Effects of one night's sleep deprivation on mood and behavior in panic disorder. Patients with panic disorder compared with depressed patients and normal controls.

The effects of one night's sleep deprivation on mood and behavior were evaluated in 12 patients with panic disorder, ten depressed patients, and ten controls. In contrast to the improvement in symptoms of anxiety and depression shown by the majority of depressed patients, the response of patients with panic disorder as a group did not differ from that of normal controls, although a subgroup did experience noticeable worsening in their symptoms of anxiety, with 40% experiencing panic attacks on the day following sleep deprivation. Electroencephalographic recordings with nasopharyngeal electrodes on the day following sleep deprivation were normal, further suggesting that patients with panic disorder do not have seizure activity characteristic of temporal lobe epilepsy.

A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care.

BACKGROUND: Effectiveness studies have tested interventions to improve quality of care for depression in primary care, but none, to our knowledge, have been completed for panic disorder (PD) in this setting. This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of "collaborative care" (CC). METHODS: One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or "usual care" (UC). Patients in CC (n = 57) received educational videotapes and pamphlets; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks; and up to 5 telephone calls between 3 and 12 months' follow-up. Usual care patients (n = 58) were treated by their primary care physician. Telephone assessments of panic, anxiety sensitivity, depression, and disability variables were performed at 3, 6, 9, and 12 months' follow-up. Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies. RESULTS: Patients in CC were more likely to receive adequate (type, dose, duration) medication and more likely to adhere to this medication at 3 and 6 months. Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety, depression, and disability measures, with the greatest effects at 3 and 6 months. CONCLUSIONS: Compared with UC, CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients. Clinical differences were greatest in the first 6 months, corresponding to the greater quality of care and the greater intensity of intervention.

Reduced benzodiazepine sensitivity in panic disorder.

We evaluated the functional sensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in 9 patients with panic disorder and 10 psychiatrically healthy control subjects by comparing the effects of four logarithmically increasing doses of intravenous diazepam on saccadic eye movement velocity, memory, and self-rated sedation. Patients with panic disorder were less sensitive than controls to diazepam using eye velocity as the dependent measure. Sedation and memory effects did not distinguish the two groups. These findings suggest that panic disorder is associated with functional subsensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in brain-stem areas controlling saccadic eye movements.

Effortful and automatic cognitive processes in depression.

Ten patients with major depression and ten age- and sex-matched normal controls were presented with two contrasting cognitive tasks: one required sustained effort and information processing, and the other required only superficial information processing that could be accomplished automatically, with little effort. Depressed patients performed more poorly only on the effort-demanding cognitive task.

Carbamazepine and thyroid function in affectively ill patients. Clinical and theoretical implications.

Thyroid function was examined in 50 affectively ill patients before and four weeks after carbamazepine treatment. Carbamazepine significantly and substantially decreased peripheral thyroid hormone levels while increases in thyrotropin levels, although significant, were of much smaller magnitude. Furthermore, the decreases in levels of thyroxine (T4) and free T4 were significantly greater in carbamazepine responders than in nonresponders. These findings are discussed in light of current theories of the role of the thyroid axis in affective illness.

Dysphoric mania. Clinical and biological correlates.

Patients studied at peak severity of a manic episode showed substantial degrees of depression (dysphoria) and anxiety. Compared with nondysphoric manics (n = 26), the dysphoric manics (n = 22) had a significantly greater number of previous hospitalizations, and they displayed less rapid cycling both in the year before and during the index hospitalization admission. The severity of manic dysphoria tended to correlate with the number of previous hospitalizations, a finding that was highly significant in women (n = 27). Medication-free manic patients (n = 22) had significant elevations in cerebrospinal fluid norepinephrine concentrations compared with depressed and euthymic patients and normal volunteers, and the degree of elevation correlated significantly with the degree of manic dysphoria, anger, and anxiety rated at the time of the lumbar puncture. Patients with dysphoric mania, recognized by Kraepelin to have poor prognoses, have been reported to respond poorly to lithium carbonate but may be among those who respond to carbamazepine. Clinical, biologic, and pharmacologic response characteristics of manic subgroups, particularly those with extreme dysphoric components to their illness, appear to be clinically meaningful and deserving of further investigation.

Thyroid function in women with premenstrual syndrome.

UNLABELLED: We have examined the relationship between thyroid function and the presence of symptoms in women with prospectively confirmed premenstrual syndrome (PMS) in the following ways: 1) basal thyroid function tests (n = 124); 2) thyroid auto-antibody levels (n = 63); 3) TRH stimulation tests performed during the follicular phase (n = 39) or during both the follicular and luteal phase (n = 21); and 4) the efficacy of L-T4 in the treatment of PMS (n = 30). RESULTS: Thirteen women (10.5%) had basal evidence of either grade I or II hypothyroidism or hyperthyroidism. Elevated thyroid auto-antibody titers were observed in eight women (13%). Eighteen women (30%) (all with normal basal TSH levels) had abnormal responses to TRH, either blunted (n = 6) or exaggerated (n = 12). L-T4 was not superior to placebo in the treatment of PMS in a double blind placebo controlled cross-over trial. Although it is clear that PMS is not simply masked hypothyroidism, abnormalities of stimulated thyroid function appear with greater than expected frequency in women with PMS and may define a subgroup of women with this disorder. L-T4 supplementation appears to have no place in the routine management of PMS.

Neuroendocrine effects of diazepam in panic and generalized anxiety disorders.

The adrenocorticotropic hormone (ACTH), cortisol, and growth hormone responses to four consecutive, logarithmically increasing doses of intravenous diazepam compared with placebo given at 15-min intervals were examined in patients with panic disorder (n = 13), generalized anxiety disorder (n = 8), and healthy controls (n = 13). Diazepam caused dose-dependent decreases in cortisol and increases in GH and dose-independent decreases in ACTH. There were no patient-control differences, possibly due to either the small sample size of the experimental paradigm, which tested subjects in an upright, sitting position in mildly arousing circumstances.

Response to lactate infusion in generalized anxiety disorder.

Intravenous sodium lactate infusion provokes symptoms of panic in patients with panic disorder at a significantly higher rate than in normal controls. Lactate sensitivity has been postulated to be specific for patients with panic attacks regardless of frequency of attacks or coexisting diagnoses. The authors present results of a pilot study of lactate infusions in patients with generalized anxiety disorder (GAD) without any history of panic attacks. Patients with GAD reacted more like panic disorder patients than like normal controls in anxiety and symptom scores during lactate infusion and in the rate of positive responses to lactate. Although preliminary, these findings raise questions regarding the specificity of lactate sensitivity and the relationship of GAD to panic disorder.

Platelet [3H]imipramine binding in patients with panic disorder.

[3H]imipramine binding to platelets was measured in 17 drug-free panic disorder patients and 14 healthy controls. No difference in Bmax or Kd values was found between the two groups. Patients with a past history of major melancholic depression or severe agoraphobia had similar binding parameters as panic disorder patients without a history of depression or severe agoraphobia.

Lactate vulnerability after alprazolam versus placebo treatment of panic disorder.

Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication.

Relationships between neuropsychological and oculomotor measures in schizophrenia patients and normal controls.

Establishing the relationship between oculomotor and neuropsychological impairments might facilitate a more coherent description of schizophrenia-associated neurocognitive deficits. Therefore, we assessed several aspects of neuropsychological and oculomotor function in 25 medicated schizophrenia patients and 24 age-matched controls. Neuropsychological tasks included the Wisconsin Cart Sort Test (WCST), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test, and finger tapping speed. Oculomotor functions assessed included smooth pursuit, initiation of smooth pursuit, predictive pursuit, fixation, visually guided saccades, remembered saccades, and antisaccades. Among the schizophrenia patients, predictive pursuit performance correlated significantly with finger tapping (dominant hand), TMT (both parts), and one WCST measure (categories completed). The only other significant correlation among the schizophrenia patients was between antisaccade performance and part A of the TMT. Perseverative errors during the WCST and antisaccade performance were the only measures significantly correlated among the normals. Closely related neurocognitive deficits may be responsible for impairments in TMT, WCST, predictive pursuit, and antisaccade performance in schizophrenia.

Thyroid function and affective illness: a reappraisal.

It has been generally accepted that increased thyroid function facilitates treatment response in depression. Recent data show that response to several antidepressant treatments, particularly lithium and carbamazepine, are associated with decreased thyroid hormone levels. An alternative hypothesis that decreased thyroid indices are related to antidepressant response is proposed and clinical and research implications are discussed.

Irritable bowel syndrome and psychiatric illness.

Psychiatric illnesses such as mood, anxiety, and somatization disorders share many common features with irritable bowel syndrome. The authors review recent developments in the definition of irritable bowel syndrome and its relationship to psychiatric illness, discuss the diagnostic validity of irritable bowel syndrome from several perspectives, and offer a pathophysiological model of irritable bowel syndrome that integrates many of the biological and psychosocial findings of earlier studies. Psychiatric evaluation appears to be an important factor in the diagnosis and treatment of patients with irritable bowel syndrome.

Graphic representation of the life course of illness in patients with affective disorder.

The authors illustrate methods for the graphic depiction of the course of unipolar and bipolar affective illness. The utility and advantages of such an approach include 1) accurate assessment of episode patterns, 2) elucidation of relationships to environmental events, endocrine and seasonal factors, and psychosocial stressors, 3) better delineation of treatment response, 4) a greater understanding of the longitudinal and characteristic patterns of illness, and 5) the associated better patient management with psychotherapeutic and pharmacological interventions.

Life events and the onset of panic disorder.

The authors examined the number, type, and effect of life events during the year before the onset of panic attacks in 44 patients with a Research Diagnostic Criteria diagnosis of panic disorder and 44 healthy control subjects matched for age, sex, and time of retrospection. The patients had significantly more life events, and these events had a more adverse impact on them. Furthermore, the types of events experienced by the patients were more typically distressing than those experienced by the control subjects. The patients reported events involving moves to other neighborhoods and/or cities far more frequently than did the control subjects.

Life events and course of illness in patients with panic disorder.

Eleven panic disorder patients who had experienced a major loss or separation in the year before they had their first panic attack were significantly more likely to develop a subsequent major depression than were 22 patients who had not suffered such a loss.

Hematological effects of carbamazepine in patients with affective illness.

The hematological effects of carbamazepine, a drug effective in the acute and prophylactic treatment of manic-depressive disorder, were assessed in 43 subjects with affective disorder. Carbamazepine was found to cause statistically significant, but clinically insubstantial, decreases in white blood cell indexes. The consistent decreases in white cell counts observed with carbamazepine should be differentiated from the extremely rare, idiosyncratic blood dyscrasias reported in the literature.

Reduced TSH and prolactin responses to TRH in patients with panic disorder.

The authors studied the TSH and prolactin responses to a standard 500-micrograms thyrotropin-releasing hormone (TRH) stimulation test in 12 patients with panic disorder and 10 control subjects. As a group, panic disorder patients had lower mean TSH and prolactin responses, and female patients accounted for the lower prolactin response. The clinical and theoretical implications of these findings are discussed.

Histories of sexual victimization in patients with irritable bowel syndrome or inflammatory bowel disease.

OBJECTIVE: Two reports have suggested a possible association between a history of sexual trauma and irritable bowel syndrome, but several factors in their study designs limited their generalizability. The authors used a more rigorous methodology to confirm this association. METHOD: They administered structured psychiatric and sexual trauma interviews to 28 patients with irritable bowel syndrome and 19 patients with inflammatory bowel disease and compared prevalence rates of sexual victimization in the two groups. RESULTS: Compared with patients diagnosed as having inflammatory bowel disease, patients with irritable bowel syndrome had a significantly higher rate of severe lifetime sexual trauma (32% versus 0%), severe childhood sexual abuse (11% versus 0%), and any lifetime sexual victimization (54% versus 5%). The nine patients who had experienced severe lifetime victimization had significantly higher odds ratios for lifetime depression, panic disorder, phobia, somatization disorder, alcohol abuse, functional dyspareunia, and inhibited sexual desire than the 38 patients who had experienced less severe sexual trauma or no trauma. A logistic regression analysis showed that gender, the number of medically unexplained physical symptoms, and self-reported anxiety and hostility accounted for all of the variance in the victimized group. CONCLUSIONS: These preliminary results suggest that sexual victimization may be an important factor in the development of irritable bowel syndrome in some patients. Future studies attempting to categorize subgroups of patients with irritable bowel syndrome should inquire into past histories of sexual victimization.

PIP: This study confirms the previously studied findings by using a more rigorous methodology concerning the association of sexual victimization history and irritable bowel syndrome or inflammatory bowel disease. Structured psychiatric and sexual trauma interviews were given to 28 patients with irritable bowel syndrome and 19 inflammatory bowel disease, and the prevalence rates of sexual victimization in the 2 groups were compared. A logistic regression analysis was performed to summarize the differences between patients who had severe trauma and those who had none, and to account for intercorrelations among the study variables. Results showed that patients with irritable bowel syndrome were more likely to have a history of previous sexual victimization. The odd ratios for current and lifetime psychiatric disorders in the 9 patients who had experienced severe forms of victimization showed that they were at significantly greater risk for affective, anxiety, and somatoform disorders as well as substance abuse and sexual dysfunction. It was also demonstrated that the best predictors of having experienced severe forms of victimization were gender, the number of medically unexplained physical symptoms, and self-reported anxiety and hostility. This study suggests that irritable bowel syndrome may be part of a chronic adjustment to previous sexual victimization in some patients.