Obsessive-compulsive dimension localized using low-resolution brain electromagnetic tomography (LORETA)

Electroencephalographic mapping techniques have been used to show differences between normal subjects and those diagnosed with various mental disorders. To date, there is no other research using the techniques of low-resolution brain electromagnetic tomography (LORETA) with the obsessive-compulsive disorder (OCD) population. The current investigation compares current source density measures of persons with OCD symptoms to an age-matched control group. The main finding is excess current source density in the Beta frequencies in the cingulate gyrus. This Beta activity is primarily located in the middle cingulate gyrus as well as adjacent frontal parieto-occipital regions. Lower frequency Beta is prominent more anteriorly in the cingulate gyrus whereas higher frequency Beta is seen more posteriorly. These preliminary findings indicate the utility of LORETA as a clinical and diagnostic tool.     

Contributing factors to changes of cerebral blood flow in major depressive disorder

BACKGROUND: Results of single photon emission computed tomography (SPECT) regarding mood disorders have been inconsistent. The aim of the study was to elucidate factors contributing to changes in cerebral blood flow in patients with major depressive disorder. METHODS: A total of 89 consecutive patients diagnosed with major depressive disorder using DSM-IV semistructured interviews were evaluated using single photon emission computed tomography, the 17-item Hamilton Rating Scale for Depression (HRSD), and the Global Assessment of Function (GAF) scale. Nineteen of these patients also underwent the same tests during remission. RESULTS: Global cerebral blood flow (gCBF) was significantly higher during remission than at the time of enrollment. Significant correlations were seen between gCBF and age, duration of previous episode of depression, and hypochondriasis. However, no correlation was seen between gCBF and HRSD, GAF, severity and duration of depressive episode, or melancholia-type depression. Correlations between gCBF and age were seen only at enrollment and disappeared during remission. No differences in regional cerebral blood flow at any site were seen between time of enrollment and remission for the same patient. LIMITATION: Analysis that adequately accounts for these factors to changes of cerebral blood flow in major depressive disorder will require a large subject population. CONCLUSIONS: These results suggest that although there is a decrease in gCBF in major depressive disorder, the level of the decrease is determined by conditions present before episode onset, rather than by the characteristics of the episode itself. The findings also suggest that the correlation between gCBF and age is state-dependent.     

Physical anhedonia in major depressive disorder.

Physical anhedonia, evaluated by the score on the physical anhedonia scale (PAS) of Chapman et al. [J. Abnorm. Psychol. 4 374-382 (1976)] was studied in 61 patients, who met RDC criteria for major depressive disorder and in 61 normal subjects. The depressed patients scored significantly higher than the normal group and presented a continuous distribution. Physical anhedonia of depressed patients seems related to the severity of the depression and does not appear to identify a qualitatively distinct subgroup.     

Motor activity and autonomic cardiac functioning in major depressive disorder

BACKGROUND: The daily pattern of motor activity and the autonomic cardiovascular regulation were studied in major depression to quantify changes in psychomotor function and autonomic cardiac functioning. Additionally, relationships between motor activity parameters, cardiovascular measures and specific clinical features were examined. METHODS: Wrist-actigraphy was used to monitor 24-h motor activity for 67 unmedicated (unipolar) depressed inpatients and 64 control subjects. During supine rest, spectral analysis was applied to assess HR and SBP variability, a baroreflex sensitivity (BRS) index and the respiratory frequency, in addition to mean heart rate (HR) and blood pressure (BP) levels for the patient group and a second control group (N=51). RESULTS: The patients showed a lower motor activity level and a reduced fragmentation of motor activity during wake, and a higher motor activity level and a decreased immobility during sleep. The mean HR and DBP level and the respiratory frequency were higher in the patient group than in the control group, but no differences in HR and SBP variability or BRS were found. Furthermore, motor activity parameters and cardiovascular measures of the patients were related to agitation and retardation and overall, patients with lower motor activity levels demonstrated lower SBP levels. CONCLUSIONS: This study confirms that the 24-h pattern of motor activity is altered in unmedicated depressed inpatients, but limited evidence was found for an autonomic cardiac dysfunction. Within the patient group there were relationships between motor activity parameters, cardiovascular measures, and clinical features, but the underlying neurobiological pathways need to be further explored.     

Differential diagnosis of chronic fatigue syndrome and major depressive disorder

The goal of this study was to identify variables that successfully differentiated patients with chronic fatigue syndrome, major depressive disorder, and controls. Fifteen participants were recruited for each of these three groups, and discriminant function analyses were conducted. Using symptom occurrence and severity data from the Fukuda et al. (1994) definitional criteria, the best predictors were postexertional malaise, unrefreshing sleep, and impaired memory-concentration. Symptom occurrence variables only correctly classified 84.4% of cases, whereas 91.1% were correctly classified when using symptom severity ratings. Finally, when using percentage of time fatigue reported, postexertional malaise severity, unrefreshing sleep severity, confusion-disorientation severity, shortness of breath severity, and self-reproach to predict group membership, 100% were classified correctly. We appreciate the financial assistance provided by the National Institute of Allergy and Infectious Diseases (grant nos. AI36295 and AI49720).     

Comorbid depression in obsessive compulsive disorder (OCD): symptomatic differences to major depressive disorder

In this study, we compared the depressive symptom profile of a group of obsessive compulsive disorder (OCD) patients, with comorbid depression, to a group of patients with major depressive disorder (MDD). The two groups (n=52 per group) were pair-wise matched on severity of depression as measured by the MADRS (mean 24.3 for each group) and we examined between-group differences on the individual MADRS item scores. The OCD group was significantly more symptomatic on items 3 (inner tension) and 9 (pessimistic thoughts) and significantly less symptomatic on items 4 (sleep) and 5 (appetite). We discuss these findings in the context of neurobiological bases for the two disorders.     

Psychotic symptoms in major depressive disorder are associated with reduced regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxel-based single photon emission computed tomography (SPECT) study

BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe major depressive episodes. Functional imaging studies of depression have been widely reported in the literature, but few of these have attempted to investigate the neurophysiological correlates of psychotic symptoms. METHODS: We measured resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique in patients with major depressive disorder with (n=9) and without (n=12) psychotic features, as well as in a group of healthy volunteers (n=12). Between-group rCBF comparisons were performed using the voxel-based statistical parametric mapping method. RESULTS: Major depressed patients with psychotic features showed decreased rCBF in the left subgenual anterior cingulate cortex relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed, uncorrected for multiple comparisons). Relative to the non-psychotic group, depressed patients with psychotic symptoms also had a focus of decreased rCBF in the right inferior frontal cortex, with the voxel of maximal significance in the insula (P<0.031, corrected for multiple comparisons). A similar pattern of significant between-group rCBF differences between psychotic and non-psychotic patients emerged after covarying the analysis for the confounding influence of overall illness severity. CONCLUSIONS: These results provide preliminary evidence that psychotic symptoms in major depression may be associated with abnormalities in ventral paralimbic regions previously implicated in mood regulation and depression.     

Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder

Although major depressive disorder (MDD) and schizophrenia (SZ) are closely associated with disrupted functions in frontal and limbic areas of cerebral cortex, cellular pathology has also been found in other brain areas, including primary sensory cortex. Auditory cortex is of particular interest, given the prominence of auditory hallucinations in SZ, and sensory deficits in MDD. We used stereological sampling methods in auditory cortex to look for cellular differences between MDD, SZ and non-psychiatric subjects. Additionally, as all of our MDD subjects died of suicide, we evaluated the association of suicide with our measurements by selecting a SZ sample that was divided between suicide and non-suicide subjects. Measurements were done in primary auditory cortex (area A1) and auditory association cortex (area Tpt), two areas with distinct roles in sensory processing and obvious differences in neuron density and size. In MDD, densities of GABAergic interneurons immunolabeled for calretinin (CR) and calbindin (CB) were 23–29% lower than non-psychiatric controls in both areas. Parvalbumin (PV) interneurons (counted only in area Tpt) showed a nominally smaller (16%) reduction that was not statistically significant. Total neuron and glia densities measured in Nissl stained sections did not show corresponding reductions. Analysis of suicide in the SZ sample indicated that reduced CR cell density was associated with suicide, whereas the densities of CB and other cells were not. Our results are consistent with previous studies in MDD that found altered GABA-associated markers throughout the cerebral cortex including primary sensory areas.     

Overgeneral autobiographical memory and depressive disorder in children.

Overgeneral autobiographical memory seems to be a stable cognitive marker in depressed adults and may predict persistence of depression. This study investigated whether depressive disorders in children are associated with overgeneral memory. Sixty children (ages 9 to 13 years) participated; 15 were diagnosed with lifetime depressive disorder, 25 had other lifetime psychiatric disorders, and 20 had no history of psychiatric disorder. Depressed children gave fewer specific memories compared to children with no or other psychiatric disorders, even after controlling for depressive mood, potential traumatic life events, verbal IQ, and verbal memory.     

Myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and chronic myeloproliferative disorder (CMPD) in cats.

Histological, enzyme histochemical and ultrastructural findings in three cases of feline bone marrow neoplasia are described. The following changes were observed: in myelodysplastic syndrome (MDS), a low medullary blast count, strongly atypical (micromegakaryocytic) proliferative megakaryocytopoiesis, hypoplastic erythrocytopoiesis with impairment of differentiation, multifocal extravasation and lymphoid aggregates; in acute myeloid leukaemia (AML), medullary proliferation of undifferentiated cell types; in chronic myeloIproliferative disorder (CMPD), trilinear medullary proliferation with complete cellular maturation, osteomyelosclerosis and extramedullary haemopoiesis. In two cases (MDS, AML), ultrastructural demonstration of C-type virus particles (feline leukaemia virus) suggested a viral aetiology.     

Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder.

The etiology of mood disorders remains elusive, despite our increasing understanding of the neurotransmitter systems and brain regions that are involved. We performed a large family-based association study to test if the human kainate receptor GluR7 gene (GRIK3) is associated with bipolar disorder (BP) or recurrent major depressive disorder (R-MDD). One hundred fifty-three multiplex BP families from the National Institute of Mental Health (NIMH) Genetics Initiative on Bipolar Disorder were analyzed with the transmission disequilibrium test (TDT). We detected a significant linkage disequilibrium (LD) indicated by preferential maternal transmission of the GluR7 S310 allele to R-MDD patients (P = 0.012), but not to bipolar I disorder (BPI) patients (P = 1.00). We performed a second independent study by applying the TDT in 81 parent-offspring triads from families that inherit recurrent early-onset major depressive disorder (RE-MDD). The results from this second study showed only a suggestive maternal association (P = 0.068). Our findings imply that the GluR7 gene is a susceptibility factor in R-MDD and that the glutamatergic receptor system plays a critical role in the disease etiology.     

Age at onset of major depressive disorder predicts reductions in NK cell number and activity

BACKGROUND: Major depressive disorder (MDD) has been associated with altered immunologic parameters including reductions in natural killer cell activity (NKCA). It remains largely unknown, however, whether alterations in immune function characterize homogeneous sub-groups of MDD. The present study addressed the question of whether age at onset of index episode and/or duration of the present episode of MDD predicted alterations in NKCA and NK cell number. METHODS: Participants met DSM-IV criteria for MDD. Age at onset of MDD, duration of the present episode, demographics, and comorbidity were obtained by SCID for all subjects (n = 36). Severity and symptom pattern of MDD was assessed by the Hamilton Depression Rating Scale. NKCA was measured using a standard chromium-release cytotoxicity assay and NK number assessed by flow cytometry. RESULTS: Age at onset of MDD significantly predicted variance in NK cell number and NKCA. Consistent with previous studies, sleep disturbance and psychomotor retardation possessed significant explanatory power for variance in NK cell number and NKCA, respectively. LIMITATIONS: Measures of age at onset of MDD and duration of the present episode were obtained by self-report and thus recall bias may attenuate the reliability of the present findings. The present study design also precludes conclusions regarding the temporal association between alterations in NK cells and MDD. CONCLUSIONS: We propose that immunologic alterations, characterized by a suppression of NKCA and NK cell number concomitant with proinflammatory processes, may constitute an immunologic phenotype unique to early-age-onset depression and may be salient factors in the pathogenesis of depression.     

Influence of electromagnetic fields on the electrical activity of rabbit cerebral cortex

Summary The effect of electromagnetic fields on the bioelectric activity of cerebral cortex was investigated on 98 rabbits. As established, the electromagnetic field provokes signal changes in the electroencephalogram: Increased intensity of the magnetic field raises the reaction of the cerebral cortex. Exclusion of various receptor fields (of hearing, vision, smell, vestibular apparatus) had no effect on the reaction of the brain to the action of the electromagnetic field. This led to a suggestion on the possibility of direct action of electromagnetic fields on the brain.Reported at the Conference on Problems of the Electrophysiology of the Central Nervous System, Moscow, 1958.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny Vol. 49, No. 5, pp. 63–67, May, 1960     

Systemic embolism in chronic sinoatrial disorder.

We attempted to estimate the prevalence of systemic embolism in patients with chronic sino-atrial disorder. In a group of 100 patients, evidence of embolism was found in 16, of whom 15 had the bradycardia-tachycardia syndrome. In 712 controls with chronic complete heart block, who were matched for age and sex, embolism had occurred in only 1.3 per cent (P less than 0.001). A second group of 41 patients with chronic ventricular bradycardia and atrial flutter or fibrillation had an embolic prevalence of 7.3 per cent, which was also greater than that in the controls (P less than 0.05). All patients with sinoatrial disorder in whom systemic embolism developed were over 54 years of age; multiple episodes occurred in six. The risk of embolization remains even if the bradycardia-tachycardia syndrome is replaced by stable atrial fibrillation. Impaired atrial function appears to be a key factor in predisposing to intracardiac thrombosis, and paroxysmal supraventricular tachycardia increases the risk of subsequent embolization.     

Minor depressive disorder in the context of miscarriage

BACKGROUND: Although minor depressive disorder is of considerable clinical and public health importance, it has received limited research attention relative to major depressive disorder. This study examines the incidence rate and relative risk for minor depressive disorder following miscarriage. METHODS: Using a cohort design we tested whether miscarrying women are at increased risk for an episode of minor depression (diagnosed based on research criteria proposed in Appendix B of DSM-IV) in the 6 months following loss. The miscarriage cohort consisted of women attending a medical center for spontaneous abortion (n=229); the comparison group was a population-based cohort of women drawn from the community (n=230). RESULTS: Among miscarrying women, 5.2% experienced an episode of minor depression, compared with 1.0% of community women. The overall relative risk for an episode of minor depression for miscarrying women was 5.2 (95% confidence interval, 1.2-23.6). Relative risk did not vary by length of gestation at the time of loss or attitude toward the pregnancy. The majority of episodes in miscarrying women began within 1 month following loss. Limitations: Minor depression was relatively rare in both study cohorts. The resulting limits on statistical power reduced our ability to identify factors, such as sociodemographic or reproductive history variables that might moderate the effect of miscarriage on risk for minor depression. CONCLUSIONS: These results, in the context of prior work showing increased risks of major depression and depressive symptoms following miscarriage, lend some support to the conceptualization of minor depressive disorder as part of a continuum of symptom severity. Miscarrying women should be evaluated for depression at their follow-up medical visits.     

The pattern of cerebral activity underlying verbal fluency shown by split-dose single photon emission tomography (SPET or SPECT) in normal volunteers

Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.     

Antidepressant decision aid for major depressive disorder patients (ADAM): Development and pilot testing

ObjectivesThis study aimed to develop and assess the effectiveness of an encounter decision aid for Malaysian patients with MDD to support treatment decision-making during the consultation.MethodsThe decision aid prototype was developed following a literature review and six focus groups. Alpha testing assessed its comprehensibility, acceptability, usability and desirability through user-centered cognitive interviews. Beta-testing evaluated preliminary evidence on its efficacy using the SDM Scale and PDMS. Feasibility was assessed by timing the consultation.ResultsThe alpha testing demonstrated that the decision aid was patient-oriented, comprehensible, comprehensive, concise and objective with an appealing design. Beta-testing indicated that PtDA significantly increased patients satisfaction with SDM from patients' [83.32 (13.92) vs 85.76 (13.80); p < 0.05] and physicians' [81.07 (10.09) vs 86.36 (10.10); p < 0.05] perspectives and prepared the patients for decision making from the patients' [PDMS patients: 84.10 (12.69)] and physicians' [PDMS physicians: 83.78 (16.62)] perspectives as well. There was no change in the consultation time between the control and the intervention groups.ConclusionsWe developed an antidepressant PtDA for Malaysian patients with MDD that increases patients’ involvement in shared decision making and enhances their preparedness for decision making.Practice implicationsUsing the PtDA can support collaborative decision-making in routine clinical practice without extending the consultation time.