The course of marriage/sustained cohabitation and parenthood among borderline patients followed prospectively for 16 years.

The purpose of this study was to determine the rate of marriage/sustained cohabitation and parenthood reported by recovered and nonrecovered borderline patients, the age first undertaken, and the stability of these relationships. Borderline patients were interviewed about these topics during their index admission and eight times over 16 years of prospective follow-up. Recovered borderline patients were significantly more likely than nonrecovered borderline patients to have married/lived with an intimate partner and to have become a parent. In addition, they first married/cohabited and became a parent at a significantly older age. They were also significantly less likely to have been divorced or ended a cohabiting relationship. In addition, they were significantly less likely to have given up or lost custody of a child. Taken together, the results of this study suggest that stable functioning as a spouse/partner and as a parent are strongly associated with recovery status for borderline patients.

Reasons for self-mutilation reported by borderline patients over 16 years of prospective follow-up.

The main objective of this study was to assess the reasons for episodes of self-mutilation engaged in by patients with borderline personality disorder (BPD) over 16 years of prospective follow-up. Two hundred and ninety patients meeting both DIB-R and DSM-III-R criteria for BPD were interviewed every 2 years. The authors divided the borderline patients into two groups: those with a more extensive and those with a less extensive lifetime history of self-mutilation at study entry. These groups were not significantly different than one another on either of the interpersonally directed reasons for self-mutilation studied. However, those in the more extensive group were significantly more likely to report each of the five internally directed reasons studied. The results of this study suggest that borderline patients with a more extensive history of self-mutilation are best distinguished from those with a less extensive history by episodes of self-harm that are motivated, at least in part, by dysphoric inner states.

Predictors of suicide threats in patients with borderline personality disorder over 16 years of prospective follow-up.

Despite their impact on interpersonal relationships and health resources, suicide threats are not often studied in those with borderline personality disorder (BPD). The primary aim of this study was to examine clinically relevant predictors of suicide threats in this patient group. Two-hundred and ninety inpatients meeting Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-III-R criteria for BPD were assessed during their index admission using a series of semistructured interviews and a self-report measure. These subjects were then reassessed using the same instruments every 2 years for 16 years. All variables in the bivariate analyses were found to be significant. In multivariate analyses, four predictors were found to be significant: feeling abandoned and hopeless, and being demanding and manipulative. The results of this study suggest that suicide threats are often related to emotions connected with interpersonal relationships. Suicide threats may function, albeit maladaptively, to regulate these emotions aroused by interpersonal relationships and bring needed support.

Cognitive experiences reported by patients with borderline personality disorder and axis II comparison subjects: a 16-year prospective follow-up study.

OBJECTIVE: The authors assessed three main types of disturbed cognition: nonpsychotic thought (odd thinking, unusual perceptual experiences, and nondelusional paranoia), quasi-psychotic thought, and true psychotic thought in patients with borderline personality disorder followed prospectively for 16 years. They also compared the rates of these disturbed cognitions with those reported by axis II comparison subjects. METHOD: The cognitive experiences of 362 inpatients (290 borderline patients and 72 axis II comparison subjects) were assessed at study entry using the cognitive section of the Revised Diagnostic Interview for Borderlines. Participants' cognitive experiences were reassessed every 2 years using the same interview. RESULTS: Each of the five main types of thought studied was reported by a significantly higher percentage of patients in the borderline group than in the axis II comparison group over time. Each of these types of thought, except true psychotic thought, declined significantly over time for participants in both groups. Eleven of the 17 more specific forms of thought studied were also reported by a significantly higher percentage of patients in the borderline group over the follow-up period: magical thinking, overvalued ideas, recurrent illusions, depersonalization, derealization, undue suspiciousness, ideas of reference, other paranoid ideation, quasi-psychotic delusions, quasi-psychotic hallucinations, and true psychotic hallucinations. Fourteen specific forms of thought were found to decline significantly over time for participants in both groups: all forms of thought mentioned above except true psychotic hallucinations plus marked superstitiousness, sixth sense, telepathy, and clairvoyance. CONCLUSIONS: Disturbed cognitions are common in patients with borderline personality disorder and are distinguishing for the disorder. They also decline substantially over time but remain a problem, particularly those of a nonpsychotic nature.

Predictors of depressive symptoms at hospital discharge in patients with major depressive disorder.

OBJECTIVE: Often patients with major depressive disorder (MDD) leave the hospital with continued significant symptomatology. This study sought to evaluate demographic, clinical, and psychosocial predictors of the presence of clinically significant depressive symptoms, defined as a Modified Hamilton Rating Scale for Depression score of ≥ 14, immediately following hospitalization for MDD. METHODS: The study enrolled 135 patients with MDD as part of a larger clinical trial investigating the efficacy of post-hospitalization pharmacologic and psychosocial treatments for depressed inpatients. Structured clinical interview and self-report data were available from 126 patients at hospital admission and discharge. RESULTS: Despite the significant decreases in depressive symptoms over the course of hospitalization, 91 (72%) displayed clinically significant depressive symptoms at discharge. Multivariate logistic regression analysis revealed that female sex, earlier age of onset, and poorer social adjustment were unique predictors of symptom outcome. CONCLUSIONS: Results suggest that a large proportion of patients leave the hospital with continued significant symptomatology, and the presence of such symptoms following hospitalization for MDD is likely to be explained by a combination of factors.

The functional assessment of maladaptive behaviors: a preliminary evaluation of binge eating and purging among women.

This study applied a functional approach to the study of bingeing and purging behaviors. Based on a four-function theoretical model of bingeing and purging, it was hypothesized that these behaviors are performed because of their intrapersonally reinforcing (e.g., emotion regulation) and/or interpersonally reinforcing (e.g., help-seeking, attention-getting behavior) properties. Participants were 298 adult females who had engaged in bingeing or purging in the last 3 months and who provided data via an online survey of these behaviors. Confirmatory factor analyses revealed support for a four-function model of bingeing and purging in which people use these behaviors for intrapersonal reinforcement functions and also for interpersonal reinforcement. Understanding the functions of binge eating and purging has direct implications for assessment and treatment of these behaviors.

The emotion reactivity scale: development, evaluation, and relation to self-injurious thoughts and behaviors.

Prior research has examined the relations between various facets of emotion and psychopathology, with a great deal of recent work highlighting the importance of emotion regulation strategies. Much less attention has been given to the examination of emotion reactivity. This study reports on the development and evaluation of the Emotion Reactivity Scale (ERS), a 21-item self-report measure of emotion sensitivity, intensity, and persistence, among a sample of 87 adolescents and young adults. Factor analysis revealed a single factor of emotion reactivity best characterized the data. The ERS showed strong internal consistency (alpha=.94), convergent and divergent validity via relations with behavioral inhibition/activation and temperament, and criterion-related validity as measured by associations with specific types of psychopathology and self-injurious thoughts and behaviors (SITB). Moreover, emotion reactivity statistically mediated the relation between psychopathology and SITB. These findings provide preliminary support for the ERS and suggest that increased emotion reactivity may help explain the association between psychopathology and SITB.

A functional MRI study of amygdala responses to angry schematic faces in social anxiety disorder.

Neuroimaging studies using angry or contemptuous human facial photographic stimuli have suggested amygdala hyper-responsivity in social anxiety disorder (SAD). We sought to determine if an angry "schematic face" (simple line drawing) would evoke exaggerated amygdalar responses in SAD patients compared with healthy control (HC) subjects. Angry, happy, and neutral schematic faces were overtly presented to matched cohorts of 11 SAD and 11 HC subjects for passive viewing, whereas brain functional magnetic resonance imaging signal was measured at 1.5 Tesla. Voxel-wise analyses were performed using a random effects model in SPM99. Compared with HC subjects, SAD patients exhibited exaggerated responses in the right amygdala for the Angry versus Neutral contrast. The findings of exaggerated amygdala responses to angry schematic faces in SAD converge with results from earlier neuroimaging studies and illustrate the potential utility of schematic faces for probing amygdala function in psychiatric disorders. One prospective advantage of schematic faces is that they may minimize confounds related to gender, age, or race effects. However, extending earlier findings in healthy subjects, schematic faces appear more effective for probing amygdala responses to arousal-based (Angry versus Neutral) as opposed to valence-based (Angry versus Happy) contrasts.

Parental expressed emotion and adolescent self-injury.

OBJECTIVE: This study examined the relationship between parental expressed emotion (EE) and adolescent self-injurious thoughts and behaviors (SITB), as well as potential mediators and moderators of this relationship. METHOD: Thirty-six adolescents ages 12 to 17 years recruited from the community (2004-2005) provided data. Parents of the adolescents completed the Five-Minute Speech Sample, a performance-based measure of EE, and adolescents completed interviews and rating scales assessing SITB, mental disorders, and related constructs. RESULTS: Analyses revealed that high parental EE was associated with each type of SITB assessed: suicide ideation, suicide plans, suicide attempts, and non-suicidal self-injury. Analyses also revealed that one specific component of EE (i.e., parental criticism) was strongly associated with SITB, whereas the other (i.e., emotional overinvolvement) was not and that the relationship between EE and SITB was not explained by the presence of mental disorders. Finally, a moderation model was supported in which the relationship between parental criticism and SITB was especially strong among adolescents with a self-critical cognitive style. CONCLUSIONS: This study indicates that parental criticism is significantly associated with SITB and suggests one specific pathway through which the family may influence adolescent SITB. Future research is needed to replicate these findings and examine the direction of these relationships.

Brain activation during implicit sequence learning in individuals with trichotillomania.

Trichotillomania (TTM) may be related to obsessive-compulsive disorder (OCD) and other neuropsychiatric conditions characterized by cortico-striatal dysfunction. Functional imaging studies of OCD using an implicit learning task have found abnormalities in striatal and hippocampal activation. The current study investigated whether similar abnormalities occur in TTM. Functional MRI and the serial reaction time (SRT) task were used to assess striatal and hippocampal activation during implicit sequence learning in TTM and healthy control (HC) subjects. The results for 20 age- and education-matched participants (10 TTM, 10 HC) are reported. In comparison with HC participants, those with TTM exhibited no significant differences in implicit learning, or in activation within the striatum, hippocampus, or other brain regions. The current findings do not provide evidence for cortico-striatal dysfunction in TTM. Future studies directly comparing OCD and TTM subjects are warranted to confirm the specificity of abnormal striatal and hippocampal findings during implicit sequence learning in OCD.

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder.

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.

Subtle neurologic compromise as a vulnerability factor for combat-related posttraumatic stress disorder: results of a twin study.

CONTEXT: Previous studies have demonstrated subtle neurologic dysfunction in chronic posttraumatic stress disorder (PTSD) manifest as increased neurologic soft signs (NSSs). The origin of this dysfunction is undetermined. OBJECTIVE: To resolve competing origins of increased NSSs in PTSD, namely, preexisting vulnerability factor vs acquired PTSD sign. DESIGN: Case-control study of identical twins. SETTING: A Veterans Affairs and academic medical center (ambulatory). PARTICIPANTS: A convenience sample of male Vietnam veteran twins with (n = 25) and without (n = 24) PTSD and their combat-unexposed identical (monozygotic) co-twins. INTERVENTIONS: Neurologic examination for 45 NSSs. MAIN OUTCOME MEASURE: Average scores for 45 NSSs, each scored on an ordinal scale from 0 to 3, masked to diagnosis and combat exposure status. RESULTS: There was a significant between-pair main effect of PTSD diagnosis (as determined in the combat-exposed twin) on average NSS score in the absence of a significant combat exposure main effect or diagnosis x exposure interaction. Combat veterans with PTSD had significantly higher NSS scores than combat veterans without PTSD. The "high-risk," unexposed co-twins of the former also had significantly higher NSS scores than the "low-risk," unexposed co-twins of the latter. This result could not be explained by age, number of potentially traumatic lifetime noncombat events, alcoholism, or the presence of a comorbid affective or anxiety disorder. The average NSS score in unexposed co-twins was not significantly associated with combat severity in combat-exposed twins. CONCLUSIONS: These results replicate previous findings of increased NSSs in Vietnam combat veterans with PTSD. Furthermore, results from their combat-unexposed identical co-twins support the conclusion that subtle neurologic dysfunction in PTSD is not acquired along with the trauma or PTSD but rather represents an antecedent familial vulnerability factor for developing chronic PTSD on exposure to a traumatic event.

Novel fearful faces activate the amygdala in healthy young and elderly adults.

Activation of the amygdala to emotionally valenced stimuli, and particularly to fearful faces, has been widely demonstrated in healthy young adults. However, recent studies assessing amygdala responses to fearful emotional faces in the normal elderly have not shown similar results. The reason for this is uncertain, but it may relate to life-span developmental changes in processing emotional stimuli or structural alterations in the amygdala with aging. In order to examine whether the amygdala could be activated in the elderly, we developed a paradigm designed to engage the amygdala on several levels. Based on recent imaging work indicating that novelty and stimulus change activates the amygdala, we assessed amygdala responses in young and elderly adults to novel fearful faces (versus familiar neutral ones). We demonstrate a robust activation in both groups, indicating that the amygdala remains responsive in aging. This activation did not differ between the two groups when we examined regions of interest in the amygdala based on functional or structural criteria. However, there were significantly greater activations in the inferior temporal cortex in the young versus elderly subjects.

Neuroanatomical correlates of extraversion and neuroticism.

Introversion/extraversion and neuroticism are 2 important and frequently studied dimensions of human personality. These dimensions describe individual differences in emotional responding across a range of situations and may contribute to a predisposition for psychiatric disorders. Recent neuroimaging research has begun to provide evidence that neuroticism and introversion/extraversion have specific functional and structural neural correlates. Previous studies in healthy adults have reported an association between neuroticism, introversion/extraversion, and the activity of the prefrontal cortex and amygdala. Studies of individuals with psychopathological states have also indicated that anatomic variations in these brain areas may relate to extraversion and neuroticism. The purpose of the present study was to examine selected structural correlates of neuroticism and extraversion in healthy subjects (n = 28) using neuroanatomic measures of the cerebral cortex and amygdala. We observed that the thickness of specific prefrontal cortex regions correlates with measures of extraversion and neuroticism. In contrast, no such correlations were observed for the volume of the amygdala. The results suggest that specific aspects of regional prefrontal anatomy are associated with specific personality traits.

Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans.

Although sex differences have been demonstrated in behavioral paradigms of fear conditioning, the findings have been inconsistent, and fear extinction has been little studied. The present study investigated the influence of sex and menstrual cycle phase on the recall of fear extinction. Three groups of healthy adult participants were studied: women at 2 different phases of the menstrual cycle (early follicular [early cycle] and late follicular [midcycle]) and men. Participants underwent a 2-day fear conditioning and extinction protocol. The paradigm entailed habituation, fear conditioning, and extinction learning on Day 1 and extinction recall and fear renewal on Day 2. Skin conductance served as the dependent variable. During fear acquisition on Day 1, men showed significantly larger conditioned responses relative to women; early cycle and midcycle women did not differ. No significant group differences were found during extinction learning. On Day 2, men and early cycle women expressed greater extinction memory than midcycle women. These data confirm sex differences in conditioned fear acquisition and suggest that midcycle hormones attenuate extinction recall.

Differential amygdala habituation to neutral faces in young and elderly adults.

Habituation is a highly adaptive property of the nervous system, which allows for the allocation of attention and other cognitive resources to more imperative environmental events. The amygdala is an important site of habituation in humans, but no studies to date have examined the effects of aging on amygdala habituation. Given the amygdala's role in evaluating the salience of a stimulus and initiating behavioral responses, the potential importance of amygdala habituation in aging may be far-reaching. Therefore, we assessed for differences in habituation in the amygdalae of healthy young and elderly adults during repeated presentations of neutral human faces using functional magnetic resonance imaging (fMRI). In addition, we evaluated the relationship between amygdala volume and habituation, to examine the effects of atrophy. Eighteen healthy young controls and 18 healthy elderly subjects were scanned with fMRI during viewing of repeatedly presented neutral human face stimuli. Significant fMRI signal decrement was observed across all subjects for early versus late face presentations. Analysis of group, condition, and hemisphere revealed a significant three-way interaction, with right greater than left habituation in the young, but left greater than right amygdala habituation in the elderly. Volumetric and correlational analyses demonstrated that amygdala volume is associated with habituation in the right, but not left, hemisphere. We conclude that, in healthy elderly adults, the amygdala retains its adaptive habituation response, but speculate that intrinsic changes in amygdala anatomy during aging may modulate its laterality.

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

BACKGROUND: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). OBJECTIVES: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions. RESULTS: The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. CONCLUSIONS: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.

Amygdala responses to human faces in obsessive-compulsive disorder.

BACKGROUND: To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI). METHODS: Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross. RESULTS: Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed. CONCLUSIONS: Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders.