Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study.

Amygdala-prefrontal cortex (PFC) functional impairments have been linked to emotion dysregulation and aggression in borderline personality disorder (BPD). Fatty acid amide hydrolase (FAAH), the major catabolic enzyme for the endocannabinoid anandamide, has been proposed as a key regulator of the amygdala-PFC circuit that subserves emotion regulation. We tested the hypothesis that FAAH levels measured with [11C]CURB positron emission tomography in amygdala and PFC would be elevated in BPD and would relate to hostility and aggression. Twenty BPD patients and 20 healthy controls underwent FAAH genotyping (rs324420) and scanning with [11C]CURB. BPD patients were medication-free and were not experiencing a current major depressive episode. Regional differences in [11C]CURB binding were assessed using multivariate analysis of covariance with PFC and amygdala [11C]CURB binding as dependent variables, diagnosis as a fixed factor, and sex and genotype as covariates. [11C]CURB binding was marginally elevated across the PFC and amygdala in BPD (p = 0.08). In a priori selected PFC, but not amygdala, [11C]CURB binding was significantly higher in BPD (11.0%, p = 0.035 versus 10.6%, p = 0.29). PFC and amygdala [11C]CURB binding was positively correlated with measures of hostility in BPD (r > 0.4; p < 0.04). This study is the first to provide preliminary evidence of elevated PFC FAAH binding in any psychiatric condition. Findings are consistent with the model that lower endocannabinoid tone could perturb PFC circuitry that regulates emotion and aggression. Replication of these findings could encourage testing of FAAH inhibitors as innovative treatments for BPD.

An evaluation of the absolute and relative stability of alexithymia over 11years in a Finnish general population.

OBJECTIVE: We investigated if alexithymia, a personality construct with difficulties in emotional processing, is stable in the general population. METHODS: Altogether 3083 unselected subjects aged 30 and older in Finland completed the 20-item Toronto Alexithymia Scale (TAS-20) in the longitudinal Health 2000 and Health 2011 general population surveys (BRIF8901). The stability of alexithymia at the 11-year follow-up was assessed with t-tests, correlations, and separate linear regression models with base-line and follow-up age, gender, marital status, education, and 12-month depressive and anxiety disorders as confounders. RESULTS: The mean score (SD) of the TAS-20 for the whole sample was 44.2 (10.4) in 2000 and 44.2 (10.9) in 2011 (p=0.731). The mean score of the TAS-20 subscale Difficulty Identifying Feelings increased by 0.3 points, Difficulty Describing Feelings decreased by 0.6 points and Externally Oriented Thinking increased by 0.3 points. The effect sizes of the changes varied from negligible to small. Age had little effect except for the group of the oldest subjects (75-97years): the TAS-20 mean (SD) score was 49.1 (10.1) in 2000 and 53.1 (10.3) in 2011 (p<0.001), the effect size for the increase was medium. TAS-20 score in 2000 explained a significant proportion of variance in TAS-20 score in 2011. Controlling for all baseline confounders improved the model incrementally; the same applied to controlling for confounders at follow-up. Baseline depression or anxiety disorders were not associated with the TAS-20 scores in 2011, whereas current diagnoses were. CONCLUSIONS: According to our large longitudinal study both the absolute and relative stability of alexithymia assessed with the TAS-20 are high in the adult general population.

Pathological gambling subtypes: A comparison of treatment-seeking and non-treatment-seeking samples from Brazil and Canada.

BACKGROUND: Pathological gambling (PG) is a heterogeneous disorder. The identification and characterization of PG subtypes could lead to tailored treatment approaches, which may, in turn, improve treatment outcomes. OBJECTIVE: To investigate PG subtypes based on personality traits across two different cultural and clinical settings. Consistent with the Pathways Model, we hypothesized the presence of three subtypes (behaviorally conditioned - BC, emotionally vulnerable - EV, and antisocial impulsivist - AI). METHODS: 140 PG adults from São Paulo, Brazil (SP sample) and 352 adults with PG (n=214) or sub-clinical PG (n=138) from Toronto, Canada (TO sample) completed the Temperament and Character Inventory (TCI). Latent-class analysis was used to investigate subtypes. RESULTS: A 2-class solution was the best model for the pooled SP and TO samples. Class 1 presented a normative personality profile and was composed exclusively of participants from Toronto (BC subtype). Class 2 was characterized by high novelty seeking, high harm avoidance, and low self-directedness, and included participants from both SP and TO (EV subtype). When sub-clinical PGs were excluded from the analysis, a single-class solution better characterized the SP and TO samples. CONCLUSIONS: Our results suggest that PG severity, rather than community or clinical settings, may have an effect on PG subtypes. The generalizability of the results is limited by the demographic and clinical features of the selected samples. Future neurobiological studies may contribute to the categorization of subjects into PG subtypes based on different underlying biological pathways.

Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits.

BACKGROUND: Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior. METHOD: Participants were aged 19-49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R). RESULTS: Prefrontal MAOA binding correlated negatively with angry-hostility (r=-0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions. CONCLUSIONS: We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

Evidence for the cognitive mediational model of cognitive behavioural therapy for depression.

BACKGROUND: Although empirical support for the efficacy of cognitive behavioural therapy (CBT) as a treatment for major depressive disorder (MDD) is well established, its mechanism of action is uncertain. In this investigation, we examined evidence for the cognitive mediational model in a randomized control trial involving CBT, interpersonal therapy (IPT) and pharmacotherapy (PHT) in patients with MDD. METHOD: One hundred and thirty participants diagnosed with MDD were treated with CBT, IPT or PHT. Participants completed the Hamilton Depression Rating Scale, Beck Depression Inventory-II and Dysfunctional Attitudes Scale prior to and following treatment. RESULTS: The cognitive mediational model, in which dysfunctional attitudes are proposed to mediate depressive symptom reduction in response to treatment, provided a good fit to the data when contrasting CBT v. IPT, with results supporting a mediational role for dysfunctional attitude change in depressive symptom reduction. The complication model, in which dysfunctional attitudes are proposed to be a consequence of depressive symptom reduction, provided a good fit to the data when contrasting CBT v. PHT, with results supporting a mediational role for depressive symptom reduction in dysfunctional attitude change. CONCLUSIONS: There was no evidence for a mediational role for dysfunctional attitude change in IPT. Changes in dysfunctional attitudes accompanied both CBT and PHT; however, empirical evidence suggests that the role of attitudes in treatment outcome may differ between these two treatments.

Measuring depressive symptoms in the naturalistic primary-care setting.

BACKGROUND: The majority of individuals with major depressive disorder are diagnosed and treated in the primary-care setting. A quantifiable critical objective in the management of depression is to achieve and sustain full symptomatic remission. The HAMD-7 is a depression metric validated in both tertiary and primary-care settings. METHODS: Herein, we further characterise the psychometric properties of the HAMD-7 in depressed patients treated in primary-care settings. Several cut-scores were evaluated for maximum agreement; diagnostic efficacy statistics with the original HAMD-7 items were also evaluated. We compared performance of the HAMD-7 in primary care to a previously characterised tertiary sample. RESULTS: The depressive symptoms most frequently endorsed (>or=70%) and most sensitive to change during antidepressant treatment in depressed primary-care patients were depressed mood, guilt, work and activities, psychic and somatic anxiety and fatigue. LIMITATIONS: This is a post hoc analysis of a primary-care database; assumptions regarding the definition of symptomatic remission in depression affect interpretation. CONCLUSION: Measurement-based care with the HAMD-7 quantifies the severity of commonly reported depressive items and their responsivity to treatment. The HAMD-7, inclusive of the suicide item, is capable of tracking symptom progress, with a validated remission cut-score.

Impact of patient suicide on psychiatrists and psychiatric trainees.

OBJECTIVE: The authors investigated the impact of patient suicides on trainees and psychiatrists and their utilization of supports. METHODS: Graduates in practice and trainees of the residency program of the University of Toronto from 1980-1995 (N=495) were surveyed, retrospectively, with 239/495 responding (48%). Demographic and educational information, exposure to suicide, impact of the suicide(s), use of support systems, acute stress disorder and posttraumatic stress disorder symptoms, and impact of events and social relationship scores were collected. RESULTS: One-half of the respondents (120/239) experienced at least one suicide of a patient, 62% of them (74/120) during postgraduate training. Biologically oriented psychiatrists in practice were more at risk for patient suicide. An important minority (one-quarter) among those who experienced patient suicide had substantially higher (morbid) scores than the overall group. They also scored higher on an acute stress disorder and a posttraumatic stress disorder symptom checklist. The impact was more severe when the patient suicide occurred during training than after graduation and was inversely correlated with clinicians' perceived social integration into their relational professional network. CONCLUSIONS: The experience of patient suicide is common during training and in clinical practice. The majority of trainees and clinicians are able to cope normally with the trauma, but in an important minority the emotional impact approaches morbid levels. Training programs should prepare students for this occupational hazard and implement systematic protocols to support those trainees who are especially vulnerable to their patient's suicide and reduce their social isolation from their peer group. Formal and informal professional networks should heighten awareness of the impact of patient suicide on practicing colleagues and take adequate measures to support them.

Assessing posttraumatic stress disorder with the MMPI-2 in a sample of workplace accident victims.

In this study, the predictive capacity of the Minnesota Multiphasic Personality Inventory-2 Posttraumatic Stress Disorder-Keane (MMPI-2 PK) scale was examined in a sample of trauma victims who experienced a serious workplace-related accident and subsequent injury. In keeping with a number of previous investigations, the PK scale was largely ineffective in identifying posttraumatic stress disorder (PTSD) beyond overall symptom and functional severity. In contrast, sets of clinical and content scales proved to be significant predictors of PTSD. These findings suggest that the PK scale is not particularly useful in detecting PTSD in civilian trauma samples. Clinicians might be best advised to use the MMPI-2 clinical and content scales in their assessment of PTSD in civilian patients presenting with a history of trauma.

Effectiveness of NEO-PI-R research validity scales for discriminating analog malingering and genuine psychopathology.

We investigated the research validity scales for the NEO Personality Inventory-Revised (NEO-PI-R) proposed by Schinka, Kinder, and Kremer (1997): Positive Presentation Management (PPM) and Negative Presentation Management (NPM). Additionally, an experimental analog to the Minnesota Multiphasic Personality Inventory-2's (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) F-K index was calculated by subtracting the raw score on PPM from the raw score on NPM (NPM-PPM). In 2 studies, all indexes showed significant between-group differences when samples of analog malingerers (n = 97) were contrasted with psychiatric outpatients (n = 272). The sensitivity and specificity of these validity indexes indicated that although none performed well in extremely low base rate environments, the NPM and NPM-PPM indexes showed promise when the base rate of faking bad rose to higher levels.

Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers.

OBJECTIVE: The authors investigated the relationship between anxiety--a facet of the Revised NEO Personality Inventory dimension of neuroticism--and serotonin 5-HT(1A) receptor binding potential. METHOD: Positron emission tomography with [(11)C]WAY-100635 was used to estimate regional 5-HT(1A) binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT(1A) binding potential and personality inventory measures. RESULTS: There was a significant negative correlation between 5-HT(1A) binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex. CONCLUSIONS: The inverse relationship between 5-HT(1A) receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT(1A) receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT(1A) agonists.

An evaluation of the absolute and relative stability of alexithymia in patients with major depression.

BACKGROUND: Previous studies demonstrating an association between alexithymia and depression have led to the proposal that alexithymia may be a state-dependent phenomenon rather than a stable and enduring personality trait. Several longitudinal studies have provided support for a trait view of alexithymia, but most of these studies evaluated absolute stability only (i.e., the extent to which alexithymia scores change over time) and did not examine the relative stability of alexithymia (i.e., the extent to which relative differences among individuals remain the same over time) in the context of changes in illness symptomatology. The present study evaluated both absolute stability and relative stability of alexithymia in depressed patients who experienced a marked reduction in the severity of depressive symptoms. METHODS: Forty-six psychiatric outpatients with major depression were assessed for alexithymia and depression with the 20-item Toronto Alexithymia Scale and the Hamilton Rating Scale for Depression at the start of treatment (baseline) and after 14 weeks of treatment (follow-up) with antidepressant medication. Paired t tests and correlational analyses were performed to evaluate absolute stability and relative stability in alexithymia. Hierarchical regression analyses were then used to assess the degree to which the relative stability in alexithymia scores was related to the severity of depressive symptoms, and the degree to which changes in alexithymia scores could be attributed to changes in depression scores. RESULTS: Alexithymia scores changed significantly from baseline to follow-up, indicating a general lack of absolute stability. There was, however, strong evidence of relative stability, as alexithymia scores at baseline correlated significantly with alexithymia scores at follow-up and were also a significant predictor of follow-up alexithymia scores, after partialling the effects of depression severity. CONCLUSIONS: Although alexithymia scores may change in the presence of large changes in the severity of depressive symptoms, the finding of relative stability of alexithymia supports the view that this construct is a stable personality trait rather a state-dependent phenomenon.

Chronic, low-grade depression in a nonclinical sample: depressive personality or dysthymia?

Depressive personality disorder (DPD) is being considered for inclusion in future editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). However, there is substantial conceptual and empirical overlap between DPD and dysthymic disorder (Dysthymia) criteria, suggesting that these two constructs may not be distinct. Confirmatory factor analysis of the DPD traits and dysthymia symptoms in a large, nonclinical sample (N = 368) indicated that a two-factor model was a better fit than a one-factor model. However, binary diagnostic analysis revealed that over half of the individuals meeting criteria for DPD also met criteria for dysthymia and that the best-fitting model allowed the psychological symptoms of dysthymia to load on both DPD and dysthymia latent factors. All of the individuals with DPD alone failed to meet criteria for dysthymia because they did not report chronic depressed mood. Our results suggest that although DPD is not synonymous with Dysthymia, it may be a milder subtype.

Predictors of success and satisfaction in the practice of psychiatry: a preliminary follow-up study.

BACKGROUND: Few studies have examined the predictors of psychiatrists' perceived success and personal satisfaction with their careers. The present study examines self-reported success and personal satisfaction with their careers in a cohort of psychiatrists followed for more than 20 years. METHODS: A total of 29 psychiatrists, all of whom had participated in a study during their residency 21 to 24 years earlier, completed a self-report questionnaire. The first set of questions addressed the type and characteristics of their professional practice; the second set assessed aspects of their nonprofessional practice; and the third set assessed aspects of their nonprofessional, personal lifestyles. The personality traits of neuroticism and extraversion were assessed during the residency years and were used as predictors. Composite measures of self-perceived external success and personal satisfaction were computed. Regression models were constructed to determine the best predictors of these composite measures. RESULTS: Neuroticism proved to be a significant predictor of external success but not of personal satisfaction, with higher scores predicting a lower rating of perceived external success. There were 2 practice characteristics--involvement with research and practising from an orientation other than psychoanalytic--that predicted perception of success. One personal lifestyle characteristic--the perception that one's nonprofessional life sustained professional life--also predicted perception of success. The best predictor of personal satisfaction was overall satisfaction with nonprofessional aspects of life. CONCLUSIONS: Personality, nonprofessional social support, and engaging in research are associated with greater perceived success and personal satisfaction with a career in psychiatry.

Personality and the affective disorders: past efforts, current models, and future directions.

The existence of a relation between personality and the affective disorders has long been observed but with little agreement as to how it can best be described. This paper reviews attempts to address this issue, beginning with an examination of subaffective personality types. The personality dimensions of two major predominant theories, the Five Factor Model of Personality and the Seven Factor Dimensional Psychobiological Model of Temperament and Character, and the relation of these dimensions with bipolar disorder and unipolar depression is also examined. Throughout, the state-versus-trait issue is explored, and the last section is a critical reexamination of this continuing controversy. The overall objective is to search for commonalities in past and present models, and to deal with ongoing concerns, in order to point the way for future research in the field.

Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine.

BACKGROUND: Recent reports suggest that adverse effects on sexual function occur in up to 50% of patients who are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants. Previously cited low rates were more likely a function of underreporting than underoccurrence. There is less evidence about rates of dysfunction with serotonin-norepinephrine reuptake inhibitor (SNRI) and reversible inhibitor of monoamine oxidase A (RIMA) antidepressants. The purpose of this report is to evaluate disturbances in sexual drive/desire and arousal/orgasm in 107 patients who met criteria for major depressive disorder and received treatment with either moclobemide, paroxetine, sertraline, or venlafaxine. METHOD: All consenting eligible patients who met DSM-IV criteria for major depressive disorder completed the Sexual Functioning Questionnaire, version 1 (SFQ) and were assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) prior to and after 8 or 14 weeks of antidepressant therapy. Analyses were carried out to examine the effect of gender, drug type, pretreatment level of sexual dysfunction, and drug response on reported sexual dysfunction. RESULTS: Compared with women, men experienced a significantly greater level of drug-related impairment in drive/desire (p < .05), whereas there were no statistically significant differences in levels of arousal/orgasm impairment between men and women. The reported impairment in drive/desire items for men ranged from 38% to 50% and from 26% to 32% for women. No differences were found across the 4 antidepressants in men, whereas in women, rates of dysfunction were generally higher with sertraline and paroxetine, but only significantly so in comparison with moclobemide on some measures (p < .03). Rates of sexual dysfunction with venlafaxine tended to fall between those of SSRIs and the RIMA agent. An unexpected relationship was found between favorable drug response and a decreased level of drug-induced sexual dysfunction. CONCLUSION: Antidepressant-induced sexual dysfunction occurs in approximately 30% to 70% of patients who are treated with sertraline or paroxetine. Lower rates are reported with moclobemide and venlafaxine. Clinicians should evaluate the various aspects of sexual dysfunction before and during antidepressant therapy.

A Swedish translation of the 20-item Toronto Alexithymia Scale: cross-validation of the factor structure.

The purpose of this study was to develop a new Swedish translation of the twenty-item Toronto Alexithymia Scale (TAS-20) and to examine if the theoretical structure that underlies the factor structure of the English version of the TAS-20 could be recovered in this Swedish translation of the instrument. A sample of 157 undergraduate students of psychology was tested. Using confirmatory factor analysis, the previously established three-factor TAS-20 model was found to be replicable in this sample. In addition, the Swedish translation of the TAS-20 showed adequate internal reliability. The present study also illustrates the importance of using back translation methodology when transposing psychometric instruments from one language to another.

Is self-criticism unique for depression? A comparison with social phobia.

BACKGROUND: This study further examined the diagnostic specificity of the self-critical personality dimension, as measured by the Depressive Experiences Questionnaire (DEQ; Blatt et al., 1976. The Depressive Experiences Questionnaire. Yale University Press, New Haven). METHODS: Patients with major depression (n=26) were compared to social phobia patients (n=32). RESULTS: Depressed patients scored significantly higher on the DEQ Self-Criticism dimension. However, when current level of depressed mood was controlled for, self-criticism was not a significant predictor of diagnostic status. Further, the level of DEQ self-criticism reported by patients with social phobia was almost three times greater than the level reported in an earlier diagnostic specificity study with panic disorder patients [Bagby et al., 1992. Diagnostic specificity of the dependent and self-critical personality dimensions in major depression. J. Affect. Disord. 26, 59-64]. LIMITATIONS: Only one measure of self-criticism was used in this study, and the research design was cross-sectional rather than prospective. CONCLUSIONS: Self-criticism is not unique to major depression, and this personality dimension may be implicated in other forms of psychopathology [Blatt, 1991. A cognitive morphology of psychopathology. J. Nerv. Ment. Dis. 179, 449-458]. Some cognitive features believed to play an important role in depression may also be salient in persons with social phobia.

Can the MMPI-2 validity scales detect depression feigned by experts?

Major depression is one of the most frequently presented disorders for claims of psychiatric disability. Evidence also suggests that many individuals making claims of disability exaggerate or even fabricate mental illness. These facts suggest that the detection of feigned depression is an important task in psychiatric disability claim assessments. In this study, the capacity of a number of MMPI-2 validity scales and indicators to detect feigned depression was examined. Twenty-three mental health professionals with specific expertise and significant experience in assessing and treating major depression were asked to complete the MMPI-2 as if they were suffering from major depression. The MMPI-2 protocols of this sample were compared to those of a sample of patients diagnosed with major depression. Results indicated that the validity scales F, back F (FB), and the Dissimulation scale (Ds) were highly successful at distinguishing MMPI-2 protocols of feigned depression from bona fide depression. Replicating results from previous studies, however, FB proved most effective, outperforming all other validity scales and indicators, including F and Ds. These findings suggest that even experts are unable to feign major depression successfully on the MMPI-2, and that the FB scale might be the most effective indicator for detecting feigned depression.

Response style and the revised NEO personality inventory: validity scales and spousal ratings in a Chinese psychiatric sample.

The effects of response style bias on profile scores from the family of NEO scales and the resultant influence of response style on the predictive capacity of these scales continues to be debated. In this study, a large sample of Chinese psychiatric patients were categorized into four response style groups based on their scores from recently developed "validity" scales for the revised NEO Personality Inventory (NEO PI-R). Mean differences and correlations between self-report and spousal ratings of these patients were examined for the NEO PI-R domain and facet scales. Excessive positive self-presentation bias resulted in mean differences between the self-report and spousal ratings for N and E. Correlations between self-report and spousal ratings were reduced in patients engaging in positive self-presentational bias compared to those who were not so categorized on three of the five NEO PI-R scales. However, these results were manifest only in a sub-sample of psychotic patients. Negative self-presentational bias did not affect mean differences or diminish the correlations between the self-report and spousal ratings.