Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective.

BACKGROUND: Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. METHOD: The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7-26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. RESULTS: Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. CONCLUSIONS: Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

A computational analysis of flanker interference in depression.

BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. METHOD: One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). RESULTS: Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). CONCLUSIONS: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.

Guidelines for the welfare and use of animals in cancer research.

Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.

Redox constituents in milk fat globule membranes and rough endoplasmic reticulum from lactating mammary gland.

Milk fat globule membranes (MFGM) and rough endoplasmic reticulum (RER) membranes were isolated from milk and lactating mammary gland from the cow and were characterized by biochemical and electron microscope methods in terms of gross composition (proteins, phospholipids, neutral lipids, cholesterol, RNA, and DNA) and purity. Both fractions contained significant amounts of a b-type cytochrome with several properties similar to those of cytochrome b5 from liver, as well as a rotenone-insensitive NADH- and NADPH-cytochrome c reductase. The b-type cytochrome content in the apical plasma membrane-derived MFGM was of the same order of magnitude as it was in RER membranes. It was characterized by a high resistance to extraction by low- and high-salt concentrations and nonionic detergents. MFGM contained much more flavin and much higher activities of xanthine oxidase than the RER membranes. The same redox components were found in MFGM and mammary RER from women, rats, mice, and goats, but in absolute contents great differences between the species were noted. The cytochromes described here differed from liver cytochrome b5 in some spectral properties. The alpha-band of the reduced hepatic cytochrome b5 is asymmetric with a maximum at 555 nm that is split into two distinct peaks at low temperatures. The alpha-band of the b-type cytochromes from MFGM and mammary RER appears as one symmetrical peak at about 560 nm that is not split at low temperatures. When treated with cyanide, MFGM and mammary microsomes showed difference spectra of a reduced b-type cytochrome. Under the same conditions, liver microsomes gave a completely different spectrum. These findings demonstrate the presence of a b-type cytochrome and associated redox enzymes in MFGM, i.e., a derivative of the apical cell surface membrane that is regularly used for envelopment of the milk fat globule during secretion.

B-type cytochromes in plasma membranes isolated from rat liver, in comparison with those of endomembranes.

Fractions of plasma membranes, Golgi apparatus, endoplasmic reticulum (ER), and nuclear envelope were isolated from rat liver and were characterized by electron microsocpe and biochemical methods. The purity of the fractions was controlled by morphometry and by marker enzyme activities. Amounts of cytochromes b5, P-450, and P-420 were measured, as well as the NADPH- and NADPH-cytochrome c reductase activities. The pigments of the microsomal electron transport system were found in all membrane fractions in relatively high amounts, thus excluding an origin by microsomal contamination. Purified preparations of plasma membrane and Golgi apparatus contained approximately 30% of the cytochrome b5 and cytochrome P-450 + P-420 found in ER membranes. Plasma membranes were also characterized by a high ratio of P-420/450. Degradation of cytochromes P-450 and P-420 was relatively rapid in all fractions, except in the ER. Cytochrome b5 extracted from plasma membranes was spectrophotometrically and enzymatically indistinguishable from ER cytochrome b5. However, immunnlogical characterization with rabbit antibodies against the trypsin-resistant core of microsomal cytochrome b5 showed the presence of at least two types of cytochrome b5 in ER membranes, in contrast to the plasma membranes in which only one of these components was detected. This immunological differentiation also demonstrates that the plasma membrane-bound cytochrome b5 is endogenous to this membrane and does not reflect contamination by ER elements. We conclude that cytochromes b5, P-450, and P-420 are not confined only to ER and nuclear membranes but also occur in signficant amounts in Golgi apparatus and plasma membranes. The findings are discussed in relation to observations of similar redox components in Golgi apparatus, secretory vesicles, and plasma membranes of other cells.

High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

The widespread occurrence of antibodies (IgG) specific to xanthine oxidase in both normal (nonimmune) human and animal sera, and in antisera raised against a diversity of unrelated antigens is described. A study of sera from 81 humans revealed that xanthine oxidase-specific IgG represents a high proportion (1-8%) of total IgG. No obvious correlation to pathological events or symptoms of disease could be found. These xanthine oxidase-specific antibodies could be isolated by immunoaffinity chromatography on purified human or bovine xanthine oxidase and showed specific binding to the enzyme polypeptide of Mr 155,000 in immunoblotting experiments. By immunofluorescence microscopy they displayed the same cell type-specific reaction as experimentally induced antibodies, i.e., the staining of lactating mammary gland epithelium and capillary endothelium. The naturally occurring xanthine oxidase-specific antibodies consisted of polyclonal IgG of various subclasses. F(ab')2 preparations gave immune-reactions identical to those of IgG. The human xanthine oxidase-specific IgG cross-reacted with the bovine enzyme and both human and animal antibodies partially inhibited its activity. The xanthine oxidase activity of human milk lipid globules and supernatant fractions from various human tissues was extremely low when compared with that of the bovine antigen. The enzyme protein, however, was effectively precipitated from these sources by both the human and bovine antibodies. We suggest that the exceptionally high concentrations of antibodies against one protein, xanthine oxidase, are due to self-immunization to the xanthine oxidase antigen present in endothelial cells of capillaries. We do not exclude, however, nutritional contributions of bovine milk antigen to the appearance of xanthine oxidase antibodies in human sera. The possible biological functions of this immunological reaction are discussed.

Plasma membranes from intestinal microvilli and erythrocytes contain cytochromes b5 and P-420.

The presence of cytochromes b5, P-450 and P-420 and activities of NADH- and NADPH-cytochrome c redutases were determined in plasma membranes isolated from microvilli of the chick and rat intestinal epithelium and erythrocyte membranes from chick, rat and man. The results are compared with the amounts of these components found in microsomal fractions from intestinal epithelium and in nuclear membranes from chick erythrocytes. Plasma membranes from intestinal microvilli and from erythrocytes contained significant amounts of NADH-cytochrome c reductase activity and of a pigment spectrophotometrically indistinguishable from rat liver microsomal cytochrome b5. In addition, cytochrome b5 fragments were prepared from the membranes by limited trypsin digestion and consisted of two to four components with Mr values in the range 10 000-13 500. In low-temperature difference spectra, the presence of a second cytochrome was noted which was similar to cytochrome P-420. Cytochrome P-450 and NADPH-cytochrome c reductase activities were not detected in plasma membrane fractions in significant concentrations but were present in the corresponding endomembrane fractions. These findings in highly purified, well defined plasma membrane fractions, in which contamination by endomembranes is minimal, strengthen the evidence for the existence of cytochrome-containing redox systems in plasma membranes of various cells and suggest that such redox components are general components of the cell surface. Possible functions and origins of these redox components in plasma membranes are discussed.

Butyrophilin, an apical plasma membrane-associated glycoprotein characteristic of lactating mammary glands of diverse species.

Lipid globule membranes were isolated from human and bovine milk and from the milk of sheep, goat, pig, rat and guinea pig, and their polypeptide compositions were analyzed. The major polypeptides with molecular weights similar to that of bovine butyrophilin were separated by gel electrophoresis, isolated and characterized with respect to isoelectric point, molecular weight, immunological cross-reactivity and peptide composition after proteolytic cleavage. We show that in all species examined these proteins are similar to bovine butyrophilin in (i) their relative insolubility in buffers of low and high ionic strength and in non-denaturing detergents, (ii) the occurrence of several isoelectric variants, and (iii) patterns of peptides obtained by protease digestion. It is concluded that closely related proteins are major constituents of the cytoplasmic coat structures associated with milk lipid globule membranes of many species, and we propose the name butyrophilins for this group of proteins. Bovine and human butyrophilins are glycosylated with relatively large amounts of glucosamine, mannose, glucose and galactose but little fucose, sialic acids or galactosamine. Most if not all of the sugar residues are associated with an acetone-soluble peptide fragment of Mr 12000-16000 focusing at about pH 4.0. We suggest that this fragment contains a membrane-spanning peptide sequence and is involved in the attachment of the cytoplasmic coat to the membrane of the milk lipid globule.

Characteristics of membrane-bound and soluble forms of xanthine oxidase from milk and endothelial cells of capillaries.

Xanthine oxidase (xanthine:O2 oxidoreductase, EC 1.2.3.2) was purified from bovine milk lipid globules to electrophoretic homogeneity (Mr 155,000) and antibodies were raised against it in rabbits. By immunolocalization techniques, the xanthine oxidase antigen was detected in milk lipid globules and mammary gland epithelium, but also in capillary endothelium from various tissues, including liver, lung and intestine. These findings were paralleled by measurements of xanthine oxidase activities in the tissues, both in a membrane-associated and a soluble form. Addition of hypoxanthine to fractions containing native xanthine oxidase did not promote lipid peroxidation, in contrast to the widely used in vitro system for lipid peroxidation which involves addition of xanthine oxidase preparations. Extraction with buffers of high ionic strength and with nonionic detergents removed only part of the enzyme from the membranes. Immunoprecipitates from the soluble supernatant fractions, using anti-xanthine oxidase IgG, were enriched in the Mr 155,000 polypeptide. Patterns of proteolytic cleavage products of the xanthine oxidase monomer from capillaries and milk lipid globules were similar but not identical. Immunoprecipitates from soluble fractions of milk lipid globules and tissues were enriched in both xanthine oxidase and NADH-cytochrome c reductase activities. Electrophoretic separation of proteins from milk lipid globule membranes under non-denaturing conditions revealed a close correlation of xanthine oxidase and part of the NADH-cytochrome c reductase activity, but showed different activity profiles of NADH-ferricyanide reductase and xanthine oxidase.

Left temporal lobe dysfunction in schizophrenia: event-related potential and behavioral evidence from phonetic and tonal dichotic listening tasks.

BACKGROUND: Asymmetric reduction of the P3 event-related potential (ERP) has provided evidence of left temporal lobe dysfunction in schizophrenia. Prior studies have been limited by reliance on simple target detection (oddball) tasks with pure tones. This study investigated the time course and topography of ERPs to binaural syllables or complex tones in dichotic listening tasks. METHODS: Event-related potentials of 26 patients meeting criteria for schizophrenia (n = 19) or schizoaffective disorder (n = 7) and 26 healthy controls were recorded from 30 scalp electrodes during 2 dichotic tasks in which different syllables or complex tones were simultaneously presented to each ear. A principal components analysis was used to derive factor scores corresponding to overlapping components in ERP waveforms--N1, N2, P3, and a late-positive potential. RESULTS: Healthy controls showed a right ear advantage for perceiving dichotic syllables, which was associated with greater N2 amplitude at left than right temporoparietal sites. Patients with schizophrenia did not show either this perceptual or N2 asymmetry. Patients also had smaller late-positive potential amplitude when compared with controls for both syllables and complex tones, with greatest decrement over left temporal sites. CONCLUSIONS: A right ear advantage in healthy adults for perceiving consonant-vowels was associated with a left-lateralized ERP component peaking at 200 milliseconds after syllable onset (N2). Patients with schizophrenia failed to show either of these task-dependent asymmetries, which may indicate a dysfunction of left temporal regions involved in phonetic classification. A task-independent asymmetric reduction of a later positive potential in patients with schizophrenia resembled left temporal P3 reductions reported for auditory oddball tasks.

Localization of xanthine oxidase in crystalline cores of peroxisomes. A cytochemical and biochemical study.

The ultrastructural cytochemical localization of xanthine oxidase activity in rat liver was investigated by the cerium technique. The reaction product was found in the cytoplasm of endothelial cells in liver sinusoids and, in addition, in crystalline cores of peroxisomes of liver parenchymal cells. Xanthine oxidase was also present in peroxisomal cores of beef liver and kidney, but not in rat kidney peroxisomes, which lack crystalline cores. The localization in peroxisomal cores of rat liver was confirmed also biochemically using highly purified peroxisomal fractions and subfractions containing exclusively the crystalline cores. Moreover, high levels of molybdenum were found in isolated peroxisomal cores by atomic absorption spectroscopy, thus corroborating the association of the molybdenum-containing enzyme with the cores. Since urate oxidase is also present within the same compartment of peroxisomes, it is possible that the crystalline cores harbor a complex of several enzymes involved in the purine metabolism.

Distribution of enzymes involved in metabolism of polycyclic aromatic hydrocarbons among rat liver endomembranes and plasma membranes.

The distribution of membrane-bound enzymes involved in the metabolism of polycyclic aromatic hydrocarbons was investigated in the same animals, in membrane fractions from rat liver: monooxygenase, cytochromes P-450 and P-420, NADPH-cytochrome P-450 reductase, cytochrome b5, NADH-cytochrome b5 reductase, epoxide hydrolase, glutathione-S-transferase, and UDP-glucuronyltransferase. The purity of the fractions (rough and smooth endoplasmic reticulum (ER), nuclei, nuclear membranes, Golgi apparatus, plasma membranes, and mitochondria) was controlled by electron microscopic morphometry, chemical analysis, and determination of marker enzyme activities. Specific activities invariably were highest in ER. With respect to the distribution between smooth and rough ER, the enzymes fell into two groups: Epoxide hydrolase, monooxygenase, NADPH-cytochrome P-450 reductase, NADH-cytochrome b5 reductase, and the concentrations of cytochromes P-450 and b5 were higher in smooth ER; by contrast, UDP-glucuronyltransferase (maximally activated) and membrane-associated glutathione-S-transferase activities were lower in smooth ER. The non-ER fractions also had significant activities of the enzymes, but to different extents: (1) Nuclei and nuclear membranes showed high UDP-glucuronyltransferase activities (on a phospholipid basis 55-65% of that of rough ER) which did not exhibit latency. (2) Plasma membrane, Golgi apparatus, and nuclear membrane fractions had relatively high epoxide hydrolase and NADH-cytochrome b5 reductase activities as well as high concentrations of cytochromes b5 and P-450 (20-30% of levels present in smooth ER on a phospholipid basis). (3) In mitochondria (whole organelles), glutathione-S-transferase. UDP-glucuronyltransferase, and NADH-cytochrome b5 reductase activities were high, in contrast to exceedingly low (or absent) amounts of cytochrome P-450 and activities of cytochrome P-450 reductase, monooxygenase, and epoxide hydrolase. The data show that (i) aromatic hydrocarbons are metabolized not only in ER membranes but also in other kinds of membranes, including Golgi apparatus and plasma membrane, and (ii) the mode and extent of this metabolism can differ in different membranes. Such differences of activities of enzymes present in the specific membranes might lead to differences of the intracellular distribution of reactive and inactive metabolites of aromatic hydrocarbons and thus may be important in diversification and regulation of metabolic pathways of carcinogenic compounds.

Auditory laterality in depression: relation to circadian patterns and EEG sleep.

Unmedicated endogenous (ED) and nonendogenous depressed (ND) patients were tested in the morning and evening on a dichotic click detection task and a dichotic consonant-vowel (CV) discrimination task. The ED and ND groups showed a morning to evening shift in lateral asymmetry for detecting dichotic clicks, which was opposite in direction to that previously seen for normal subjects. In contrast, there was no morning to evening shift in asymmetry for dichotic CV discrimination. Lateral asymmetry for dichotic click detection was significantly correlated with EEG sleep characteristics (sleep latency, REM period latency, REM time) and ratings of diurnal variation on the Hamilton Depression Scale. A reversal of the normal lateral asymmetry in the morning was associated with lengthened sleep latencies and with clinical ratings of diurnal variation.

Endogenous event-related potentials in obsessive-compulsive disorder.

Brain event-related potentials (ERPs) were used to investigate central nervous system (CNS) correlates of cognitive function in obsessive-compulsive disorder (OCD). ERPs of 10 unmedicated OCD patients and 10 normal controls were measured in an auditory "oddball" task. Increasing task difficulty resulted in longer N200 and P300 latencies in normal subjects, but not in OCD patients. Moreover, OCD patients displayed shorter P300 latency than normal controls for the more difficult discrimination conditions. This replicates prior findings of Beech et al. (1983) for a visual task. For both levels of task difficulty, OCD patients also showed greater negativity than normal controls in the N200 region, which extended into the subsequent slow wave region. Negativities in the N200 and slow wave regions were larger at sites over the left hemisphere than the right hemisphere. The enhanced negativities and reduced P300 latency in OCD patients are discussed in terms of current theories postulating cortical hyperarousal and left hemisphere involvement in OCD.

Event-related potentials in schizophrenia during tonal and phonetic oddball tasks: relations to diagnostic subtype, symptom features and verbal memory.

BACKGROUND: This study compares event-related potentials for paranoid patients (n = 13) versus matched undifferentiated patients and unmedicated patients (n = 14) versus matched healthy adults. METHODS: Event-related potentials of right-handed patients and control subjects were recorded from 30 electrodes during oddball tasks using consonant-vowel syllables or complex tones. Patients were also assessed using the Positive and Negative Syndrome Scale, the Thought Disorder Index, and the Wechsler Memory Scale. RESULTS: Paranoid patients did not differ from undifferentiated patients in N1 or P3 amplitude but showed larger N2 at frontocentral sites to phonetic stimuli, as well as larger N2 over left than right hemisphere. Unmedicated patients showed reduced N2, but not N1 or P3, compared to control subjects. CONCLUSIONS: The N2 findings are consistent with neuropsychological evidence of greater verbal abilities and left hemisphere dominance in paranoid than nonparanoid schizophrenia. The findings also confirm the relationship of P3 to total Brief Psychiatric Rating Scale score, negative symptoms, and verbal associative memory.

Event-related potentials in depression: influence of task, stimulus hemifield and clinical features on P3 latency.

P3 latency, a brain event-related potential (ERP) correlate of stimulus evaluation time, was measured in 25 unmedicated depressed patients and 27 normal controls during auditory temporal and spatial discrimination tasks. Patients were divided into two subgroups, one having a typical major depression (melancholia or simple mood reactive depression) and one having an atypical depression. Typical depressives had abnormally long P3 latency for the spatial task but not the temporal task. They also showed an abnormal lateral asymmetry, with longer P3 latency for stimuli in the right hemifield than the left. In contrast, atypical depressives did not differ from normals in either respect. Longer P3 latency correlated with ratings of insomnia, while abnormal lateral asymmetry correlated with reduced right visual field advantage for syllables. The P3 latency findings point to a task-related slowing of perceptual decisions in a subgroup of depression.

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.

Event-related brain potentials (ERPs) in schizophrenia for tonal and phonetic oddball tasks.

BACKGROUND: Prior studies using simple target detection ("oddball") tasks with pure tones have reported asymmetric reduction of the P3 event-related potential (ERP). This study investigated the time course and topography of ERPs recorded during both tonal and phonetic oddball tasks. METHODS: Event-related potentials of 66 patients (14 unmedicated) diagnosed with schizophrenia (n = 46) or schizoaffective disorder (n = 20) and 32 healthy adults were recorded from 30 scalp electrodes during two oddball tasks using consonant-vowel syllables or complex tones. Overlapping ERP components were identified and measured by covariance-based principal components analysis. RESULTS: Schizophrenic patients showed marked, task-independent reductions of early negative potentials (N1, N2) but not reduced P3 amplitude or abnormal P3 asymmetry. Task-related hemispheric asymmetries of the N2/P3 complex were similar in healthy adults and schizophrenic patients. Poorer task performance in patients was related to ERP amplitudes, but could not account for reductions of early negativities. CONCLUSIONS: The findings suggest that both patients and control subjects activated lateralized cortical networks required for pitch (right frontotemporal) and phoneme (left parietotemporal) discrimination. Task-independent reductions of negativities between 80 and 280 msec after stimulus onset suggest a deficit of automatic stimulus classification in schizophrenia, which may be partly compensated by later effortful processing.

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.

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.