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Biomedical subjects

W Berrettini

Publications and source records attributed to W Berrettini.

At least 19 recordsLinked to original sources

Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder.

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.

Adolescent

Evaluation of seasonality in six clinical populations and two normal populations.

The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations: patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed.

Adult

Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa.

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Adult

CSF neuropeptide Y in alcoholics and normal controls.

Neuropeptide Y is found in brain tissue. In dogs it has been shown to enhance activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone. It is localized in certain catecholamine neurons and to some extent colocalized with somatostatin. Disturbances of the central noradrenergic system may underlie some forms of alcoholism. Therefore, we compared male alcoholics and normal controls on cerebrospinal fluid (CSF) levels of neuropeptide Y. There was no significant difference between the two groups for neuropeptide Y. There was also no significant difference for CSF levels of growth hormone releasing hormone. However, there were significant positive correlations between CSF levels of neuropeptide Y and CSF levels of corticotropin-releasing hormone, somatostatin, and growth hormone releasing hormone.

Adult

Blunted ACTH and cortisol response to afternoon tryptophan infusion in euthymic bipolar patients.

The serotonin precursor tryptophan was used to test neuroendocrine responses in remitted bipolar patients and controls. Tryptophan was administered in the afternoon when spontaneous cortisol secretion is lower than in the morning. Following pilot studies at various doses, 50 mg/kg L-tryptophan was given i.v. over 20 min to 11 patients and 14 controls. Controls demonstrated cortisol release, whereas the response curve for patients was indistinguishable from placebo. Differences between groups were significant at 15, 30, and 45 min. Changes in adrenocorticotropic hormone were consistent with those in cortisol. Prolactin and growth hormone levels increased in both patients and controls following tryptophan. Higher doses caused gastrointestinal upset in some subjects.

Adrenocorticotropic Hormone

A cerebrospinal fluid study of the pathophysiology of panic disorder associated with alcoholism.

In order to investigate the neurochemistry of panic disorder in alcoholics, we measured various cerebrospinal fluid (CSF) parameters in subjects with both conditions and compared them with an age- and sex-matched population of alcoholics and normal controls. When height, age and weight were covaried, subjects with panic disorder had higher levels of B-endorphin in CSF. There were no differences in other CSF measures between the groups. Alcoholics with panic disorder had higher plasma MHPG concentrations compared with alcoholics without panic disorder but these were not statistically different from controls.

Adult

Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders.

Recently a linkage study on five Icelandic and two English pedigrees has provided evidence for a dominant gene for schizophrenia on 5q11-13 (ref. 1). In that study, families with bipolar illness were not included. Using the same probes, two similar but independent investigations on one Swedish pedigree and on fifteen Scottish families excluded linkage to schizophrenia. To evaluate whether the susceptibility gene on 5q11-13 is a common cause of schizophrenia in other populations, we examined five affected North American pedigrees using probes to the D5S39, D5S76 and dihydrofolate reductase loci. Two families in the present series had cases of bipolar disorder. We found that linkage can be excluded by multipoint analysis. These results, taken together, suggest that the disease gene on 5q11-13 does not account for most cases of familial schizophrenia.

Bipolar Disorder

Measuring cholinergic sensitivity: I. Arecoline effects in bipolar patients.

In a previous study, bipolar patients were found to be more sensitive than controls to induction of rapid eye movement (REM) sleep by the direct muscarinic agonist arecoline. We have replicated this observation in a new group of patients and controls. However, much overlap between groups was seen. Muscarinic supersensitivity appears to be present in some bipolar affective patients, but the REM induction procedure may not be the optimal method for measuring it.

Adult

Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia.

Magnetic resonance imaging (MRI) brain scans were performed on 24 schizophrenic patients, 22 bipolar affective patients, and 25 normal control subjects without medical or psychiatric illness using a Picker Vista 0.5 tesla scanner. Specific callosal regions and the cerebral area on the midsagittal slice were measured utilizing the technique described by Nasrallah et al. (1986). No significant differences were found among diagnostic groups in anterior, mid, or posterior callosal width, callosal area, cerebral area, callosal to cerebral area ratio, or the genu (first quartile) to splenium (fourth quartile) ratio. However, male subjects had a significantly greater callosal and cerebral area than female subjects. Gender differences were shown in the genu to splenium ratio in the control groups, but not the affective or schizophrenic groups. The implications of these gender differences are discussed in relation to other studies.

Adult

Temporal lobe measurement in primary affective disorder by magnetic resonance imaging.

Magnetic resonance imaging brain scans were performed on 17 patients with primary affective disorder and 21 normal subjects. A coronal slice through the temporal lobes at the level of the pons and interpeduncular cistern was selected in each subject, and specific temporal lobe structures and the cerebral area were measured. Ratios between structures of the same hemisphere were calculated. The ratio of the temporal lobe to cerebral area was smaller in patients than controls both on the left (p less than .02) and on the right (p less than .03). The data suggest that patients with primary affective disorder may have a relative decrease in the size of the temporal lobe compared with normal controls.

Adult

Supersensitivity to melatonin suppression by light in young people at high risk for affective disorder. A preliminary report.

Affective illness aggregates in families and appears to be heritable. Bipolar affective patients have been found to be supersensitive to the suppressive effect of light on the nocturnal secretion of melatonin, both in ill and well states. We tested young people aged 15 to 25 years with one manic-depressive parent (n = 18), major affective disorder on both sides of the family (n = 7), and age-matched controls (n = 20). The subjects in the high-risk groups were more likely to show supersensitivity in melatonin response to light at night than controls. Follow-up studies are necessary to assess the predictive value of this response.

Adolescent

Different neurotransmitter metabolite concentrations in CSF samples from inpatient and outpatient normal volunteers.

Cerebrospinal fluid concentrations of the neurotransmitter metabolites 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared in two groups of healthy volunteer subjects. One group (outpatient) was composed of 27 subjects who were transported to the outpatient clinic on the day of the lumbar puncture (LP). The other group (inpatient) was composed of 10 subjects who were admitted to the NIMH Research Ward on the evening prior to the LP. After statistical adjustment for age, height, sex and season in which LP was performed the inpatient group had significantly higher concentrations of both 5HIAA and HVA (P less than 0.005 and P less than 0.05, respectively) than the outpatient group. The difference in DOPAC concentration approached significance (P = 0.056), but there was no difference in MHPG concentration between the groups. This result indicates the need for strict control of environment in studies of CSF monoamines and their metabolites.

3,4-Dihydroxyphenylacetic Acid