BRIEF REPORT
Childhood Trauma, Temperament, and Character in Subjects With Major Depressive Disorder and Bipolar Disorder Giampaolo Perna, MD, PhD,*†‡ Giovanna Vanni, MD,* Nunzia Valentina Di Chiaro, MSc,* Paolo Cavedini, MD, PhD,* and Daniela Caldirola, MD, PhD* Abstract: In nonclinical samples, childhood trauma (CT) has been found to negatively affect temperament/character traits. In major depressive disorder (MDD) and bipolar disorder (BD), abnormal personality traits have been found to impair clinical course/treatment outcome. Although a link between CT and MDD/BD is firmly established, no previous studies explored the relationship between CT and temperament/character in these populations. We investigated this issue in a preliminary sample of inpatients with MDD (n = 29) or BD (n = 50). We assessed CT (sexual/physical/emotional abuse, physical/emotional neglect) (Childhood Trauma Questionnaire), personality traits (Temperament and Character Inventory-Revised version), and illness severity (Brief Psychiatric Rating Scale). We found significant ( p < 0.01) associations between emotional neglect, emotional abuse, physical neglect, and low self-directedness (SD). Potential underlying mechanisms are discussed. Because low SD has been previously associated with illness severity and poor outcome, the relationship between CT and low SD might partly explain the well-known negative impact of CT on course and outcome of MDD/BD. Key Words: Childhood trauma, temperament, character, major depressive disorder, bipolar disorder (J Nerv Ment Dis 2014;202: 695–698)
T
he relationship between childhood trauma (CT) and major depressive disorder (MDD) or bipolar disorder (BD) is firmly established (Heim et al., 2008; Watson et al., 2013); however, the moderators of this link are not yet fully understood. Among them, abnormal personality traits might be relevant. In nonclinical samples, low self-directedness (SD), self-transcendence, and cooperativeness and high novelty seeking were found in adult survivors of CT (Godet-Mardirossian et al., 2011; Rademaker et al., 2008), according to the Cloninger’s psychobiological model of personality (Cloninger, 1994b). Similarly, a large population study found an association between inadequate parental caregiving/home-environment and low SD and cooperativeness in adult offspring (Josefsson et al., 2013). Abnormal personality traits were also found in MDD/BD subjects. Most studies found higher harm avoidance, lower SD and cooperativeness, and higher self-transcendence in MDD and BD populations than in healthy subjects, whereas in BD, a higher novelty seeking was also found (Greenwood et al., 2013; Hansenne and Bianchi, 2009). These personality traits may predispose individuals to depression and/or negatively affect clinical course and treatment outcome in MDD and BD (Cloninger et al., 2006; Harnic et al., 2013; Kampman and Poutanen, 2011; Margetic and Jakovljevic, 2013; Serretti et al., 2009), and a cyclothymic-depressive-anxious
*Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, FoRiPsi, Como, Italy; †Faculty of Health, Medicine and Life Sciences, Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands; and ‡Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, FL. Send reprint requests to Paolo Cavedini, MD, PhD, Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, FoRiPsi, via Roma 16, 22032, Albese con Cassano, Como, Italy. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0022-3018/14/20209–0695 DOI: 10.1097/NMD.0000000000000186
temperament pattern has been found to increase risk for suicidal behavior in these populations (Pompili et al., 2012). The CT has been associated to a greater risk for adulthood MDD/BD (Heim et al., 2008; Watson et al., 2013) and to an earlier age at onset, greater illness severity, and poor treatment response (Larsson et al., 2013; Teicher and Samson, 2013); however, no published studies investigated the influence of CT on temperament/character in MDD/BD subjects. We hypothesized that a negative impact of CT on personality traits may be one of the pathways through which CTexerts its negative effects on course/outcome of MDD/BD. For the potential clinical implications, we aimed to study the influence of CT on temperament/ character in a sample of inpatients with MDD or BD. We expected that CT negatively affects personality traits in these populations.
METHODS Participants Fifty subjects with BD (type I/II) and 29 with MDD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria; American Psychiatric Association, 2000) were recruited from the inpatients consecutively referred to Villa San Benedetto Menni Hospital, Albese con Cassano, Como, Italy, to undergo a 4-week hospitalization for a psychiatric rehabilitation program. Inclusion criteria were depressive episode without suicide risk, current pharmacological treatment recommended for the disorders, and age of 18 years or higher. Exclusion criteria were relevant modifications of pharmacologic treatments in the last 4 weeks preceding hospitalization including addition or discontinuation of drug, current/previous history of schizophrenia/ other psychotic disorders, suspected or diagnosed (IQ < 70) mental retardation, and any neurological disease/medical condition potentially affecting the reliability of the self-administered assessment. The study was performed in accordance with the Declaration of Helsinki and approved by the ethical committee of the Local Health Authority of the Province of Como, Italy. All participants voluntarily provided written informed consent after the procedure had been fully explained. Data were collected from April 2012 to August 2013.
Procedure and Measures Within 3 days of admission to the hospital, before any pharmacological modification and at the beginning of the rehabilitation program, the following variables were assessed: a) CT occurring before the age of 18 years, with the Childhood Trauma Questionnaire (CTQ) (Bernstein and Fink, 1998), a 28-item selfreport questionnaire asking the subjects to rate the frequency of childhood traumatic experiences using a 5-point Likert scale ranging from 1 (“never true”) to 5 (“very often true”). Five different types of CT are evaluated: sexual/physical/emotional abuse, physical/emotional neglect (score range for each type of CT, 5–25). The CTQ also includes a three-item minimization/denial scale (score range, 0–3): a score of 1 or higher associated with very low trauma scores in most CT types indicates probable false-negative trauma reports (Bernstein and Fink, 1998); b) personality dimensions, with the Temperament
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and Character Inventory-Revised version (TCI-R) (Cloninger, 1994a; Martinotti et al., 2008), a 240-item self-report questionnaire measuring four temperament dimensions (novelty seeking, harm avoidance, reward dependence, persistence) and three character dimensions (SD, cooperativeness, self-transcendence). The items are rated on a 5-point Likert scale ranging from “absolutely false” to “absolutely true”; c) illness severity, with the 18-item psychiatrist-administered Brief Psychiatric Rating Scale (BPRS) (Overall and Beller, 1984). Total score was 18–126, from no symptoms to extremely severe condition.
Statistical Analyses Continuous and nominal data were respectively analyzed by independent-sample Welsh t-test (equality of variances not assumed) and chi-square analysis. Associations between CTQ and TCI-R scores were analyzed by partial linear correlations, inserting age, sex, years of education, and clinical severity as controlling variables to take into account confounding effects. Because of the high number of statistical tests, we lowered the significance level (α) from 0.05 to 0.01. The Statistical Package for Windows (Statistica 10.0; Statsoft Inc, Tulsa, Oklahoma) was used.
RESULTS Three subjects with MDD and two with BD were excluded from the analyses because of probable false-negative trauma reports. Demographic and clinical characteristics of the sample are described in Table 1. No significant differences between MDD and BD were found (Table 1). In MDD subjects, emotional neglect was negatively associated with SD (r = −.532, p = 0.009). In BD subjects, emotional abuse (r = −0.436, p = 0.004) and physical neglect (r = −.393, p = 0.009) were negatively associated with SD. No other significant associations were found (Table 2).
DISCUSSION We found preliminary evidence that childhood emotional neglect, emotional abuse, and physical neglect are associated with
low SD in a sample of inpatients with MDD or BD, in line with previous findings in nonclinical samples (Josefsson et al., 2013; Rademaker et al., 2008). No influence of demographic or clinical variables on this association was found. Rates of CT were similar to those previously reported in subjects with MDD/BD (Baes et al., 2014; Fowke et al., 2012). Compared with nonclinical Italian population samples (Martinotti et al., 2008), all TCI traits, except for novelty seeking, self-transcendence and, in the BD group, reward dependence, were different, partially in line with previous studies that also found high novelty seeking/self-transcendence (Greenwood et al., 2013; Hansenne and Bianchi, 2009). There were no significant differences in CT or personality dimensions between MDD and BD, although the small sample size may have masked potential differences. SD refers to the ability of an individual to adapt, regulate, and control behavior to fit a situation in accord with one's chosen goals and values, thus encompassing cognitive functions such as self-esteem, internal locus of control, problem solving, coping behaviors, and perceived support resources. Thus, SD reflects the executive functions of personality, probably involving highorder neural systems such as the hippocampus and neocortex (Cloninger, 1994b). Several preclinical and human studies showed that early-life stress induces long-lasting alterations in corticotropinreleasing factor neurotransmission and in other neurotransmitter systems, such as serotonergic, noradrenergic, and GABA-ergic, all transmitter-modulating emotions and cognition (Heim and Nemeroff, 2001). Recent findings showed effects of CT on neural plasticity in different cortical regions, including those relevant to self-awareness and self-evaluation (Heim et al., 2013). CT might induce persistent changes in brain areas crucial to the regulation of emotion and behaviors, including the hippocampus, the temporal/anterior cingulated/frontal cortices, and the prefrontal cortex-limbic system network (Lee, 2006), thus impairing the abilities to integrate emotions, cognition, and behaviors into the development of a mature concept of the self, expressed by a low SD in adulthood. The relationship we found among CT, personality, and MDD/BD might be explained in the framework of a
TABLE 1. Demographic and Clinical Variables: Comparisons Between MDD and BD Samples
Female/male, n Age, mean (SD), yrs Education, mean (SD), yrs BPRS, mean (SD) CTQ, mean (SD), scores Sexual abuse Physical abuse Emotional abuse Physical neglect Emotional neglect TCI, mean (SD), scores Novelty seeking Harm avoidance Reward dependence Persistence Self-directedness Cooperativeness Self-transcendence
MDD (n = 27)
BD (n = 47)
Statistic, t
p
22/5 58.63 (11.50) 11.04 (4.86) 34.29 (6.12)
34/13 55.74 (12.14) 11.87 (4.48) 31.72 (4.93)
χ2 = 0.78 1.00 −0.75 1.97
0.37 0.32 0.46 0.05
6.30 (1.94) 6.93 (3.65) 9.70 (5.17) 8.04 (2.36) 14.48 (5.69)
7.68 (3.82) 8.04 (4.90) 9.91 (5.17) 9.40 (4.59) 13.68 (5.95)
−1.75 −1.03 −0.17 −1.44 0.57
0.08 0.31 0.86 0.15 0.57
95.41 (15.46) 115.26 (12.48) 100.22 (13.23) 105.22 (17.88) 120.63 (19.00) 126.22 (15.51) 74.41 (14.71)
100.15 (13.26) 112.57 (21.33) 95.23 (14.27) 102.94 (21.66) 117.68 (19.86) 125.11 (18.21) 72.98 (13.81)
−1.39 0.60 1.49 0.46 0.62 0.27 0.42
0.17 0.55 0.14 0.64 0.54 0.79 0.67
Statistical significance, p < 0.01. SD indicates standard deviation.
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TABLE 2. Correlations Between CT, Temperament, and Character CTQ MDD (n = 27) TCI
NS HA RD P SD C ST
r p r p r p r p r p r p r p
BD (n = 47)
SA
PA
EA
PN
EN
SA
PA
EA
PN
EN
−0.212 0.330 −0.004 0.986 −0.026 0.907 0.435 0.038 0.069 0.754 −0.089 0.688 0.489 0.018
0.095 0.666 0.088 0.688 −0.055 0.805 0.041 0.851 −0.187 0.392 −0.280 0.196 0.398 0.060
0.513 0.012 0.053 0.811 0.144 0.512 −0.116 0.597 −0.485 0.019 −0.273 0.207 0.073 0.740
0.069 0.754 0.056 0.800 0.047 0.831 −0.059 0.788 −0.141 0.522 −0.063 0.776 0.296 0.171
0.415 0.049 0.353 0.098 0.042 0.849 −0.205 0.347 −0.532 0.009* −0.224 0.305 0.035 0.874
−0.065 0.679 0.247 0.111 −0.041 0.792 0.003 0.984 −0.211 0.175 0.006 0.97 0.142 0.363
−0.225 0.147 0.247 0.111 −0.099 0.527 −0.137 0.38 −0.229 0.14 0.152 0.331 0.239 0.123
0.055 0.726 0.261 0.092 −0.119 0.449 −0.141 0.368 −0.436 0.004* −0.007 0.965 0.239 0.123
−0.151 0.333 0.138 0.378 −0.199 0.2 −0.055 0.727 −0.393 0.009* 0.027 0.862 0.008 0.961
−0.135 0.39 0.136 0.384 0.034 0.828 −0.04 0.797 −0.211 0.174 −0.037 0.814 −0.009 0.953
C indicates cooperativeness; EA, emotional abuse; EN, emotional neglect; HA, harm avoidance; NS, novelty seeking; P, persistence; PA, physical abuse; PN, physical neglect; RD, reward dependence; SA, sexual abuse; SD, self-directedness; ST, self-transcendence. *Statistical significance, p < 0.01.
gene-environment interaction. Consistent with this, in nonclinical samples, associations between genetic polymorphisms of serotonin receptors, serotonin transporter (5-HTT), 5-HTT promoter gene, GABA receptors, and SD were found (Alfimova et al., 2010; Saiz et al., 2010). Similarly, interactions were showed between polymorphisms of 5-HTT promoter gene and SD in seasonal affective disorder (Thierry et al., 2004) and between polymorphisms of catechol-O-methyltransferase and SD in BD (Davila et al., 2013). As well, these polymorphisms may also influence the likelihood that exposure to CTwill result in adulthood MDD/BP (Nugent et al., 2011). Thus, a common genetic vulnerability may modulate the occurrence of low SD and MDD/BD in subjects exposed to CT. The cross-sectional design of our study did not allow us to disentangle the complex relationships between CT, personality, and MDD/BD or to draw any conclusion about causality. Indeed, CT may influence both personality and occurrence of MDD/BD; CT may influence the occurrence of MDD/BD that, in turn, may modify personality; and CT may influence personality that, in turn, may predispose an individual to MDD/BD or affect the clinical features of the disorders. Longitudinal studies are needed to clarify these issues. We found no associations between CT and other personality dimensions or between sexual/physical abuse and TCI-R scores. This may be related to the small sample size. However, because CTQ does not provide information about the timing/duration of trauma or perpetrators, we cannot exclude that the lack of these variables may have masked potential trauma effects on other personality traits. Moreover, sexual and physical abuse, unlike emotional/ physical neglect and emotional abuse, include a committal that may have differential neurobiological effects (Heim and Nemeroff, 2001) not captured by TCI-R scores. Finally, in addition to the above limitations, all patients of our study were in a depressive episode and receiving pharmacotherapy. Thus, we cannot exclude an influence of clinical symptoms or treatment on TCI scores (Spittlehouse et al., 2010) or CT self-reports. Further studies on larger samples in different clinical conditions are needed. Finally, the use of more detailed CT assessment instruments, direct interviews, and pooled information from multiple sources to support © 2014 Lippincott Williams & Wilkins
the validity of retrospective CT self-reports might help to address the limitations of the CTQ. Keeping in mind these limitations, our results provided preliminary indications that CT is associated with low SD in both MDD and BD. Low SD has been previously associated to poor treatment outcome, suicide attempts, suicidal ideation, and presence of personality disorders in MDD/BD (Conrad et al., 2009; Jylha et al., 2013; Margetic and Jakovljevic, 2013; Sarisoy et al., 2012; Serretti et al., 2009). Thus, the association between CT and low SD might represent one of the pathways through which CT negatively affects the course, illness severity, and treatment outcome in these disorders (Larsson et al., 2013; Teicher and Samson, 2013).
CONCLUSIONS To the best of our knowledge, this is the first study that showed a relationship between CT and low SD in MDD/BD. Our study highlights the usefulness of evaluating CT and personality traits in clinical practice in these populations. The CTQ and TCI-R might be useful clinical tools that contribute to the identification of those patients with higher risk for poor outcome. Further studies on larger samples are needed. ACKNOWLEDGMENTS The authors thank the staff of the Center for Mood Disorders, Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, Albese con Cassano, Como, Italy, for the contribution to collect data and Massimiliano Grassi, MSc, for reviewing of the article. DISCLOSURES The authors declare no conflicts of interest. REFERENCES Alfimova MV, Monakhov MV, Golimbet VE, Korovaitseva GI, Lyashenko GL (2010) Analysis of associations between 5-HTT, 5-HTR2A, and GABRA6
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Childhood Trauma, Temperament, and Character in Subjects With Major Depressive Disorder and Bipolar Disorder Giampaolo Perna, MD, PhD,*†‡ Giovanna Vanni, MD,* Nunzia Valentina Di Chiaro, MSc,* Paolo Cavedini, MD, PhD,* and Daniela Caldirola, MD, PhD* Abstract: In nonclinical samples, childhood trauma (CT) has been found to negatively affect temperament/character traits. In major depressive disorder (MDD) and bipolar disorder (BD), abnormal personality traits have been found to impair clinical course/treatment outcome. Although a link between CT and MDD/BD is firmly established, no previous studies explored the relationship between CT and temperament/character in these populations. We investigated this issue in a preliminary sample of inpatients with MDD (n = 29) or BD (n = 50). We assessed CT (sexual/physical/emotional abuse, physical/emotional neglect) (Childhood Trauma Questionnaire), personality traits (Temperament and Character Inventory-Revised version), and illness severity (Brief Psychiatric Rating Scale). We found significant ( p < 0.01) associations between emotional neglect, emotional abuse, physical neglect, and low self-directedness (SD). Potential underlying mechanisms are discussed. Because low SD has been previously associated with illness severity and poor outcome, the relationship between CT and low SD might partly explain the well-known negative impact of CT on course and outcome of MDD/BD. Key Words: Childhood trauma, temperament, character, major depressive disorder, bipolar disorder (J Nerv Ment Dis 2014;202: 695–698)
T
he relationship between childhood trauma (CT) and major depressive disorder (MDD) or bipolar disorder (BD) is firmly established (Heim et al., 2008; Watson et al., 2013); however, the moderators of this link are not yet fully understood. Among them, abnormal personality traits might be relevant. In nonclinical samples, low self-directedness (SD), self-transcendence, and cooperativeness and high novelty seeking were found in adult survivors of CT (Godet-Mardirossian et al., 2011; Rademaker et al., 2008), according to the Cloninger’s psychobiological model of personality (Cloninger, 1994b). Similarly, a large population study found an association between inadequate parental caregiving/home-environment and low SD and cooperativeness in adult offspring (Josefsson et al., 2013). Abnormal personality traits were also found in MDD/BD subjects. Most studies found higher harm avoidance, lower SD and cooperativeness, and higher self-transcendence in MDD and BD populations than in healthy subjects, whereas in BD, a higher novelty seeking was also found (Greenwood et al., 2013; Hansenne and Bianchi, 2009). These personality traits may predispose individuals to depression and/or negatively affect clinical course and treatment outcome in MDD and BD (Cloninger et al., 2006; Harnic et al., 2013; Kampman and Poutanen, 2011; Margetic and Jakovljevic, 2013; Serretti et al., 2009), and a cyclothymic-depressive-anxious
*Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, FoRiPsi, Como, Italy; †Faculty of Health, Medicine and Life Sciences, Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands; and ‡Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, FL. Send reprint requests to Paolo Cavedini, MD, PhD, Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, FoRiPsi, via Roma 16, 22032, Albese con Cassano, Como, Italy. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0022-3018/14/20209–0695 DOI: 10.1097/NMD.0000000000000186
temperament pattern has been found to increase risk for suicidal behavior in these populations (Pompili et al., 2012). The CT has been associated to a greater risk for adulthood MDD/BD (Heim et al., 2008; Watson et al., 2013) and to an earlier age at onset, greater illness severity, and poor treatment response (Larsson et al., 2013; Teicher and Samson, 2013); however, no published studies investigated the influence of CT on temperament/character in MDD/BD subjects. We hypothesized that a negative impact of CT on personality traits may be one of the pathways through which CTexerts its negative effects on course/outcome of MDD/BD. For the potential clinical implications, we aimed to study the influence of CT on temperament/ character in a sample of inpatients with MDD or BD. We expected that CT negatively affects personality traits in these populations.
METHODS Participants Fifty subjects with BD (type I/II) and 29 with MDD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria; American Psychiatric Association, 2000) were recruited from the inpatients consecutively referred to Villa San Benedetto Menni Hospital, Albese con Cassano, Como, Italy, to undergo a 4-week hospitalization for a psychiatric rehabilitation program. Inclusion criteria were depressive episode without suicide risk, current pharmacological treatment recommended for the disorders, and age of 18 years or higher. Exclusion criteria were relevant modifications of pharmacologic treatments in the last 4 weeks preceding hospitalization including addition or discontinuation of drug, current/previous history of schizophrenia/ other psychotic disorders, suspected or diagnosed (IQ < 70) mental retardation, and any neurological disease/medical condition potentially affecting the reliability of the self-administered assessment. The study was performed in accordance with the Declaration of Helsinki and approved by the ethical committee of the Local Health Authority of the Province of Como, Italy. All participants voluntarily provided written informed consent after the procedure had been fully explained. Data were collected from April 2012 to August 2013.
Procedure and Measures Within 3 days of admission to the hospital, before any pharmacological modification and at the beginning of the rehabilitation program, the following variables were assessed: a) CT occurring before the age of 18 years, with the Childhood Trauma Questionnaire (CTQ) (Bernstein and Fink, 1998), a 28-item selfreport questionnaire asking the subjects to rate the frequency of childhood traumatic experiences using a 5-point Likert scale ranging from 1 (“never true”) to 5 (“very often true”). Five different types of CT are evaluated: sexual/physical/emotional abuse, physical/emotional neglect (score range for each type of CT, 5–25). The CTQ also includes a three-item minimization/denial scale (score range, 0–3): a score of 1 or higher associated with very low trauma scores in most CT types indicates probable false-negative trauma reports (Bernstein and Fink, 1998); b) personality dimensions, with the Temperament
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and Character Inventory-Revised version (TCI-R) (Cloninger, 1994a; Martinotti et al., 2008), a 240-item self-report questionnaire measuring four temperament dimensions (novelty seeking, harm avoidance, reward dependence, persistence) and three character dimensions (SD, cooperativeness, self-transcendence). The items are rated on a 5-point Likert scale ranging from “absolutely false” to “absolutely true”; c) illness severity, with the 18-item psychiatrist-administered Brief Psychiatric Rating Scale (BPRS) (Overall and Beller, 1984). Total score was 18–126, from no symptoms to extremely severe condition.
Statistical Analyses Continuous and nominal data were respectively analyzed by independent-sample Welsh t-test (equality of variances not assumed) and chi-square analysis. Associations between CTQ and TCI-R scores were analyzed by partial linear correlations, inserting age, sex, years of education, and clinical severity as controlling variables to take into account confounding effects. Because of the high number of statistical tests, we lowered the significance level (α) from 0.05 to 0.01. The Statistical Package for Windows (Statistica 10.0; Statsoft Inc, Tulsa, Oklahoma) was used.
RESULTS Three subjects with MDD and two with BD were excluded from the analyses because of probable false-negative trauma reports. Demographic and clinical characteristics of the sample are described in Table 1. No significant differences between MDD and BD were found (Table 1). In MDD subjects, emotional neglect was negatively associated with SD (r = −.532, p = 0.009). In BD subjects, emotional abuse (r = −0.436, p = 0.004) and physical neglect (r = −.393, p = 0.009) were negatively associated with SD. No other significant associations were found (Table 2).
DISCUSSION We found preliminary evidence that childhood emotional neglect, emotional abuse, and physical neglect are associated with
low SD in a sample of inpatients with MDD or BD, in line with previous findings in nonclinical samples (Josefsson et al., 2013; Rademaker et al., 2008). No influence of demographic or clinical variables on this association was found. Rates of CT were similar to those previously reported in subjects with MDD/BD (Baes et al., 2014; Fowke et al., 2012). Compared with nonclinical Italian population samples (Martinotti et al., 2008), all TCI traits, except for novelty seeking, self-transcendence and, in the BD group, reward dependence, were different, partially in line with previous studies that also found high novelty seeking/self-transcendence (Greenwood et al., 2013; Hansenne and Bianchi, 2009). There were no significant differences in CT or personality dimensions between MDD and BD, although the small sample size may have masked potential differences. SD refers to the ability of an individual to adapt, regulate, and control behavior to fit a situation in accord with one's chosen goals and values, thus encompassing cognitive functions such as self-esteem, internal locus of control, problem solving, coping behaviors, and perceived support resources. Thus, SD reflects the executive functions of personality, probably involving highorder neural systems such as the hippocampus and neocortex (Cloninger, 1994b). Several preclinical and human studies showed that early-life stress induces long-lasting alterations in corticotropinreleasing factor neurotransmission and in other neurotransmitter systems, such as serotonergic, noradrenergic, and GABA-ergic, all transmitter-modulating emotions and cognition (Heim and Nemeroff, 2001). Recent findings showed effects of CT on neural plasticity in different cortical regions, including those relevant to self-awareness and self-evaluation (Heim et al., 2013). CT might induce persistent changes in brain areas crucial to the regulation of emotion and behaviors, including the hippocampus, the temporal/anterior cingulated/frontal cortices, and the prefrontal cortex-limbic system network (Lee, 2006), thus impairing the abilities to integrate emotions, cognition, and behaviors into the development of a mature concept of the self, expressed by a low SD in adulthood. The relationship we found among CT, personality, and MDD/BD might be explained in the framework of a
TABLE 1. Demographic and Clinical Variables: Comparisons Between MDD and BD Samples
Female/male, n Age, mean (SD), yrs Education, mean (SD), yrs BPRS, mean (SD) CTQ, mean (SD), scores Sexual abuse Physical abuse Emotional abuse Physical neglect Emotional neglect TCI, mean (SD), scores Novelty seeking Harm avoidance Reward dependence Persistence Self-directedness Cooperativeness Self-transcendence
MDD (n = 27)
BD (n = 47)
Statistic, t
p
22/5 58.63 (11.50) 11.04 (4.86) 34.29 (6.12)
34/13 55.74 (12.14) 11.87 (4.48) 31.72 (4.93)
χ2 = 0.78 1.00 −0.75 1.97
0.37 0.32 0.46 0.05
6.30 (1.94) 6.93 (3.65) 9.70 (5.17) 8.04 (2.36) 14.48 (5.69)
7.68 (3.82) 8.04 (4.90) 9.91 (5.17) 9.40 (4.59) 13.68 (5.95)
−1.75 −1.03 −0.17 −1.44 0.57
0.08 0.31 0.86 0.15 0.57
95.41 (15.46) 115.26 (12.48) 100.22 (13.23) 105.22 (17.88) 120.63 (19.00) 126.22 (15.51) 74.41 (14.71)
100.15 (13.26) 112.57 (21.33) 95.23 (14.27) 102.94 (21.66) 117.68 (19.86) 125.11 (18.21) 72.98 (13.81)
−1.39 0.60 1.49 0.46 0.62 0.27 0.42
0.17 0.55 0.14 0.64 0.54 0.79 0.67
Statistical significance, p < 0.01. SD indicates standard deviation.
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TABLE 2. Correlations Between CT, Temperament, and Character CTQ MDD (n = 27) TCI
NS HA RD P SD C ST
r p r p r p r p r p r p r p
BD (n = 47)
SA
PA
EA
PN
EN
SA
PA
EA
PN
EN
−0.212 0.330 −0.004 0.986 −0.026 0.907 0.435 0.038 0.069 0.754 −0.089 0.688 0.489 0.018
0.095 0.666 0.088 0.688 −0.055 0.805 0.041 0.851 −0.187 0.392 −0.280 0.196 0.398 0.060
0.513 0.012 0.053 0.811 0.144 0.512 −0.116 0.597 −0.485 0.019 −0.273 0.207 0.073 0.740
0.069 0.754 0.056 0.800 0.047 0.831 −0.059 0.788 −0.141 0.522 −0.063 0.776 0.296 0.171
0.415 0.049 0.353 0.098 0.042 0.849 −0.205 0.347 −0.532 0.009* −0.224 0.305 0.035 0.874
−0.065 0.679 0.247 0.111 −0.041 0.792 0.003 0.984 −0.211 0.175 0.006 0.97 0.142 0.363
−0.225 0.147 0.247 0.111 −0.099 0.527 −0.137 0.38 −0.229 0.14 0.152 0.331 0.239 0.123
0.055 0.726 0.261 0.092 −0.119 0.449 −0.141 0.368 −0.436 0.004* −0.007 0.965 0.239 0.123
−0.151 0.333 0.138 0.378 −0.199 0.2 −0.055 0.727 −0.393 0.009* 0.027 0.862 0.008 0.961
−0.135 0.39 0.136 0.384 0.034 0.828 −0.04 0.797 −0.211 0.174 −0.037 0.814 −0.009 0.953
C indicates cooperativeness; EA, emotional abuse; EN, emotional neglect; HA, harm avoidance; NS, novelty seeking; P, persistence; PA, physical abuse; PN, physical neglect; RD, reward dependence; SA, sexual abuse; SD, self-directedness; ST, self-transcendence. *Statistical significance, p < 0.01.
gene-environment interaction. Consistent with this, in nonclinical samples, associations between genetic polymorphisms of serotonin receptors, serotonin transporter (5-HTT), 5-HTT promoter gene, GABA receptors, and SD were found (Alfimova et al., 2010; Saiz et al., 2010). Similarly, interactions were showed between polymorphisms of 5-HTT promoter gene and SD in seasonal affective disorder (Thierry et al., 2004) and between polymorphisms of catechol-O-methyltransferase and SD in BD (Davila et al., 2013). As well, these polymorphisms may also influence the likelihood that exposure to CTwill result in adulthood MDD/BP (Nugent et al., 2011). Thus, a common genetic vulnerability may modulate the occurrence of low SD and MDD/BD in subjects exposed to CT. The cross-sectional design of our study did not allow us to disentangle the complex relationships between CT, personality, and MDD/BD or to draw any conclusion about causality. Indeed, CT may influence both personality and occurrence of MDD/BD; CT may influence the occurrence of MDD/BD that, in turn, may modify personality; and CT may influence personality that, in turn, may predispose an individual to MDD/BD or affect the clinical features of the disorders. Longitudinal studies are needed to clarify these issues. We found no associations between CT and other personality dimensions or between sexual/physical abuse and TCI-R scores. This may be related to the small sample size. However, because CTQ does not provide information about the timing/duration of trauma or perpetrators, we cannot exclude that the lack of these variables may have masked potential trauma effects on other personality traits. Moreover, sexual and physical abuse, unlike emotional/ physical neglect and emotional abuse, include a committal that may have differential neurobiological effects (Heim and Nemeroff, 2001) not captured by TCI-R scores. Finally, in addition to the above limitations, all patients of our study were in a depressive episode and receiving pharmacotherapy. Thus, we cannot exclude an influence of clinical symptoms or treatment on TCI scores (Spittlehouse et al., 2010) or CT self-reports. Further studies on larger samples in different clinical conditions are needed. Finally, the use of more detailed CT assessment instruments, direct interviews, and pooled information from multiple sources to support © 2014 Lippincott Williams & Wilkins
the validity of retrospective CT self-reports might help to address the limitations of the CTQ. Keeping in mind these limitations, our results provided preliminary indications that CT is associated with low SD in both MDD and BD. Low SD has been previously associated to poor treatment outcome, suicide attempts, suicidal ideation, and presence of personality disorders in MDD/BD (Conrad et al., 2009; Jylha et al., 2013; Margetic and Jakovljevic, 2013; Sarisoy et al., 2012; Serretti et al., 2009). Thus, the association between CT and low SD might represent one of the pathways through which CT negatively affects the course, illness severity, and treatment outcome in these disorders (Larsson et al., 2013; Teicher and Samson, 2013).
CONCLUSIONS To the best of our knowledge, this is the first study that showed a relationship between CT and low SD in MDD/BD. Our study highlights the usefulness of evaluating CT and personality traits in clinical practice in these populations. The CTQ and TCI-R might be useful clinical tools that contribute to the identification of those patients with higher risk for poor outcome. Further studies on larger samples are needed. ACKNOWLEDGMENTS The authors thank the staff of the Center for Mood Disorders, Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, Albese con Cassano, Como, Italy, for the contribution to collect data and Massimiliano Grassi, MSc, for reviewing of the article. DISCLOSURES The authors declare no conflicts of interest. REFERENCES Alfimova MV, Monakhov MV, Golimbet VE, Korovaitseva GI, Lyashenko GL (2010) Analysis of associations between 5-HTT, 5-HTR2A, and GABRA6
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