The complete nucleotide sequence of the ilvGMEDA cluster of Escherichia coli K-12.

The ilvGMEDA gene cluster of Escherichia coli K-12 has been the focus of intensive genetic and biochemical analysis for the past 30 years. Genetic regulation of the ilvGMEDA cluster involves attenuation, internal promoters, internal Rho-dependent termination sites, a site of polarity in the ilvG pseudogene of the wild-type organism, and autoregulation by the ilvA gene product, the biosynthetic L-threonine deaminase. We have now completed the nucleotide sequence of the 6600-bp cluster and have analyzed it, along with the ilvYC, ilvBN, and ilvIH genes, for codon frequencies and possible evolutionary relationships. The isoleucine content of each of the gene products of the ilvGMEDA cluster is quite similar (less than a two-fold variation), thus excluding one possible interpretation of the isoleucine-specific downstream amplification phenomenon. There is no evidence for retrograde evolution in the cluster since no significant homologies are detectable among genes that catalyze sequential reactions of the pathway. A highly significant homology does exist, however, between the threonine deaminases of yeast mitochondria and E. coli. The sequence at the boundary of the ilvA and ilvD genes is TAATAATG, so that the second TAA stop codon of ilvD overlaps the ATG initiation codon of ilvA.

Symptoms of PTSD in 124 survivors of the Holocaust.

OBJECTIVE: Survivors of the Holocaust are expected to be at risk for posttraumatic stress disorder (PTSD), but few empirical data are available. This study investigated PTSD symptoms in Holocaust survivors with well-documented exposure to trauma. METHOD: The German files of 124 Jewish Holocaust survivors who were judged to be free from bipolar affective disorder, obsessive-compulsive disorder, and organic brain syndrome were selected from those of 145 applicants to West German compensation boards. The psychiatric assessments were reexamined for explicit descriptions of current PTSD symptoms according to the DSM-III-R diagnostic criteria. A subgroup of 20 Auschwitz survivors with tattooed identification numbers were also compared with the 45 survivors who had not been in concentration camps. RESULTS: Sixty-three percent of the total sample had been detained in concentration camps, and an average of 78% of their first-degree relatives were reported killed in the Holocaust. Forty-six percent of the total sample met the DSM-III-R criteria for PTSD. The most common symptoms were sleep disturbance, recurrent nightmares, and intense distress over reminders. The tattooed Auschwitz survivors had significantly more symptoms and were three times more likely to meet diagnostic criteria for PTSD than the survivors who had not been in concentration camps. CONCLUSIONS: The results suggest a greater risk of chronic PTSD in survivors who were exposed to atrocities. Most survivors had not received adequate psychiatric care.

Anxiety sensitivity and response to cholecystokinin tetrapeptide in healthy volunteers.

The authors determined whether fear of anxiety symptoms mediates panicogenic responses to cholecystokinin tetrapeptide (CCK-4) in healthy subjects. Individuals with a preexisting high level of anxiety sensitivity (N = 10) experienced significantly more catastrophic cognitions and fear of somatic symptoms than did subjects with low (N = 9) or medium (N = 17) anxiety sensitivity, but they were not more susceptible to experiencing a panic attack. Thus, cognitive factors do not appear to be critical determinants of CCK-4-induced panic attacks.

Citation patterns in anxiety disorders research in 14 journals: 1990-1991.

The authors reviewed the distribution of citations in 278 anxiety disorder studies published in 14 journals in 1990 and 1991. Although both psychiatrists and psychologists frequently authored studies, few journals showed evidence of a substantial interdisciplinary perspective. The 278 anxiety disorder studies contained 3,199 references to articles in the 14 journals. There was a high percentage of "self-citation" in some of the journals and only limited evidence of citations across journal and author disciplines. These findings suggest that anxiety disorder research findings are often not widely disseminated across disciplines.

Brief treatment of emergency room patients with panic attacks.

OBJECTIVE: Most research on treatment for panic disorder has involved chronic forms of the illness. To determine the efficacy of early intervention, the authors examined the effects of treatment for patients with panic attacks who were seen in the emergency room, which is the first point of contact with the health delivery system for many persons with panic attacks. METHOD: The subjects were 33 patients with panic attacks seen in two emergency rooms. The presence of panic attacks was confirmed with a modified version of the Structured Clinical Interview for DSM-III-R; approximately 40% of the patients met the DSM-III-R criteria for panic disorder with agoraphobia. The patients were randomly assigned to groups receiving reassurance (N = 16) or exposure instruction (N = 17). Scores on the Fear Questionnaire agoraphobia subscale, Mobility Inventory, and Beck Depression Inventory and the frequency of panic attacks were determined at baseline, 3 months, and 6 months. RESULTS: The subjects who received exposure instruction significantly improved over the 6-month period on depression, avoidance, and panic frequency. The reassurance subjects did not improve on any measure and eventually reported more agoraphobic avoidance. CONCLUSIONS: These results suggest that early intervention with exposure instruction may reduce the long-term consequences of panic attacks. The exposure instruction was of value even though the subjects had relatively low levels of avoidance at the outset of the study.

Suicidal ideation and suicide attempts in panic disorder and social phobia.

OBJECTIVE: Using the original National Institute of Mental Health Epidemiologic Catchment Area (ECA) suicide questions in a clinical setting and including a comparison group of patients with social phobia, the authors attempted to replicate the finding of Weissman and associates of a greater risk of suicidal ideation and suicide attempts associated with panic disorder. METHOD: One hundred six patients with panic disorder and 41 patients with social phobia answered the five ECA suicide questions and completed a psychometric assessment package at an anxiety disorders clinic. RESULTS: Thirty-three (31%) of the patients with panic disorder and 14 (34%) of the patients with social phobia reported suicidal ideation in the past year, but only one of the patients with panic disorder and two of the patients with social phobia actually made suicide attempts in the past year. Nineteen (18%) of the patients with panic disorder and five (12%) of the patients with social phobia reported making suicide attempts at other times in their lives. Patients who had made past suicide attempts were significantly more likely to report previous psychiatric hospitalizations and past treatment for depression than were patients who had never attempted suicide. CONCLUSIONS: These results are consistent with the findings of Weissman and associates that a large proportion of individuals with panic disorder report suicidal ideation. However, many patients with social phobia also reported suicidal ideation, and few individuals in either diagnostic group had actually made recent suicide attempts. Although 12%-18% of the patients reported lifetime suicide attempts, there is evidence to suggest that these were in the context of depressive symptoms.

Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome.

In in vitro fertilization (IVF) cycles using gonadotropin-releasing hormone agonist (GnRH-a) suppression, we investigated whether an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration indicates premature luteinization and is associated with a lower pregnancy rate. We retrospectively studied 101 patients treated with the GnRH-a leuprolide acetate, begun in the luteal phase of the prior menstrual cycle and continued until the day of hCG administration. On the day of hCG, 72 patients had P less than 0.9 ng/mL and 29 had less than or equal to 0.9 ng/mL. Patients in the high P group had a significantly greater estradiol level on the day of hCG. No significant difference in clinical pregnancy rates or ongoing pregnancy rates occurred between the low P and high P groups. We conclude that in IVF cycles pretreated with GnRH-a, P levels on the day of hCG are not predictive of conceiving in that cycle.

Discrepancies between self and observer ratings of depression. The relationship to demographic, clinical and personality variables.

BACKGROUND: The observer-rated Hamilton depression scale (HamD) and the self-report Beck Depression Inventory (BDI) are among the most commonly used rating scales for depression, and both have well demonstrated reliability and validity. However, many depressed subjects have discrepant scores on these two assessment methods. The present study evaluated the ability of demographic, clinical and personality factors to account for the discrepancies observed between BDI and HamD ratings. METHOD: The study group consisted of 94 SCID-diagnosed outpatients with a current major depressive disorder. Subjects were rated with the 21-item HamD and completed the BDI and the NEO-Five Factor Inventory. RESULTS: Younger age, higher educational attainment, and depressive subtype (atypical, non-melancholic) were predictive of higher BDI scores relative to HamD observer ratings. In addition, high neuroticism, low extraversion and low agreeableness were associated with higher endorsement of depressive symptoms on the BDI relative to the HamD. In general, these predictive variables showed a greater ability to explain discrepancies between self and observer ratings of psychological symptoms of depression compared to somatic symptoms of depression. LIMITATIONS: The study does not determine which aspects of neuroticism and extraversion contribute to the observed BDI/HamD discrepancies. CONCLUSIONS: Depression ratings obtained with the BDI and HamD are frequently discordant and a number of patient characteristics robustly predict the discrepancy between these two rating methods. The value of multi-modal assessment in the conduct of research on depressive disorders is re-affirmed.

Correlates of analogue and clinical depression: a further test of the phenomenological continuity hypothesis.

BACKGROUND: The use of college students with high scores on a depression rating scale as analogues for depression by psychological researchers has generated controversy. Critics of analogue research argue that depression is qualitatively different in analogue and clinical samples. OBJECTIVE: To conduct a further comparison of the phenomenology of clinical and analogue depression to determine if the differences between these groups are best understood as quantitative (consistent with the continuity hypothesis) or whether these forms of depression are qualitatively distinct. METHOD: This study compared 161 outpatients with major depressive disorder to 148 "analogue" subjects (college students with a Beck Depression Inventory score > or =9) and 141 non-distressed controls. Study measures included several proposed personality vulnerability factors for depression, a measure of developmental experiences that may confer vulnerability to adult depression, and family history of emotional disorders. RESULTS: Most comparisons of personality vulnerability factors, developmental experiences and family history information followed a pattern of greatest risk in the clinical group, intermediate risk in the analogue group and lowest risk in the non-distressed group. Noteworthy exceptions included several aspects of perfectionism and a number of childhood experiences reflecting parental over-control, which appeared to be more strongly associated with analogue depression than clinical depression. IMPLICATIONS: Several personality and developmental variables could represent important areas of discontinuity between clinical and analogue depression. However, the overall results were consistent with a growing body of literature suggesting continuity between subthreshold depression symptoms and syndromal depression.

The continuity of depression symptoms: use of cluster analysis for profile identification in patient and student samples.

BACKGROUND: Findings from several sources suggest that depression lies on a continuum whereby mild and severe variants are thought to differ in severity (i.e., quantitatively), but not in kind (i.e., qualitatively). The current study used cluster analysis to extend this work to examination of depression symptom profiles obtained in distressed student 'analogue' samples and clinically depressed samples. METHOD: Patients with major depressive disorder (n = 101) provided seed points for the depressed cluster, and 176 non-distressed university students (Beck Depression Inventory score < or = 8) provided seed points for the non-depressed cluster. The symptom profiles of three levels of analogue depressed samples were then evaluated (BDI > or = 9, BDI > or = 16, and BDI > or = 21). RESULTS: Only 35.4% of BDI > or = 9 analogue respondents were empirically sorted to the depression cluster and the majority were assigned to the non-depressed cluster. The proportion assigned to the depression cluster increased to 70.5% and to 86.2% when higher BDI cutoffs of 16 and 21 were examined, respectively. The DSM-IV depression symptom profile of the BDI > or = 21 group was very similar to the profile defined by clinical patients. LIMITATIONS: The study relied solely on self-report to assess symptom severity. CONCLUSIONS: It is recommended that higher BDI cutoffs be utilized in analogue depression research than is currently common. On quantitative grounds, analogue subjects who were sorted to the clinically defined depression cluster seem to best represent the idea of depression continuity.

Confirmatory factor analysis of the Beck Anxiety and Depression Inventories in patients with major depression.

The Beck Anxiety Inventory (BAI; Beck, A.T., Epstein, N., Brown, G., Steer, R.A., 1988. An inventory for measuring clinical anxiety: psychometric properties. J. Consult. Clin. Psychol. 56, 893-897) is intended to assess clinical anxiety symptoms that are distinct from depressed mood, and there is some preliminary empirical support for this differential assessment. The BAI may serve a useful complementary role when used with the popular Beck Depression Inventory (BDI; Beck, A.T., Rush, A.J., Shaw, B.F., Emery, G., 1979. Cognitive Therapy of Depression: A Treatment Manual. Guilford Press, New York, NY; Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Erbaugh, J., 1961. An inventory for measuring depression. Arch. Gen. Psychiatry 4, 561-571), in patients with mood and/or anxiety disorders. Accordingly, the present paper reports the results of the first confirmatory factor analysis of the Beck scales in a homogeneous, clinically depressed sample (137 outpatients with non-psychotic major depressive disorder). Results indicated that a multidimensional model of separate anxiety and depression factors had good fit to the data. However, the parameter estimate was very high (0.784) and a unidimensional, single-factor model of negative affectivity approached the criteria for good fit. It was concluded that the Beck Anxiety and Depression Inventories assess distinct anxiety and depression phenomena to a limited extent when used in a clinically depressed sample.

Diagnostic specificity of the dependent and self-critical personality dimensions in major depression.

Validational studies of self-critical and dependent personality dimensions as vulnerability factors for depression have been tested primarily with depressed samples, employing research designs devised to address state vs. trait and trait-situational congruity issues. In this study we examined the diagnostic specificity to depression of these two personality dimensions, comparing Self-Criticism and Dependency scores as measured by the Depressive Experiences Questionnaire (DEQ) in two samples of outpatients: (1) panic disorder with agoraphobia; and (2) non-psychotic, unipolar major depression. As hypothesized, the two groups differed on Self-Criticism, with the depressed group scoring higher, but no differences were found for Dependency. These findings were similar even when depressed mood was partialed out. These results complement a growing body of research associating Self-Criticism, as specifically measured by the DEQ, with depression.

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

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

Impact of adult attachment styles on pain and disability associated with arthritis in a nationally representative sample.

OBJECTIVE: The objective of this study was to evaluate Mikail et al.'s hypothesis that adult attachment styles are associated with important pain-related variables such as pain and disability levels. DESIGN: A cross-sectional design was used to examine the relation between measures of adult attachment styles and both pain and disability. SETTING: The data used were obtained from the National Comorbidity Survey, a large and nationally representative sample of community-dwelling individuals aged 15 to 54 years. In the present study, individuals (n = 381) in the National Comorbidity Survey with arthritis or related conditions were included. OUTCOME MEASURES: Ratings regarding three adult attachment styles (secure, anxious, and avoidant) were obtained by administering Hazan and Shaver's attachment self-report in an interview format. Pain and disability were assessed in a similar manner using four-point rating scales. RESULTS: Ratings of insecure attachment were positively and significantly correlated with both pain and disability. A multiple regression analysis revealed that pain severity and the rating of anxious attachment could account for 20.3% of the variance in disability. CONCLUSIONS: The attachment theory holds promise for understanding reactions to pain conditions, and Mikail et al.'s model warrants further investigation.

Multidimensionality of state and trait anxiety: factor structure of the Endler Multidimensional Anxiety Scales.

The Endler Multidimensional Anxiety Scales (EMAS) are derived from an interactional model of personality that proposes that anxiety is a function of the interaction of person and situation variables. The EMAS distinguish between state and trait anxiety and assume that both are multidimensional constructs. The EMAS were administered to 2,009 students in a neutral situation. Three factor analyses were performed to clarify the empirical relation between state and trait anxiety and the variables within the 2 domains. Results support the distinction between state and trait anxiety. Factor analysis of the state items provided support for the separate dimensions of cognitive and autonomic state anxiety. Factor analysis of the trait items provided support for trait anxiety multidimensionality. Four congruent factors were associated with increases in state anxiety in 4 general situations: Social Evaluation, Physical Danger, Ambiguous, and Daily Routines.

Self-reports of depression and state-trait anxiety: evidence for differential assessment.

Several researchers have found anxiety and depression to be indistinguishable in nonclinical samples and have suggested that both constructs may be components of a general psychological distress process. Another possibility is that overlap is due to the psychometric limitations of scales used. A series of exploratory factor analyses were conducted in a nonclinical sample (N = 605) using the Beck Depression Inventory (BDI; Beck, 1978), the State-Trait Anxiety Inventory (STAI; Spielberger, 1983), and the Endler Multidimensional Anxiety Scales (EMAS; Endler, Edwards, & Vitelli, 1991). Both state and trait anxiety and depression could be differentiated with the BDI and the EMAS but not with the STAI. Some theoretical models of negative affectivity or general psychopathology may be premature.

Alexithymia in somatoform disorder patients with chronic pain.

The prevalence of alexithymia in fifty-five motor vehicle accident survivors who had chronic pain complaints and met DSM-III-R criteria for somatoform pain disorder was 53%. Alexithymic and non-alexithymic patients did not differ on self-reports of current pain severity or in the number of pain locations. Alexithymic patients were found to use significantly more words to describe their pain, suggesting they may have a more diffuse style in communicating their pain experience.

The nature and assessment of catastrophic thoughts in panic disorder.

This essay describes the current status of our conceptualization and assessment of catastrophic thoughts in panic disorder, an area that is more heterogeneous than may first appear. It is suggested that a heuristic approach would involve assessing both 'state' catastrophic cognitions (automatic thoughts) and the underlying 'trait' cognitive factors (beliefs). The cognitive symptoms listed in the DSM-IV and the self-report Anxiety Sensitivity Index serve as useful preliminary measures for assessing these respective domains. The trait cognitive domain is seen as multidimensional and congruence is required with internal or external stimuli in producing state catastrophic thoughts and accompanying panic attacks. Pressing challenges and controversies in this field are also highlighted and strategies for potentially resolving these issues are offered. Accordingly, several directions for future investigation are presented throughout the paper. Examples of innovative assessment techniques are briefly described.

Overprediction of fear in panic disorder with agoraphobia.

The overprediction of fear model is discussed in relation to the development and maintenance of panic disorder with agoraphobia. Data are presented which demonstrate a significant relationship between self-reports of phobic avoidance and anticipation of panic, both before and after treatment, and the occurrence of panic. Implications of the overprediction model for exposure-based therapy are also discussed along with its limitations and some directions for future research.

Perfectionism and depression symptom severity in major depressive disorder.

In recent years it has been recognized that perfectionism is a multidimensional construct and two Multidimensional Perfectionism Scales have been developed and investigated in relative isolation [Frost, R.O., Marten, P., Lahart, C., & Rosenblate, R. (1990). The dimensions of perfectionism. Cognitive Therapy and Research, 14, 449-468; Hewitt, P.L., & Flett, G.L. (1991). Perfectionism in the self and social contexts: Conceptualization, assessment and association with psychopathology. Journal of Personality and Social Psychology, 60, 456-470]. The present study sought to evaluate the association between various dimensions of perfectionism, higher-order personality dimensions, and self and observer rated depressive symptoms in a group of 145 patients with major depressive disorder. Only three of ten perfectionism dimensions (socially prescribed perfectionism, concern over mistakes and self-criticism) displayed medium to large correlations with depressive symptoms, especially self-report symptoms reflecting depressive cognitive distortions. The results are discussed in relation to the specificity of perfectionism dimensions to depression, adaptive versus maladaptive aspects of perfectionism, and in the context of previous research, much of which has relied on college student samples.