Background
Growing evidence has suggested that negative symptoms in psychotic disorders are intractable and associated with poor functional outcome [
1‐
3]. According to the most recent National Institute of Mental Health (NIMH) consensus statement, the negative symptom construct includes blunted affect, anhedonia, alogia, asociality and avolition [
4]. However, broadly classifying negative symptoms into 5 categories does not take into account etiology and duration, which contribute to the heterogeneity of these symptoms [
5]. Thus, negative symptoms are further subdivided into the following subtypes: 1) primary or idiopathic negative symptoms, 2) secondary negative symptoms (caused by positive symptoms, depression, or extrapyramidal symptoms), 3) deficit syndrome or deficit schizophrenia (DS), believed to be a pathophysiological distinct disease within schizophrenia and is diagnosed based on the presence of primary enduring (minimum of 12 consecutive months) [
6], and 4) persistent negative symptoms (PNS) (primary or secondary negative symptoms evident for 6 consecutive months after the stabilization of a first episode of psychosis) [
5].
Persistent negative symptoms have become a major concern given their resistance to treatment and persistence throughout the illness, leading to poor prognosis. Varying terminology and criteria have been used to describe and identify PNS. Consequently, this lack of a consensus definition has yielded mixed results in terms of structural, neuropsychological and functional correlates of PNS [for review see [
7]]. Recently, Buchanan suggested that the duration and severity of negative symptoms must be taken into account when identifying PNS. The following criteria were proposed: having at least moderate negative symptoms, having negligible positive, depressive or extrapyramidal symptoms, and clinical stability for an extended period of time [
5]. Empirical evidence on the proposed criteria for PNS has been scant.
Some have suggested that PNS may represent a broader concept than deficit syndrome [
5,
8]. Deficit syndrome, which is proposed to identify a putatively more homogenous subgroup in schizophrenia, highlights the manifestation of prominent, primary and enduring negative symptoms that are resistant to treatment. The criteria for DS requires that negative symptoms of significant severity be present for a minimum of one year, to have been present at baseline (during periods of relative remission) and are not secondary in nature [
6]. Furthermore, patients must meet the DSM criteria for schizophrenia spectrum disorder [
6]. Deficit syndrome is assessed using the Schedule for the Deficit Syndrome (SDS), which is a semi-structured interview measuring the persistence of 6 negative symptoms including restricted affect, diminished emotional range, poverty of speech, curbed interests, diminished sense of purpose, and diminished social drive [
6]. An individual must have moderate to severe scores on at least 2 of these 6 symptoms. After the introduction of the SDS, the Proxy for the Deficit Syndrome (PDS) was introduced as a case identification for measuring deficit symptoms [
9]. This tool allows one to administer common negative symptoms scales such as the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) and to apply the PDS formula to obtain a score determining whether the patient meets the criteria for DS. The PDS is defined as the sum of the scores for Anxiety, Guilt Feelings, Depressive Mood and Hostility items from the scales subtracted from the score of Blunted Affect [
9].
Unlike DS which is quantified using the SDS [
6], negative symptom severity for PNS can be measured using any validated negative symptom scale. According to the NIMH consensus statement [
4] the Scale for the Assessment of Negative Symptoms (SANS) [
10] has the most extensive coverage. Other scales such as the PANSS [
11] are also widely used, but do not provide as much detail on negative symptoms as the SANS. However, some concerns regarding these scales have been raised. For instance, early evidence suggests that some items from the SANS including, “poverty of content of speech” and “inappropriate affect” represent a disorganization dimension rather than negative symptoms of schizophrenia [
12]. Exploratory and confirmatory factor analytical studies identified three underlying factors in the negative symptoms construct including 1) affective flattening 2) avolition/apathy and anhedonia/asociality and 3) inattention/alogia [
13‐
15]. Concordant factors have been documented in a FEP cohort [
16]. These factors are incorporated into the SANS [
10]. However, there is now a general consensus that inattention may not be conceptually related to negative symptoms [
8,
17,
18]. Furthermore, some findings are suggestive of interrelated yet separate subdomains of negative symptoms in schizophrenia including, 1) diminished expression, composed of affective flattening and poverty of speech, and 2) amotivation, consisting of avolition/apathy and anhedonia/asociality [
4,
8,
17]. Similarly, in patients with DS, a principle component analysis using the Schedule for Deficit Syndrome indicated that DS is best described by two factors including avolition and reduced emotional expression [
19]. It is possible that this multidimensionality within negative symptoms is relevant not only to chronic schizophrenia but to FEP patients with PNS as well; this has not been investigated.
The lack of “gold standard” for PNS has brought up some major concerns [
4,
20‐
22]. Also, studies have not employed comparable criteria to identify PNS. For instance, while one study included patients in the “negative symptom group” if they scored 2 or more on a minimum of 1 global SANS subscales [
23], others have used a score of 3 or more [
3]. In addition, some have also applied criteria that involve having clinically significant symptoms (score ≥3) on a minimum of 2 global items of the SANS [
24].
Given this variability, it is likely that using different criteria for identifying PNS will yield mixed results. Hence, there is a need for PNS criteria that are clinically useful in identifying PNS. The first episode of psychosis may be a critical time to identify individuals with PNS in order to potentially influence these symptoms through more focused intervention such as intensive psychosocial interventions. Further, given the lack of consensus definition for PNS, its prevalence in FEP using well-defined criteria remains unknown. The main objective of this paper was to examine the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis. Second, given that DS also represents a subgroup of patients with enduring negative symptoms, we wanted to contrast the PNS definitions with the proxy definition for deficit syndrome in a FEP cohort. To substantiate the clinical predictive validity of the abovementioned definitions, all were explored in association with patient function followed over a 12-month period in a cohort of first-episode of psychosis patients. We hypothesize that patients meeting the PNS criteria will have poorer functioning than those not meeting the criteria [
25‐
27].
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CLH drafted the first manuscript. RJ, AKM and ML contributed to the design of the study. AKM and JM managed all patient recruitment and clinical assessments. CLH and MB carried out the data analysis. All authors contributed significantly to the interpretation of the data as well as having read and approved the final manuscript.