Psychiatry Research 127 (2004) 8599

Depressive syndrome in major psychoses: a study on 1351 subjects

Alessandro Serretti*, Laura Mandelli, Enrico Lattuada, Enrico Smeraldi
Department of Psychiatry, San Raffaele Institute, Vita-Salute University, School of Medicine, Via Luigi Prinetti 29, 20127 Milan, Italy Received 16 April 2003; received in revised form 23 December 2003; accepted 23 December 2003

Abstract The aim of this study was to investigate depressive symptomatology across distinct major psychiatric disorders. A total of 1351 subjects affected by major depressive disorder (MDDs389), bipolar disorder (BPs511), delusional disorder (DDs93) and schizophrenia (SKZs358) were included in our study. Subjects were assessed using the Operational Criteria for Psychotic Illness checklist (OPCRIT). The most frequently represented depressive symptoms in MDD were Loss of energyytiredness, Loss of pleasure, Poor concentration, and Sleep disorders. Compared with MDD, BP had higher occurrences of Agitated activity, Excessive sleep, and Increased appetite andyor Weight gain, as well as lower Loss of pleasure. In our sample, 32.3% and 26.8% of DD and SKZ, respectively, had quite consistent depressive symptomatology, with at least four or more depressive symptoms. The most common depressive symptoms were Sleep disorders, Poor concentration and Loss of energyyTiredness, followed by Psychomotor symptoms in SKZ only. Excessive self-reproach, Suicidal ideation, and Appetite andyor Weight changes were more specific to mood disorders. Finally, compared with SKZ, DD suffered from more depressive symptoms and had more severe depressive symptomatology. A quite consistent level of depressive symptomatology is therefore present in subpopulations of delusional and schizophrenic subjects other than in affective subjects. We identified some symptoms that are common across all major psychoses and symptoms that are more specific to each group. 2004 Elsevier Ireland Ltd. All rights reserved.
Keywords: Depression; Bipolar disorder; Depressive disorder; Delusional disorder; Schizophrenia; Symptomatology

1. Introduction Depression is a condition mainly characterized by depressed mood andyor loss of pleasure in all or almost all activities. The state can be accompanied by loss of energy or tiredness, excessive and inappropriate guilt and feelings of worthless*Corresponding author. Tel.: q39-02-2643-3250; fax: q3902-2643-3265. E-mail address: serretti.alessandro@hsr.it (A. Serretti). 0165-1781/04/$ - see front matter doi:10.1016/j.psychres.2003.12.025

ness, as well as other cognitive, speech and vegetative dysfunctions. A depressive syndrome is typical of affective disorders, but it is well known that depressive symptoms occur in a wide range of other conditions. However, there is no general agreement on the definition of common and specific features of depressive symptomatology across disorders. Several differences have been reported for depression in bipolar and major depressive sub-

2004 Elsevier Ireland Ltd. All rights reserved.

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jects. In 1921, Kraepelin advised that manic depression differed from melancholia in respect to a more pronounced volition inhibition and less prominent dysphoria (Kraepelin, 19091915). In the following years, bipolar disorder has been well characterized with regard to a number of clinical and demographic features (Goodwin and Jamison, 1990) but has been less studied at the level of symptoms. In this area, a greater incidence of psychotic features (Akiskal et al., 1983; Weissman et al., 1984; Serretti et al., 2002), a greater risk of completed or attempted suicide (Goodwin and Jamison, 1990; Lester, 1993), a lower illness perception (Serretti et al., 2002), more atypical features (Bourgeois et al., 1988; Mitchell et al., 2001; Serretti et al., 2002), more marked excessive self-reproach and guilt (Winokur and Wesner, 1987), and greater psychomotor retardation (Bourgeois et al., 1988; Goodwin and Jamison, 1990; Mitchell et al., 2001) were observed, although in other studies psychomotor retardation is considered less common and agitation more likely in bipolar patients (Mitchell et al., 1992; Serretti et al., 2002). Major depressives have been characterized by more agitation (Goodwin and Jamison, 1990; Cvjetkovic-Bosnjak, 1998), more anxiety (Donnelly et al., 1978; Goodwin and Jamison, 1990; Cvjetkovic-Bosnjak, 1998), weight loss (Goodwin and Jamison, 1990) and a higher risk of completed suicide (Lester, 1993) compared with bipolar patients. From the above-mentioned studies, we see that some differences between the two diagnoses are well established, while others are still controversial. Depression in schizophrenia has been much less studied. Bleuler (1911y1950) and Kraepelin (19091915) observed the presence of depressive symptoms during the course of the illness. The incidence of depressive features is currently accepted as frequent, though the reported rate of depression ranges from 7 to 75%, with a modal rate of 25% (Siris et al., 2001). Diagnostic criteria to assess depression in schizophrenia are still discussed (Becker et al., 1985; Addington et al., 1990; Newcomer et al., 1990; Addington et al., 1992; Collins et al., 1996; Sax et al., 1996; Kontaxakis et al., 2000; Ramirez et al., 2001). The

latest international classifications include specific categories for depression in schizophrenia: postpsychotic depression (ICD-10) and post-psychotic depressive disorder (DSM-IV). Post-psychotic depression is a controversial issue that has been considered from several different perspectives: as a phase of psychotic evolution, as secondary to neuroleptic treatment, or as a state that was present but hidden by acute psychosis (Fadda and Muller, 1975; Rigaud, 1991). Depressive symptoms sometimes appear to bode well for outcome in schizophrenia, while a contrary view is that depressive symptoms relate to increased risk self-harm, suicide, schizophrenic relapse, poor outcome and social dysfunctions (Becker et al., 1985; Herrman, 1987; Rigaud, 1991; Sands and Harrow, 1999; Siris et al., 2001). Depressive symptoms were found to occur not only in the post-psychotic phase, but during all phases of schizophrenia (Bartels and Drake, 1988; Rigaud, 1991). A relatively high incidence of depressive symptoms was found in acute schizophrenia (Montgomery, 1979), up to 60% (Martin et al., 1985) and even higher, in other phases (Knights and Hirsch, 1981). Other studies showed similar occurrences of depressive symptoms in acute and chronic schizophrenia (Hinterhuber and Neumann, 1985). High incidences of depressive symptoms were also found at the first episodes of the illness (House et al., 1987; Koreen et al., 1993). A study of Subotnik et al. (1997) found an association between depressive symptoms in the early course of schizophrenia and a positive family history of unipolar affective illness, suggesting that the expression of depressive symptoms in schizophrenia could be influenced by a familial liability. The relationships between depressive symptoms, neuroleptic treatment, and negative and positive symptoms are controversial. The effect of neuroleptic medication on depressive symptoms is uncertain (Berrios and Bulbena, 1987; House et al., 1987; Siris et al., 2001). The severity of depressive symptoms was found to decrease with effective neuroleptic treatment (Knights and Hirsch, 1981; Moller and von Zerssen, 1982; Tapp et al., 2001) or not to be related (Hinterhuber and Neumann, 1985; Hirsch et al., 1989; Baynes et al., 2000). Furthermore, neuroleptics were found to

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87

ameliorate depressive symptoms during the acute phase, and contribute to depression over time (Krakowski et al., 1997). Relations between the negative syndrome of schizophrenia and depressive symptoms are also controversial (Rigaud, 1991). The majority of studies found no significant associations between negative symptoms and depressive symptoms (House et al., 1987; Hirsch et al., 1989; Lindenmayer et al., 1991; Kuck et al., 1992; Miller et al., 1994; Nakaya et al., 1997; Perenyi et al., 1998; Mauri et al., 1999; Zisook et al., 1999; Baynes et al., 2000), but significant associations have also been reported (Kulhara et al., 1989; Sax et al., 1996). A comparison between schizophrenic and major depressed patients found either a difference (Serretti et al., 1996) or no significant difference concerning negative symptomatology (Gerbaldo et al., 1995). During acute phases, the course and severity of depressive symptoms were found by some to be related to the course of psychotic symptoms (Leff et al., 1988; Lindenmayer et al., 1991; Mauri et al., 1995; Sax et al., 1996; Nakaya et al., 1997; Mauri et al., 1999; Zisook et al., 1999; Baynes et al., 2000; Tapp et al., 2001), while others found no significant correlation at the post-acute and residual phases (Dollfus et al., 1993). Some have reported that the depressive profile in schizophrenia differs from primary depression in showing lesser severity as measured by the Hamilton Depression Rating Scale. Therefore, it was interpreted as a milder form of, but not qualitatively distinguishable from, primary depression (Weissman et al., 1977). Others observed that the two disorders differed qualitatively: in schizophrenic patients, symptom profile expressed in part the schizophrenic syndrome and in part a secondary depression syndrome (Becker et al., 1985). A lower prevalence of depressive symptoms was reported in so-called Kraepelinian schizophrenia (Keefe et al., 1991, 1996; Kilzieh et al., 2003), suggesting a potential relationship between nonKraepelinian schizophrenia and mood disorders. Delusional disorder is a condition characterized by the presence of one or more non-bizarre delusions, in which mood is generally congruent with delusional themes. In order to diagnose delusional disorder, mood symptoms should not be wide-

spread (American Psychiatric Association, 1994); nevertheless, a high frequency of mood disturbances in delusional disorder has been observed (Marino et al., 1993). A co-diagnosis of true mood disorder has also been hypothesized (Manschreck, 1996; Schanda, 2000; Maina et al., 2001). But detailed analyses are lacking. This study evaluated depression symptomatology across the following major psychiatric disorders: mood disorders (major depressive and bipolar), schizophrenia and delusional disorder. 2. Methods 2.1. Sample A total of 1351 patients affected by major depressive disorder (MDD, ns389), bipolar disorder (BP, ns511), delusional disorder (DD, ns 93) and schizophrenia (including schizoaffective subjects) (SKZ, ns358), admitted to the Department of Psychiatry at San Raffaele Hospital, Milano, were included in the study. Lifetime diagnoses were assigned by two independent psychiatrists on the basis of interviews and medical records, according to DSM-III-R and DSM-IV criteria (American Psychiatric Association, 1987, 1994). Other information was gathered from the patients family and, wherever possible, from clinical records following a best estimate procedure (Leckman et al., 1982). The present sample includes subjects from clinical (Bellini et al., 1992; Benedetti et al., 1996a,b; Gatti et al., 1996; Benedetti et al., 1999a,b; Lattuada et al., 1999; Serretti et al., 1999a,b, 1998a; Zanardi et al., 1997, 1998, 2000a,b) and genetic studies (Serretti et al., 1998b, 2000, 2001a,b). Among the sample, 118 subjects were collected in the context of the European Collaborative Project on Affective Disorders (Souery et al., 1998). Our Research Center for Mood Disorders is a specialized institution for treatment of mood disorders with 50 acute inpatients and approximately 3000 outpatients; over 2000 new cases visited our Center for Mood Disorders during the study period (19932001). Of those, we selected 1351 subjects, excluding from the sample individuals with mental retardation, dementia, substance abuseydependence, neu-

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rological disorder or clinicalylaboratory indications of severe organic disease. The patients were included in the study after they had given informed consent. The sample consisted of 758 females and 593 males (56.11y43.89%); they were all Caucasians. The mean age at admission was 44.99"14.69 years. The mean age at onset was 31.42"12.70 years. For further analysis (see Section 3), we selected from the DD and SKZ groups those subjects having a more consistent depressive symptomatology, choosing patients who had at least four or more depressive symptoms. After this selection, the DD and SKZ subgroups were, respectively, 30 (32.3%) and 96 (26.8%). In those subsamples, female ratios were 66.7% for DD and 41.7% for SKZ. DD had a mean age of 50.4"12.6 years and a mean age at onset of 40.1"9.6. SKZ had a mean age of 36.1"11.7 years and a mean age at onset of 23.9"7.3. 2.2. Ratings All patients were assessed using the Operational Criteria for Psychotic Illness checklist (OPCRIT; McGuffin et al., 1991) with a lifetime perspective (Farmer et al., 1994). The factoring process of the OPCRIT checklist has been previously reported (Cardno et al., 1996; Serretti et al., 1996). The factor composition of depression and negative factors is as follows: Depression (items: Loss of pleasure, Loss of energyytiredness, Diminished libido, Excessive self-reproach, Slowed activity, Poor appetite, Poor concentration, Suicidal ideation, Weight Loss, Diurnal variation, Early morning waking, Delusions of guilt), Negative (items: Blunted affect, Negative formal thought disorder, Restricted affect, Catatonia). Factor scores were calculated as the sum of binarized items divided by the number of items in each factor. Depressive symptoms were defined using the following OPCRIT items: Loss of pleasure, Agitated activity, Slowed activity, Loss of energyytiredness, Poor concentration, Excessive self-reproach, Suicidal ideation, Initial insomnia, Middle insomnia, Early morning waking, Excessive Sleep, Poor appetite, Weight Loss, Increased appetite, Increased weight. We also derived from pooled OPCRIT items the

following: Psychomotor symptoms (Agitated activity andyor Slowed activity), Sleep disorders (Initial insomnia andyor Middle insomnia andyor Early morning waking, Insomnia andyor Excessive Sleep), AppetiteyWeight Changes (Poor appetite andyor Weight loss andyor Increased appetite andy or Increased weight). Depressed mood is included in the OPCRIT checklist in the item Dysphoria together with irritable and sad mood or pervasive loss of interest, so we did not include this item in the analysis since it was not possible to consider it separately. 2.3. Statistical analysis Differences were assessed by t-test (with pooled or separate variances). Frequencies were compared by chi-square test. Alpha was considered significant when -0.0025 (Bonferroni-corrected). For categorical analyses, the power of our sample to detect differences between groups was calculated considering an alpha value of 0.25%, two-tailed. With these parameters in our sample, we had a high power (0.80) to detect a small effect size (ws0.13) that corresponded to a difference of approximately 12% of symptom rate between the two main groups (Cohen, 1988). 3. Results 3.1. Demographic and clinical features (Table 1) In the present sample, the male to female ratio was approximately 1:2 for MDD, BP and DD, while it was reversed in SKZ. At admission, SKZ subjects were younger compared with all other subjects and they were also younger at onset. BP subjects were significantly younger than MDD subjects and with a lower age at onset than both MDD and DD subjects (Table 1). 3.2. Depressive and negative OPCRIT scores (Table 2) MDD subjects had higher scores for depression compared with all other subjects, but not significantly different from BP subjects. BP subjects had higher scores than DD and SKZ subjects. Negative

A. Serretti et al. / Psychiatry Research 127 (2004) 8599 Table 1 Demographic and clinical features of the sample MDD N (%) Female Male 266 (68.38%) 123 (31.62%) 389 Mean"S.D. 50.27"13.64 36.96"13.60 BP N (%) 314 (61.45%) 197 (38.55%) 511 Mean"S.D. 46.56"14.89 31.03"11.86 SKZ N (%) 119 (33.24%) 239 (66.76%) 358 Mean"S.D. 50.30"12.81 40.02"12.49 DD N (%) 59 (63.44%) 34 (36.56%) 93 Mean"S.D. 35.07"10.65 23.13"6.45 N totals 758 593 1351 1252 1275 Chi-sq. 108.46 P 0.0001

89

Notes
a

Age Onset

F 82.51 130.26

P 0.0001 0.0001

b c

a Female sex incidence is significantly higher in MDD, BP and DD; lower in SKZ. SKZ are more likely male than MDD (chisquares93.56; d.f.s1; Ps0.0001), BP (chi-squares68.03; d.f.s1; Ps0.0001) and DD (chi-squares27.65; d.f.s1; Ps0.0001). MDD show a trend to be more likely female than BP (chi-squares4.66; d.f.s1; Ps0.0309). DD are not significantly different from MDD and BP. b Age significantly differs between diagnoses. SKZ are younger than MDD (t-values15.98; d.f.s675; Ps0.0001), BP (t-values 11.89; d.f.s805; Ps0.0001) and DD (t-values11.09; d.f.s396; Ps0.0001). BP are younger than MDD (t-valuesy3.73; d.f.s 852; Ps0.0002) and BP show a similar trend towards DD (t-valuesy2.16; d.f.s573; Ps0.0314). c SKZ have lower age at onset: than MDD (t-values16.61; d.f.s695; Ps0.0001), BP (t-values10.87; d.f.s809; Ps0.0001) and DD (t-values17.02; d.f.s399; Ps0.0001). BP have lower age at onset than MDD (t-valuesy6.88; d.f.s872; Ps0.0001) and DD (t-valuesy6.38; d.f.s576; Ps0.0001).

scores were higher for SKZ than for all other subjects (Table 2). 3.3. Depressive symptoms (Table 3) The MDD sample showed elevated rates for all depressive symptoms (see Fig. 1). Psychomotor symptoms were mostly represented by Slowed activity (85.3%) rather than Agitated activity (21.8%); Sleep disorders were represented mostly by Insomnia (93.1%) rather than Excessive sleep (10.0%); finally Appetite andyor Weight changes mostly involved Poor appetite andyor Loss of weight (85.1%) instead of Appetite andyor Weight increase (6.4%). The BP sample showed a depressive pattern similar to MDD concerning symptoms such as Loss of Pleasure, Poor concentration, Slowed activity, Excessive self-reproach, Sleep disorders and AppetiteyWeight changes. Nevertheless, the BP sample showed significantly higher incidences of Agitated activity (74.8%) and more atypical features such as Excessive sleep (20.5%) and Appetite andyor Weight increase (18.0%). Finally, the BP sample had lower incidences of Loss of energyyTiredness compared with the MDD sample and a trend for less Suicidal ideation (Table 3).

Among SKZ, Poor concentration was the most common symptom (55.9%), followed by Psychomotor symptoms (44.7%), Loss of energy (34.6%) and Sleep disorders (30.4%). In DD, the most common depressive symptoms were Sleep disorders (47.3%), Poor concentration (40.9%) and Loss of energy (36.6%). Compared with SKZ, DD had fewer Psychomotor symptoms and less Agitated activity, but a higher incidence of Excessive self-reproach, Suicidal ideation, Insomnia and Poor appetite andyor Weight loss. 3.4. SKZ and DD with four or more depressive symptoms (Table 4, Fig. 2) Among DD and SKZ, we selected those subjects with a more consistent pattern of depressive symptomatology by choosing those patients who had at least four or more depressive symptoms. After the selection, DD and SKZ were, respectively, 30 (32.3%) and 96 (26.8%) (Table 4; Fig. 2). Compared with these SKZ and DD subjects, the combined sample of MDD and BP (AFF) still had more depressive symptoms and a greater severity of depressive symptomatology (i.e. higher OPCRIT factor scores for depression). Compared

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Table 2 Depression and negative OPCRIT scores, calculated for 1351 subjects MDD Mean"S.D. Depression Negative Totals
a

BP Mean"S.D. 0.7984"0.16 0.0758"0.16 511

SKZ Mean"S.D. 0.1618"0.15 0.493"0.26 358

DD Mean"S.D. 0.2088"0.26 0.1102"0.18 93

F 1589.00 438.66

P 0.0001 0.0001

Notes
a b

0.8168"0.13 0.0553"0.14 389

Depressive: MDD have the highest scores, significantly higher than DD (t-values32.05; d.f.s480; Ps0.0001) and SKZ (tvalues63.57; d.f.s745; Ps0.0001). BP have higher scores than DD (t-values29.04; d.f.s602; Ps0.0001) and SKZ (t-values 58.92; d.f.s867; Ps0.0001). b Negative: SKZ have higher scores than MDD (t-valuesy28.90; d.f.s745; Ps0.0001), BP (t-valuesy28.97; d.f.s867; Ps 0.0001) and DD (t-valuesy13.25; d.f.s449; Ps0.0001). DD have higher scores than MDD (t-valuesy3.24; d.f.s480; Ps 0.0013).

with SKZ, DD showed a higher number of depressive symptoms and a more severe level of depressive symptomatology. SKZ still had higher OPCRIT factor scores for negative symptomatology than both DD and AFF. This SKZ subsample mainly showed Poor concentration (94.8%), Psychomotor symptoms (93.8%), both Slowed (61.5%) and Agitated activity (53.1%), Loss of energy (90.6%), Loss of pleasure (74.0%) and Insomnia (72.9%). Less frequently represented symptoms were Suicidal ideation (20.8%), Excessive self-reproach (7.3%) and Excessive sleep (6.2%). These SKZ subjects did not significantly differ from AFF subjects regarding Agitated activity, Loss of EnergyyTiredness, Loss of pleasure and Poor concentration, but they showed less Slowed activity, Excessive selfreproach, Suicidal ideation, Sleep disorders, and Appetite andyor Weight changes. Those DD having four or more depressive symptoms mainly showed Loss of energyyTiredness (90.0%), Poor concentration (90.0%), Insomnia (86.7%) and Loss of pleasure (80.0%). Occurrences of Suicidal ideation (56.7%), Poor appetite (53.3%), Slowed activity (50.0%), Excessive selfreproach (50.0%) and Agitated activity (30.0%) were moderate. Less common symptoms were Excessive sleep (13.3%) and Increased appetite (13.3%). This subsample of DD was not different from AFF regarding the occurrence of Agitated activity, Loss of energyyTiredness, Poor concentration, Sleep disorders and Suicidal ideation, whereas DD

had lower incidences of Slowed activity, Loss of pleasure, Excessive self-reproach, and Appetite andyor Weight changes compared with AFF. From a general point of view, symptoms such as Loss of energyyTiredness, Poor concentration, Sleep disorders and Psychomotor symptoms are highly represented throughout the various disorders, although significant differences were observed between diagnostic subgroups. Loss of pleasure, Excessive self-reproach, Appetiteyweight changes and Suicidal ideation were highly represented in AFF, moderately represented in DD and less represented in SKZ. 4. Discussion This study analyzed depressive profiles in major psychoses and found a considerable occurrence of depressive symptoms in schizophrenia and delusional disorders, particularly Loss of energyyTiredness, Poor concentration and Sleep disorders. Demographic data were substantially consistent with the literature: MDD subjects were more likely female (Goodwin and Jamison, 1990; Winokur et al., 1993; Rouillon, 1997); BP subjects were younger than MDD (Goodwin and Jamison, 1990; Cvjetkovic-Bosnjak, 1998), they had an earlier onset (Goodwin and Jamison, 1990; Winokur et al., 1993; McMahon et al., 1994; Angst and Preisig, 1995; Rouillon, 1997), but departed from the accepted 1:1 female-to-male ratio (Perris, 1966; Goodwin and Jamison, 1990). Our data support the mean onset age of 40 for DD and a

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Fig. 1. Incidence (%) of depressive symptoms stratified for diagnosis (MDDs389; BPs511; DDs93; SKZs358).

slight predominance of females (Kaplan and Sadock, 1995). In disagreement with the literature (Kaplan and Sadock, 1995), we found a predominance of males in schizophrenia instead than an equal proportion of men and woman. According to previous studies, BP had more atypical features (Bourgeois et al., 1988; Mitchell et al., 2001), more overall Psychomotor symptoms and more Agitated activity, though the lifetime perspective does not allow these symptoms to be unequivocally ascribed to the depressive phases. Consistent with some studies (Mitchell et al., 1992) and in contrast to others (Bourgeois et al., 1988; Goodwin and Jamison, 1990; Mitchell et al., 2001), Slowed activity occurred equally in BP and MDD. Unlike previously reported findings (Winokur and Wesner, 1987), BP did not have more Excessive selfreproach than MDD. We did not have data on suicide attempts, but in spite of a higher risk of completed andyor attempted suicide in BP compared with MDD (Goodwin and Jamison, 1990), we found a trend for less Suicidal ideation in BP. However, Suicidal ideation and Suicide attempt refer to distinct dimensions, ideational and behavioral, and they may not be related. Regarding the symptomatology of schizophrenia and delusional disorder, in disagreement with reported findings (Gerbaldo et al., 1995) but con-

firming our previous analysis (Serretti et al., 1996), negative symptomatology was different in MDD and SKZ. Those discrepancies could be due to different assessment procedures; in fact, the majority of studies in the field used the Scales for the Assessment of Positive and Negative Symptoms, which slightly differ from the OPCRIT in the presentation of items. Overall, a number of depressive symptoms were present in SKZ and DD. We have no data about the percentage of subjects diagnosed as schizoaffective, but the restrictive criteria requested by DSM-IV cast doubt on the validity of this diagnosis (Levinson et al., 1999). The fact that more than one quarter of SKZ subjects presented more than four depressive symptoms suggests that depression should be considered as a separate entity from pure schizophrenia symptomatology. Moreover, we observed that it is not due to negative symptomatology, which is clearly separate in the two diagnoses. Further studies from other approaches (neuropsychology, biology, genetics) may help to disentangle the issue. The purpose of this study was to evaluate depressive symptoms across diagnoses. Therefore, we considered symptomatological features between samples but we did not consider possible demographic and clinical differences between patients

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Table 3 Incidence of depressive symptoms for diagnosis; calculated for 1351 subjects (MDDs389; BPs511; DDs93; SKZs358) MDD N (%) Psychomotor symptoms Absent Present Agitated activity Absent Present Slowed activity Absent Present Loss of energyytiredness Absent Present Loss of pleasure Absent Present Poor concentration Absent Present Excessive self-reproach Absent Present Suicidal ideation Absent Present Sleep disorders Absent Present Insomnia Absent Present Excessive sleep Absent Present AppetiteyWeight changes Absent Present Poor appetite andyor weight loss Absent Present 51 (13.11%) 338 (86.89%) 304 (78.15%) 85 (21.85%) 57 (14.65%) 332 (85.35%) 5 (1.29%) 384 (98.71%) 6 (1.54%) 383 (98.46%) 10 (2.57%) 379 (97.43%) 26 (6.68%) 363 (93.32%) 102 (26.22%) 287 (73.78%) 13 (3.34%) 376 (96.66%) 27 (6.94%) 362 (93.06%) 350 (89.97%) 39 (10.03%) 41 (10.54%) 348 (89.46%) 58 (14.91%) 331 (85.09%) BP N (%) 24 (4.70%) 487 (95.30%) 129 (25.24%) 382 (74.76%) 69 (13.50%) 442 (86.50%) 27 (5.28%) 484 (94.72%) 20 (3.91%) 491 (96.09%) 8 (1.57%) 503 (98.43%) 52 (10.18%) 459 (89.82%) 179 (35.03%) 332 (64.97%) 11 (2.15%) 500 (97.85%) 23 (4.50%) 488 (95.50%) 406 (79.45%) 105 (20.55%) 65 (12.72%) 446 (87.28%) 92 (18.00%) 419 (82.00%) SKZ N (%) 198 (55.31%) 160 (44.69%) 255 (71.23%) 103 (28.77%) 275 (76.82%) 83 (23.18%) 234 (65.36%) 124 (34.64%) 258 (72.07%) 100 (27.93%) 158 (44.13%) 200 (55.87%) 344 (96.09%) 14 (3.91%) 326 (91.06%) 32 (8.94%) 249 (69.55%) 109 (30.45%) 257 (71.79%) 101 (28.21%) 344 (96.09%) 14 (3.91%) 312 (87.15%) 46 (12.85%) 337 (94.13%) 21 (5.87%) DD N (%) 67 (72.04%) 26 (27.96%) 79 (84.95%) 14 (15.05%) 77 (82.80%) 16 (17.20%) 59 (63.44%) 34 (36.56%) 67 (72.04%) 26 (27.96%) 55 (59.14%) 38 (40.86%) 77 (82.80%) 16 (17.20%) 75 (80.65%) 18 (19.35%9 49 (52.69%9 44 (47.31%) 50 (53.76%) 43 (46.24%) 89 (95.70%) 4 (4.30%) 70 (75.27%) 23 (24.73%) 73 (78.49%) 20 (21.51%) N Chi-sq 425.00 340 1011 353.66 767 584 553.89 478 873 641.89 325 1026 782.74 351 1000 443.51 231 1120 1048.89 499 852 456.27 682 669 694.99 322 1029 622.17 357 994 67.32 1189 162 737.35 488 863 767.03 560 791 0.0001
o

P 0.0001

Notes
a

0.0001

0.0001

A. Serretti et al. / Psychiatry Research 127 (2004) 8599

0.0001

0.0001

0.0001

0.0001

0.0001

0.0001

0.0001

0.0001

0.0001

Table 3 (Continued) MDD N (%) Increased appetite andyor weight gain Absent Present No. symptoms
a

BP N (%)

SKZ N (%)

DD N (%)

Chi-sq 40.92

P 0.0001

Notes
p

364 (93.57%) 25 (6.43%) Mean"S.D. 7.347"0.9196

419 (82.00%) 92 (18.00%) Mean"S.D. 7.2446"1.0426

332 (92.74%) 26 (7.26%) Mean"S.D. 2.1927"1.8933

88 (94.62%) 5 (5.38%) Mean"S.D. 2.4194"2.6015

1203 148 N 1351

F 1236.02

P 0.0001

Notes
q

AFF had more Psychomotor symptoms than DD (Chi-sqs188.48; d.f.s1; Ps0.0001) and SKZ (Chi-sqs307.56; d.f.s1; Ps0.0001). SKZ had more Psychomotor symptoms than DD (Chi-sqs8.84; d.f.s1; Ps0.0001). b BP had higher incidence of Agitated activity than MDD (Chi-sqs260.48; d.f.s1; Ps0.0001), than DD (Chi-sqs121.59; d.f.s1; Ps0.0001) and SKZ (Chisqs185.82; d.f.s1; Ps0.0001). SKZ had a trend for more Agitated activity than DD (Chi-sqs7.89; d.f.s1; Ps0.0050). c AFF had a higher incidence of Slowed activity than DD (Chi-sqs191.55; d.f.s1; Ps0.0001) and SKZ (Chi-sqs458.2; d.f.s1; Ps0.0001). d AFF had more Slowed activity than DD (Chi-sqs209.83; d.f.s1; Ps0.0001) and SKZ (Chi-sqs559.89; d.f.s1; Ps0.0001). MDD had a higher incidence of Loss of energyyTiredness than BP (Chi-sqs11.58; d.f.s1; Ps0.0007). e AFF had a higher incidence of Loss of pleasure than DD (Chi-sqs271.72; d.f.s1; Ps0.0001) and SKZ (Chi-sqs684.14; d.f.s1; Ps0.0001). f AFF had a higher incidence of Poor concentration than DD (Chi-sqs219.33; d.f.s1; Ps0.0001) and SKZ (Chi-sqs350.63; d.f.s1; Ps0.0001). g AFF had more Excessive self-reproach than DD (Chi-sqs244.25; d.f.s1; Ps0.0001) and SKZ (Chi-sqs956.37; d.f.s1; Ps0.0001). DD had a higher incidence of Excessive self-reproach than SKZ (Chi-sqs16.97; d.f.s1; Ps0.0001). h AFF had more Suicidal ideation than DD (Chi-sqs97.03; d.f.s1; Ps0.0001) and SKZ (Chi-sqs409.26; d.f.s1; Ps0.0001). MDD had a trend for more Suicidal ideation than BP (Chi-sqs0.0045; d.f.s1; Ps0.0045). DD showed a trend for more Suicidal ideation than SKZ (Chi-sqs7.2; d.f.s1; Ps0.0073). i AFF had more Sleep disorders than DD (Chi-sqs171.62; d.f.s1; Ps0.0001) and SKZ (Chi-sqs654.74; d.f.s1; Ps0.0001). DD had a trend for a higher incidence of sleep disorders than SKZ (Chi-sqs9.05; d.f.s1; Ps0.0026). l AFF had a higher incidence of Insomnia than DD (Chi-sqs134.08; d.f.s1; Ps0.0001) and SKZ (Chi-sqs585.93; d.f.s1; Ps0.0001). DD had more Insomnia than SKZ (Chi-sqs10.57; d.f.s1; Ps0.0011). m BP had a higher incidence of Excessive sleep than MDD (Chi-sqs18.97; d.f.s1; Ps0.0001), DD (Chi-sqs18.22; d.f.s1; Ps0.0001) and SKZ (Chi-sqs 56.81; d.f.s1; Ps0.0001). MDD had more Excessive sleep than SKZ (Chi-sqs13.04; d.f.s1; Ps0.0009) but not more than DD. n AFF had more AppetiteyWeight changes than DD (Chi-sqs171.33; d.f.s1; Ps0.0001) and SKZ (Chi-sqs672.57; d.f.s1; Ps0.0001). DD had a trend for more AppetiteyWeight changes than SKZ (Chi-sqs7.30; d.f.s1; Ps0.0069). o AFF had more Poor appetite andyor Weight loos than DD (Chi-sqs149.97; d.f.s1; Ps0.0001) and SKZ (Chi-sqs708.42; d.f.s1; Ps0.0001). DD had more Poor appetite andyor Weight loss than SKZ (Chi-sqs18.10; d.f.s1; Ps0.0001). p BP had more Increased appetite andyor Weight gain than MDD (Chi-sqs28.08; d.f.s1; Ps0.0001), DD (Chi-sqs11.53; d.f.s1; Ps0.0007) and SKZ (Chisqs22.15; d.f.s1; Ps0.0001). q AFF had more Depressive symptoms than DD (t-tests36.25; d.f.s991; Ps0.0001) and SKZ (t-tests62.13; d.f.s1256; Ps0.0001).

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Table 4 Depressive symptoms, depression and negative OPCRIT factor scores for AFF (ns900), DEL (ns30) and SKZ (ns96). DD and SKZ included had four or more depressive symptoms AFF N (%) Psychmotor symptoms Absent Present Loss of energy Absent Present Loss of pleasure Absent Present Poor concentration Absent Present Excessive self-reproach Absent Present Suicidal ideation Absent Present Sleep disorders Absent Present Appetite andyor Weight changes Absent Present No. Symptoms Depression Negative 75 (8.33%) 825 (91.67%) 32 (3.56%) 868 (96.44%) 26 (2.89%) 874 (97.11%) 18 (2.00%) 882 (98.00%) 78 (8.67%) 822 (91.33%) 281 (31.22%) 619 (68.78%) 24 (2.67%) 876 (97.33%) 106 (11.78%) 794 (88.22%) Mean"S.D. 7.29"0.99 0.81"0.15 0.07"0.15 SKZ N (%) 6 (6.25%) 90 (93.75%) 9 (9.38%) 87 (90.63%) 25 (26.04%) 71 (73.96%) 5 (5.21%) 91 (94.79%) 89 (92.71%) 7 (7.29%) 76 (79.17%) 20 (20.83%) 23 (23.96%) 73 (76.04%) 70 (72.92%) 26 (27.08%) Mean"S.D. 4.84"0.76 0.35"0.10 0.65"0.22 DEL N (%) 10 (33.33%) 20 (66.67%) 7.58 3 (10.00%) 27 (90.00%) 64.6 6 (20.00%) 24 (80.00%) 7.19 3 (10.00%) 27 (90.00%) 336.84 15 (50.00%) 15 (50.00%) 84.68 13 (43.33%) 17 (56.67%) 53.12 3 (10.00%) 27 (90.00%) 172.32 12 (40.00%) 18 (60.00%) Mean"S.D. 5.83"1.32 0.53"0.20 0.10"0.17 F 290.44 444.73 590.01 P 0.0001 0.0001 0.0001 Notes
g h i

Chi-sq 15.2

P 0.0005

Notes
a

n.s.

0.0001

n.s.

0.0001

0.0001

0.0001

0.0001

a DD had fewer Psychomotor symptoms than AFF (Chi-sqs14.22; d.f.s1; Ps0.0002), in particular less Slowed activity (Chisqs20.90; d.f.s1; Ps0.0001). SKZ had less Slower activity than AFF (Chi-sqs30.86; d.f.s1; Ps0.0001). b AFF had more Loss of pleasure than DD (Chi-sqs12.96; d.f.s1; Ps0.0003) and SKZ (Chi-sqs56.82; d.f.s1; Ps0.0001). c AFF had more Excessive self-reproach than DD (Chi-sqs32.50; d.f.s1; Ps0.0001) and SKZ (Chi-sqs320.03; d.f.s1; Ps 0.0001). d SKZ had less Suicidal ideation than AFF (Chi-sqs83.99; d.f.s1; Ps0.0001). e SKZ had fewer Sleep disorders (Chi-sqs51.75; d.f.s1; Ps0.0001), in particular less Insomnia (Chi-sqs38.79; d.f.s1; Ps 0.0001) than AFF. f AFF had more Appetite andyor Weight changes than DD (Chi-sqs14.74; d.f.s1; Ps0.0001) and SKZ (Chi-sqs164.40; d.f.s 1; Ps0.0001). In particular AFF had more Poor appetite andyor Weight loss than DD (Chi-sqs13.93; d.f.s1; Ps0.0002) and SKZ (Chi-sqs215.53; d.f.s1; Ps0.0001). g AFF had more depressive symptoms than DD (t-values7.81; d.f.s928; Ps0.0001) and SKZ (t-values23.42; d.f.s994; Ps 0.0001); DD had more Depressive symptoms than SKZ (t-values5.14; d.f.s124; Ps0.0001). h AFF had higher OPCRIT factor scores for depression than DD (t-values9.79; d.f.s928; Ps0.0001) and SKZ (t-values28.98; d.f.s994; Ps0.0001); DD had higher scores than SKZ (t-values6.51; d.f.s124; Ps0.0001). i SKZ had higher OPCRIT factor scores for negative symptomatology than AFF (t-valuesy34.40; d.f.s994; Ps0.0001) and DD (t-valuesy12.87; d.f.s124; Ps0.0001).

suffering and not suffering from depression within the same diagnosis. We were thus unable to test the potential to differentiate within each diagnosis.

Regarding schizophrenia, we did not take into account features such as the phase in which depression occurred (onset, acute, post-psychotic) or

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Fig. 2. Incidence (%) of depressive symptoms among AFF (ns900), in DD (ns30) and SKZ (ns96). DD and SKZ included had four or more depressive symptoms.

administration of neuroleptics before the onset or concurrent with depressive symptomatology. Nevertheless, depressive symptoms were found to occur during all phases of schizophrenia (Montgomery, 1979; Knights and Hirsch, 1981; Hinterhuber and Neumann, 1985; Martin et al., 1985; Bartels and Drake, 1988; Rigaud, 1991). Further, the relation between depressive symptoms and neuroleptic treatment is uncertain (Berrios and Bulbena, 1987; House et al., 1987; Siris et al., 2001). Finally, because our intention was to evaluate depressive symptomatology, we did not consider positive and disorganized symptoms. Criteria to assess depression in schizophrenia are still debated (Becker et al., 1985; Addington et al., 1990; Newcomer et al., 1990; Addington et al., 1992; Collins et al., 1996; Sax et al., 1996; Kontaxakis et al., 2000; Ramirez et al., 2001). We chose to use a single tool not specific for depression, the OPCRIT checklist, but quite functional to derive almost all depressive symptoms to evaluate depressive symptomatology as specified by DSM-IV (Section 2). The only inadequacy was represented by the assessment of depressed mood,

not specified in the OPCRIT and not obtainable from other items. Because of the great importance of this symptom for the diagnosis of major depression, we could not make a diagnosis of major depression in SKZ and DD. Thus, our approach was limited to analyze symptoms of depression across diagnoses, and not the full depressive syndrome, as defined by DSM-IV criteria. However, for more accurate examinations, in order to reach a more specific comprehension of depressive symptoms occurring in delusional disorder and schizophrenia, we selected within the delusional and schizophrenic groups those patients with a more consistent clinical form, defined by the presence of four or more symptoms. In fact, the presence of four or more symptoms is quite reliable as an index of depression. A major limitation of our study is its retrospective approach. This could bias data collection towards detection of unreliable estimates of clinical variables (Keller et al., 1987). To limit this bias, we used a set of strategies: information about the illness was collected by an experienced psychiatrist in interviews with subjects, from family members,

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A. Serretti et al. / Psychiatry Research 127 (2004) 8599 American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Author, Washington, DC. Angst, J., Preisig, M., 1995. Course of a clinical cohort of unipolar, bipolar and schizoaffective patients. Results of a prospective study from 1959 to 1985. Schweizer Archiv fuer Neurologie und Psychiatrie 146, 516. Bartels, S.J., Drake, R.E., 1988. Depressive symptoms in schizophrenia: comprehensive differential diagnosis. Comprehensive Psychiatry 29, 467483. Baynes, D., Mulholland, C., Cooper, S.J., Montgomery, R.C., MacFlynn, G., Lynch, G., Kelly, C., King, D.J., 2000. Depressive symptoms in stable chronic schizophrenia: prevalence and relationship to psychopathology and treatment. Schizophrenia Research 45, 4756. Becker, R.E., Colliver, J.A., Verhulst, S.J., 1985. Diagnosis of secondary depression in schizophrenia. Journal of Clinical Psychiatry 46, 48. Bellini, L., Gatti, F., Gasperini, M., Smeraldi, E., 1992. A comparison between delusional and non-delusional depressives. Journal of Affective Disorders 25, 129138. Benedetti, F., Barbini, B., Campori, E., Colombo, C., Smeraldi, E., 1996a. Dopamine agonist amineptine prevents the antidepressant effect of sleep deprivation. Psychiatry Research 65, 179184. Benedetti, F., Barbini, B., Colombo, C., Campori, E., Smeraldi, E., 1996b. Infradian mood fluctuations during a major depressive episode. Journal of Affective Disorders 41, 8187. Benedetti, F., Colombo, C., Barbini, B., Campori, E., Smeraldi, E., 1999a. Ongoing lithium treatment prevents relapse after total sleep deprivation. Journal of Clinical Psychopharmacology 19, 240245. Benedetti, F., Serretti, A., Colombo, C., Campori, E., Barbini, B., Di Bella, D., Smeraldi, E., 1999b. Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression. American Journal of Psychiatry 156, 14501452. Berrios, G.E., Bulbena, A., 1987. Postpsychotic depression: the Fulbourn cohort. Acta Psychiatrica Scandinavica 76, 8993. Bleuler, E., 1911y1950. Dementia Praecox or the Group of Schizophrenias. International Universities Press, New York. Bourgeois, M., Martinez, R., Degeilh, B., Peyre, F., 1988. Predictive factors in the bipolarization of depressive disorders. Encephale 14, 353357. Cardno, A.G., Jones, L.A., Murphy, K.C., Asherson, P., Scott, L.C., Williams, J., Owen, M.J., McGuffin, P., 1996. Factor analysis of schizophrenic symptoms using the OPCRIT checklist. Schizophrenia Research 22, 233239. Cohen, J., 1988. Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates, Hillsdale, NJ, pp. 814. Collins, A.A., Remington, G., Coulter, K., Birkett, K., 1996. Depression in schizophrenia: a comparison of three measures. Schizophrenia Research 20, 205209.

from previous health professionals and from records when possible (Leckman et al., 1982); a second experienced psychiatrist reviewed chart unreliability which was assessed and considered an exclusion criterion (Shapira et al., 1996). A further limitation is linked to the inclusion criteria: this sample was intentionally selected to exclude individuals with mental retardation, dementia, substance abuseydependence, neurological disorder or clinicalylaboratory indications of severe organic disease. Selection criteria certainly limit any generalization to subjects characterized by features considered as exclusion criteria for the present sample. Our Center is a tertiary care setting, and therefore we cannot exclude a potential bias associated with severity of illness as revealed, for example, by the high proportion of delusional subjects. It has been reported that only a subsample of individuals with major depression receive psychiatric treatment for depression (Hirschfeld et al., 1997), and patients may only seek treatment for the most persistent or most severe of their episodes, and such cases probably constituted the subjects included in our study. In conclusion, our findings both indicate that many psychotic subjects suffer from depressive symptoms and that the symptomatologic profile is partially specific for each diagnostic group. This finding may provide useful guidance both to clinicians, who may consider specific therapeutic interventions for each symptomatology profile, and researchers, who can more reliably identify subgroups of subjects for biological analyses. References
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