Diurnal mood variation in major depressive disorder.

Depression disturbs mood, but a clear picture of diurnal mood rhythms in depression has yet to emerge. This study examined variations in positive affect (PA) and negative affect (NA), two dimensions of mood that generate diurnal patterns among healthy individuals. Repeated measurements of NA and PA in daily life were obtained over 6 days from 47 depressed outpatients and 39 healthy individuals using the Experience Sampling Method. Relative to healthy individuals, depressed individuals exhibited increasing PA levels during the day with a later acrophase. In contrast, depressed persons' NA exhibited a more pronounced diurnal rhythm and was more variable from moment to moment than healthy individuals'. Ambulatory mood measurements in depression suggest distinct diurnal disturbances of positive and negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Breastfeeding and shorter hospital stays

Contingent negative variation (CNV) was examined in 14 epileptic patients (5 with generalized and 9 with partial fits) both before and after 24 hours of sleep deprivation. Background CNV indices differed significantly by higher amplitudes of nearly all CNV components from the ones of healthy individuals. Amplitudes of postimperative negative waves (PINW) and general waves differed most of all. After sleep deprivation there was an PINW increase as well as the tendency to the late CNV component amplitude's increase. Elevation of CNV amplitudes after sleep deprivation was more pronounced in patients in which the deprivation provoked development of epileptic fits in comparison with patients which endured sleep deprivation rather favourably. The changes revealed in CNV components of the patients with epilepsy were considered in terms of disorders in regulatory mechanisms at the level of apical dendrites of cortical neurons' excitation.     

Endothelin: role in hypertension

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.     

Diagnostic differences in social anhedonia: A longitudinal study of schizophrenia and major depressive disorder.

This study examined the hypothesis that, in schizophrenia, elevated trait social anhedonia (SA) is a stable individual difference, whereas in depression, increased SA is a reflection of a current clinical state that will diminish with recovery. Differences in trait Negative Affect (NA) and Positive Affect (PA) were also examined. Individuals with schizophrenia (n?=?55) and depression (n?=?34) were evaluated at baseline during hospitalization and compared with nonpsychiatric control participants (n?=?41). Participants were assessed again at a 1-year follow-up. At baseline, compared with control participants, individuals with schizophrenia and depression were both characterized by elevated SA, greater NA, and lower PA. In schizophrenic individuals, elevated SA remained stable over the follow-up. However, in recovered depressed patients, SA declined over the follow-up period. Group differences remained in NA and PA over the 1-year follow-up. These results support the view that elevated SA is enduring in schizophrenia but that elevated SA is transiently related to clinical status in depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Event-related potentials (P300) in primary headache in childhood and adolescence

There is strong evidence for a loss of habituation during cognitive processing in migraine as measured by P300 and contingent negative variation in adults. Event-related potentials evoked by an oddball paradigm have not yet been studied in children and adolescents suffering from different primary headache types. We recorded visually evoked event-related potentials (two consecutive trials, 200 stimuli each) in 48 children and adolescents suffering from migraine without or with aura, from episodic tension-type headache, and from ergotamine-induced headache and analyzed the latencies, amplitudes, and reaction times. No statistically significant differences were noted between all headache types and healthy controls analyzing the averaged parameters for the whole measurement. However, a highly significant loss of cortical habituation as measured by P300 amplitude and latency could be observed in migraine without and with aura by analyzing the first and the second trial of measurement separately. This phenomenon increased with age and could not be seen in healthy controls, or patients with tension-type headache or ergotamine-induced headache. Our data suggest a specific cognitive processing in migraine even in children and adolescents. Measurement of the habituation effect in P300 latency and amplitude provides a specific method to differentiate between primary headache types in childhood and adolescence.     

Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.     

Complement activation in septic shock due to gram-negative and gram-positive bacteria

Whole serum complement (CH50) and C3, C4, and C3PA plasma values were studied in 48 patients: 9 with nonseptic shock; 20 with sepsis; 14 with septic shock caused by gram-negative bacteria; 5 with septic shock caused by gram-positive bacteria. All were compared with a control group of 25 healthy individuals. Determinations were made upon admission and again 48 and 96 h later. No significant differences in complement values were found between the patients with nonseptic shock and the control group. In the patients with sepsis, decreased CH50 (p less than 0.001) and increased C3PA (p less than 0.02) values were observed, while C3 and C4 remained unaltered. In the patients with septic shock, markedly decreased levels of CH50, C3, and C4 were seen (p less than 0.001, and p less than 0.001, and p less than 0.001, respectively) without changes in C3PA levels. There were no differences between septic shock due to gram-negative and gram-positive bacteria, or between patients who died and those who survived. After 96 h, the altered values returned to the normal range. This underlines the transitory activation of the complement system through the classic pathway and suggests its possible role in the pathogenesis of septic shock in man.     

Interpersonal pathoplasticity in individuals with generalized anxiety disorder.

Recent theories of generalized anxiety disorder (GAD) have emphasized interpersonal and personality functioning as important aspects of the disorder. We examined heterogeneity in interpersonal problems in 2 studies of individuals with GAD (n = 47 and n = 83). Interpersonal subtypes were assessed with the Inventory of Interpersonal Problems–Circumplex (Alden, Wiggins, & Pincus, 1990). Across both studies, individuals with GAD exhibited heterogeneous interpersonal problems, and cluster analyses of these patients' interpersonal characteristics yielded 4 replicable clusters, identified as intrusive, exploitable, cold, and nonassertive subtypes. Consistent with our pathoplasticity hypotheses, clusters did not differ with GAD severity, anxiety severity, or depression severity. Clusters in Study 2 differed on rates of personality disorders, including avoidant personality disorder, further providing support for the validity of interpersonal subtypes. The presence of interpersonal subtypes in GAD may have important implications for treatment planning and efficacy. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Association between HLA and islet cell antibodies in diabetic patients with a mitochondrial DNA mutation at base pair 3243

Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GAD) and HLA genotypes were examined in 31 patients with diabetes and a mitochondrial gene mutation located at base pair 3243 (mtDNA 3243 mutation). ICA was detected in 42% (13/31) of these patients compared to 0 of 90 among healthy control subjects. The ICA showed a "non-restricted" pattern of staining in all 13 ICA-positive patients. In a sensitive radioligand assay only 2 of 31 (6%) diabetic patients with the mutation were positive for both GAD65 autoantibodies and ICA, while the remaining 29 patients were GAD65 antibody negative. The ICA-positive patients had an increased frequency of the HLA-DQA1*0301 allele compared to control subjects (p < 0.05). Of the diabetic patients with the mutation 45% (14/31) had progressive clinical course of beta-cell failure. These results indicate that patients with an mtDNA 3243 mutation may develop islet autoimmunity associated with ICA and GAD autoantibodies. We hypothesize that the presence of HLA-DQA1*0301 in individuals with the mtDNA 3243 mutation increases the risk for diabetes and associated autoantibodies against islet cell antigens.     

Comparison of auditory P300 habituation from active and passive conditions

The P3(00) event-related brain potential (ERP) was elicited using auditory stimuli and tasks in which the subject discriminated between standard and target tones or with passive task conditions in which the subject did not respond to either the standard or target stimuli. All stimulus presentations consisted of a series of ten-tone sequences in which the first six tones were always the standard and one of the last four tones was the target. The passive tasks were presented twice to assess for habituation effects. P3 amplitude was largest for the oddball task compared to the passive tasks, and repetition of the passive paradigm demonstrated a decrease in amplitude between conditions. P3 amplitude did not decrease across trials within any of the separate response conditions. P3 latency was shorter for the active discrimination relative to the passive tasks. The results suggest that the P3 component can be obtained reliably with passive procedures and does not habituate within a trial block. However, repeated blocks of passive stimulus presentations will cause the P3 ERP to diminish in size.     

Dopaminergic and glutamatergic blocking drugs differentially regulate glutamic acid decarboxylase mRNA in mouse brain

Dopaminergic and glutamatergic inputs play an important role in regulating the activity of GABAergic neurons in basal ganglia. To understand more fully the biochemical interactions between these neurotransmitter systems, the effects of blocking dopamine and glutamate (N-methyl-D-aspartate) (NMDA) receptors on the expression of glutamic acid decarboxylase (GAD) mRNA were examined. Persistent blockade of dopamine receptors was achieved by daily injections of EEDQ, a relatively non-selective irreversible D1 and D2 dopamine receptor antagonist, or FNM, a relatively selective irreversible D2 dopamine receptor antagonist. Persistent blockade of NMDA receptors was achieved by continuously infusing dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. The levels of GAD mRNA in mouse brain were measured by in situ hybridization histochemistry following treatment with these agents. Repeated administration of EEDQ increased the levels of GAD mRNA in corpus striatum and frontal and parietal cortex; the first significant effects were seen after 4 days of treatment. Treatment with FNM elicited effects similar to those produced by EEDQ, except FNM also significantly increased GAD mRNA in nucleus accumbens. Neither EEDQ nor FNM produced significant effects on GAD mRNA in olfactory tubercle or septum. Infusion of MK-801 produced a rapid and marked decrease in the levels of GAD mRNA in corpus striatum, nucleus accumbens, olfactory tubercle, septum and frontal and parietal cortex; significant changes were seen as early as 2 days of treatment. No significant effects were seen in globus pallidus. Cellular analysis of emulsion autoradiograms from corpus striatum revealed that MK-801 reduced the amount of GAD mRNA in individual cells as well as the proportion of cells expressing high levels of GAD mRNA. These results suggest that dopamine, though its interaction with D2 dopamine receptors, exerts an inhibitory effect on the expression of GAD mRNA, and that glutamate, though its interaction with NMDA receptors, exerts a stimulatory effect on GAD mRNA expression. They show further that the regulation of gene expression by dopamine receptors or NMDA receptors is different in different regions of the brain.     

Testing the robustness of the dysphoria factor of the Simms et al. (2002) model of posttraumatic stress disorder.

The Simms et al. (2002) four-factor structure of posttraumatic stress disorder (PTSD) has been supported in many factor analytic studies, and the specificity of the dysphoria factor has been questioned because of its strong associations with measures of depression and anxiety. This study addressed this issue by conducting a confirmatory factor analysis while controlling for the symptoms of major depression (MD) and generalized anxiety disorder (GAD). Data from individuals who satisfied Criterion A of the diagnostic criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM–IV) diagnosis of PTSD (n = 12,467) in the 2004–2005 National Epidemiologic Study on Alcohol and Related Conditions (NESARC) were used in the analysis. The results showed that after controlling for MD and GAD, the factor loadings for dysphoria items were significantly attenuated, although they remained relatively high and statistically significant. The present findings contribute to the debate regarding how PTSD should be conceptualized and assessed in future issues of the DSM. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Marital quality moderates genetic and environmental influences on the internalizing spectrum.

Poor marital quality is a reliable correlate of internalizing problems, but the etiology of this association has yet to be examined. Marital distress may exert its influence by acting as a stressor that enables the expression of latent genetic risk for internalizing psychopathology. The authors examined this question using 379 twin pairs, assessed for marital quality, symptoms of major depression (MD), generalized anxiety disorder (GAD), panic attacks (PA), and neuroticism (N). A phenotypic factor analysis confirmed that one factor best accounted for the variance shared between MD, GAD, PA, and N. After accounting for genetic influences on the general Internalizing factor, there were residual genetic influences on N but no specific genetic influences on any other individual internalizing syndrome. The authors found overlap between the genetic influences on marital quality and the internalizing spectrum. Finally, biometrical moderation models revealed that genetic effects on the Internalizing factor increased as the marital quality deteriorated (marital quality high: h2 = 0.05; marital quality low: h2 = 0.29), suggesting that those with a genetic predisposition to internalizing syndromes may be more likely to express this predisposition in the context of a dissatisfying marriage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: implications for sexual differentiation

Sexual differentiation of rodent brain is dependent upon hormonal exposure during a "critical period" beginning in late gestation and ending in early neonatal life. Steroid hormone action at this time results in anatomical and physiological sexual dimorphisms in adult brain, but the mechanism mediating these changes is essentially unknown. The inhibitory neurotransmitter, GABA, is involved in regulation of sexually dimorphic patterns of behavior and gonadotropin secretion in the adult. Recent evidence suggests that during development GABA is excitatory and provides critical neurotrophic and neuromodulatory influences. We hypothesized that steroid-induced changes in GABAergic neurotransmission during this critical period are important mediators of sexual differentiation in brain. Therefore, we quantified levels of mRNA for GAD, the rate-limiting enzyme in GABA synthesis. On Postnatal Day 1, males had significantly higher levels of GAD mRNA in the dorsomedial nucleus, arcuate nucleus, and CA1 region of hippocampus. On Postnatal Day 15, after the critical period for sexual differentiation has ended, these differences were no longer present. We examined the role of gonadal steroids in regulating GAD by removing testes of males and administering testosterone to females at birth. Exposure to testosterone was correlated with increased GAD mRNA in the dorsomedial nucleus. A sex difference in GAD mRNA was also observed in the medial preoptic area, but the influence of testosterone was inconclusive. We conclude that sex differences in the GABAergic system during development are partially hormonally mediated, and that these differences may contribute to the development of sexually dimorphic characteristics in adult brain.     

Selective processing of negative information: Effects of clinical anxiety, concurrent depression, and awareness.

Anxious patients (n?=?20) and normal controls (n?=?20) carried out a modified Stroop color-naming task with anxiety- and depression-related words in supraliminal and subliminal exposure conditions. Within the anxious group, patients with generalized anxiety disorder (GAD) without concurrent depression (n?=?11) showed more color-naming interference for anxiety words than neutral words in comparison with patients with a combined diagnosis of GAD and depression (n?=?9). Compared with controls, the GAD subgroup without concurrent depression showed slower color naming for negative than neutral words, in both supraliminal and subliminal conditions, replicating K. Mogg, B. R. Bradley, R. Williams, and A. Mathews's (1993) results. These findings provide further evidence of an anxiety-related bias for negative information in preconscious processes and highlight the importance of assessing concurrent depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes

Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65). GAD67 antibodies (GAD67Ab) were similarly analyzed but without antigen competition. In 73 Japanese diabetic patients, GAD65Ab were found in 11/16 (69%) of patients with short-duration (less than 5 yrs) IDDM, 6/23 (26%) with long-duration (5 or more yrs) IDDM and 10/20 (50%) with slowly progressive diabetes. High GAD65Ab levels were associated with concomitant autoimmune diseases (p = 0.021). GAD67Ab were found in 4/16 (25%) of patients with short-duration IDDM, 3/23 (13%) with long-duration IDDM and 2/20 (10%) with slowly progressive diabetes. In 14 non-insulin dependent diabetic (NIDDM) patients, GAD65Ab and GAD67Ab were not found (0/14) and 1/50 (2%) healthy controls were positive in either assay. Among the GAD67Ab-positive samples, 8/9 (88%) were also high level GAD65Ab positive, 7/9 (77%) were displaced by an excess of rhGAD65 and the antibody levels correlated (r2 = 0.573; p = 0.003). Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67.     

Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: A dichotic listening study.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevalence of comorbid anxiety disorders in primary care outpatients

OBJECTIVE: To estimate the extent to which anxiety disorders (eg, panic disorder, phobia, and generalized anxiety disorder [GAD]) co-occur in patients with major medical and psychiatric conditions. DESIGN: Observational study. SETTING: Offices of primary care providers in three US cities, with mental health specialty providers included for comparative purposes. PATIENTS: Adult patients (N = 2494) with hypertension, diabetes, heart disease (congestive heart failure or myocardial infarction), current depressive disorder, or subthreshold depression. MEASURES: Current (past 12 months) and lifetime panic disorder, phobia, GAD, perceived need for help for emotional or family problems, and unmet need (ie, failure to get help that was needed). METHODS: Comparisons of the prevalence of anxiety comorbidity in medically ill nondepressed patients of primary care providers and in depressed patients of both primary care and mental health specialty providers. RESULTS: Among primary care patients, those with chronic medical illnesses or subthreshold depression had low rates of lifetime (1.5% to 3.5%) and current (1.0% to 1.7%) panic disorder, but those with current depressive disorder had much higher rates (10.9% lifetime and 9.4% current panic disorder). Concurrent phobia and GAD were more common (10.4% to 12.4% current GAD), especially among depressed patients (25% to 54% current GAD). Depending on the type of medical illness or depression, 14% to 66% of primary care patients had at least one concurrent anxiety disorder. Patient-perceived unmet need for care for personal or emotional problems was high among all primary care patients (54.6% to 72.9%). CONCLUSION: Primary care clinicians should be aware of the possible coexistence of anxiety disorders (especially GAD) among their patients with chronic medical conditions, but especially among those with current depressive disorder.     

Salivary testosterone concentrations in left-handers: An association with cerebral language lateralization.

The level of testosterone exposure in early brain development may influence the direction or degree of cerebral language lateralization. Possible links between individual differences in testosterone levels and patterns of speech representation were investigated in 180 healthy young adults (97 left handed, 83 right handed) using the Fused Dichotic Words Test (T. Halwes, 1991). Among left-handed participants, significantly higher testosterone concentrations were observed in individuals with a left-ear advantage on dichotic listening than in individuals with a right-ear advantage. Among right-handed participants, the pattern of group differences in testosterone tended to be reversed, resulting in a statistically significant interaction. Results extend prior findings by S. D. Moffat and E. Hampson (see record 1996-03260-006) and raise the possibility that higher testosterone is associated with patterns of brain organization in which speech and praxic functions are lateralized to the same hemisphere. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High prevalence of antibodies to glutamic acid decarboxylase in comparison to islet cell antibodies in patients with long-standing insulin-dependent diabetes mellitus

To elucidate the clinical significance of antibodies to glutamic acid decarboxylase (GAD Ab) compared to islet cell antibodies (ICA) in recent-onset and long-standing insulin-dependent diabetes mellitus (IDDM). We examined GAD Ab and ICA in 29 recent-onset and 85 long-standing patients with IDDM. GAD Ab was detected by a radioimmunoassay kit using purified pig brain GAD as an antigen. The prevalence of GAD Ab in the recent-onset diabetic patients was 55.2%, slightly lower than that of ICA (65.5%). In contrast, the prevalence of GAD Ab in long-standing diabetic patients was 42.4%, which was significantly higher than that of ICA (23.5%) (p < 0.01). GAD Ab were consistently detected in approximately 40% of patients with long-standing disease, while ICA decreased according to duration of disease. The GAD Ab titer in ICA-positive patients (mean +/- SD, 1588.2 +/- 6755.1; range, 6-38574) was significantly higher than that in ICA-negative patients (mean +/- SD, 13.4 +/- 17.9; and range, 5-72 units) (p < 0.001). These findings suggest that GAD Ab are more useful than ICA to know participation of immune disorders in long-standing patients with IDDM.