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.

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.

Effects of DMSO, pH, stretch and calcium on the thick filaments in an amphibian smooth muscle.

Conventional fixation with glutaraldehyde fixatives at pH 7.4 did not preserve/promote thick filaments in Bufo smooth muscle. However, if pH was lowered to 6.0, thick filaments were present and addition of dimethyl sulfoxide (DMSO) led to a greater number of thick filaments. Stretch alone had little effect on the presence of thiber seen. Calcium had little effect on the numbers of thick filaments, but it affected the appearance of the thick filaments. Low calcium (10(-7) M) caused a higher proportion of rod-shaped filaments, while in high calcium (10(-3) M) most thick filaments were ribbons. The great lability of the thick filaments in amphibian smooth muscles makes them ideal for studying factors which affect the appearance of thick filaments in smooth muscle, but it also raises the question of the degree of aggregation of myosin in the living cell.

Anxious and nonanxious depression.

The authors used the anxiety summary score described by Clayton and associates to assess anxious and nonanxious subtypes of depression in a group of 134 outpatients with major depression. Patients with anxious depression were only slightly less likely to respond to their first tricyclic antidepressant than patients with nonanxious depression. When functional severity or symptom severity was controlled for, this differential treatment response did not hold.

Diagnostic legitimacy of factitious disorder with psychological symptoms.

The authors question the clinical status of factitious disorder with psychological symptoms as a mental disorder. In particular, they argue that unresolved issues regarding the motivational basis of this disorder and the lack of clearly delineated inclusion, exclusion, and outcome criteria seriously compromise its diagnostic legitimacy. Two case reports are presented to illustrate these difficulties. Future studies should consider these empirical and conceptual difficulties in refining the diagnosis of factitious disorder with psychological symptoms for DSM-IV.

A preliminary investigation of alexithymia in men with psychoactive substance dependence.

The prevalence of alexithymia in a group of newly abstinent male substance abusers (N = 44) was 50%. The alexithymic patients had significantly less ego strength and repressive defensive behavior and significantly higher levels of somatic complaints and general dysphoria.

Decision making in psychiatric civil commitment: an experimental analysis.

OBJECTIVE: Legislation in Canada and the United States that was intended to decrease the use of civil commitment has resulted in a paradoxical increase in involuntary hospital admissions. To elucidate the reasons for this increase, this study was designed to assess the relative importance of various factors involved in the decision to commit a patient. METHOD: All psychiatrists in Ontario were sent a questionnaire asking them to make commitment decisions based on hypothetical case vignettes. Four factors were systematically varied in the vignettes: the patients' legal commitability, clinical treatability, alternative resources, and psychotic symptoms. Completed questionnaires, with three vignettes each, were returned by 495 respondents. RESULTS: All four variables were statistically significant in the expected direction; legal commitability (i.e., dangerousness to self and/or others, inability to care for self) and presence of psychotic symptoms accounted for the majority of the variance in the final decision to commit. CONCLUSIONS: These results suggest that psychiatrists in Ontario rely primarily on legally mandated factors (i.e., psychosis and dangerousness) in making their decisions to commit, although a considerable amount of individual variation is also evident.

Negative attributional style in seasonal and nonseasonal depression.

OBJECTIVE: There is a substantial relationship between dysfunctional cognitions and the clinical course of major depression. This study examined whether this association extends to patients with seasonal affective disorder. METHOD: A revised version of the Attributional Style Questionnaire was used to assess negative attributional style and predict response to treatment in a group of depressed outpatients, 26 with seasonal depression and 30 with nonseasonal, unipolar major depression. RESULTS: Pretreatment scores on negative attributional style did not differ between the patients with seasonal affective disorder and those with nonseasonal depression. Negative attributional style predicted poor response to pharmacotherapy in the nonseasonal depression group but did not predict response to light therapy in the group with seasonal affective disorder. CONCLUSIONS: Dysfunctional cognitions may play a lesser role in seasonal affective disorder than in nonseasonal depression.

Alexithymia in panic disorder and simple phobia: a comparative study.

The authors found that 14 (46.7%) of 30 patients with panic disorder had alexithymia, compared with four (12.5%) of 32 patients with simple phobia. Consistent with the conceptualization of alexithymia as a psychological deficit affecting emotion regulation, the patients with panic disorder had significantly less ego strength and independence and significantly higher levels of anxiety and somatic complaints than the patients with simple phobia.

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.

The Tridimensional Personality Questionnaire in major depression.

The authors examined Tridimensional Personality Questionnaire scores in 40 patients with unipolar nonpsychotic major depression before and after antidepressant treatment. They found that scores on the novelty seeking and reward dependence dimensions were not affected by depressed state or by treatment response status. However, scores on the harm avoidance dimension were significantly lower in antidepressant responders and were altered by depressed state.

Major depression and the self-criticism and dependency personality dimensions.

The Depressive Experiences Questionnaire was used to assess the personality dimensions of dependency and self-criticism in 52 depressed patients before and after treatment and in 22 healthy family practice patients. Neither personality dimension was significantly influenced by change in depressed mood, and the recovered depressed patients had higher levels of dependency and self-criticism than the comparison subjects.

Self-report ratings and informants' ratings of personalities of depressed outpatients.

OBJECTIVE: This study sought to determine whether personality traits of depressed patients could be assessed similarly by informants and self-reports of the patients themselves. METHOD: Forty-six depressed outpatients completed the self-report (first-person) version of the Revised NEO Personality Inventory and nominated informants who knew them well to complete the third-person version of that instrument. RESULTS: Agreement between the self-ratings and informants' ratings on the five factors of the inventory--neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness--was high. The only significant difference between the self-ratings and informants' ratings was on the extraversion scale, where the patients rated themselves as significantly more introverted than did the informants. CONCLUSIONS: Informants' ratings of personality are similar to self-report ratings of depressed patients. Depressed mood may not influence the self-report of personality traits.

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.

Measurement of alexithymia. Recommendations for clinical practice and future research.

The clinical assessment of alexithymia and research investigating its neurobiologic correlates require standardized assessment instruments. Observer-rated questionnaires, self-report scales, and projective techniques are currently available for measuring alexithymia, but most of these lack adequate reliability and validity. The Toronto Alexithymia Scale appears to have excellent psychometric properties, but a multimethod, multimeasure approach will enhance both measurement and further evaluation of the alexithymia construct.

Personality and symptom profiles of the angry hostile depressed patient.

Fava, Rosenbaum, McCarthy, Pava, Steingard and Bless (1991) have recently proposed the existence of a subtype of depressed patients who experience anger attacks. The aim of this study was to assess if depressed patients categorized as high angry hostile have symptoms and personality profiles distinct from depressed patients categorized as low angry hostile. From a sample of 125 depressed outpatients, 26 patients were classified as high angry hostile and 25 patients as low angry hostile. The symptom profiles of these tow groups were remarkably similar, with the high angry hostile patients exhibiting more interpersonal sensitivity. The high angry hostile patients were rated as less interpersonally agreeable and less conscientious than low angry hostile patients. These results provide only partial support for the angry hostile subtype of depression.

Seasonal and non-seasonal depression and the five-factor model of personality.

The purpose of this study was to compare the personality characteristics of patients with non-psychotic, major depression, seasonal subtype (SAD) to patients with non-psychotic, major depression, without seasonality (non-SAD). The patients were consecutive referrals to a university-affiliated mood disorders outpatient clinic. The personality characteristics were assessed using the five-factor model of personality (FFM) as measured by the revised NEO Personality Inventory (NEO PI-R). Patients were assessed during the acute depressive episode. Controlling for severity of depression, differences were found on only one of the five dimensions, with the SAD patients (n = 43) scoring significantly higher on the Openness dimension than non-SAD patients (n = 57). Based on these results we infer SAD patients may represent a psychologically distinct subgroup of depressed patients-more imaginative, more emotionally sensitive and likely to entertain unconventional ideas than non-SAD patients. This personality constellation may explain why individuals with SAD are more sensitive to and may amplify the mild dysphoria typically associated with winter months.

Sexual dysfunction before antidepressant therapy in major depression.

BACKGROUND: Decreased sexual interest and function both occur as a consequence of antidepressant medication use, and are especially associated with serotonin reuptake inhibitors (SRIs). However, few investigators have reported the base rate for disturbances in sexual desire, arousal and orgasm or ejaculation in patients with major depression (MD) prior to antidepressant treatment. The purpose of this report is to define the frequency of sexual dysfunction (SD) in 134 patients with MD and examine the relationship between SD and demographic, clinical and personality variables. METHOD: A consecutive series of 55 male and 79 female MD patients diagnosed by SCID-DSM IV assessment completed a series of psychometric measures including a Sexual Function Questionnaire, which asked about change in sexual interest and function as well as sexual activity during the preceding month. RESULTS: Only 50% of women and 75% of men reported sexual activity during the preceding month. Over 40% of men and 50% of women reported decreased sexual interest. Reduced levels of arousal were more common in both men and women (40-50%) than ejaculatory or orgasm difficulties (15-20%). In women, problems with arousal and orgasm correlated with higher neuroticism and lower extraversion. There was no relationship between SD and personality measures in men. While age at onset of depression and number of prior episodes showed a modest correlation with SD measures, there were no correlations with severity of depression or specific symptoms clusters. LIMITATIONS AND CONCLUSIONS: Although limited by a relatively small sample of drug free patients with MD, and by the absence of a non-depressed comparison sample, these results emphasize the importance of factors beyond specific drug effects in the assessment of antidepressant related sexual dysfunction.