George C. Curtis

Urinary free Cortisol excretion in depression

Urinary free cortisol (UFC) excretion was determined in 60 depressed inpatients and in 35 psychiatric inpatients with other disorders. The depressed patients had high daily UFC values, while the other patients excreted normal amounts. Over 40% of the depressed patients had UFC excretions in the range seen in Cushings disease, while only 6% of the other patients excreted such high amounts of cortisol. Age and sex differences did not account for the results. Among the depressed patients those with depressive neuroses excreted less than unipolar or bipolar depressives. Following treatment, more normal UFC excretion was found in depressed patients. The estimation of UFC and its clinical utility are discussed in detail. UFC determination is a simple and informative indicator of adrenal cortical activation and its application to psychoendocrine studies is recommended.

Cerebrospinal fluid and plasma free cortisol concentrations in depression

Cerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excesssve CNS exposure to glucocorticoids.

Ages of onset of DSM-III anxiety disorders

Abstract The Diagnostic and Statistical Manual (DSM-III) contains little specific information pertaining to the ages of onset of anxiety disorders. Such information is of clinical and research value in understanding the natural history of mental illnesses, in determining which of several possible etiologies for a given diagnosis may be relevant for a particular patient, and in testing theories of psychopathology or pathophysiology. Age-of-onset data is presented for 423 psychiatric outpatients seen at a University Hospital—based anxiety disorders program. All adult anxiety disorders are represented except posttraumatic stress disorder. The relevance of this information is discussed in terms of past research on ages of onset of the anxiety disorders, and in its bearing on the psychiatric diagnosis of these conditions.

Endocrine and Cardiovascular Responses During Phobic Anxiety

&NA; In vivo exposure therapy for phobias is uniquely suited for controlled studies of endocrine and physiologic responses during psychologic stress. In this study, exposure therapy induced significant increases in subjective anxiety, pulse, blood pressure, plasma norepinephrine, epinephrine, insulin, cortisol, and growth hormone, but did not change plasma glucagon or pancreatic polypeptide. Although the subjective and behavioral manifestations of anxiety were consistent and intense, the magnitude, consistency, timing, and concordance of endocrine and cardiovascular responses showed considerable variation.

Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder.

The serotonin transporter (HTT) is a candidate gene for obsessive-compulsive disorder (OCD) that has been associated with anxiety-related traits. The long (l) and short (s) variants of the HTT promoter have different transcriptional efficiencies. HTT promoter genotype and blood 5-HT concentration were examined in 70 subjects from 20 families ascertained through children and adolescents with a DSM-III-R diagnosis of OCD. The HTT promoter variant had a significant effect on blood 5-HT content. Subjects with the l/l and l/s genotypes had significantly higher blood 5-HT levels than did those with the s/s genotype. There was a significant interaction between HTT promoter genotype and seasonal variation in blood 5-HT content, with significant seasonal differences in 5-HT occurring only in the subjects with thel/l genotype. Further studies of the regulation of HTT gene expression are indicated.

Pretreatment Nausea in Cancer Chemotherapy: A Conditioned Response?*

&NA; Many patients receiving cancer chemotherapy become nauseated as they anticipate their treatments. We studied this phenomenon in eighteen cancer chemotherapy patients. The eight patients who reported pretreatment nausea had more extensive disease than the other patients and had received twice as much chemotherapy. In most cases pretreatment nausea developed only a after a number of months of treatment. Nausea was usually precipitated by the odor of the clinic and similar odors elsewhere also caused nausea. Patients continued to experience nausea during follow‐up visits after treatment was completed. This syndrome of pretreatment nausea can be understood as a classically conditioned response. Clinical recommendations can be made on this basis.

A family study of obsessive-compulsive disorder with pediatric probands

Obsessive‐compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. We examined the lifetime history of obsessions, compulsions, and OCD in the first‐ and second‐degree relatives of 35 pediatric probands with OCD and 17 controls with no psychiatric diagnosis. All available first‐degree relatives were directly interviewed blind to proband status with two semi‐structured interviews. Parents were also interviewed to systematically assess the family psychiatric history of first‐ and second‐degree relatives. Best‐estimate lifetime diagnoses were made using all available sources of information. Data were analyzed with logistic regression by the generalized estimating equation method and with robust Cox regression models. The lifetime prevalence of definite OCD was significantly higher in case than control first‐degree relatives (22.5% vs. 2.6%, P < 0.05). Compared to controls, case first‐degree relatives also had significantly higher lifetime rates of obsessions and compulsions (both P < 0.05). There was no significant difference between case and control second‐degree relatives in lifetime rates of OCD. First‐degree relatives of case probands with ordering compulsions had a significantly higher lifetime rate of definite and subthreshold OCD than relatives of case probands without ordering compulsions (45.4% vs. 18.8%, P < 0.05). The lifetime prevalence of definite OCD was significantly higher in case first‐degree relatives with a history of tics than in case first‐degree relatives without a tic history (57.1% vs. 20.9%, P < 0.01). The results provide further evidence that early‐onset OCD is highly familial and suggest that two clinical variables are associated with its familial aggregation.

Childhood adversity and vulnerability to mood and anxiety disorders

Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability. Depression and Anxiety 5:66–72, 1997.

Blood-injury-illness phobia: A review

The empirical literature that pertains to phobias of blood, injury, or illness (BII) is surveyed. BII phobia is selectively associated with a vasovagal fainting response upon exposure to phobic stimuli, and the clinical entity may represent an exaggeration of a response that is relatively prevalent in the general population. Clinical, demographic and etiological information obtained from a series of 15 BII phobics is presented, and the suggestion is made that this disorder warrants a diagnostic category separate from simple phobia.

Adrenergic status in anxiety disorders: Platelet alpha2-adrenergic receptor binding, blood pressure, pulse, and plasma catecholamines in panic and generalized anxiety disorders patients and in normal subjects

In order to evaluate adrenergic function in anxiety disorders, platelet alpha 2-adrenergic binding parameters and supine and standing blood pressure, pulse, and venous plasma epinephrine and norepinephrine were determined in patients with panic attacks or generalized anxiety disorder and in normal subjects. The maximum number of binding sites (Bmax) for the partial agonist tritiated clonidine was significantly lower for both patient groups than for normal subjects, and the Bmax for the antagonist tritiated yohimbine was significantly lower for panic patients. There were no other substantive differences across groups. Prior exposure to psychotropic drugs might account for the results for clonidine binding, but not for yohimbine. The Bmax for clonidine was correlated with norepinephrine increases upon standing and, for panic patients, with the severity of full unexpected panic attacks. These data provide further evidence of adrenergic receptor abnormalities in people with anxiety disorders.