The past decade has witnessed a dramatic resurgence of interest in the negative symptoms of schizophrenia, which had been seen as core features of the disorder by both Kraepelin and Bleuler.  A substantial literature has emerged demonstrating relationships between negative symptoms and a wide variety of phenomenological and neurobiological variables (for example, poor premorbid functioning, generalized impairment of neuropsychological tests, and an increased likelihood of structural and functional brain abnormalities).  Negative symptoms are also now recognized as important target symptoms for treatments, and measures of negative symptoms have become routine components of clinical drug trials.  This renewed interest has been reflected in the creation of DSM-IV, in which one of the few substantive changes in the schizophrenia criteria (relative to DSM-III R) involves placing a greater emphasis on negative symptoms.

Negative symptoms
It is widely recognized that negative symptoms are aetiologically heterogeneous, and may be mimicked and/or exacerbated by a variety of factors that are common in schizophrenia and other psychotic disorders.  Examples include affective flattening secondary to antipsychotic-induced akinesia, social withdrawal as a consequence of prominent hallucinations or delusions, apathy resulting from chronic institutionalization, and anhedonia in the context of depression⁴⁸.

In addition to these state-dependent, or ‘secondary,’ causes of negative symptoms, it is presumed that neural mechanisms underlying trait-like, or ‘primary’, negative symptoms occur in at least a subset of individuals with schizophrenic disorders.

EPS are problematic even in isolation, but the combination of EPS and negative symptoms poses substantial difficulties.  Several factors may overlap with negative symptoms and interfere with their evaluation, prognosis and treatment.  Interrelationships are known to exist among negative schizophrenic symptoms, antipsychotic drug side-effects, and disturbances of mood.

New antipsychotic drugs
New antipsychotic drugs in general show a reduced propensity to cause EPS.  Several scales have been developed for rating EPS, such as that developed by Simpson and Angus⁴⁹.  Recently, it has become clear that, in addition to motor side-effects, antipsychotic drugs have mental side-effects.  The neuroleptic-induced deficit syndrome (NIDS) is described in terms such as ‘emotional parkinsonism’ (emotional indifference, blunted affect, anhedonia), ‘social parkinsonism’ (reduced initiative, apathy, reduced energy, lack of social drive) and ‘cognitive parkinsonism’ (slow thought processes, concentration problems)⁵⁰.

Among the overlapping syndromes, akinesia is a poorly recognized drug-induced extrapyramidal behavioral disorder.  It is characterized by a lessening of spontaneity, paucity of gestures, diminished conversation, and apathy.  It may easily be confused with depression, demoralization, and residual schizophrenic defect⁵¹.

The latest version of DSM-IV includes antipsychotic-induced parkinsonism and antipsychotic-induced acute akathisia under the heading Medication-Induced Movement Disorders.  These conditions are now considered in the differential diagnosis with other causes of parkinsonism.  The DSM-IV acknowledges that ‘negative symptoms of schizophrenia may also be difficult to differentiate from akinesia’.  DSM-IV provides criteria and text to facilitate research and to encourage appropriate diagnosis and treatment.

Recently, Bermanzohn and Siris⁵² proposed the concept of the hypokinetic syndrome.  This is characterized by:

• slowed motor activity with difficulty initiating and sustaining behaviours
• anhedonia with depressed mood and reduced affective range
• cognitive impairment.

Conclusion
This is a difficult area to evaluate.  Novel rating scales capable of evaluating both negative symptoms and drug-related psychopathological cognitive symptoms should be used to help us better understand and treat these conditions.

In general, the occurrence of drug-induced EPS is under-recognized; instead, may be the condition is misdiagnosed as depression and the expression of negative symptoms of schizophrenia.  Sadly, the recognition of EPS is certainly one area of diagnosis that should be improved.

[back] [contents] [forward]