Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses.

The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1042 youths (ages 11-23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. CBF at rest was quantified on a voxelwise basis using arterial spin labeled perfusion MRI at 3T. A dimensional measure of psychopathology was constructed using a bifactor model of item-level data from a psychiatric screening interview, which delineated four factors (fear, anxious-misery, psychosis and behavioral symptoms) plus a general factor: overall psychopathology. Overall psychopathology was associated with elevated perfusion in several regions including the right dorsal anterior cingulate cortex (ACC) and left rostral ACC. Furthermore, several clusters were associated with specific dimensions of psychopathology. Psychosis symptoms were related to reduced perfusion in the left frontal operculum and insula, whereas fear symptoms were associated with less perfusion in the right occipital/fusiform gyrus and left subgenual ACC. Follow-up functional connectivity analyses using resting-state functional MRI collected in the same participants revealed that overall psychopathology was associated with decreased connectivity between the dorsal ACC and bilateral caudate. Together, the results of this study demonstrate common and dissociable CBF abnormalities across neuropsychiatric disorders in youth.

Moderators and predictors of response to cognitive-behavioral therapy augmentation of pharmacotherapy in obsessive-compulsive disorder.

BACKGROUND: Cognitive-behavioral therapy (CBT) consisting of exposure and response prevention (EX/RP) is efficacious as a treatment for obsessive-compulsive disorder (OCD). However, about half of patients have a partial or poor response to EX/RP treatment. This study examined potential predictors and moderators of CBT augmentation of pharmacotherapy, to identify variables associated with a poorer response to OCD treatment. METHOD: Data were drawn from a large randomized controlled trial that compared the augmenting effects of EX/RP to stress management training (SMT; an active CBT control) among 108 participants receiving a therapeutic dose of a serotonin reuptake inhibitor (SRI). Stepwise regression was used to determine the model specification. RESULTS: Pretreatment OCD severity and gender were significant moderators of outcome: severity affected SMT (but not EX/RP) outcome; and gender affected EX/RP (but not SMT) outcome. Adjusting for treatment type and pretreatment severity, significant predictors included greater co-morbidity, number of past SRI trials, and lower quality of life (QoL). Significant moderators, including their main-effects, and predictors accounted for 37.2% of the total variance in outcome, comparable to the impact of treatment type alone (R2=30.5%). These findings were replicated in the subgroup analysis of EX/RP alone (R2=55.2%). CONCLUSIONS: This is the first randomized controlled study to examine moderators and predictors of CBT augmentation of SRI pharmacotherapy. Although effect sizes for individual predictors tended to be small, their combined effect was comparable to that of treatment. Thus, future research should examine whether monitoring for a combination of these risk factors and targeting them with multi-modular strategies can improve EX/RP outcome.

Validation of the Chinese Version of Obsessive-Compulsive Inventory-Revised.

BACKGROUND: The Obsessive-Compulsive Inventory-Revised (OCI-R) is a psychometrically sound and valid self-report measure for evaluating the severity of six dimensions of obsessive-compulsive symptoms: washing, obsessing, hoarding, ordering, checking, and neutralising. We aimed to validate the Chinese version of the OCI-R (C-OCI-R) in patients with obsessive-compulsive disorder (OCD) in Hong Kong. METHODS: The C-OCI-R was forward and backward translated and reviewed by an expert panel and a focus group. The internal consistency and test-retest reliability (2-week interval) were examined. Confirmatory factor analysis was used to examine the construct validity of the C-OCI-R. Concurrent validity was examined by the correlation between the C-OCI-R and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), whereas divergent validity was examined by the correlation of the C-OCI-R with the Beck Depression Inventory-Second Edition and the Hamilton Depression Rating Scale. RESULTS: 130 OCD patients were recruited. The C-OCI-R showed excellent internal consistency (Cronbach's alpha = 0.92) and test-retest reliability (Spearman's rho correlation coefficient = 0.96). The original six-factor model was supported by confirmatory factor analysis. Concurrent validity and divergent validity were established. However, the neutralising subscale may need further development, and the divergent validity of the obsessing subscale was unsatisfactory. The structure of OCD symptoms was similar in Chinese and western patients. CONCLUSION: The C-OCI-R is a valid and reliable measure for assessing the severity of obsessive-compulsive symptoms in local Chinese patients with OCD.

Recent advances in the behavioral treatment of obsessive-compulsives.

The last decade has witnessed remarkable progress in the treatment of obsessive-compulsives, with the introduction of response prevention and deliberate exposure to feared situations in vivo and in imagination. In a series of studies, the effects of the single components of this program were investigated. The results suggest that the optimal treatment includes a combination of all three procedures. It appears that in vivo exposure mainly affects anxiety/discomfort associated with cues for ritualizing; response prevention affects primarily compulsive behavior; and imaginal exposure assists in maintenance of treatment gains, perhaps through its impact on fears of future catastrophes associated with obsessions.

Anxiety and cerebral blood flow during behavioral challenge. Dissociation of central from peripheral and subjective measures.

To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO2 did not change across the three conditions. Regional cerebral blood flow increased slightly (in the temporal region) during imaginal flooding, but decreased markedly in several cortical regions during in vivo exposure, when anxiety was highest by subjective and peripheral autonomic measures. These results demonstrate that intense anxiety can be associated with decreased rather than increased cortical perfusion and that ostensibly related states of anxiety (eg, anticipatory and obsessional anxiety) may be associated with opposite effects on regional cerebral blood flow.

Effects of imipramine on the autonomic responses of obsessive-compulsives to auditory tones.

It has been argued that a mechanism of clomipramine's efficacy for obsessive-compulsive disorder is its reduction of excessive autonomic reactivity. The present study evaluated this proposed mechanism of action by assessing the effect on autonomic responding of imipramine, which is structurally similar to clomipramine, but lacks therapeutic efficacy for obsessive-compulsives. Twenty-three obsessive-compulsive patients received three sessions of 20 unsignalled 1000-Hz, 100-dB tones of 1-sec duration and 100-msec rise-time. Skin conductance level, response frequency and magnitude, and heart rate were scored for an adaptation period and for each tone onset. Six weeks after the first tone session, during which half of the subjects received imipramine while the remainder received placebo, the second tone assessment was performed. A third tone assessment was performed after an additional 4 weeks of medication. Percentage of nonresponders was also evaluated for each group. Imipramine reduced electrodermal activity and increased heart rate. Skin conductance level and both number and amplitude of responses decreased significantly after 6 weeks of imipramine, compared with placebo, with further attenuation of electrodermal activity after 10 weeks of the drug. Electrodermal nonresponding increased dramatically for the imipramine group as compared to the nondrug group. These results reveal effects of imipramine on autonomic responding, and cast doubt on the hypothesis that a mechanism for successful drug treatment of obsessive-compulsive disorder is decreased autonomic reactivity.

Arousal, numbing, and intrusion: symptom structure of PTSD following assault.

OBJECTIVE: This study investigated hypotheses concerning the importance of symptoms of numbing in posttraumatic stress disorder (PTSD). METHODS: Symptoms of PTSD were assessed in 72 female rape victims and 86 female victims of nonsexual assault approximately 3 months after the crimes occurred. A principal-components factor analysis of subjects' symptoms was then undertaken. RESULTS: The analysis yielded three factors: arousal/avoidance, numbing, and intrusion. These were somewhat different from the symptom clusters in DSM-III-R, since effortful avoidance and numbing symptoms did not load on the same factor. Numbing symptoms appeared to be particularly important in identifying individuals with PTSD. CONCLUSIONS: The results imply that there are two patterns of posttrauma symptoms, one characterizing PTSD and the second characterizing a phobic reaction.

DSM-IV field trial: obsessive-compulsive disorder.

OBJECTIVE: Three issues relevant to revising the DSM-III-R criteria for obsessive-compulsive disorder were examined in a field trial: 1) the requirement that symptoms of obsessive-compulsive disorder be viewed by the patient as excessive or unreasonable, 2) the presence of mental compulsions in addition to behavioral compulsions, and 3) ICD-10 subcategories. METHOD: The authors studied symptom patterns of obsessive-compulsive disorder as well as strength of obsessive belief among 431 patients with obsessive-compulsive disorder at seven hospital outpatient clinics. Two methods of subject selection were used: consecutive entry of everyone who contacted the clinics for evaluation of obsessive-compulsive disorder and entry of patients with obsessive-compulsive disorder who had continuing contact with the clinics since before the field trial and who were still symptomatic. Primary measures were the Yale-Brown Obsessive Compulsive Scale and face-valid questions about fixity of obsessive-compulsive beliefs. RESULTS: The large majority of patients were uncertain about whether their obsessive-compulsive symptoms were unreasonable or excessive, and most had both mental and behavioral compulsions. Results on the ICD-10 subcategories were equivocal. CONCLUSIONS: The present results converge with previous findings to indicate a broad range of insight among patients with obsessive-compulsive disorder. The DSM-III-R requirement for insight should be de-emphasized in DSM-IV, and mental rituals should be included in the definition of compulsions.

Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model.

The disturbances observed in animals subjected to unpredictable and uncontrollable aversive events resemble post-traumatic stress disorder (PTSD) symptoms and thus may constitute an animal model of this disorder. It is argued that the similarity between animals' symptoms and those of trauma victims may reflect common etiological factors. Relevant experiments in which animals exhibit generalized fear and arousal, discrete fear of a conditioned stimulus (CS), analgesia, and avoidance are reviewed with the view that these manifestations may be analogous to the PTSD symptom clusters of persistent arousal, reexperiencing, numbing, and avoidance, respectively. Finally, animal paradigms are suggested to test the validity of the model and specific hypotheses are derived from the animal literature regarding trauma variables that are predictive of particular PTSD symptom clusters.

Trauma and women: course, predictors, and treatment.

Posttraumatic stress disorder (PTSD) resulting from aggravated assault, rape, or noncrime trauma affects over 4 million women in the United States, according to retrospective studies. Prospective studies reviewed here found that 3 months post assault the prevalence of PTSD was 48% in rape victims and 25% in nonsexual crime victims. Prolonged exposure treatment and stress inoculation training are both effective psychotherapeutic treatments for PTSD. Prolonged exposure involves having the patient relive the traumatic memory and recount the event in detail. This description is audiotaped and the patient is asked to listen to it as part of assigned homework. In vivo exposure to feared objects or situations is also assigned as homework. Stress inoculation training consists of teaching patients a variety of techniques for managing anxiety, including controlled breathing, deep muscle relaxation, thought-stopping, cognitive restructuring, preparation for stressors, covert modeling, and role-play. Both treatments have been proven to be effective alone and in combination in ameliorating chronic PTSD in women after traumatic sexual or nonsexual assault. This efficacy was maintained for 3 months of follow-up.

Psychosocial treatment of posttraumatic stress disorder.

This article reviews empirically validated psychosocial treatments for posttraumatic stress disorder (PTSD) and considers factors associated with successful therapy outcome. Most of the treatments whose efficacy was studied empirically fall within the broad category of cognitive-behavioral therapy. These include exposure therapy, anxiety management programs, and cognitive therapy. These therapy modalities have been developed to modify conditioned fear and erroneous cognitions that are thought to underlie PTSD. Exposure therapy has the most empirical support because it was found to be effective across different populations of trauma victims with PTSD. Combinations of therapies have also been used, and the value of these is discussed. In addition, this article presents recent evidence about the efficacy of eye movement and desensitization reprocessing. A growing body of evidence supports the use of psychosocial treatments for PTSD, but not all patients benefit. Future research should develop programs that increase the motivation of patients to take advantage of these efficacious treatments.

Women and traumatic events.

Posttraumatic stress disorder (PTSD) gained the status of a psychiatric disorder in 1980, although the syndrome had already been recognized widely for many years. PTSD is distinguished by alternations between reexperiencing of the traumatic event that triggered the PTSD in the first place and avoidance and numbing. Increased arousal (e.g., exaggerated startle reaction) also forms part of the diagnosis. Although the majority of trauma victims recover spontaneously, more than 30% develop persistent PTSD symptoms, with women being twice as likely as men to suffer PTSD. To date, the most studied psychosocial treatments for PTSD are the cognitive-behavioral interventions. Exposure therapy (systematic exposure to the traumatic memory in a safe environment) has been demonstrated to be quite effective with adult women who were sexually or nonsexually assaulted in adulthood as well as with women who were sexually abused in childhood. Supportive counseling does not appear as effective as exposure therapy, but is better than no therapy.

Posttraumatic stress disorder: psychological factors and psychosocial interventions.

In this article, we propose that successful processing of traumatic events involves emotional engagement with the trauma memory, organization of the trauma narrative, and correction of dysfunctional cognitions that often follow trauma. We further propose that the success of psychosocial treatments of posttraumatic stress disorder hinges on the ability of the treatments to address impairments in these processes. We focus our presentation of psychosocial interventions on cognitive-behavioral treatments (CBT), since this approach had gained the most empirical support to date, and describe the results of controlled trials that compare the relative efficacy of several CBT interventions.

Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in posttraumatic stress disorder (PTSD) and guide clinical practice with recommendations on the appropriate management strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Edna B. Foa, Ronald C. Kessler, Alexander C. McFarlane, and Arieh Y. Shalev. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: PTSD is often a chronic and recurring condition associated with an increased risk of developing secondary comorbid disorders, such as depression. Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

Cognitive-behavioral treatment of pediatric obsessive-compulsive disorder: an open clinical trial.

OBJECTIVE: The purpose of this open clinical trial was to examine the efficacy of cognitive-behavioral treatment involving exposure and ritual prevention for pediatric obsessive-compulsive disorder (OCD). METHOD: Children and adolescents with diagnosed OCD (N = 14) received cognitive-behavioral treatment, seven patients received intensive treatment (mean = 18 sessions over 1 month) and seven received weekly treatment (mean = 16 sessions over 4 months). Eight of these patients received concurrent treatment with serotonin reuptake inhibitors and six received cognitive-behavioral treatment alone. Outcome was assessed via interviewer ratings on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Obsessive Compulsive Rating Scales for Main Fear and Main Ritual, and Hamilton Depression Rating Scale. RESULTS: Cognitive-behavioral treatment was effective in ameliorating OCD symptoms. Twelve of the 14 patients were at least 50% improved over pretreatment Y-BOCS severity, and the vast majority remained improved at follow-up; mean reduction in Y-BOCS was 67% at posttreatment and 62% at follow-up (mean time to follow-up = 9 months). CONCLUSIONS: Results suggest that cognitive-behavioral treatment by exposure and ritual prevention is effective for pediatric OCD. Controlled studies with random assignment to conditions are warranted to evaluate the relative efficacy of cognitive-behavioral pharmacological, and combined treatments.

The investigation of exposure and cognitive therapy: comment on Tarrier et al (1999).

This article outlines concerns relating to the N. Tarrier et al. (1999) investigation comparing imaginal exposure and cognitive therapy. Specifically, the authors offer N. Tarrier et al. the opportunity to operationally define and clarify the claim that more patients treated by imaginal exposure "worsened" during treatment. Equally, in light of N. Tarrier et al.'s low effect sizes in relation to past research the authors also highlight the need to utilize accountable treatment integrity checks.

Relapse prevention program for treatment of obsessive-compulsive disorder.

Eighteen participants with obsessive-compulsive disorder received 3 weeks of intensive treatment by exposure and response prevention, which were followed by either a relapse prevention (RP) program or associative therapy (AT; an attention-control program). Independent evaluators conducted assessments of obsessive-compulsive symptoms, anxiety, and depression, before and after intensive behavior therapy, after the week of intensive RP or AT and at a 6-month follow-up. Results indicated that the RP program was effective in preventing relapse: Both treatment groups improved immediately after the intensive treatment, but the RP group remained improved at follow-up, whereas the AT group showed some return of symptoms.

Influence of emotional engagement and habituation on exposure therapy for PTSD.

This study examined 2 process variables, emotional engagement and habituation, and outcome of exposure therapy for posttraumatic stress disorder. Thirty-seven female assault victims received treatment that involved repeated imaginal reliving of their trauma, and rated their distress at 10-min intervals. The average distress levels during each of 6 exposure sessions were submitted to a cluster analysis. Three distinct groups of clients with different patterns of distress were found: high initial engagement and gradual habituation between sessions, high initial engagement without habituation, and moderate initial engagement without habituation. Clients with the 1st distress pattern improved more in treatment than the other clients. The results are discussed within the framework of emotional processing theory, emphasizing the crucial role of emotional engagement and habituation in exposure therapy.

Evaluation of a brief cognitive-behavioral program for the prevention of chronic PTSD in recent assault victims.

The efficacy of a brief prevention program (BP) aimed at arresting the development of chronic PTSD was examined with 10 recent female victims of sexual and nonsexual assault who received 4 sessions of a cognitive-behavioral program shortly after the assault. Their PTSD and depression severity was compared with that of 10 matched recent female assault victims who received repeated assessments of their trauma-related psychopathology (assessment control; AC). The BP program consisted of education about common reactions to assault and cognitive-behavioral procedures. Two months postassault, victims who received the BP program had significantly less severe PTSD symptoms than victims in the control condition; 10% of the former group met criteria for PTSD versus 70% of the latter group. Five and a half months postassault, victims in the BP group were significantly less depressed than victims in the AC group and had significantly less severe reexperiencing symptoms.

Treatment of posttraumatic stress disorder in rape victims: a comparison between cognitive-behavioral procedures and counseling.

Rape victims with posttraumatic stress disorder (PTSD; N = 45) were randomly assigned to one of four conditions: stress inoculation training (SIT), prolonged exposure (PE), supportive counseling (SC), or wait-list control (WL). Treatments consisted of nine biweekly 90-min individual sessions conducted by a female therapist. Measures of PTSD symptoms, rape-related distress, general anxiety, and depression were administered at pretreatment, posttreatment, and follow-up (M = 3.5 months posttreatment). All conditions produced improvement on all measures immediately post-treatment and at follow-up. However, SIT produced significantly more improvement on PTSD symptoms than did SC and WL immediately following treatment. At follow-up, PE produced superior outcome on PTSD symptoms. The implications of these findings and direction for treatment and future research are discussed.