NEGATIVE SYMPTOMS OF SCHIZOPFRENIA: FROM KRAEPELIN TO DSM 5

INTRODUCTION
Schizophrenia is a chronic, debilitating disorder of the young adult, with a multifactorial etiology, characterized by significant dysfunctions in cognition, thought process, perception, affect and social functioning.
The diagnosis of schizophrenia is based on positive, negative, cognitive, disorganized and affective symptoms. The dichotomy between negative and positive symptoms reflects for the negative symptoms the absence or the lack of emotional and behavioral functioning and for the positive symptoms add-ons to normal experiences.(1) These terms were first used by the neurologist Sir John Reynolds to describe the ”loss or the excess of vital properties” which he observed in patients with epilepsy. (2)
The negative symptoms of schizophrenia encompass blunted affect, alogia, apathy, abulia, social withdrawal, anhedonia. The positive symptoms, which were known in the classical literature as productive symptoms, comprise hallucinations and delusions. (3) EARLY DESCRIPTIONS OF NEGATIVE SYMPTOMS
The description of negative symptoms goes back over a century to Kraepelin’s dementia praecox concept. Kraepelin considered the affect deficit as a core symptom of the disease and to be underpinning the motivational deficits: the lack of interest, the indifference, the lack of pleasure. He sustained this model based on the assumption that all mental processes include an affective component. Kraepelin named the disease dementia praecox because he ascribed the emotional deficit to a degenerative process. (1, 4) Kurt Schneider in 1959 used a different system of classification for the symptoms of schizophrenia, he introduced the terms of first rank and second rank symptoms. The first rank symptoms are all positive symptoms while the blunted affect is considered to be a second rank symptom (1).
CONCEPTUALIZATIONS
There are different studies that led to the dichotomy between positive and negative symptoms, from which the most important conceptualizations belong to Crow, Andreasen and Carpenter.
Crow’s model (1980) distinguishes two types of schizophrenia: type I dominated by positive symptoms and in which case the brain imaging does not reveal structural abnormalities and type II characterized, from a clinical point of view, by a deficit syndrome (negative symptoms) and brain imaging emphesising underlying structural changes.(5)
In 1982, Andreasen considered that positive and negative symptoms of schizophrenia were the extremes of one dimension (the bipolar theory) and attributed the appearance of negative symptoms to a dopaminergic deficit. She defined five constitutive factors of the negative symptoms: alogia, flat affect, avolition/apathy, anhedonia/asociality and attentional impairment. (6) It is noteworthy that these factors are the same as used today, with the exception of attentional impairment.
Carpenter in 1988 introduced a new perspective towards negative symptoms, distinguishing the primary negative symptoms from the secondary ones, which can be caused by depression, extrapyramidal syndrome induced by antipsychotics, positive symptoms (the paranoid social withdrawal), hospitalism or lack of stimulation. Diagnosing a primary negative symptom implies excluding the potential causes for secondary negative symptoms.(7) Both primary and secondary negative symptoms can be temporary or enduring, and both are associated with poor functional outcomes and poor response to current treatments.(8) Carpenter also defines the deficit subtype of schizophrenia in patients with primary enduring negative symptoms that cannot be explained as sequelae of depression or other psychopathology.(3) The deficit syndrome can be found in drug-naïve patients and perhaps in a third of chronic patients.(7)
A current approach to negative symptoms is based on identifying the persistence of these symptoms during periods of clinical stability regardless of them being primary or secondary as long as they don’t respond to treatment.(8) In clinical trials on persistent negative symptoms it is recommended a minimal severity level, PANSS scores >3 for at least one of the following symptoms: blunted affect, poor rapport, passive withdrawal, emotional withdrawal, lack of spontaneity and a restricted severity of the potential confounders: depression, parkinsonism, positive symptoms and social deprivation. The duration of persistent negative symptoms can be less than 12 months, but preferably more than 6 months. (9, 10, 11)
The International Classification of Diseases Tenth Edition (ICD-10)-Chapter F and the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) are authoritative documents for defining mental disorders. ICD-10 adopted as criteria for schizophrenia Schneider’s first rank symptoms and also included negative symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses (it must be clear that these are not due to depression or neuroleptic medication). (12) DSM-IV- TR recognizes the negative symptoms (blunted affect, alogia and avolition) as being one the five core features of schizophrenia. (13)
MOVING TO DSM-V
There have been controversial opinions in the last decade over the constituent factors of the negative symptoms, so in 2006 the National Institute of Mental Health (NIMH) – the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project- gathered experts in this matter to establish which factors should be included. As a result of this consensus the following factors were included: blunted affect, alogia, social withdrawal, avolition and anhedonia. (14) The validity of these factors was reviewed in subsequent studies. (15, 16). It was also suggested, in the NIMH-MATRICS consensus that these five factors can be classified in two domains: diminished expressivity and avolition/apathy. Diminished expressivity e n c o m p a s s e s b l u n t e d a ff e c t a n d a l o g i a w h i l e avolition/apathy includes social withdrawal, amotivation and anhedonia. Subsequently this hypothesis was validated by several studies. (14, 17, 18)
Recent studies, from 2013 and 2014, confirmed the existence of the two domains, but more importantly, they emphasized the fact that the domains should be analyzed separately, due to the different clinical presentation, but mostly because of the different outcomes of the patients, in terms of functioning and quality of life. (19, 20)
This is the point of view is also embraced in the DSM V. In the DSM-V the negative symptoms are considered one of the five defining domains among hallucinations, delusions, abnormal psychomotor function and disorganized speech. A new approach of DSM-V is the fact that these symptoms are quantifiable on a scale from 0 to 4, which might be useful in terms of evaluation and comparison. According to DSM-V, the negative symptoms comprise: 1. avolition, including decreased motivation, social withdrawal (asociality) and anticipatory anhedonia and 2. diminished emotional expression covering blunted affect and poverty of speech (alogia). Avolition stands for the lack of goal and initiative, while the diminished expressivity implies the reduced emotional expression represented in verbal or non-verbal modes (decreased spontaneity, fluency and quantity of speech, reduced facial expressions, gestures, body movements). (21)

CONCLUSIONS
Negative symptoms are considered, nowadays, to be a core feature of the phenomenology of schizophrenia, being a distinct domain and representing a separate therapeutic target. (14)
The prevalence of primary negative symptoms according to recent studies is around 52%-57% in outpatients with schizophrenia. (22, 23) It has been suggested that the negative symptoms have a greater impact on everyday functioning than other categories of symptoms. They may affect the patients’ capacity to work or study, to maintain relationships, to participate in everyday activities, and to live independently (24). These outcomes were confirmed after the statistical control of the possible sources of secondary negative symptoms (depression, extrapyramidal symptoms, positive symptoms, hospitalism, lack of environmental stimulation) (25). Schizophrenia has strong economic impact, given the costs of medical care for inpatients or outpatients, the community services, treatments, social services. The socioeconomic burden of this disease implies direct costs like hospitalization and medication and indirect costs: social support and the loss of employment. A worldwide study conducted between 2011 and 2013 showed that only 15% of the patients with schizophrenia are employed, which infers that the greatest costs of schizophrenia are related to unemployment (26).
Present treatments, like first-generation neuroleptics and second-generation antipsychotics, mostly address the positive symptoms, while the negative ones are poorly influenced (27). The persistence of these symptoms holds back the reinstatement of the patients, making them incapable to fulfill their social, professional or family roles.

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