Characterization of premorbid functioning during childhood in patients with deficit vs. non-deficit schizophrenia and in their healthy siblings

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Abstract

Impaired premorbid adjustment has been reported in patients with schizophrenia, generally in association with unfavorable aspects of the illness (e.g., poor outcome and severe negative symptoms). Several studies attempted to define the domains of premorbid dysfunction associated with negative symptoms and poor outcome; however, most of them assessed broadly defined negative symptoms. The present study was aimed to characterize premorbid functioning in a group of patients with deficit schizophrenia (DS), characterized by the presence of at least two primary and persistent negative symptoms (PPNS), and one of patients with a diagnosis of schizophrenia who did not meet criteria for DS (NDS).

The presence of emotional/behavioral problems during childhood was investigated using the Childhood Behavior Checklist (CBCL) in both patient groups and in their respective healthy siblings. The Premorbid Adjustment Scale (PAS) was also used to assess premorbid functioning during childhood in the two patient groups. PPNS were also treated as a continuous variable and correlated with the indices of premorbid functioning regardless the DS/NDS categorization.

DS patients, as compared to NDS, showed higher scores on the CBCL subscale “Withdrawn”. Both DS and NDS patients showed, as compared to their healthy siblings, a greater impairment on almost all CBCL subscales. PAS findings revealed that DS patients had poorer premorbid adjustment than NDS. No significant correlation between premorbid functioning and PPNS was observed.

These findings support the hypothesis that DS has a different developmental trajectory with respect to NDS, and that premorbid adjustment is one of the essential aspects of its characterization.

Introduction

In patients with schizophrenia, an impairment of premorbid adjustment involving several areas of functioning has been widely reported (Hans et al., 1992, Addington and Addington, 1993, Cannon et al., 2001, Reichenberg et al., 2002). Such an impairment is not found in all patients, as a proportion of them present an abrupt onset with a relatively good premorbid functioning (Neumann et al., 1995, McGlashan, 2008). Moreover, when present, the impairment may vary in its age of onset and course over time, degree of severity, and functional domains involved (Neumann et al., 1995). Many authors reported associations between impaired premorbid functioning and some unfavorable aspects of schizophrenia, including a chronic clinical course, a poor outcome and a higher severity of negative symptoms (Kelley et al., 1992, Haim et al., 2006, Rabinowitz et al., 2002, Rabinowitz et al., 2006, Galderisi et al., 2002, Galderisi et al., 2013, Ayesa-Arriola et al., 2013). Several studies attempted to define the domains of premorbid dysfunction associated with negative symptoms and poor outcome. Most of them used the Premorbid Adjustment Scale (PAS, Cannon-Spoor et al., 1982), extracting two distinct functional subdomains, i.e. a social and an academic one, and found that the impairment of the social domain was more strongly related to the severity of negative symptoms than the impairment of the academic domain (McClellan et al., 2003, Monte et al., 2008, Chang et al., 2013, Strauss et al., 2012).

In these studies, broadly defined negative symptoms were considered, notwithstanding the largely acknowledged heterogeneity within this psychopathological dimension, including negative symptoms that are inherent to the disease (generally referred to as primary) and negative symptoms caused by factors other than the core disease process (generally referred to as secondary negative symptoms, and due to medication side-effects, concurrent depression, and limited social stimulation). Primary negative symptoms are usually enduring and resistant to pharmacological and non-pharmacological interventions, contrary to secondary negative symptoms that are related to identifiable sources, are generally not enduring and are often modifiable with adequate treatment interventions addressing their causes.

Primary and persistent negative symptoms (PPNS) are considered as the main clinical aspect of deficit schizophrenia, a diagnosis requiring the presence during the 12 months preceding the diagnosis of at least two primary negative symptoms.

A poor premorbid adjustment, in conjunction with an insidious onset and a poor response to treatment with antipsychotic drugs, has been reported among the characteristics of deficit schizophrenia (DS) (Carpenter et al., 1988, Kirkpatrick et al., 1996, Fenton and McGlashan, 1994, Galderisi et al., 2002, Kirkpatrick and Galderisi, 2008, Galderisi and Maj, 2009).

Two investigations (Strous et al., 2004, Strauss et al., 2012) focused on PPNS so far. In the former one, the criteria proposed by Mayerhoff et al. (1994) to assess the deficit state in first-episode schizophrenia were used, while in the latter one the Schedule for the Deficit Syndrome was administered to assess PPNS. The two PAS subdomains (i.e., Social and Academic) were analyzed only in the study by Strauss et al. (2012): a greater deterioration of academic than social premorbid functioning was observed in NDS patients, while DS showed comparable deterioration in both premorbid domains, as well as a poorer social premorbid adjustment as compared to NDS.

Two studies (Baum and Walker, 1995, Rossi et al., 2000) explored the relationships between negative symptoms and premorbid adjustment assessed by the Childhood Behavioral Checklist (CBCL; Achenbach, 1991), an instrument evaluating several behavioral and emotional aspects in five age periods in patients as compared to their siblings. Baum and Walker (1995) found that the negative psychopathological dimension was associated with withdrawn behavior, while Rossi et al. (2000) found that patients showing a higher level of behavioral abnormalities during childhood and adolescence had more severe negative symptoms. Neither study assessed PPNS.

The present study was aimed to characterize premorbid functioning in patients with PPNS. In particular, here we tested the hypothesis that patients with DS, as compared to those with NDS, have poorer premorbid functioning since childhood, and that aspects relevant to the negative dimensions (i.e., withdrawal) are also found in healthy siblings of subjects with DS, due to their high genetic load (Smyrnis et al., 2007, Pelayo-Terán et al., 2011, Li et al., 2012). To this aim, the presence of emotional/behavioral problems during childhood was investigated by means of the CBCL in both DS and NDS patients, as well as in their respective healthy siblings; the assessment of premorbid functioning during childhood was also carried out by means of the PAS in the two patient groups. Moreover, since PPNS can still be present in patients with NDS, we also treated them as a continuous quantitative variable and investigated their correlations with the indices of premorbid functioning regardless the DS/NDS categorization.

Section snippets

Subjects

Subjects were recruited in four university departments of psychiatry (Naples, L'Aquila, Milan and Pisa) within a multicenter project aimed at characterizing historical, clinical, neuropsychological and neuroradiological aspects of DS (Galderisi et al., 2013).

Before entering the study, patients participated in a 1-h clinical interview to verify their conformity to the following inclusion criteria: 1) a DSM-IV diagnosis of schizophrenia, confirmed by the Structured Clinical Interview for DSM-IV

Subject characteristics

The initial sample consisted of 51 patients with DS and 44 patients with NDS, recruited within a multicenter study on the historical, clinical, neuropsychological and neuroradiological aspects of DS (Galderisi et al., 2013). From that sample, 43 patients with DS (31 males, 12 females) and 41 with NDS (31 males, 10 females) were included in the present study, since they had at least one sibling and their mother (or father) available for the interview. No difference was observed between the

Discussion

A first prominent finding of this study is that DS patients, as compared to NDS, show higher scores on the CBCL subscale “Withdrawn” over the three considered age periods (0–3, 8–7 and 4–11 years). This subscale is composed by items such as “would rather be alone than with others”, “secretive, keep things to self”, “refused to talk” and “withdrawn, didn't get involved with others”, i.e. aspects that probably interfere since childhood with the socialization processes of the child.

The presence of

Conflicts of interest

AM received fees from the following companies, for the described activities: Amgen Dompè for advisory board and Janssen-Cilag for educational activity.

SG received honoraria from the following companies, for the described activities: Janssen-Cilag and Eli-Lilly for lectures; Amgen-Dompé and Gedeon-Richter for Advisory boards.

AR has received funding for advisory board membership and sponsored lectures from: Astra Zeneca, Bristol-Meyers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer, Stroder.

Contributors

MM, SG, AV, AR and SP contributed to the conception and design of the study. GP coordinated data collection. MN and PB analyzed the data. SG, AM and PB interpreted the data and drafted the manuscript. All Authors participated in the critical revision of the manuscript and provided the final approval of the version to be published.

Role of the funding source

None.

Acknowledgments

The present multicenter study was supported by grant 2003064871 from the Italian Ministry of University and Scientific Research.

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