Raymond R. Goetz

High-Dose Carbon Dioxide Challenge Test in Anxiety Disorder Patients

Many investigators have shown that panic disorder patients and possibly social phobics are hypersensitive to the anxiogenic effects of inhaled carbon dioxide (CO2). In this study we administered double-breath inhalation of 35% CO2 and 65% oxygen (O2) to panic disorder patients, social phobics, and normal controls. At baseline, panic disorder patients were characterized by higher pulse, anxiety score, and evidence of hyperventilation. Panic patients and social phobics panicked more often to 35% CO2 than to room air; normal controls did not have a higher rate of panic to CO2 than to room air. However, we did not find significant group differences in anxiety level, physiological measures, or biochemical measures in response to CO2 breathing compared with room air breathing. These results confirm earlier reports of baseline hyperventilation in panic disorder patients. However, 35% CO2 may be too high a dose to differentiate respiratory responses of patients compared with normals.

Posttraumatic Growth in Former Vietnam Prisoners of War

This study examined posttraumatic growth in 30 male veterans captured and held as prisoners of war during the Vietnam War. Participants were assessed with structured diagnostic interviews administered by trained clinicians as well as with the Posttraumatic Growth Inventory (PTGI) and other questionnaires measuring dispositional optimism, religious coping, social supports, and purpose in life. Mean age (standard deviation-SD) of participants was 66.7 (6.0) years. Mean total PTGI score (SD) was 66.3 (17.5), indicating a moderate degree of posttraumatic growth. The most strongly endorsed items corresponded to the Appreciation of Life and Personal Strength factors. The group as a whole was optimistic and reported moderate use of positive religious coping. Posttraumatic growth did not significantly differ in repatriates with and without psychopathology, but it was significantly positively correlated with dispositional optimism. In the final regression model, length of captivity and optimism were significant predictors of posttraumatic growth. Our findings confirm that it is possible to achieve long-lasting personal growth even in the face of prolonged extreme adversity. Prospective studies are needed to further evaluate whether pre-existing traits such as optimism can predict growth after trauma.

Visual backward-masking deficits in schizophrenia: relationship to visual pathway function and symptomatology

Patients with schizophrenia have information processing deficits which can be measured using visual backward-masking (VBM) tasks. There are two types of visual pathways: transient and sustained. The former is more sensitive to low spatial frequency (LSF) and the latter to high spatial frequency (HSF) stimuli. It has been hypothesized that the VBM deficit in schizophrenia is due to an overactive transient channel response to the mask. To examine this hypothesis, patients with schizophrenia and comparison volunteers were tested on a traditional backward-masking task as well as on tasks that altered the mask to bias stimulation toward transient (LSF) or sustained (HSF) channels. Medication effects and relationship to symptomatology were also examined. Patients with schizophrenia showed a significant deficit on the traditional backward-masking task and were also significantly impaired on the LSF- and HSF-masking tasks, though a differential deficit was not found on the latter two tasks. A U-shaped function, indicative of masking by interruption, was found on the LSF- and HSF-masking tasks. Masking performance was not altered when the same patients were tested on and off medication, and performance was related to positive and negative symptoms. In conclusion, the finding of a deficit in patients with schizophrenia on tasks producing a U-shaped function suggests that an aberrant transient response to the mask is producing increased interruption of the sustained response to the target.

Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety or depressive disorders.

BACKGROUND Previous studies found few abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function in prepubertal children with anxiety or depressive disorders. In this study, we combined data from two independent, consecutive studies to achieve a larger sample size. Our goal was to identify potential alterations in the circadian pattern of cortisol secretion in anxious or depressed children. METHODS A total of 124 prepubertal subjects from two independent samples (76 with major depressive disorder, 31 with anxiety disorders, and 17 healthy control subjects) were studied. Blood samples collected for cortisol at hourly intervals over a 24-hour period were examined. Analyses were performed aligning cortisol samples by clock-time. Additional analyses aligning samples by sleep-onset time were performed with a subsample of subjects. RESULTS In the combined sample, significant findings emerged that were previously undetected. Anxious children exhibited significantly lower nighttime cortisol levels and an initially sluggish rise in cortisol during the nighttime when compared with depressed and healthy control children. In contrast, depressed children did not show a clear-cut pattern of differences compared with healthy control children. CONCLUSIONS Anxious children seem to exhibit an altered pattern of nighttime cortisol secretion, with an initially sluggish or delayed nocturnal rise before reaching similar peak levels of cortisol near the time of awakening. These findings suggest subtle alterations in HPA axis function in prepubertal children with anxiety disorders.

Effect of antipanic treatment on response to carbon dioxide.

BACKGROUND Disordered breathing among patients with panic disorder, including hyperventilation during attacks and increased anxiogenic response to carbon dioxide (CO2) inhalation, is well established. We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy (CBT). METHODS Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment (n = 21) or CBT (n = 8). After completing treatment, CO2 testing was repeated. A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests, separated by an average of 21.6 (SD = 8.8) weeks. RESULTS Using a liberal standard, in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used, patients, but not controls, demonstrated a significant reduction in CO2 sensitivity between the first and second test. Using a more conservative .90 correlation standard reduced the sample size available and resulted in trend reduction in patients but no significant change in controls. There was a suggestion that the change was most pronounced in treatment responders, although the number of patient nonresponders is extremely small in this sample. CONCLUSIONS These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder. We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems, both known to play a role in the control of respiration, may have a specific effect in reducing respiratory hyperactivity in panic disorder.

Cortisol secretion in adolescents with major depressive disorder

Plasma cortisol concentrations were determined every 20 min for 24 h, in a nonstressful environment, among 48 rigorously assessed, mostly outpatient, drug‐free adolescent subjects during an episode of major depression (MDD) and among 40 normal adolescent subjects. There were no significant differences in the 24‐h mean, peak, or nadir, or the time of the nocturnal rise, in plasma cortisol in the 2 groups. Analyses of different subgroups of MDD adolescents according to suicidality, severity of depression, separation anxiety, psychotic subtype, endogenicity, duration of episode, and sex also revealed no significant group differences. Only one adolescent (with MDD) was identified clearly as a hypersecretor of cortisol. These results indicate that abnormalities of spontaneous cortisol secretion are an unusual finding among adolescents with major depression when studied in a nonstressful environment.

Prevalence of fatigue and depression in ALS patients and change over time

Background: Amyotrophic lateral sclerosis (ALS) patients report both fatigue and depression. It is not clear how frequently each occurs, to what extent they occur together, how each relates to ALS disease status, or their stability over time. Objective: To assess frequency and persistence of fatigue and depression, and relationship to ALS disease status, for patients attending an ALS interdisciplinary centre for routine 3-month visits. Method: Measures included the Fatigue Severity Scale, Patient Health Questionnaire-9. ALS Functional Rating Scale—Revised and forced vital capacity, rate of disease progression, and bulbar/nonbulbar disease onset. Results: 223 patients completed the ratings once; of these, 113 completed them twice, and 65 on three visits. At baseline, 44% (99/223) had clinically significant fatigue, including 34 patients who also had a depressive disorder; 7% (16/223) had major or minor depression only, and 48% (108/223) had neither condition. Fatigue was associated with greater ALS severity, but depression was not. Among the 113 patients seen 3 months later, 75% (33/44) who were fatigued at Time 1 remained fatigued, while 48% (10/21) remained depressed. New-onset fatigue was reported by 22% (25/113), and new-onset depression by 6% (7/113). For the 65 patients seen a third time, rates remained nearly the same. Conclusion: Fatigue was more prevalent and persistent than depression, although 15% (34/223) of patients had both conditions. Fatigue but not depression was associated with ALS severity. The two conditions appear to be independent, although sometimes co-occurring, and both warrant consideration in evaluating patient functioning and treatment.

Anxiety and substance use comorbidity among inpatients with schizophrenia

OBJECTIVE To determine the association between lifetime anxiety symptoms and anxiety disorders and substance use disorders among patients with schizophrenia. METHOD Participants were 184 inpatients with schizophrenia at the Schizophrenia Research Unit (SRU) at the New York State Psychiatric Institute (NYSPI). Multivariate logistic regression analyses were used to determine the relationship between specific anxiety symptoms and anxiety disorders and substance use disorders among inpatients with schizophrenia. RESULTS Anxiety symptoms and anxiety disorders were prevalent among 31.5% of the sample. Panic attacks were associated with a significantly increased odds (OR=7.4 (1.2, 47.1)) of comorbid alcohol or substance use disorders (lifetime). This association was specific to panic attacks and persisted after adjusting for differences in sociodemographic characteristics and comorbid anxiety symptoms and anxiety disorders. CONCLUSIONS These findings are consistent with and extend previous data by providing evidence of an association between panic attacks and increased likelihood of substance use disorders among inpatients with schizophrenia. Future studies that determine the nature of this relationship, the sequence of symptom onsets, and examine whether treatment of anxiety can influence the onset or outcome associated with substance use are needed.

EEG-monitored sleep in anorexia nervosa and bulimia

We compared the EEG-monitored sleep of 8 women with anorexia nervosa and 16 normal weight women with bulimia to that of 14 normal women. The patients with anorexia nervosa spent less time asleep and spent less of their sleep time in Stage 1. The sleep of the normal weight patients with bulimia was remarkably similar to that of the controls. These data suggest that most patients with anorexia nervosa and bulimia do not exhibit the type of sleep disturbances characteristic of patients with major depressive illness.

Odor Identification, Eye Tracking and Deficit Syndrome Schizophrenia

BACKGROUND Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye movement (SPEM) dysfunction. We examined if they also had smell identification deficits, since social affiliation is related to olfaction in other mammals. METHODS Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had Smell Identification Test (SIT) assessments, and 14 patients had both measurements. RESULTS DS patients had worse SPEM and SIT performance than the non-DS patients. Areas under the receiver-operator characteristic (ROC) curves for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23, 88.18). Further analyses showed that the association of SIT with both SPEM and the DS could account for the SPEM-DS association. CONCLUSIONS We found a strong association between the DS and SIT scores suggesting that the neural substrates of olfaction may be related to social affiliation in humans, as they are in other mammals. These data further support the notion that the DS defines a homogeneous subgroup of schizophrenia patients and further suggest that dysfunction in the neural circuitry of olfaction may contribute to its pathophysiology.