Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients.

BACKGROUND: We studied the relationship between regional cerebral metabolism and the severity of anxiety in mood disorder patients, controlling for depression severity. METHODS: Fifty-two medication-free patients with unipolar or bipolar illness underwent positron emission tomography with [(18)F]-fluorodeoxyglucose. Hamilton Depression Rating Scale and Spielberger Anxiety-State Scale scores were obtained for the week of the scan. Analyses were performed on globally normalized images and were corrected for multiple comparisons. RESULTS: After covarying for depression scores, age, and gender, Spielberger Anxiety-State Scale scores correlated directly with regional cerebral metabolism in the right parahippocampal and left anterior cingulate regions, and inversely with metabolism in the cerebellum, left fusiform, left superior temporal, left angular gyrus, and left insula. In contrast, covarying for anxiety scores, age, and gender, Hamilton Depression Rating Scale scores correlated directly with regional cerebral metabolism in the bilateral medial frontal, right anterior cingulate, and right dorsolateral prefrontal cortices. CONCLUSIONS: Comorbid anxiety symptoms are associated with specific cerebral metabolic correlates that partially overlap with those in the primary anxiety disorders and differ from those associated with depression severity.     

Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy

BACKGROUND: Functional imaging studies of major depressive disorder demonstrate response-specific regional changes following various modes of antidepressant treatment. OBJECTIVE: To examine changes associated with cognitive behavior therapy (CBT). METHODS: Brain changes underlying response to CBT were examined using resting-state fluorine-18-labeled deoxyglucose positron emission tomography. Seventeen unmedicated, unipolar depressed outpatients (mean +/- SD age, 41 +/- 9 years; mean +/- SD initial 17-item Hamilton Depression Rating Scale score, 20 +/- 3) were scanned before and after a 15- to 20-session course of outpatient CBT. Whole-brain, voxel-based methods were used to assess response-specific CBT effects. A post hoc comparison to an independent group of 13 paroxetine-treated responders was also performed to interpret the specificity of identified CBT effects. RESULTS: A full course of CBT resulted in significant clinical improvement in the 14 study completers (mean +/- SD posttreatment Hamilton Depression Rating Scale score of 6.7 +/- 4). Treatment response was associated with significant metabolic changes: increases in hippocampus and dorsal cingulate (Brodmann area [BA] 24) and decreases in dorsal (BA 9/46), ventral (BA 47/11), and medial (BA 9/10/11) frontal cortex. This pattern is distinct from that seen with paroxetine-facilitated clinical recovery where prefrontal increases and hippocampal and subgenual cingulate decreases were seen. CONCLUSIONS: Like other antidepressant treatments, CBT seems to affect clinical recovery by modulating the functioning of specific sites in limbic and cortical regions. Unique directional changes in frontal cortex, cingulate, and hippocampus with CBT relative to paroxetine may reflect modality-specific effects with implications for understanding mechanisms underlying different treatment strategies.     

Antipsychotic effect of electroconvulsive therapy is related to normalization of subgenual cingulate theta activity in psychotic depression

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most effective options available for treating depressive and psychotic symptoms in a variety of disorders. While the exact mechanism of ECT is unclear, it is known to increase metabolism and blood flow specifically in the anterior cingulate cortex (ACC). The ACC is a cortical generator of theta rhythms, which are abnormal in patients with depression and psychotic disorders. Since patients with psychotic depression are known to respond particularly robustly to ECT, we investigated whether the therapeutic effect of ECT in this population was related to normalization of abnormal theta activity in the ACC. METHOD: We obtained 19-lead electroencephalography (EEG) data from 17 participants with psychotic depression before and 2-3 weeks after a full course of ECT. EEG data was analyzed with quantitative measures and low-resolution electromagnetic tomography (LORETA) compared to an age-adjusted normative database. RESULTS: Quantitative EEG analyses revealed that theta band (4-7 Hz) activity was the only frequency band that changed with ECT. LORETA analyses revealed that the primary site of theta activity change was within the subgenual ACC (Brodmann area 25). There was a positive association between increased subgenual ACC theta activity and decreased psychotic symptoms. The degree of low theta activity in the subgenual ACC prior to ECT predicted the antipsychotic response of ECT. CONCLUSIONS: The antipsychotic effect of ECT is related to normalization of subgenual ACC theta hypoactivity.     

Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with (99m)Tc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.     

Effect of sleep deprivation on brain metabolism of depressed patients.

OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with [18F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression.     

Cerebral perfusion is related to antidepressant effect and cognitive side effects of Electroconvulsive Therapy

BackgroundThe mechanisms underlying the antidepressant effect and cognitive side effects of Electroconvulsive Therapy (ECT) remain elusive. The measurement of cerebral perfusion provides an insight into brain physiology.ObjectiveWe investigated ECT-related perfusion changes in depressed patients and tested whether these changes correlate with clinical effects.MethodsA sample of 22 in-patients was examined at three time points: 1) within two days before, 2) within one week after, and 3) six months after an ECT series. Cerebral perfusion was quantified using arterial spin labeling magnetic resonance imaging. The primary regions of interest were the bilateral dorsolateral prefrontal cortices (DL-PFC) and hippocampi. The depression severity was assessed by the six-item Hamilton Depression Rating Scale, and cognitive performance by the Screen for Cognitive Impairment in Psychiatry. A linear mixed model and partial correlation were used for statistical analyses.ResultsFollowing an ECT series, perfusion decreased in the right (?6.0%, p = .01) and left DL-PFC (?5.6%, p = .001). Perfusion increased in the left hippocampus (4.8%, p = .03), while on the right side the increase was insignificant (2.3%, p = .23). A larger perfusion reduction in the right DL-PFC correlated with a better antidepressant effect, and a larger perfusion increase in the right hippocampus with worse cognitive impairment.ConclusionECT-induced attenuation of prefrontal activity may be related to clinical improvement, whereas a hippocampal process triggered by the treatment is likely associated with cognitive side effects.     

The effects of ECT on brain glucose: a pilot FDG PET study

BACKGROUND: Regional brain activity was measured before and after electroconvulsive therapy (ECT) using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS: 6 patients (4 females) with major depression were free of psychotropic medications for at least 2 weeks prior to baseline FDG scans. Patients were treated with bifrontotemporal ECT, and posttreatment scans were obtained after the last treatment. RESULTS: A region of interest (ROI) analysis of absolute metabolic rate showed a decrease in CMRglu after ECT in all 61 regions examined. In 17 of the 61 regions, the decrease was significant at the p < 0.05 level. In the right parietal lobe, and the right anterior and left posterior frontal lobes, the decrease in CMRglu significantly correlated with the decrease in Hamilton Depression Rating Scale (HDRS) scores (r = 0.83, 0.82, and 0.84, respectively). The analysis of CMRglu normalized to global metabolic rate showed significant increases in 8 of 61 regions, including basal ganglia, upper brainstem, and occipital lobe. DISCUSSION: The decreases in global glucose metabolism and correlation of changes in frontal metabolism with decreases in HDRS are consistent with earlier brain imaging studies of ECT. The relative increases in CMRglu observed in regions with known dopaminergic innervation (caudate and upper brainstem) have not been previously reported.     

Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression.

OBJECTIVE: The treatment of geriatric depression is complicated by a variable and delayed response to antidepressant treatment. The present study was undertaken to test the hypothesis that combined total sleep deprivation and paroxetine treatment would produce a persistent reduction in glucose metabolism in the anterior cingulate cortex similar to that reported after long-term antidepressant treatment. METHOD: Six elderly depressed patients who met the DSM-IV criteria for major depressive disorder and six age-matched comparison subjects underwent serial positron emission tomography (PET) studies at baseline, after total sleep deprivation, after recovery sleep (after the initial paroxetine dose), and after 2 weeks of paroxetine treatment (patients only). The PET data were analyzed by using statistical parametric mapping methods. RESULTS: The patients' scores on a 13-item version of the Hamilton Depression Rating Scale were decreased after total sleep deprivation, after recovery sleep, and after 2 weeks of treatment. The Hamilton depression scores of the comparison subjects were not significantly altered. In the patients, the greatest reductions in normalized, relative glucose metabolism after sleep deprivation were observed in the anterior cingulate cortex (Brodmann area 24), and they persisted after recovery sleep and antidepressant treatment. The comparison subjects demonstrated increased metabolism in these areas. CONCLUSIONS: Improvement in the patients' depressive symptoms was accompanied by reduced glucose metabolism in the right anterior cingulate cortex and right medial frontal cortex. These preliminary data indicate that in elderly depressed patients, total sleep deprivation may accelerate the clinical and glucose metabolic response to antidepressant treatment.     

Neuroanatomical correlates of therapeutic efficacy of low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Aims: Low‐frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment‐resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low‐frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment‐resistant depression. Methods: Twenty‐six patients with treatment‐resistant depression received five 60‐s 1‐Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with ^99mTc‐ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS). Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion: The antidepressant effects of LFRS in treatment‐resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.     

The impact of medical comorbidity on acute treatment in major depressive disorder

OBJECTIVE: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (>/=50% reduction in score) and clinical remission (score 相似文献   

Changes in regional cerebral blood flow with venlafaxine in the treatment of major depression

OBJECTIVE: Neuroimaging studies reveal abnormalities of regional cerebral blood flow (rCBF) in major depression. In this study the authors prospectively investigated rCBF and clinical response to venlafaxine, a novel antidepressant. METHOD: A trial of venlafaxine was performed with seven patients referred with ICD-10 major depression. At entry and 6-week follow-up, the Beck Depression Inventory and Hamilton Depression Rating Scale were administered and rCBF was measured by means of single photon emission computed tomography with [(99m)Tc]hexamethylpropyleneamine oxime. Blood flow changes were explored with statistical parametric mapping. RESULTS: The subjects showed significant improvement after treatment. Statistical parametric mapping analysis revealed increased rCBF bilaterally in the thalamus and decreased rCBF in the left occipital lobe, right cerebellum, and temporal cortex bilaterally. CONCLUSIONS: These data confirm limbic cortical rCBF changes associated with effective antidepressant treatment.     

Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study.

BACKGROUND: Previous studies have shown that major depression is frequently accompanied by hypercortisolemia. There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia, hypoglycemia, or excitatory neurotransmitters. Using magnetic resonance imaging (MRI), the hippocampi of patients with major depression were measured and compared with values observed in control subjects. METHODS: Thirty-eight patients with primary unipolar major depression were recruited. Twenty control subjects were matched for age, gender, and years of education. The hippocampal volume was measured from coronal MRI scans in all of the subjects. Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day, for 8 weeks. Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depression. RESULTS: No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects; however, a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values. In addition, female responders had a statistically significant higher mean right hippocampal volume than nonresponders. CONCLUSIONS: The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression. Nonetheless, the results do suggest that the effects of disease severity, gender, and treatment response may influence hippocampal volume.     

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study

OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.     

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.     

Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression

Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy.Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist.Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials.     

Nicardipine improves the antidepressant action of ECT but does not improve cognition

INTRODUCTION: Cognitive impairment, the most important adverse effect of electroconvulsive therapy (ECT), may involve elevated intracellular calcium ion signaling. Animal research suggests that calcium channel-blocking agents, which attenuate excessive intracellular calcium activity, may reduce cognitive dysfunction caused by ECT. METHOD: The lipid-soluble calcium channel-blocking drug nicardipine or matching placebo were randomly assigned to 26 patients with major depressive disorder receiving ECT. A rater blind to the experimental condition administered the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Beck Depression Inventory, the Mini-Mental State Examination and a comprehensive battery of neuropsychological tests prior to ECT, at the completion of ECT, and 6 months after ECT completion. RESULTS: Compared with patients receiving placebo, patients taking nicardipine had significantly lower scores on the Hamilton and Montgomery-Asberg but not the Beck Depression rating scale scores at the completion of ECT. There were no differences between placebo and nicardipine groups in depression scores 6 months after ECT. Cognitive function declined over the course of ECT and improved over the next 6 months in both groups, but changes were statistically significant for only two subtests on the neuropsychological battery. Changes in Mini-Mental State Examination scores were small and were not significant at any point. There were no significant differences between nicardipine and placebo treated groups in any assessment of cognition. DISCUSSION: Standard approaches to ECT in younger patients without preexisting neurological impairment do not produce cognitive side effects of sufficient severity for calcium channel-blocking agents to reduce these side effects demonstrably. Studies of treatments for cognitive impairment should be conducted in patients with risk factors for more severe cognitive impairment such as geriatric patients or patients with a history of interictal delirium during previous treatment with ECT. A possible effect of nicardipine in enhancing the antidepressant action of ECT requires further investigation in a study designed to test this action.     

Neural correlates of memory in depression measured by brain perfusion SPECT at rest

Aim:  Brain metabolism activated studies have indicated associations between memory and the anterior cingulate cortex and hippocampus in patients with depression. The aim of the present study was therefore to investigate memory function, measured as performance on the Wechsler Memory Scale–Revised (WMS-R), and its relationship to brain perfusion using single-photon emission computed tomography (SPECT) at rest in patients with depression.
Methods:  The Hamilton Rating Scale for Depression (HAMD) and WMS-R were measured for 17 patients with depression by an independent clinical evaluation team. Voxel-based correlation analyses were performed with statistical parametric mapping at an extent threshold of 200 voxels. Associations were controlled for state and trait factors.
Results:  WMS-R measurements of verbal, visual, and general memory were inversely correlated with brain perfusion in the right anterior cingulate cortex, left premotor cortices, and both regions, respectively. The HAMD directly correlated with brain perfusion in the right anterior cingulate cortex.
Conclusion:  Brain perfusion SPECT measurements of the anterior cingulate cortex at rest were associated with the severity of depression and immediate memory scores measured with the WMS-R.     

A controlled trial of daily left prefrontal cortex TMS for treating depression.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain. Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham. METHODS: Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects were equally divided between slower (5 Hz) and faster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD. RESULTS: Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi(2) = 6.42, p <.01). The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham. CONCLUSIONS: Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham. The two forms of active TMS treatment did not differ significantly.     

Improvement in depressive illness is not associated with altered release of neurophysins over a course of ECT

The hypothesis that the release of vasopressin-associated neurophysin (hNpI) or oxytocin-associated neurophysin (hNpII) is modified by a course of electroconvulsive therapy (ECT) was tested by the measurement of serum neurophysins before and after the first and last ECTs given to 17 unipolar depressed patients. Neither basal nor ECT-induced neurophysin release changed between the first and last ECTs. Data from the present study were combined with data from a previous published study to provide a sample of 29 unipolar depressed patients. In this extended sample, the release of hNpII after the first ECT was significantly correlated with improvement in symptoms of depression over a course of ECT as measured by the Hamilton Rating Scale for Depression and the Montgomery-Asberg Depression Rating Scale.