Serial dexamethasone suppression tests in initial suppressors and nonsuppressors treated with electroconvulsive therapy

Four different methods of quantifying the 1-mg Dexamethasone Suppression Test (DST) were contrasted with serial testing in endogenous depressives receiving electroconvulsive therapy (ECT). Of three continuous measures in 38 patients with pretreatment DSTs, only the log-transformed value for plasma cortisol was normally distributed, indicating that it possessed superior psychometric properties. Pretreatment Hamilton Depression Rating Scores (HAM-D) correlated positively with pretreatment DST status, with a similar association noted between posttreatment DST status and HAM-D scores. There was no uniform effect of ECT on the DST. Although pretreatment nonsuppressors showed a trend toward decreased postdexamethasone cortisol values, initial suppressors (cutoff: 5 micrograms/dl) evidenced a significant increase in these values, and 35.3% of initial suppressors were nonsuppressors at final DST assessment. These trends were noted in the DST assessment done following the third ECT treatment, suggesting an effect of regression to the mean. The findings highlight the importance of following initial DST suppressors in studies of this type.     

Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats.

Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.     

Inflammatory response after acute ischemic stroke

BACKGROUND AND PURPOSE: This study aimed to characterize the time course of inflammatory parameters after acute ischemic stroke. METHODS: We serially determined high sensitivity C-reactive protein (CRP), fibrinogen, and leukocyte counts at 10 time points between days 1 and 90 after ischemic stroke and in control subjects. RESULTS: CRP did not significantly change, whereas fibrinogen increased after stroke. At all time points, CRP and fibrinogen were higher than in healthy control subjects, but not risk factor control subjects. The leukocyte count declined after stroke and was significantly elevated as compared to both control groups only on day 1 but not later. NIHSS levels were positively correlated with CRP and fibrinogen at all time points. Larger infarcts were associated with a higher CRP and leukocyte counts on day 90. Treatment with aspirin was associated with lower values for all three inflammatory parameters in the subacute phase after ischemia. CONCLUSIONS: The course after stroke was different between the parameters of inflammation. Only the leukocytes followed the paradigm of an acute phase response.     

Symptomatic predictors of ECT response in medication-nonresponsive manic patients.

BACKGROUND: Relations between pretreatment symptom ratings and ECT outcome were examined in acute manic patients admitted at a state psychiatric center who were nonresponsive to medication. METHOD: One or 2 days after undergoing pretreatment clinical ratings, patients were randomly assigned to intensive pharmacotherapy, right unilateral ECT, left unilateral ECT, or bilateral ECT. Patients who failed to respond to any of the first three treatment conditions were assigned to crossover bilateral ECT. Patients who failed to respond to a primary treatment condition other than bilateral ECT but refused crossover bilateral ECT and those in whom ECT was terminated due to an organic brain syndrome were not considered for this study. No psychotropic drugs were prescribed for 4-7 days before, or during, the course of ECT. Of the 24 patients who entered the study, 18 patients completed the protocol. Based on independent clinical assessments by two research psychiatrists, a favorable treatment response was defined as a complete recovery from manic episode that was sustained for 1 week during which no psychotropic medications were prescribed. RESULTS: ECT nonresponders were significantly more angry, irritable, and suspicious than ECT responders. Severity of mania and depression ratings at baseline were not related to ECT response. CONCLUSION: Symptoms associated with poor response to ECT may overlap with those that have been reported to predict nonresponse to treatment with lithium. Our evidence also may support the view that differential symptom patterns may predict treatment outcomes to ECT and carbamazepine, respectively, in manic patients who do not respond to treatment with lithium or neuroleptics.     

Cocaine treatment increases expression of a 40 kDa catecholamine-regulated protein in discrete brain regions

Previous reports from our laboratory have described brain-specific catecholamine-regulated proteins, which bind dopamine and related catecholamines. Evidence from the molecular cloning of a 40 kDa catecholamine-regulated protein (CRP40) revealed that CRP40 is dopamine-inducible and has properties similar to those of the 70 kDa heat shock protein (HSP70) family. The present study investigates the effects of acute and chronic cocaine treatment on CRP40 expression in the striatum, nucleus accumbens, prefrontal cortex, and medulla. Acute treatment with cocaine increased CRP40 expression in the nucleus accumbens and striatum, whereas chronic treatment with cocaine increased CRP40 expression in the nucleus accumbens only. Neither of these treatments affected CRP40 levels in the prefrontal cortex or medulla. In addition, pretreatment with the spin-trapping agent alpha-phenyl-tert-butylnitrone did not attenuate cocaine-induced expression of CRP40, suggesting that the observed increases in CRP40 levels were not caused by free radicals. On the other hand, pretreatment with anisomycin, a protein synthesis inhibitor, blocked the cocaine-induced expression of CRP40. Thus, protein synthesis may be involved in the observed CRP40 level increases. Furthermore, neither acute nor chronic cocaine treatment affected levels of inducible or constitutively expressed HSP70, which indicates a specificity of cocaine's effects on CRP40. Since cocaine has been shown to increase extracellular dopamine levels, these findings suggest that increased expression of CRP40 is associated with high extracellular levels of dopamine (or its metabolites). Elevated levels of CRP40 could play a protective role for dopamine neurons in response to increased oxidative stress that has been shown to be induced by cocaine and that can lead to apoptosis and neurodegeneration.     

The sham ECT literature: implications for consent to ECT

The author reviewed the placebo-controlled literature on electroconvulsive therapy (ECT) for depression. No study demonstrated a significant difference between real and placebo (sham) ECT at 1 month posttreatment. Many studies failed to find a difference between real and sham ECT even during the period of treatment. Claims in textbooks and review articles that ECT is effective are not consistent with the published data. A large, properly designed study of real versus sham ECT should be undertaken. In the absence of such a study, consent forms for ECT should include statements that there is no controlled evidence demonstrating any benefit from ECT at 1 month posttreatment. Consent forms should also state that real ECT is only marginally more effective than placebo.     

Pretreatment neurophysiologic function and ECT response in depression

OBJECTIVES: Recent brain imaging studies have provided evidence that brain function assessed prior to treatment of depression may be associated with eventual treatment response. The present study tested the hypothesis that brain activity in midline apical quantitative EEG (QEEG) electrodes would be associated with therapeutic response to electroconvulsive therapy (ECT). METHODS: Ten treatment-refractory patients with unipolar or bipolar depression received a Hamilton Rating Scale for Depression (Ham-D) at baseline, during, and following ECT treatment. Resting, eyes-closed, 35-lead QEEG recordings were done 1 day before the initial ECT treatment. Data were analyzed using QEEG power and cordance. RESULTS: The mean of the theta-band pretreatment cordance from the central brain region was strongly associated with percentage decrease in Ham-D score over the course of treatment (r = 0.80, P = 0.005). QEEG cordance from other brain regions and power from all brain regions did not show an association with clinical improvement. CONCLUSIONS: Depressed subjects with higher pretreatment central cordance appear to be more likely to experience therapeutic benefits of ECT. The location of central electrodes over the cingulate cortex may indicate that pretreatment cingulate activity is associated with response to ECT.     

Simultaneous pattern of rCBF and rCMRGlu in continuation ECT: case reports

This report presents the simultaneous pattern of cerebral blood flow and cerebral glucose metabolism in two patients with a major depressive disorder who were undergoing continuation ECT. The regional cerebral blood flow and regional cerebral metabolic rate of these patients were imaged using double isotope 18F-FDG and 99mTc-HMPAO single-photon emission computed tomography before acute ECT and after the completion of continuation ECT; bilateral electrode placement (11 and 12 sessions, respectively) was chosen for the acute treatment course whereas unilateral placement was the method chosen during the continuation phase (6 and 7 sessions, respectively). Baseline SPECT scans of our patients, who continued to receive treatment with medication, were normal as compared with controls; however, scans at the end of continuation ECT revealed decreased uptake activities of both isotopes in prefrontal regions on both sides, which might be associated with the therapeutic impact and efficacy. These results are consistent with previous brain imaging studies of acute ECT. Furthermore, marked changes in both basal ganglia regions were found. The pattern of the isotope uptake ratios did not show any similarities to neurodegenerative processes, which might confirm the high safety profile of ECT also during the continuation phase of treatment.     

Relationship of self-effecacy to cholesterol lowering and dietary change in hyperlipidemia

This study examined whether self-efficacy was associated with lipid lowering and dietary change among men undergoing dietary counseling to lower cholesterol levels. Twenty-five hyperlipidemic men (total cholesterol ≧220 mg/dL) participated in four weeks of dietary instruction. Plasma lipids were measured prior to treatment, at posttreatment, and at three- and twelvemonth follow-up. Dietary intake and self-efficacy as measured by the revised Eating Self-Efficacy Scale (ESES-R) were assessed at pretreatment, posttreatment, and three-month follow-up. Pre-treatment to posttreatment increases in self-efficacy in situations characterized by negative affect were related to extent of lipid lowering and dietary change. Although subjects showed significant reductions in cholesterol levels following treatment, by one year, lipid levels had returned to pretreatment values. Factors related to long-term maintenance of dietary change and lipid lowering among hyperlipidemics merit further research.     

Evaluation of intrathecal serum amyloid P (SAP) and C-reactive protein (CRP) synthesis in Alzheimer's disease with the use of index values

Serum amyloid P (SAP) and C-reactive protein (CRP) are proteins involved in innate immunity. The expression of SAP and CRP is increased in Alzheimer's disease (AD) brain tissue, compared to healthy controls. Although both proteins are found in cerebrospinal fluid (CSF), their origin is unclear. We investigated if increased local production of SAP and CRP in AD brain results in higher levels in CSF with the use of index values. To study this, SAP, CRP, and albumin levels were determined in CSF and serum samples of 30 control (65 ± 11 years; 57% female) and 140 AD subjects (65 ± 9 years; 53% female). To correct for inter-individual differences in protein diffusion from blood to CSF, quotients (Q =CSF/serum) of SAP, CRP, and albumin and index values (Qprotein/Qalb) were calculated. The results showed no significant differences in SAP and CRP index values between control and AD subjects, although eight percent of individual AD patients showed evidence of intrathecal SAP or CRP production using the Reiber hyperbolic model. Interestingly, the SAP index value was much lower than expected, based on its molecular size. In conclusion, these data suggest that local production of SAP and CRP in the AD brain does not substantially contribute to the CSF levels.     

An efficacy study of single- versus double-seizure induction with ECT in major depression

Twenty-nine patients with major depression, with and without psychosis, were randomly assigned to bilateral conventional electroconvulsive therapy (ECT) or modified multiple monitored ECT (MMECT) limited to two seizure inductions in a session. From pretreatment to after the fourth treatment session, modified MMECT was associated with more rapid amelioration of depressive symptoms on the basis of blindly rated Hamilton Rating Scale for Depression scores. No medical complications occurred. Sixty-two percent of patients in the modified MMECT group had posttreatment confusion, whereas 15% of patients treated with conventional ECT were confused. Modified MMECT appears to confer some clinical advantage over conventional ECT in the treatment of major depression while carrying an increased risk of treatment-related reversible confusion.     

Intravascular microaggregation and in vitro platelet aggregation in coronary artery disease

The amount and protein composition of heparin precipitable fraction (HPF), and the plasma concentrations of fibrinogen, fibronectin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, haptoglobin and C-reactive protein (CRP) were determined in healthy subjects as well as during the course of acute myocardial infarction (AMI). In all samples tested, HPF consisted nearly exclusively of fibrinogen and fibronectin. In the small precipitates from healthy subjects, approximately equal amounts of these two proteins were recovered. During the first days of AMI, plasma fibrinogen increased 2-3 fold. At the same time, however, the amount of HPF increased 5-10 fold. This increase was associated with increased precipitation of fibrinogen, whereas no simultaneous increase in fibronectin was found. In fact, a slight drop in plasma as well as HPF-fibronectin was regularly observed during this period. During the following week HPF returned to normal values, whereas the plasma fibrinogen remained elevated. No satisfactory explanation for this discrepancy can be offered at present. Thus, no evidence could be provided that other acute phase proteins than fibrinogen itself were involved. Some experiments, however, indicated qualitative changes in the fibrinogen participating in the HPF precipitation. Further studies are necessary to clarify this point. Such studies are in progress.     

Continuation electroconvulsive therapy for relapse prevention in middle-aged and elderly patients with intractable catatonic schizophrenia

The authors have previously studied the short-term effect of the first acute electroconvulsive therapy (ECT) course (phase 1 study) on intractable catatonic schizophrenia and the 1-year relapse rate after response to the acute ECT (phase 2 study) in middle-aged and elderly patients. Results indicated that, although acute ECT has an excellent short-term effect, the 1-year relapse rate after response to acute ECT is high despite the use of continuation neuroleptics. In the present prospective study the effect was explored of continuation ECT with neuroleptics on the prevention of relapse after response to a second acute ECT course in the relapsed participants of the phase 2 study. The present study included seven consecutive patients > 45 years of age with catatonic schizophrenia (Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) who relapsed (despite the use of neuroleptics) within 1 year after response to the first acute ECT course, and then responded to the second acute ECT course. The patients were given continuation ECT combined with neuroleptics; four ECT sessions at weekly intervals, then four ECT sessions every 2 weeks, then three ECT sessions every 4 weeks. Clinical symptoms were evaluated by means of the Brief Psychiatric Rating Scale (BPRS) weekly for 48 weeks or until relapse. Relapse was defined as a BPRS score of at least 37 for 3 consecutive days. Three out of the seven patients (42.9%) had a sustained response to ECT during the 1-year follow-up period. In the seven patients the probability of relapse within 1 year under treatment with neuroleptics alone (phase 2 study) was statistically higher than that under continuation ECT combined with neuroleptics (present study). No statistical differences were seen between the phase 2 study and the present study in the severity of psychiatric symptoms, global social function, the number of acute ECT sessions or the dosage of neuroleptics. No patient experienced a severe cognitive or physical adverse effect resulting from continuation ECT. Continuation ECT with neuroleptics is an efficacious and safe treatment for maintaining a response in middle-aged and elderly patients with intractable catatonic schizophrenia who have relapsed after a positive response to acute ECT despite the use of continuation neuroleptics.     

Unmodified Electroconvulsive Therapy of Acute Mania: A Retrospective Naturalistic Study

In this retrospective naturalistic study, clinical records were reviewed to examine the effects of unmodified electroconvulsive therapy (ECT) in 30 manic patients at a psychiatric institute in India. Twenty of the patients were experiencing their first episode of a major mood disorder. ECT was associated with complete remission of mania in 26 (87%) of the patients. The remaining four patients were discharged home with residual hypomanic symptoms. On average, the patients received 5.4 treatments, and the duration from initiation of ECT to discharge from hospital was 12.9 days. The number of treatments was not related to age, age at onset, duration of index episode prior to treatment, or presence of psychosis. No patient developed an organic brain syndrome or sustained a bone fracture during unmodified ECT. One month follow-up data were available in 27 of the 30 patients. Recurrence of manic symptoms following discharge occurred in three (11%) patients. For those in whom 3 month follow-up data were available, all 15 were in complete clinical remission. The induced convulsion, and not repeated administration of general anesthetics, is integral to the antimanic effect of ECT.     

Serial dexamethasone suppression tests and plasma dexamethasone levels. Effects of clinical response to electroconvulsive therapy in major depression

Serial 1-mg dexamethasone suppression tests with concurrent plasma dexamethasone assessments were conducted in 58 patients with endogenous depression treated with electroconvulsive therapy (ECT). Plasma cortisol levels decreased significantly from pretreatment to immediately posttreatment, and they declined further during the first week after the ECT course, when patients remained drug free. Plasma dexamethasone levels showed an opposite pattern of progressive increases over these three time points. The progressive changes in plasma dexamethasone and cortisol levels seen during the week after ECT indicate that alterations in the bioavailability of dexamethasone and in hypothalamic-pituitary-adrenal axis function may be incomplete immediately after the ECT course. This may partly account for previous inconsistencies in serial dexamethasone suppression test findings with this treatment modality. The major finding was that clinical response was associated with increased plasma dexamethasone levels, whereas changes in cortisol levels were independent of clinical outcome. With ECT, changes in plasma dexamethasone levels may be more related to changes in clinical state than changes in postdexamethasone cortisol levels. The extent to which clinical recovery with other treatments in depression is associated with altered bioavailability of dexamethasone and perhaps other compounds is unknown and in need of investigation.     

Immune responses to myelin antigens in Guillain-Barré syndrome

Antibodies to nerve antigens were sought in the sera of 17 patients with acute Guillain-Barré syndrome (GBS), 11 with chronic relapsing demyelinating poly-radiculoneuropathy (CRP), 20 with other neuropathies (ON), 15 with other neurological diseases (OND) and 19 normal subjects. Complement-fixing antibodies to a suspension of human peripheral nerve tissue were identified in only 2 patients with GBS and 1 with chronic progressive neuropathy. Five GBS sera gave complement fixation reactions with rabbit sciatic nerve. The sera were also tested for galactocerebroside (Gal-C) binding activity using a solid phase assay. The range of values in all groups was the same, although the mean values for patients with GBS, ON and OND were higher than those of normal subjects. In a radioimmunoassay for antibodies to bovine P2 slightly more radiolabelled antigen was precipitated by the GBS group of sera than by sera from the other groups, but only one serum from the GBS and another from the CRP patients precipitated more than 10% of the label. Addition of bovine P2 to cultures of peripheral blood mononuclear cells from 11 patients with GBS did not cause significant stimulation. Immunoassay for antibody to myelin basic protein (MBP) showed an increased proportion of sera with low binding activity in the GBS and CRP groups. The results suggest that humoral immune responses to potentially neuritogenic antigens are found with marginally increased frequency in patients with GBS and CRP.     

Polymorphisms of the macrophage inhibitory factor and C-reactive protein genes in subjects with Alzheimer's dementia

Neuroinflammation is a central feature of Alzheimer's disease (AD). C-reactive protein (CRP) is a key molecule of the acute phase of inflammation that has been localized in the two characteristic lesions of AD brain, senile plaque and neurofibrillary tangles. On the other hand, the macrophage migration inhibitory factor (MIF) is a cytokine with multiple biological activities, including the ability to act as potent amyloid beta (A-beta)-binding protein. Two common polymorphisms have been recently detected in the genes encoding for CRP and MIF and have been associated with significant modifications of plasma levels and activity of the corresponding proteins. Following these observations, we hypothesized that CRP and MIF gene polymorphisms might contribute to the development and progression of neurodegenerative disorders and evaluated their association with AD. CRP and MIF gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis in 116 Italian subjects affected by probable AD and 184 age- and sex-matched controls. We did not find a statistically significant difference in the distribution of CRP and MIF genotypes and alleles between AD subjects and controls. Although these data need further confirmation, they indicate that CRP and MIF gene polymorphisms are not associated with AD.     

Summary of the practice parameter for the use of electroconvulsive therapy with adolescents

Electroconvulsive therapy (ECT) may be an effective treatment for adolescents with severe mood disorders and other Axis I psychiatric disorders when more conservative treatments have been unsuccessful. ECT may be considered when there is a lack of response to two or more trials of pharmacotherapy or when the severity of symptoms precludes waiting for a response to pharmacological treatment. The literature on ECT in adolescents, including studies and case reports, was reviewed and then integrated into clinically relevant guidelines for practitioners. Mood disorders have a high rate of response to ECT (75-100%), whereas psychotic disorders have a lower response rate (50-60%). Consent of the adolescent's legal guardian is mandatory, and the patient's consent or assent should be obtained. State legal guidelines and institutional guidelines must be followed. ECT techniques associated with the fewest adverse effects and greatest efficacy should be used. The presence of comorbid psychiatric disorder is not a contraindication. Systematic pretreatment and posttreatment evaluation, including symptom and cognitive assessment, is recommended.     

Double-blind randomized controlled study comparing short-term efficacy of bifrontal and bitemporal electroconvulsive therapy in acute mania

Background:  Bifrontal electrode placement is as efficacious as bitemporal placement during electroconvulsive therapy (ECT) in depression but is associated with fewer cognitive adverse effects. There are no studies comparing these techniques in acute mania. This study compared the short-term efficacy and adverse effects of bifrontal and bitemporal ECT in the treatment of acute mania.
Method:  Thirty-six DSM-IV mania inpatients referred for ECT were recruited for study. They were randomized to receive bifrontal (BFECT; n = 17) or bitemporal (BTECT; n = 19) ECT. None of the subjects were on mood stabilizers during the course of ECT. Severity of mania was measured on the Young Mania Rating Scale (YMRS) before beginning ECT and then on Days 3, 7, 11, 14, and 21 of treatment. Cognitive functions were assessed eight hours after the fifth ECT session using the Mini-Mental Status Examination (MMSE), Paired Associate Learning Test, Complex Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail Making Test, Part A.
Results:  The subjects in the two groups were comparable on sociodemographic and clinical variables, including severity of mania at baseline. They were also similar in ECT parameters, including seizure threshold and seizure duration. Mean YMRS scores showed faster decline in the BFECT than in the BTECT group. Kaplan–Meier survival analysis showed that a greater proportion of subjects in the BFECT group responded (50% reduction in YMRS score) significantly earlier than in the BTECT group. There were no significant differences between the groups in performance on cognitive function tests.
Conclusion:  In this pilot study, mania patients treated with BFECT responded faster than those treated with BTECT, with comparable cognitive adverse effects. Since ECT is usually prescribed for rapid control of symptoms, BFECT may be preferred over BTECT in the treatment of acute mania.