid in schizophrenia and are one of the key factors contributing to the increased risk for suicide in this disorder. Individuals with schizophrenia attempt suicide more often than people in the general population, and a high percentage, in particular younger adult males, succeeds in the attempt. Controversy remains over whether these mood disorders are in fact a manifestation of the disorder (i.e., share a common etiology), or an epiphenomenon associated with either the disease state or treatment. Regardless of the actual cause, comorbid mood disorders represent a clear risk in treating the schizophrenic patient population and are carefully considered along with the more traditional positive, negative, and cognitive symptoms. Schizophrenia is usually diagnosed in adolescence and the symptoms follow a characteristic pattern of development. Cognitive symptoms are first manifest during adolescence, accompanied by changes in social interactions. The first signs can include a change in peer group, declining academic performance, and increased irritability. Unfortunately, many of these symptoms are observed, albeit to a lesser degree, in normal adolescents. Therefore, diagnosis is not commonly made until the emergence of positive symptoms. Positive symptoms usually develop in men in their late teens and early twenties and in women in their mid-twenties to early thirties. While this describes the most common progression, rare cases of schizophrenia have been reported to emerge in children as young as 5 years, and adults past 45 years of age. The disorder is equally prevalent in both sexes and occurs at similar rates worldwide in all ethnic groups.

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