Paul Leite

Regional brain asymmetries in major depression with or without an anxiety disorder: A quantitative electroencephalographic study

Studies of brain activity in affective disorders need to distinguish between effects of depression and anxiety because of the substantial comorbidity of these disorders. Based on a model of asymmetric hemispheric activity in depression and anxiety, it was predicted that anxious and nonanxious depressed patients would differ on electroencephalographic (EEG) measures of parietotemporal activity. Resting EEG (eyes closed and eyes open) was recorded from 44 unmedicated outpatients having a unipolar major depressive disorder (19 with and 25 without an anxiety disorder), and 26 normal controls using 30 scalp electrodes (13 homologous pairs over the two hemispheres and four midline sites). As predicted, depressed patients with an anxiety disorder differed from those without an anxiety disorder in alpha asymmetry. Nonanxious depressed patients showed an alpha asymmetry indicative of less activation over right than left posterior sites, whereas anxious depressed patients showed evidence of greater activation over right than left anterior and posterior sites. The findings are discussed in terms of a model in which specific symptom features of depression and anxiety are related to different patterns of regional brain activity.

Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.

BACKGROUND Recent reports suggest the value of electroencephalographic and dichotic listening measures as predictors of response to antidepressants. This study examines the potential of electroencephalographic alpha asymmetry and dichotic measures of perceptual asymmetry as predictors of clinical response to 12 weeks of treatment with fluoxetine (Prozac). METHODS Resting electroencephalography (eyes open and eyes closed) and dichotic listening with word or complex tone stimuli were assessed in depressed outpatients during a pretreatment period. RESULTS Fluoxetine responders (n = 34) differed from nonresponders (n = 19) in favoring left over right hemisphere processing of dichotic stimuli. They also differed in their resting electroencephalographic alpha asymmetry, particularly in the eyes open condition. Nonresponders showed an alpha asymmetry indicative of overall greater activation of the right hemisphere than the left, whereas responders did not. The relationship between hemispheric asymmetry and treatment response interacted with gender, being evident among depressed women but not men. CONCLUSIONS The results are consistent with the hypothesis that a characteristic tendency toward greater left than right hemisphere activation is associated with favorable response to fluoxetine, whereas the opposite hemispheric asymmetry predicts poor response.

Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders

BACKGROUND Electroencephalographic (EEG) studies have found abnormal regional hemispheric asymmetries in depressive disorders, which have been hypothesized to be vulnerability markers for depression. In a longitudinal high-risk study, resting EEG was measured in primarily adult offspring of depressed or nondepressed probands. METHODS Electroencephalograms from12 homologous sites over each hemisphere (digitally linked-ears reference) were analyzed in right-handed offspring for whom both parents (n = 18), one parent (n = 40), or neither parent (n = 29) had a major depressive disorder (MDD). RESULTS Offspring with both parents having MDD showed greater alpha asymmetry at medial sites, with relatively less activity (more alpha) over right central and parietal regions, compared with offspring having one or no parent with MDD. Relatively less left frontal activity at lateral sites was associated with lifetime MDD in offspring but not with parental MDD. Offspring with both parents having a MDD also showed markedly greater anterior-to- posterior increase in alpha with eyes closed compared with those with one or no parent with a MDD. CONCLUSIONS Alpha asymmetry indicative of right parietotemporal hypoactivity, previously reported for depressed adolescents and adults, and heightened anterior-to-posterior gradient of alpha are present in high-risk offspring having parents concordant for MDD.

Brain ERPs of depressed patients to complex tones in an oddball task : Relation of reduced P3 asymmetry to physical anhedonia

Event-related potentials to binaural complex tones were recorded from 40 depressed outpatients and 22 normal control participants at 30 electrode sites. Patients did not differ from control participants in N1 or P3 amplitude but showed greater N2. N2 was greater over right than over the left hemisphere at lateral sites in patients and control participants. A P3 asymmetry was found for control participants and patients with low scores on a physical anhedonia scale, but not for patients with high anhedonia scores. Topographic (local Laplacian) maps corresponding to P3 showed greater radial current flow over right than over left central regions in control participants. Patients with high anhedonia did not show this asymmetry, whereas patients with low anhedonia showed an intermediate asymmetry. These findings support the hypothesis that anhedonic depression is associated with dysfunction of right hemisphere mechanisms mediating the processing of complex pitch information.

Cognitive ERPs in Depressive and Anxiety Disorders during Tonal and Phonetic Oddball Tasks

This report compares event-related brain potentials (ERPs) of patients having a depressive disorder alone (n=58), an anxiety disorder alone (n=22), comorbidity of these disorders (n=18), and healthy controls (n=49). ERPs were recorded from 30 electrode sites during auditory oddball tasks using consonant-vowel syllables (phonetic) or complex tones (tonal). Overlapping ERP components were identified and measured using covariance-based principal components analysis. An early P3 subcomponent (P315) was larger in patients having an anxiety disorder alone when compared to depressed patients with or without an anxiety disorder and healthy controls, whereas a late P3 subcomponent (P400) was larger in patients having comorbidity of anxiety and depressive disorders than in the other groups. Also, the N2-P3 complex showed task-dependent hemispheric asymmetries, including larger N2-P3 amplitude over left than right temporoparietal sites during the phonetic oddball task. This hemispheric asymmetry was greatest in patients having a depressive disorder alone and smallest in patients having an anxiety disorder alone. The opposite nature of the alterations of hemispheric asymmetry and early P3 amplitude in depressive and anxiety disorders underscores the importance of taking comorbidity with anxiety into account in studies of cognitive ERPs in depressive disorders.

Abnormal cerebral laterality in bipolar depression : Convergence of behavioral and brain event-related potential findings

Cerebral laterality in bipolar and unipolar major depression was compared using visual half-field and dichotic listening measures of perceptual asymmetry. The results replicate our prior finding of abnormal laterality in bipolar depressed patients on a visuospatial test. Bipolar patients (n = 11) failed to show the left visual field (right hemisphere) advantage for dot enumeration seen for both unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients performed significantly poorer than unipolar patients on normal controls for left visual field, but not right visual field stimuli. An electrophysiological correlate of abnormal visual field asymmetry in bipolar depression was found in brain event-related potentials recorded during audiospatial and temporal discrimination tasks. Bipolar patients had smaller N100 amplitudes for test stimuli in the left than right hemifield, whereas unipolar patients and normals did not. The origins of left hemifield deficits in bipolar depression are discussed in terms of right-sided dysfunction of an arousal/attentional system involving temporoparietal and possibly frontal regions.

Response- and stimulus-related ERP asymmetries in a tonal oddball task: a Laplacian analysis.

Previous studies have found greater P3 amplitude over right than left hemisphere sites in a tonal oddball task with a reaction time (RT) response. This asymmetry had a central topography, and interacted with response hand. Identification of the processes underlying these asymmetries requires the use of additional methods for separating response- and stimulus-related contributions. We applied local Hjorth and spherical spline algorithms to compute surface Laplacian topographies of ERP data recorded from 30 scalp electrodes in a pooled sample of 46 right-handed healthy adults. For both methods, the current sources underlying the late positive complex were largest at medial parietal regions, but were asymmetric at central and frontocentral sites. Although a frontocentral sink contralateral to the response hand contributed to the asymmetry of the classic P3 peak, the source asymmetry was most robust after the sink had resolved. The late source was largest at electrode C4 for right hand responses, and was further enhanced in subjects showing a dichotic left ear advantage, but was unrelated to response speed. We conclude that the right hemisphere source reflects an interaction of response-related asymmetries with right hemisphere processes responsible for pitch discrimination.

Abnormality of EEG alpha asymmetry in female adolescent suicide attempters

Abnormal electroencephalographic (EEG) activity has been associated with various psychiatric disorders and behaviors, including depression, suicide, and aggression. We examined quantitative resting EEG in Hispanic female adolescent suicide attempters and matched normal controls. Computerized EEG measures were recorded at 11 scalp sites during eyes open and eyes closed periods from 16 suicide attempters and 22 normal controls. Suicide attempters differed from normal controls in alpha asymmetry. Normal adolescents had greater alpha (less activation) over right than left hemisphere, whereas suicidal adolescents had a nonsignificant asymmetry in the opposite direction. Nondepressed attempters were distinguished from depressed attempters in that they accounted for the preponderance of abnormal asymmetry, particularly in posterior regions. Alpha asymmetry over posterior regions was related to ratings of suicidal intent, but not depression severity. The alpha asymmetry in suicidal adolescents resembled that seen for depressed adults in its abnormal direction, but not in its regional distribution. Findings for suicidal adolescents are discussed in terms of a hypothesis of reduced left posterior activation, which is not related to depression but to suicidal or aggressive behavior.

Cerebral laterality in adolescent major depression

This study tests the hypothesis that adolescents with major depression exhibit abnormalities in cerebral asymmetry previously found among adults. Perceptual asymmetry was assessed through tests of verbal and non-verbal dichotic listening in four groups - 48 adolescents with major depression, 22 adolescent comparisons with no history of Axis I disorders, 149 adults with major depression, and 57 comparison adults with no history of Axis I disorders. Data from adults have been previously reported. In both age groups, subjects with major depression were further divided based on the presence or absence of an anxiety disorder. Procedures used to collect perceptual asymmetry data in adolescents and adults were identical. In both age groups, depressed and healthy subjects showed perceptual asymmetry in expected directions for verbal and non-verbal dichotic tasks. Depressed and comparison subjects differed in performance on the Fused-Word Test, though these differences varied as a function of anxiety and developmental level. Relative to comparisons, both adolescents and adults with major depression exhibited an increased right ear/left hemisphere advantage for fused words. Adults but not adolescents with comorbid major depressive and anxiety disorders exhibited a reduced right ear/left hemisphere advantage for fused words. These findings suggest similarities and differences across development in the relationship between cerebral laterality and psychopathology. Further studies using longitudinal and family-based designs, as well as various measures of regional brain activity, are needed to enhance understanding of associations between cerebral laterality and psychopathology across development.