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Biomedical subjects

Gerard E Bruder

Publications and source records attributed to Gerard E Bruder.

17 recordsLinked to original sources
PubMed2006

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.

Adolescent↗
PubMed2006

Behavioral activation system deficits predict the six-month course of depression.

BACKGROUND: Behavioral activation system (BAS) deficits are hypothesized to increase risk for depression. This study tested the hypothesis that BAS deficits, measured with both self-report and electrophysiological methods, would predict the six-month course of depression. METHODS: 67 participants with major depressive disorder (MDD) with or without pre-existing dysthymia were assessed at baseline with Carver and White's [Carver, C.S., White, T.L., 1994. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J. Pers. Soc. Psychol. 67, 319-333.] BIS/BAS scales and resting EEG. The week-by-week course of their depressive symptoms was assessed six months later with the Longitudinal Interval Follow-up Evaluation (LIFE). RESULTS: Baseline self-reported BAS sensitivity predicted depression diagnosis (MDD or dysthymia) at follow-up, number of MDD symptoms at follow-up, average weekly level of depression, and time to recovery. These effects persisted after controlling for baseline clinical variables associated with a worse course. Baseline resting EEG alpha asymmetry did not significantly predict the course of depression. LIMITATIONS: Although BAS sensitivity predicted the subsequent course of depression, we cannot determine whether it played a causal role in maintaining depression. CONCLUSIONS: Lower self-reported BAS sensitivity predicts a worse course of depression but EEG asymmetries do not.

Adolescent↗
PubMed2006

ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia.

To disentangle subprocesses of verbal working memory deficits in schizophrenia, long EEG epochs (>10 s) were recorded from 13 patients and 17 healthy adults during a visual word serial position test. ERP generator patterns were summarized by temporal PCA from reference-free current source density (CSD) waveforms to sharpen 31-channel topographies. Patients showed poorer performance and reduced left inferior parietotemporal P3 source. Build-up of mid-frontal negative slow wave (SW) in controls during item encoding, integration, and active maintenance was absent in patients, whereas a sustained mid-frontal SW sink during the retention interval was comparable across groups. Mid-frontal SW sinks (encoding and retention periods) and posterior SW sinks and sources (encoding only) were related to performance in controls only. Data suggest disturbed processes in a frontal-parietotemporal network in schizophrenia, affecting encoding and early item storage.

Adolescent↗
PubMed2006

Psychomotor slowing as a predictor of fluoxetine nonresponse in depressed outpatients.

OBJECTIVE: This study examined the utility of baseline psychomotor speed, measured with neuropsychological tests, to predict fluoxetine response in moderately depressed outpatients. The authors hypothesized that since psychomotor slowing in depressed patients has been linked to reduced dopaminergic neurotransmission, patients with slowing would be unresponsive to fluoxetine, a selective serotonin reuptake inhibitor. METHOD: After baseline neuropsychological testing, patients were treated openly with fluoxetine for 12 weeks. Thirty-seven patients completed the trial. RESULTS: Compared to the 25 patients who responded, the 12 patients who did not respond to fluoxetine exhibited significantly poorer performance in verbal fluency on the Controlled Oral Word Association Test FAS and in color naming on the Stroop Color and Word Test. In addition, the nonresponders tended to perform worse than the responders on the Stroop Color and Word Test reading subtest and the WAIS-III digit symbol subtest. Differential treatment response was specific to psychomotor speed because responders and nonresponders did not perform differently on tasks of executive functioning, attention, visuospatial functioning, or verbal intelligence. CONCLUSIONS: Psychomotor slowing may identify a subgroup of depressed patients who have a dopaminergic deficit that is unresponsive to fluoxetine monotherapy and who should therefore receive an alternative treatment.

Adolescent↗
PubMed2005

Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. METHODS: A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter-Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. RESULTS: Letter-Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. CONCLUSIONS: COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter-Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.

Adolescent↗
PubMed2005

Families at high and low risk for depression: a three-generation startle study.

BACKGROUND: Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD). Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. METHODS: The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation). RESULTS: Startle discriminated between the low- and high-risk groups. In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. CONCLUSIONS: Increased startle reactivity in threatening contexts, previously found in patients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD. These findings suggest that there might be common biologic diatheses underlying depression and anxiety.

Acoustic Stimulation↗
PubMed2005

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.

Adult↗
PubMed2005

Low positive emotionality in young children: association with EEG asymmetry.

Low positive emotionality (PE; e.g., listlessness, anhedonia, and lack of enthusiasm) has been hypothesized to be a temperamental precursor or risk factor for depression. The present study sought to evaluate the validity of this hypothesis by testing whether low PE children have similar external correlates as individuals with depression. This paper focused on the external correlate of EEG asymmetry. Previous studies have reported that individuals at risk for depression exhibited a frontal EEG asymmetry (greater right than left activity). Others have reported an association with posterior asymmetries (greater left than right activity). In the present study, children classified as having low PE at age 3 exhibited an overall asymmetry at age 5-6 with less relative activity in the right hemisphere. This asymmetry appeared to be largely due to a difference in the posterior region because children with low PE exhibited decreased right posterior activity whereas high PE children exhibited no posterior asymmetry. These findings support the construct validity of the hypothesis that low PE may be a temperamental precursor or risk factor for depression.

Cerebral Cortex↗
PubMed2004

Verbal memory in schizophrenia: additional evidence of subtypes having different cognitive deficits.

A prior study found a selective deficit in verbal working memory in a subgroup of patients with schizophrenia who performed as well as healthy controls on a screening test of attention and auditory perception [Arch. Gen. Psychiatry 55 (1998) 1093]. Given the importance of defining pathophysiologically distinct subtypes of schizophrenia, the present study aimed to replicate and extend this finding. Patients with schizophrenia who passed the screening test (discriminators or Dsz patients) were compared to those who did not (nondiscriminators, NDsz patients), and healthy controls on a word serial position test (WSPT) and on other tests of verbal and nonverbal cognitive function. Dsz patients performed more poorly than controls on the WSPT and showed serial position effects consistent with a verbal memory deficit. They also showed a deficit in verbal memory but not visual memory on the Wechsler Memory Scale-Revised. In contrast, the NDsz patients showed overall poor performance on both verbal and nonverbal tests, consistent with a generalized deficit. Verbal working memory deficits were not related to education, gender, severity of symptoms, medication status, or hemispheric dominance for perceiving dichotic words. The findings add to growing evidence for the existence of a subgroup of schizophrenia having a specific verbal memory deficit that is not limited to working memory, but extends to learning and recall of verbal material.

Adult↗
PubMed2004

Dichotic listening tests of functional brain asymmetry predict response to fluoxetine in depressed women and men.

Patients having a depressive disorder vary widely in their therapeutic responsiveness to a selective serotonin reuptake inhibitor (SSRI), but there are no clinical predictors of treatment outcome. Studies using dichotic listening, electrophysiologic and neuroimaging measures suggest that pretreatment differences among depressed patients in functional brain asymmetry are related to responsiveness to antidepressants. Two new studies replicate differences in dichotic listening asymmetry between fluoxetine responders and nonresponders, and demonstrate the importance of gender in this context. Right-handed outpatients who met DSM-IV criteria for major depression, dysthymia, or depression not otherwise specified were tested on dichotic fused-words and complex tones tests before completing 12 weeks of fluoxetine treatment. Perceptual asymmetry (PA) scores were compared for 75 patients (38 women) who responded to treatment and 39 patients (14 women) who were nonresponders. Normative data were also obtained for 101 healthy adults (61 women). Patients who responded to fluoxetine differed from nonresponders and healthy adults in favoring left- over right-hemisphere processing of dichotic stimuli, and this difference was dependent on gender and test. Heightened left-hemisphere advantage for dichotic words in responders was present among women but not men, whereas reduced right-hemisphere advantage for dichotic tones in responders was present among men but not women. Pretreatment PA was also predictive of change in depression severity following treatment. Responder vs nonresponder differences for verbal dichotic listening in women and nonverbal dichotic listening in men are discussed in terms of differences in cognitive function, hemispheric organization, and neurotransmitter function.

Adolescent↗
PubMed2004

Left hemisphere dysfunction during verbal dichotic listening tests in patients who have social phobia with or without comorbid depressive disorder.

OBJECTIVE: Behavioral, electrophysiological, and imaging studies have found evidence that anxiety disorders are associated with left hemisphere dysfunction or higher than normal activation of right hemisphere regions. Few studies, however, have examined hemispheric asymmetries of function in social phobia, and the influence of comorbidity with depressive disorders is unknown. The present study used dichotic listening tests to assess lateralized cognitive processing in patients with social phobia, depression, or comorbid social phobia and depression. METHOD: The study used a two-by-two factorial design in which one factor was social phobia (present versus absent) and the second factor was depressive disorder (present versus absent). A total of 125 unmedicated patients with social phobia, depressive disorder, or comorbid social phobia and depressive disorder and 44 healthy comparison subjects were tested on dichotic fused-words, consonant-vowel syllable, and complex tone tests. RESULTS: Patients with social phobia with or without a comorbid depressive disorder had a smaller left hemisphere advantage for processing words and syllables, compared with subjects without social phobia, whereas no difference between groups was found in the right hemisphere advantage for processing complex tones. Depressed women had a larger left hemisphere advantage for processing words, compared with nondepressed women, but this difference was not seen among men. CONCLUSIONS: The results support the hypothesis that social phobia is associated with dysfunction of left hemisphere regions mediating verbal processing. Given the importance of verbal processes in social interactions, this dysfunction may contribute to the stress and difficulty experienced by patients with social phobia in social situations.

Adult↗
PubMed2003

Event-related brain potentials during auditory and visual word recognition memory tasks.

Event-related brain potentials (ERPs) recorded during presentation of a series of words or pictures show enhanced positivity between 300 and 800 ms after presentation of repeated items. However, little attention has been directed to the characterization of this ERP recognition memory effect using auditory stimuli. The present study directly compared the ERP 'old/new effect' for words presented in the visual and auditory modalities. Nose-referenced ERPs were recorded from 30 electrode sites while participants (N=16) were engaged in visual and auditory continuous word recognition memory tasks. Spatially and temporally overlapping ERP components were identified and measured by covariance-based principal components analysis. The expected old/new effect was observed in both modalities, with a comparable time course peaking at 560 ms, but having a more anterior scalp topography for visual items. This suggests a common cognitive process (i.e. successful retrieval of information from memory) associated with separable neural generators in each modality. Despite this temporal synchronization, the old/new effect overlapped ERP components having distinct scalp topographies (N2) or peak latencies (P3) for each modality. The positive-going old/new effect was preceded by an earlier negativity peaking at 370 ms that was greater across modalities for old than new words, likely reflecting semantic processing aspects of word recognition memory. A late (beyond 900 ms), broadly-distributed negativity was also greater for old than new words, prolonged for auditory items, and may represent activity of a post-retrieval process.

Acoustic Stimulation↗
PubMed2003

Do age of onset and course of illness define biologically distinct groups within atypical depression?

Illness course separates patients with atypical depression into tricyclic responders and nonresponders as does perceptual asymmetry. The authors therefore investigated whether the course-of-illness parameters would define groups within atypical depression differing in brain laterality. Patients with atypical depression were assessed for illness course and brain laterality. Two patient groups were defined, 1 with onset prior to age 20 plus a very chronic course, and a 2nd group having later onset or less chronic illness. Patients reporting early onset of very chronic dysphoria showed significantly less right-ear (left-hemisphere) accuracy and also differed in characteristic perceptual asymmetry when compared to patients with later onset or less chronicity. Course of illness may usefully define more homogeneous depressive subgroups within atypical depression.

Adult↗
PubMed2002

Atypical depression: enhanced right hemispheric dominance for perceiving emotional chimeric faces.

Two studies compared hemispatial bias for perceiving chimeric faces in patients having either atypical or typical depression and healthy controls. A total of 245 patients having major depressive disorder (MDD) or dysthymia (164 with atypical features) and 115 controls were tested on the Chimeric Faces Test. Atypical depression differed from typical depression and controls in showing abnormally large right hemisphere bias. This was present in patients having either MDD or dysthymia and was not related to anxiety, physical anhedonia, or vegetative symptoms. In contrast, patients having MDD with melancholia showed essentially no right hemisphere bias. This is further evidence that atypical depression is a biologically distinct subtype and underscores the importance of this diagnostic distinction for neurophysiologic studies.

Adult↗
PubMed2002

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.

Adult↗