Teresa Huggins

Low Cerebrospinal Fluid Glutamate and Glycine in Refractory Affective Disorder

BACKGROUND Glutamatergic dysregulation has been documented in schizophrenia but has received less systematic study in affective illness. METHODS Cerebrospinal fluid (CSF) levels of the excitatory amino acids glutamate (Glu) and aspartate (Asp) and the N-methyl-D-aspartate (NMDA) receptor modulator, glycine (GLY) were measured by high performance liquid chromatography in 32 patients with refractory affective disorder (16 female/16 male, 12 bipolar I, 12 bipolar II, and 8 unipolar) and in 14 age-matched controls. RESULTS There was a significant reduction in CSF glutamate and glycine in patients versus controls. A diagnosis by sex interaction was present for CSF glycine with lower levels in female patients compared to female controls. Levels of the excitatory amino acids were highly inter-correlated in patients, but not in controls. In patients studied after 6 weeks of lamotrigine, there was a trend for CSF glutamate levels to increase. CONCLUSIONS These data suggest that in patients with refractory affective disorder, excitatory amino acids are dysregulated, as exemplified both by the decreased CSF glutamate and glycine and their high intercorrelation compared to controls. Further controlled study of glutamatergic dysregulation and its relationship to the pathophysiology of affective disorders and potential mechanism of action of mood stabilizers appears indicated.

Rapid cycling bipolar affective disorder: Lack of relation to hypothyroidism

Thyroid indices were measured after an extended period of medication-free evaluation averaging 6 weeks in 67 consecutively admitted patients with bipolar illness. Thyroid hormone levels -- thyroxine (T4), free T4 and triiodothyronine (T3) -- were not significantly different in the 31 rapid cyclers (> or = 4 affective episodes/year) than in 36 non-rapid cyclers. Analysis of covariance indicated a non-significant trend relation between higher T4 and a greater number of affective episodes in the year prior to admission and male gender when age was covaried. Several previous reports, primarily in medicated subjects, have suggested a link between rapid cycling patients and decreased peripheral thyroid indices (low hormone levels and elevated TSH), but now the majority of studies do not support such a relation. Among those in the literature, this study includes patients studied for the longest time off medications and further suggests that the commonly-cited relation between subclinical hypothyroidism and rapid cycling bipolar illness be reevaluated.

Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: Clinical and theoretical implications

The pattern and time course of antidepressant response to different treatment modalities provide important clinical information and hints about underlying neurobiological mechanisms. Depressed patients who responded to 1 nights sleep deprivation (11 of 33 patients) showed maximal improvement on day 1 and deterioration in mood thereafter. In contrast, slower onset and more sustained effects were observed following carbamazepine (12 of 37) or electroconvulsive therapy (ECT) (8 of 8). Nearly maximal improvement required about 2 weeks for ECT and 3 weeks for carbamazepine. Possible differential or common biological mechanisms with differential times of action are implied by these data, which are of importance to the neuroscientist attempting to uncover neural substrates of antidepressant response and the clinician attempting to find rapid onset, yet sustained antidepressant treatments.

Cerebrospinal fluid total protein in patients with affective disorders

Cerebrospinal fluid (CSF) total protein was evaluated in 240 patients with affective disorders and compared with findings in 55 normal comparison subjects. Subtype diagnoses were as follows: bipolar I (n = 108, 47 men, 61 women); bipolar type II (n = 67, 26 men, 41 women); and unipolar (n = 65, 22 men, 43 women). Men had significantly elevated values compared with women. In men with bipolar I disorder, mean CSF protein levels were found to be significantly elevated over those in normal subjects, with 31.9% above the traditional normal range cutoff of 45 mg/dl. Moreover, CSF protein levels in male bipolar I patients were found to be positively correlated with severity of depression at the time of the lumbar puncture and with duration of illness. It thus appears that increased protein levels may be associated with illness severity or progression in male patients with bipolar I disorder. Although elevated CSF protein is a nonspecific marker of cerebral pathology, further search for the potential underlying pathophysiological mechanisms related to this finding would now appear to be warranted.

Post-dexamethasone cortisol correlates with severity of depression before and during carbamazepine treatment in women but not men: Gender differences in DST on placebo and CBZ

Objective:  Previous studies show a state‐dependent relationship between depression and post‐dexamethasone suppression test (DST) cortisol level, as well as differences in DST response with age and gender.

339. CSF neuropeptide y correlates with anxiety in patients with affective disorders

present in humanswith seasonrdaffectivedisorder(SAD)and if their olfactoryperformancecorrelateswithdepressivescores.Becausepreviousstudiessuggesta predominant righthemisphericdysfunctionin SAD and olfactoryneurons’primaryprojectionsare largely ipsilatersf,we tested olfactory identificationperformance on each side of the nose. Twenty-fourSAD patients and twenty-fourmatched controls were studied using bilateraJphenyl ethyl alcohol detectionthresholdsand urrilaterrdUniversityof PennsylvaniaSmellIdentificationTestwithtwo booklets randorrdypresentedto each nostril, the contrafaterrdnostril beingoccluded.Subjectsratedtheirmoodon the SelfAssessmentMood ScaIe for SAD. Patients’ testing was performedin “depressed”and “improvedon light” state. We foundno differencein olfactoryperformancebetweenpatientaandcontrols,norbetweenpatientsbeforevsatler light treatment. A negative correlationemerged between right-sided identification scores and “typical” depression scores (r=–O.56, p=o.006).A similarnegativecorrelationbetwmr the asymmetryindex (Right -Left)/(Right+Left)and typical depressive scores (r=–O.64, p< O.001)was found.These results add to previousevidenceof right hemisphericinvolvementin mood dysregulation.