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Background Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). Objectives To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. Methods Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. Results The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7–15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0–90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values

Objective Pantothenate kinase‐associated neurodegeneration (PKAN) is an autosomal‐recessive, neurodegenerative disorder with a mixed‐motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient‐reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. Methods A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12‐item Pantothenate Kinase‐Associated Neurodegeneration Activities of Daily Living (PKAN‐ADL). The PKAN‐ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro‐QoL) measures, selected attributes of the Health Utilities Index (HUI)‐2/3, and the Stroke Aphasia Depression Questionnaire (SADQ‐10) to assess construct validity. Results Internal consistency was 0.93, with excellent test‐retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31–54) and 42% (n = 5) showed a floor effect >30% (range, 31–46), reflecting disease heterogeneity. Convergent validity was shown with Neuro‐QoL measures (rs > 0.90) and HUI‐2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ‐10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0–10 scale) ranged from 7.0 to 9.9. Conclusion The PKAN‐ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN‐ADL scale in clinical trials.

Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief. We describe the treatment of the first, later-onset PKAN patient with oral fosmetpantotenate (previously known as RE-024), a novel replacement therapy developed to bypass the enzymatic defect. Methods. This was an open-label, uncontrolled, 12-month treatment with fosmetpantotenate of a single patient with a later-onset, moderately severe, and slowly progressive form of PKAN. Results. The patient showed improvement in all clinical parameters including the Unified Parkinson’s Disease Rating Scale (UPDRS), Barry-Albright Dystonia Scale, the EuroQol five-dimensional three-level (EQ-5D-3L) scale, timed 25-foot walk test, and electroglottographic speech analysis. Fosmetpantotenate was well-tolerated with only transient liver enzyme elevation which normalized after dose reduction and did not recur after subsequent dose increases. Conclusions. Fosmetpantotenate showed promising results in a single PKAN patient and should be further studied in controlled trials.

The elevated rate of current posttraumatic stress disorder (PTSD) among Hispanic Vietnam veterans has been attributed to culturally based expressiveness that inflates symptom self-reports. To investigate this possibility, the authors conducted three hypothesis-driven analyses with National Vietnam Veterans Readjustment Study (NVVRS) data from the Structured Clinical Interview for DSM-III-R (SCID-) diagnosed subsample of male Vietnam Theater veterans (N = 260). First, persistence of the Hispanic elevation after adjusting for war-zone stress exposure initially suggested the effect of greater expressiveness. Second, symptom-based analyses isolated this effect to the self-report Mississippi Scale for Combat-Related PTSD and not to the clinician-rated SCID interview. Third, objective measures of functioning did not reveal a unique Hispanic pattern of lower impairment associated with current PTSD. These tests suggest that greater Hispanic expressiveness does not account for the Hispanic elevation in current PTSD in the NVVRS SCID-diagnosed subsample.

A 70.9% majority of the U.S. male veterans in a nationwide sample appraised the impact of their service in Vietnam on their present lives as mainly positive. A substantial minority, 41.7%, judged the effects to be highly salient. With controls on level of exposure to war-zone stressors measured with data from military records, the valence and salience of these appraisals are investigated in relation to posttraumatic stress disorder (PTSD) and other indicators of wartime and postwar functioning. The results are consistent with the hypothesis that mainly positive tertiary appraisals are affirmations of successful wartime and postwar adaptation rather than defensive denials related to maladaptive outcomes. The possibility that mainly positive tertiary appraisals also contribute to successful postwar adaptation is discussed.

To date, all clinical trials using a single therapeutic modality (psychotherapy or pharmacotherapy) have found that even the best validated treatments for adults with chronic Posttraumatic Stress Disorder (PTSD) leave a substantial proportion of patients with disabling residual symptoms.We reviewed the treatment course of three research patients with PTSD who received trauma-focused psychotherapy after experiencing a partial response to medication. Structured diagnostic interviews, validated symptom measures, and standardized treatment approaches were used to assess treatment response.All patients partially benefited from medication treatment, and the degree of benefit varied substantially. Also, all patients experienced an additional reduction in PTSD symptoms after a time-limited course of prolonged exposure therapy (PE). This finding differs from anecdotal observations among U.S. War veterans and has never been documented systematically among civilian adults with chronic PTSD.Maximizing treatment outcome in adults with chronic PTSD may require additional psychotherapy after a partial medication response, and further study is warranted.

Alternative therapies and therapy modalities for SAD are needed because: Established treatments (CBT and pharmacologic) do not help everyone who seeks help. Established treatments provide only partial decrease in symptoms for many patients. Patients may experience recurrence of symptoms in long-term follow-up. CBT does not reach enough patients in need. Alternative treatment approaches and modalities may also be needed to address the successful outcomes of CBT. Success in overcoming social anxiety symptoms can generate a whole new set of challenges. For example, a 31-year-old man who overcomes his fear of dating and begins his first romantic relationship may need a less symptomatically focused therapy to deal with issues that arise in this relationship. Likewise, a woman whose decreased social anxiety enables her to get a long-awaited promotion may need to deal with the stress of adjusting to her new responsibilities. An individual who overcomes phobia of public speaking and still has mild anxiety may need to graduate to a forum such as Toastmasters to provide continued exposure to further develop confidence and skills in public speaking.

Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD.On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation.Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder.Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.

A new diagnosis can greatly influence scientific research, access to resources, and treatment selection in clinical practice. The authors review the historical evolution, rationale, empirical foundation, and clinical utility to date of the recently introduced diagnosis of acute stress disorder.The conceptual basis and relevant methods for identifying a psychiatric syndrome are reviewed with respect to acute stress disorder, including selection of criteria for core symptoms; considerations of sensitivity and specificity of a syndrome definition; longitudinal course; and distinctions between normative and pathological phenomena. Particular attention is devoted to two major issues: the implications of the core feature requirement of three of five dissociative symptoms, and the question of whether there should be two separate diagnoses (acute stress disorder and post-traumatic stress disorder [PTSD]) describing posttraumatic syndromes. The widely divergent approaches in DSM-IV and ICD-10 are also reviewed.The diagnosis of acute stress disorder does not appear to achieve the important objective of providing adequate clinical coverage for individuals with acute posttraumatic symptoms. The validity and utility of requiring peritraumatic dissociative symptoms as a core feature are questionable, as is the separation of essentially continuous clinical phenomena into two disorders with different criteria sets (acute stress disorder and PTSD) based on persistence of symptoms for 30 or more days.Longitudinal studies using acute stress disorder criteria, as well as broader considerations of the clinical and scientific functions that posttraumatic diagnoses should serve, suggest a need to reevaluate the current DSM-IV approach to posttraumatic syndromes.

We report the results of an 8-week open trial of imipramine in 15 patients with social phobia. Nine patients completed the trial; six dropped out early because of adverse effects. The mean reduction in the Liebowitz Social Anxiety Scale was 15% and 18% for the intent-to-treat and completer groups, respectively; the overall response rate (based on the Clinical Global Impression Scale of 1 or 2, very much or much improved) was 20% (3/15) and 22% (2/9), respectively. The results from this open trial do not support the efficacy of imipramine as a treatment for social phobia.

BackgroundMoclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.MethodSeventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.ResultsIntention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.ConclusionsMoclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.

We compared personality profiles of men with sexual dysfunction (n = 51) to those of age-matched men with a primary diagnosis of paraphilia (n = 51) employing the NEO Personality Inventory (NEO-PI), a measure of the five-factor model. Preliminary analyses in a large sample of patients in a sexual behaviors consultation unit supported the reliability and factorial validity of the NEO-PI for this population. Analysis of variance showed significant differences between the dysfunctional and the paraphilic groups on two of the five NEO-PI domains, Neuroticism (N) and Agreeableness (A). The group personality profile of the sexually dysfunctional men was comparable to the normative sample of the NEO-PI, except for a slight elevation in N. By contrast, men with paraphilia had a personality profile marked by high N, low A, and low Conscientiousness (C). Treatment implications of the average personality profile of the sexual dysfunction group and the distinctive personality profile of paraphilic men are discussed.

Objective: To determine whether maternal violence-related posttraumatic stress disorder (PTSD), reflective functioning (RF), and/or quality of mental representations of her child predicts maternal behavior within a referred sample of mothers exposed to interpersonal violence and their children (aged 8–50 months). Method: A total of 41 dyads completed 2 videotaped visits including measures of maternal mental representations and behavior. Results: Negative and distorted maternal mental representations predicted atypical behavior (Cohen's d > 1.0). Although maternal PTSD and RF impacted mental representations, no significant relationships were found between PTSD, RF, and overall atypical caregiving behavior. Severity of maternal PTSD was, however, positively correlated with the avoidant caregiving behavior subscale. Conclusions: Maternal mental representations of her child are useful risk indicators that mark dysregulation of trauma-associated emotions in the caregiver.

Bipolar disorder (BD) is among the 10 most disabling medical conditions in the world (1), and has been associated with increased risk of morbidity, mortality (2) and psychiatric comorbidity (3) including post-traumatic stress disorder (PTSD) (4–8). The rate of PTSD among persons with BD has been estimated to range from 11% in patients with first-admission psychosis (7) to approximately 40% in the subgroup of respondents with BD in a nationwide community sample (8) and among ambulatory and hospitalized bipolar patients (4). Emerging evidence suggests that history of trauma may be related to both etiology and illness course of BD (5, 6). For example, early parental loss has been found to increase the risk for BD (9), and high-impact trauma, such as sexual and physical abuse, has been associated with poor illness course of BD (7, 8). Bipolar illness might be both a consequence of traumatic events (e.g., disasters, physical or sexual assaults) and a generator of additional traumatic events such as interpersonal adversities (e.g., violent events) (5, 10). The study of these trajectories can complement research on the role of family psychiatric history and genetics (11–13). It has been suggested, but not yet systematically studied, that exposure to interpersonal trauma following BD onset may result from the poor judgment and risky behaviors (e.g., substance use, reckless driving, and irritability) that partially define hypomanic and manic episodes (5). This report is based on data from a cross-sectional study of a systematic sample of 997 low-income primary care patients attending a large primary care clinic in New York City (14–16). We aimed to examine whether patients with a history of BD are at increased risk (i) to experience psychological trauma in general, physical and sexual assault in particular; and (ii) to develop PTSD following exposure to trauma. We also explored whether exposure to trauma increases the risk of BD independent from PTSD and whether comorbidity of PTSD increases the risk for impairment and functioning problems among patients with BD. We hypothesized that: (i) a history of exposure to trauma and especially assaultive trauma would be more common in patients with BD than in those without BD; (ii) the prevalence of current PTSD would be higher in patients with BD than in those without BD; (iii) exposure to trauma would increase the risk of BD independent of PTSD; and (iv) patients with BD who have comorbid PTSD would manifest greater functional impairment then those with BD but without PTSD.

Editor's note Stress reactions run from Acute Stress Reactions and Adjustment Disorders to Post-traumatic Stress Disorder (PTSD). The first two, in many instances, may be thought of as time limited in their impact and respond to many different types of psychosocial interventions. The primary purpose of intervening in these disorders is to facilitate more effecting coping with the stressor, reduce functional impairment, and return the individual to his previous level of active functioning in the community. PTSD has been shown to respond to both trauma-focused cognitive-behavioral psychotherapies and to pharmacological agents, particularly the SSRIs, though other pharmacologic interventions may impact some of the disturbed affect, anxiety, and lability, and to psychosocial interventions. As with many other disorders, there is a treatment resistant group that remain significantly impaired despite treatment, and long-term management of symptoms becomes the primary goal. Introduction: differences in classification of stress disorders The adjustment disorders, acute stress disorder, and post-traumatic stress disorder (DSM-IV) all share the common feature of occurring as a response to an adverse environmental event or cluster of events. The distinction appears clear cut; post-traumatic stress disorders follow extreme stressors that are operationally defined, whereas adjustment disorders may follow any kind of stressor of a less serious degree. Adjustment disorders are defined as “clinically significant emotional or behavioral symptoms in response to an identifiable psychosocial stressor or stressors” (DSM-IV), and must develop within 3 months of the stressor (DSM-IV).

A Web-based survey of adults who experienced loss during the September 11, 2001, terrorist attacks was conducted to examine the prevalence and correlates of complicated grief (CG) 2.5-3.5 years after the attacks. Forty-three percent of a study group of 704 bereaved adults across the United States screened positive for CG. In multivariate analyses, CG was associated with female gender, loss of a child, death of deceased at the World Trade Center, and live exposure to coverage of the attacks on television. Posttraumatic stress disorder, major depression, anxiety, suicidal ideation, and increase in post-9/11 smoking were common among participants with CG. A majority of the participants with CG reported receiving grief counseling and psychiatric medication after 9/11. Clinical and policy implications are discussed. Language: en

INTRODUCTION From the first chaotic days after the attacks of September 11, 2001, the co-directors of the Consortium – Marylene Cloitre, PhD, Spencer Eth, MD, Randall Marshall, MD, and Rachel Yehuda, PhD – shared a collective sense of alarm that the need for mental health services in our community would greatly exceed capacity to provide evidence-based treatment for trauma-related problems and disorders. Because federal programs almost exclusively emphasize the public health objective of restoring the general population to a semblance of normal functioning, we worried that there would not be adequate programs devoted to helping persons developing serious psychiatric disorder as a result of the attacks. Subsequent epidemiological studies (reviewed in this volume) confirmed our impression, but by the time these data were available – many months after 9/11 – we were already well underway with the project of providing intensive training to a group of clinicians at each of our centers, who could then serve as expert treatment providers, and, more importantly, clinician experts available to the community for educational programs. In sum, the Consortium was a rapidly implemented large-scale project with the overall objective of disseminating evidence-based treatments for trauma-related disorders to the greater New York community. During the first year alone, approximately 920 patients were evaluated and treated at all sites. Treatment was provided in English, Spanish, Hebrew, German, Korean, and several Chinese dialects. Some sites developed intensive trainings for clinicians, and other focused on clinical work or other kinds of educational programs (e.g. intensive training and supervision for a small group of community clinicians).

This study explored the use of a brief experimental intervention that integrates principles of infant-parent psychotherapy, videofeedback, controlled exposure to child distress in the context of parental posttraumatic stress disorder (PTSD), and stimulation of parental reflective functioning (RF). The Clinician Assisted Videofeedback Exposure Session (CAVES) was applied to 32 interpersonal violence-exposed mothers of very young children (8-50 months) with respect to change of maternal perception of her child. While we found no significant reduction over two videotaped assessment visits with a mental health professional, we did find a significant reduction in the degree of negativity of maternal attributions towards her child following the videotaped visit focused on the CAVES (p

In 1988, the National Vietnam Veterans Readjustment Study (NVVRS) of a representative sample of 1200 veterans estimated that 30.9% had developed posttraumatic stress disorder (PTSD) during their lifetimes and that 15.2% were currently suffering from PTSD. The study also found a strong dose-response relationship: As retrospective reports of combat exposure increased, PTSD occurrence increased. Skeptics have argued that these results are inflated by recall bias and other flaws. We used military records to construct a new exposure measure and to cross-check exposure reports in diagnoses of 260 NVVRS veterans. We found little evidence of falsification, an even stronger dose-response relationship, and psychological costs that were lower than previously estimated but still substantial. According to our fully adjusted PTSD rates, 18.7% of the veterans had developed war-related PTSD during their lifetimes and 9.1% were currently suffering from PTSD 11 to 12 years after the war; current PTSD was typically associated with moderate impairment.

A subsample of 255 male Vietnam veterans from the National Vietnam Veterans Readjustment Study received in-depth psychiatric diagnostic interviews. This paper focuses on the 88 veterans with a war-related onset of PTSD. Among these veterans, the avoidance cluster, especially its symptoms of numbing, was most strongly associated with chronic PTSD; less strongly but also significantly associated was the hyperarousal cluster. Further analyses show that these associations are not artifacts of the relationship of symptom patterns to prewar demographic factors (race/ethnicity, socioeconomic status, age at entry into Vietnam), comorbidity, treatment and compensation seeking, or probable severity of war-related trauma. We conclude that certain symptom profiles may predict enduring pathological responses to trauma and therefore provide targets for intervention efforts.

Objective To screen for posttraumatic stress disorder (PTSD) in primary care patients 7–16 months after 9/11 attacks and to examine its comorbidity, clinical presentation and relationships with mental health treatment and service utilization. Method A systematic sample (n=930) of adult primary care patients who were seeking primary care at an urban general medicine clinic were interviewed using the PTSD Checklist: the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire and the Medical Outcome Study 12-Item Short Form Health Survey (SF-12). Health care utilization data were obtained by a cross linkage to the administrative computerized database. Results Prevalence estimates of current 9/11-related probable PTSD ranged from 4.7% (based on a cutoff PCL-C score of 50 and over) to 10.2% (based on the DSM-IV criteria). A comorbid mental disorder was more common among patients with PTSD than patients without PTSD (80% vs. 30%). Patients with PTSD were more functionally impaired and reported increased use of mental health medication as compared to patients without PTSD (70% vs. 18%). Among patients with PTSD there was no increase in hospital and emergency room (ER) admissions or outpatient care during the first year after the attacks. Conclusions In an urban general medicine setting, 1 year after 9/11, the frequency of probable PTSD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this clinical population and are especially important in view of available treatments for PTSD.

Parental mental representations of the child have been described in the clinical literature as potentially useful risk-indicators for the intergenerational transmission of violent trauma. This study explored factors associated with the quality and content of maternal mental representations of her child and relationship with her child within an inner-city sample of referred, traumatized mothers. Specifically, it examined factors that have been hypothesized to support versus interfere with maternal self- and mutual-regulation of affect: posttraumatic stress disorder (PTSD) and maternal reflective functioning (RF). More severe PTSD, irrespective of level of RF, was significantly associated with the distorted classification of non-balanced mental representations on the Working Model of the Child Interview (WMCI) within this traumatized sample. Higher Levels of RF, irrespective of PTSD severity, were significantly associated with the balanced classification of maternal mental representations on the WMCI. Level of maternal reflective functioning and severity of PTSD were not significantly correlated in this sample. Clinical implications are discussed.

To understand the determinants of frightening/frightened and other atypical maternal behavior, the authors studied a sample of 41 inner-city mothers of very young children (ages 8-50 months), the mothers of whom had lifetime histories of interpersonal violent trauma (i.e., physical or sexual abuse, and domestic violence) and related posttraumatic stress.The authors measured (1) maternal salivary cortisol levels before and 30 minutes after a videotaped play paradigm with their children, involving two separations and reunions; and (2) cortisol reactivity 30 minutes after separation stress. Data were analyzed using Pearson bivariate correlations, ANOVA, and multiple linear regressions.Salivary cortisol "baseline" values were significantly negatively correlated with childhood interpersonal violent trauma severity (i.e., trauma severity prior to age 16). However, cortisol reactivity was not significantly correlated with interpersonal violent trauma severity at this level of analysis. Although baseline salivary cortisol values were not significantly correlated with current overall psychiatric or depressive symptoms, they were negatively correlated with severity of current posttraumatic stress symptoms (PTSS) and with dissociative symptoms. Neither dimensions of negativity nor distortion of maternal attributions showed any significant association with prestress or poststress salivary cortisol levels. Salivary cortisol baseline was negatively correlated with atypical maternal behavior via measurement of the level of disrupted communication, at a trend-level of significance.Violent trauma-associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may be a marker for increased risk for intergenerational transmission via parenting behavior with young children. Low salivary cortisol prior to separation stress and blunted cortisol reactivity to separation may also be markers for posttraumatic stress.

There is little research on the consequences of large-scale violent disasters in a community despite their unfortunate prevalence over many decades. The primary source of epidemiological data for the greater New York community in dealing with the September 11, 2001, attacks was the Oklahoma City bombing. In the latter event, 45% of directly exposed adults met criteria for a major psychiatric disorder 6 months later, including 34% with posttraumatic stress disorder (PTSD). The first survey after the World Trade Center and Pentagon attacks, conducted within one week, revealed a remarkable degree of symptomatology across the nation in both adults and children. Forty-four percent of adults reported at least 1 of 5 PTSD screening symptoms in the 3–5 days after the attacks; 35% of parents reported children who had at least one symptom, and 47% of children worried about their own or someone else's safety. Coping behaviors were consistent with a community mental health model and included turning to open discussion (98%), religion (90%), and community activities (60%) in order to cope with their reactions.Rates of disorder were also high in a survey conducted 5–8 weeks later in Manhattan below 110th Street, with 38% saying they directly witnessed the World Trade Center attack. The current prevalence of new-onset PTSD was 7.5%, and of new-onset major depressive disorder, 9.7%. This translates into 67,000 persons with PTSD and 87,000 persons with major depression. This survey also found a significant increase in tobacco, alcohol, and marijuana use, but primarily among adults already using these substances. All surveys found strong associations between media exposure and symptomatology. The greatest need at this point in the literature is therapeutics research after such traumatic events.

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.

Phenylpropanolamine (PPA) is a sympathomimetic drug contained in numerous over-the-counter and prescription decongestants and appetite suppressants. A range of adverse effects have been reported, including neuropsychiatric reactions in patients known to be taking recommended doses. Given that psychiatric symptoms are not included in the manufacturer's lists of adverse drug reactions, the incidence may be significantly higher. We report a case of paranoid psychosis following use of a decongestant containing PPA and summarize the case report literature of psychiatric adverse effects to PPA in which doses were known and stated to be within recommended guidelines. A pattern of possible risk factors emerges from these reports. These may include 1) symptoms or history of mood spectrum disorder, 2) history of psychosis, 3) female sex, 4) family history of psychiatric disorder. The possibility that a higher incidence of adverse events occurs in a vulnerable population has not been systematically addressed, and seems called for. We recommend that physicians specifically inquire about patients' use of decongestants and diet aids. In half of the above cases, symptoms resolved without the use of antipsychotics.

The biological literature in the anxiety disorders has focused on comparisons between patient groups and normal volunteers, with relatively little comparative study of the anxiety disorders. We therefore conducted this pilot study to compare a group of patients with post-traumatic stress disorder (PTSD) (n = 7) to a contiguously studied panic disorder group (n = 17) and healthy control subjects (n = 16) on baseline levels of cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG), and response to clonidine challenge. Despite the small sample size, highly significant differences were found on the following measures: PTSD patients had lower cortisol, lower MHPG, reduced MHPG volatility to clonidine challenge, and marginally reduced cortisol volatility compared to patients with panic disorder. These biological findings support existing clinical, epidemiologic, family study, and clinical trial findings that distinguish these two disorders as distinct syndromes.

Objective This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD). Method Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale. Results Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated. Conclusions Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.

Objective: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/ derealization during panic attacks would be more likely to have a history of childhood trauma. Method: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. Results: Contrary to the authors’ hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. Conclusions: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder. (Am J Psychiatry 2000; 157:451–453)

The symptom overlap between posttraumatic stress disorder (PTSD) and other pharmacotherapy-responsive disorders suggests that pharmacotherapy might be effective. Nevertheless, of the eight published placebo-controlled trials investigating the pharmacotherapy of PTSD, only four found statistically significant efficacy for the treatment being studied. This literature possesses a number of methodologic limitations, including the fact that most studies have been conducted with war veterans, who may constitute a more treatment-refractory population. Several open trials and one controlled trial with selective serotonin reuptake inhibitors have reported improvement in some or all core PTSD symptoms (reexperiencing, avoidance, numbing, and hyperarousal). The authors hypothesized that paroxetine might be effective in PTSD, based on findings of its particular efficacy for anxiety and agitation in studies of depressed patients. The study presented here summarizes a 12-week, open-label trial of paroxetine among patients with noncombat-related, chronic PTSD. Outcome was assessed by an independent evaluator, the treating physician, and the patient, with the use of established rating scales for depression, anxiety, general symptoms, and PTSD core symptoms. A repeated-measures analysis of variance revealed highly significant improvement in all three symptom clusters, as well as in associated anxiety, depressive, and dissociative symptoms, with 11 of 17 (65%) patients rated as much or very much improved. The mean reduction in PTSD symptom scores was 48%. Exploratory analyses revealed that cumulative childhood trauma was negatively correlated with pharmacotherapy response (r = -0.52, p = 0.03). There was also significant variation in the time course of response across symptom clusters, which is suggestive of multiple mechanisms of response. Because paroxetine seems a highly promising treatment for all three symptom clusters of PTSD, a placebo-controlled clinical trial is warranted.

Background/aims Pantothenate kinase-associated neurodegeneration is a rare neurodegenerative disease with a variable clinical phenotype. Fosmetpantotenate is in clinical development as a replacement therapy that targets the underlying cause of pantothenate kinase-associated neurodegeneration. The FOsmetpantotenate Replacement Therapy pivotal trial—an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter trial—examines the efficacy and safety of fosmetpantotenate in patients with pantothenate kinase-associated neurodegeneration aged 6–65 years. The FOsmetpantotenate Replacement Therapy trial required the development and validation of a novel patient-reported outcome measure specifically relevant to pantothenate kinase-associated neurodegeneration. The Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living scale was developed to assess activities of daily living related to motor functioning in patients with pantothenate kinase-associated neurodegeneration to evaluate clinically meaningful change as the primary efficacy endpoint in clinical trials. This article describes the design of the FOsmetpantotenate Replacement Therapy pivotal trial and the development of the Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living scale. Methods A systematic, iterative process consistent with the US Food and Drug Administration guidance and advice from the Committee for Medicinal Products for Human Use at the European Medicines Agency was used to evaluate and adapt or remove scale items of an existing widely used instrument for movement disorders to be pantothenate kinase-associated neurodegeneration–specific, and to create new items. Modification of scale items was based on input from international experts, patient advocacy leaders, and primary caregivers. A clinimetric study of the Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living scale conducted in patients with pantothenate kinase-associated neurodegeneration or their caregivers (N = 40 at first assessment; N = 39 at second assessment) demonstrated high content and construct validity and excellent test–retest reliability over an approximately 2-week period. The Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living scale was developed to be broadly useful within clinical and research settings in the examination of patient response to pantothenate kinase-associated neurodegeneration therapies. Results Approximately 82 patients will be enrolled in the ongoing FOsmetpantotenate Replacement Therapy pivotal trial. Change from baseline in Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living score over the 24-week double-blind period is the primary efficacy endpoint for the FOsmetpantotenate Replacement Therapy trial. Treatment effect will be evaluated using a mixed model for repeated measures analysis to assess data from all visits simultaneously. Conclusion The development and implementation of the Pantothenate Kinase-Associated Neurodegeneration–Activities of Daily Living scale in the FOsmetpantotenate Replacement Therapy trial illustrates the feasibility and potential patient benefit of putting into practice the current regulatory guidance on the use of patient-reported outcomes in clinical trials. These processes can be broadly applied to clinical trial methodology that requires newly created or revised patient-reported outcome measures to evaluate outcome change as a primary efficacy endpoint. The goal of such measures in patients with pantothenate kinase-associated neurodegeneration is to facilitate development of disease-modifying therapeutics in multiple drug development programs.