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A letter to the editor is presented in response to an article about the frequency of thyroid disease and dementia in relatives of Down's syndrome patients.

Objective: The mechanism of action of CO2-induced anxiety is unknown and has been little studied. The authors studied healthy volunteers for the possible influence of serotonin (5-HT) on CO2-induced anxiety., Method: Fourteen healthy volunteers received two vital capacity inhalations each of 35% CO2 and of air, preceded once by placebo and once by the 5-HT antagonist metergoline in a double-blind, randomized crossover design., Results: Mean National Institute of Mental Health self-rating anxiety subscale scores increased nonsignificantly after CO2 inhalation; this effect was significantly enhanced by the administration of metergoline., Conclusions: The authors hypothesize that 5-HT may inhibit CO2-induced anxiety, a function that is lessened by metergoline.

Objective: The relationship between genetic liability for antisocial behavior and CSF 5-hydroxyindoleacetic acid (5-HIAA) in newborns was explored., Method: The authors assayed 5-HIAA in "leftover" CSF from 193 neurologically normal newborns and obtained family psychiatric histories of the newborns' first- and second-degree relatives., Results: Levels of 5-HIAA were significantly lower in the infants with family histories of antisocial personality disorder than in the newborns without such family histories., Conclusions: These findings support the possibility that serotonin mediates one component of genetic liability to antisocial outcome, but the magnitude of that component may be less than what has been inferred from previously published reports.

Objective: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms., Method: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward., Results: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation., Conclusions: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.

Objective: The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects., Method: The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion., Results: m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype., Conclusions: Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects.

In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each. There were no significant differences between buspirone and placebo in obsessive-compulsive, depressive, or anxiety symptoms.

Objective: Because the central administration of somatostatin to experimental animals produces behaviors with some similarities to the compulsions of patients with obsessive-compulsive disorder and because serotonin reuptake inhibitors have been reported to reduce brain content of somatostatin, the authors examined central somatostatin activity in patients with obsessive-compulsive disorder., Method: CSF for measurement of somatostatin was obtained from 15 drug-free outpatients with obsessive-compulsive disorder and 27 normal volunteers., Results: The mean CSF somatostatin level was significantly higher in the patients with obsessive-compulsive disorder than in the normal subjects., Conclusions: Although the functional significance of this finding is unknown, these data are consistent with a role for somatostatin in the clinical symptomatology of obsessive-compulsive disorder and its response to neuropharmacological agents. The high levels of CSF somatostatin reported here in a patient subgroup whose predominant symptoms consisted of overly focused, perseverative thought processes are in contrast to the consistently low levels of CSF somatostatin seen in patients with a spectrum of disorders characterized by substantial cognitive deficits.

Objective: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders., Method: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory., Results: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects., Conclusions: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders.

Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.

The authors studied 53 patients hospitalized for depression to evaluate possible associations between pretreatment responses to the Minnesota Multiphasic Personality Inventory and behaviorally rated responses to lithium. Patients were randomly assigned to two groups (A and B) in which responders and nonresponders were balanced for sex. For the 18 women in group A, a lithium response scale discriminated responders with 89% accuracy. For the 9 males, a separate scale discriminated responders with 100% accuracy. In a cross-validation, the two scales discriminated responders and nonresponders with 100% accuracy in group B. The empirical methodology of this study suggests an alternative to the theoretical-rational approach of predicting response to antidepressant drugs based on pretreatment depressive symptoms.

The authors found that patients with major affective disorder had higher levels of plasma norepinephrine and higher pulse rates (tachycardia) than healthy control subjects, but their blood pressures were normal. These measurements were similar in all three subgroups of patients with affective disorder--manic, bipolar depressed, and unipolar. Because norepinephrine is the primary neurotransmitter of the sympathetic nervous system, these data suggest sympathetic hyperactivity in the major affective disorders. This conclusion is compatible with recent speculation based on the effect of antidepressants on noradrenergic receptors and a failure of alpha-receptors to downregulate normally in patients with major affective disorder.

The authors compared the correlation between platelet monoamine oxidase (MAO) activity and the Paranoia (Pa) scale of the Minnesota Multiphasic Personality Inventory in several groups. The data suggest that there is a positive association between high MAO activity and high scores on the Pa scale but only in samples with psychopathology.

The authors found normal monoamine oxidase (MAO) activity in 40 acute schizophrenic patients, in contrast to previous reports of a genetically linked platelet MAO deficit in chronic schizophrenia. Variations in MAO activity were not significantly associated with the 65 clinical variables analyzed, although there was a tendency for patients in the low-MAO group to have more severely impaired reality testing, more paranoid and grandiose delusions, better prognostic scores, and less restlessness.

Impaired smooth pursuit eye movement has been proposed as a possible biologic marker for schizophrenia. Preliminary studies have suggested that this impairment may be associated with social introversion and related psychopathology in a nonpsychiatric population. To evaluate the relationship between dysfunctional smooth pursuit eye movement and schizophrenia-related psychopathology, the authors screened a new, volunteer sample of 284 male college students for eye tracking accuracy. Volunteers identified as low-accuracy trackers were significantly more likely to be diagnosed (blindly) as having a schizotypal personality disorder by DSM-III criteria than those identified as high-accuracy trackers. The authors suggest that disordered smooth pursuit eye movement may reflect a vulnerability marker for schizotypal personality disorder.

The authors review studies of platelet and white cell monoamine oxidase (MAO) activity in schizophrenic patients. The data on acute schizophrenic patients remain inconclusive. Review of 26 reports of chronic schizophrenic patients leaves little doubt, however, that there is a subgroup in which the enzyme activity is decreased. Despite the strong association of decreased MAO activity and chronic schizophrenia, the etiological relationship of low platelet MAO activity to schizophrenia has not been demonstrated. More complete diagnostic descriptions will shed light on precisely which patients have lowered MAO activity. Further metabolic investigations with such patients are needed to determine the physiological significance of this phenomenon.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Platelet monoamine oxidase (MAO) activity and amine metabolites in cerebrospinal fluid were compared in 22 schizophrenic patients, 8 of whom improved during a 30-day drug-free period. CSF 5-hydroxyindoleacetic acid and homovanillic acid did not distinguish between drug-free improvers and nonimprovers. However, drug-free improvers had lower platelet MAO activities than did normal controls. The authors suggest that looking at clinical variables in patients with low MAO activity might provide a means of biologically subtyping schizophrenic patients.

This study provides additional evidence that there is a moderate association between the acute activation, euphoria, and antidepressant responses to dextro-amphetamine and the antidepressant response to imipramine during a four-week trial. Comparison of the responses of 13 patients to dextro-amphetamine on two different days during a double blind trial indicated that differences in dextro-amphetamine response are consistent, replicable characteristics of individual depressed patients. The variables of sex, diagnosis, diurnal mood variation, platelet MAO activity, and MMPI scale scores were of minimal assistance in revealing factors that might be associated with activation or antidepressant responses to dextro-amphetamine in this small patient group. The authors suggest the need for larger-scale studies in this area.

Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients.

Steady state intravenous tyramine dose pressor-response tests were administered to a patient with bipolar illness during depressed and hypomanic phases of her illness. The greatest tyramine sensitivity while unmedicated occurred when the patient was hypomanic, and the least sensitivity when she was depressed before her first switch. The data raise the possibility that changes in peripheral alpha-adrenergic receptor sensitivity accompany spontaneous mood cycles. Tyramine produced a replicable mood and cognitive alteration only in the infusion closest to the switch from hypomania to depression, suggesting that the CNS may be particularly susceptible to peripheral noradrenergic inputs at specific points in bipolar illness.

Abnormal central catecholamine neurotransmission has been suggested in Gilles de la Tourette's syndrome. The authors evaluated the sympathetic nervous system in both the basal state and in its responsivity to postural and exercise stress. Plasma norepinephrine and the activities of its synthetic and degradative enzymes were not different in 33 Tourette patients, a control group of unaffected relatives, and another control group of unrelated healthy volunteers. This finding suggests that these patients have neither a generalized dysfunction of norepinephrine metabolism nor a defect in the central control of sympathetic function.

The authors collected clinical diagnostic, neurophysiological, electrophysiological, and biochemical data on 9 adolescents who had primary obsessive-compulsive disorder. The results indicate considerable descriptive validity of the syndrome in childhood and its independence from obsessional traits; however, all of the children had a history of major depressive disorder, and their sleep EEG measures resembled those of young adults with primary depressive disorder. The patients' families did not have a more consistent pattern of anxiety disorder or any other psychiatric disorder than do families of adult obsessive patients. Psycholinguistic test results showed a lack of normal laterality, which has been reported for other psychiatric illness.

The authors measured plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine, blood pressure, and heart rate responses to the alpha 2-adrenergic agonist clonidine in 25 depressed patients and 25 normal control subjects. In the control subjects clonidine reduced plasma norepinephrine, blood pressure, and heart rate significantly more than placebo. In the depressed patients clonidine reduced blood pressure and the percent fall in plasma norepinephrine but not plasma MHPG or heart rate significantly more than placebo. The absolute and percent reductions in plasma MHPG and heart rate following clonidine were significantly less than in control subjects. These results raise the possibility that the sensitivity of the alpha 2-adrenergic receptors inhibitory to noradrenergic output may be reduced in depression.

To evaluate the need for maintenance drug therapy in patients with obsessive-compulsive disorder, the authors assessed 21 patients with obsessive-compulsive disorder who manifested sustained improvement during 5 to 27 months of clomipramine treatment and who agreed to participate in a double-blind discontinuation study. Of 18 patients who completed the study, 16 had substantial recurrence of obsessive-compulsive symptoms by the end of the 7-week placebo period. In addition, 11 had a significant increase in depressive symptoms. Treatment duration before discontinuation of clomipramine was not related to the frequency or severity of obsessive-compulsive or depressive symptom appearance. These findings suggest that prolonged drug treatment may be warranted for obsessive-compulsive disorder.

The authors investigated platelet monoamine (MAO) activity in 40 chronic schizophrenic patients, 55 normal control subjects, and 16 hospitalized control subjects. The mean platelet MAO activity for the chronic schizophrenic patients was significantly lower than the mean in either control group. There were no significant differences between the mean platelet MAO activities in 21 chronic paranoid schizophrenic patients compared with 18 chronic undifferentiated schizophrenic patients.