Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression

BACKGROUND: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted. METHODS: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls. FINDINGS: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects. INTERPRETATION: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.     

The interaction between mood and cognitive function studied with PET

BACKGROUND: Experimentally induced depressed mood is a suggested model for retarded depression. We describe the neural response associated with induced mood and the locus of the interaction between systems mediating mood and cognitive function. METHODS: Normal subjects performed a verbal fluency task during induced elated and depressed mood states. Regional cerebral blood flow (rCBF) was measured as an index of neural activity using Positron Emission Tomography (PET). RESULTS: In both elated and depressed mood state rCBF was increased in lateral orbitofrontal cortex, rCBF was also increased in the midbrain in elated mood. In the depressed condition rCBF was decreased in rostral medial prefrontal cortex. Verbal fluency produced an expected increase of rCBF in left dorsolateral prefrontal, inferior frontal and premotor cortex, anterior cingulate and insula cortex bilaterally, the left supramarginal gyrus posteriorly and the thalamus. Activation in the verbal fluency task was attenuated throughout the left prefrontal, premotor and cingulate cortex and thalamus in both elated and depressed mood conditions. An attenuation of anterior cingulate activation was specific to depressed mood. CONCLUSIONS: Alteration of mood is associated with activation of orbitofrontal cortex which may be critical to the experience of emotion. The mood induced modulation of verbal fluency induced activations is consistent with resting state findings of decreased function in these regions in depressed patients. The present data suggest that resting state rCBF profile may represent the modulation of spontaneous activity in this network by a core system that is dysfunctional in depression.     

The donor lung: conservation of a precious resource

OBJECTIVE: The Stroke Aphasic Depression Questionnaire (SADQ) was developed to detect depressed mood in aphasic patients in the community. DESIGN: Correlation analysis between new questionnaire and established measures. SETTING: Patients at home. METHODS: Seventy stroke patients who had been discharged from hospital were assessed on the SADQ, the Hospital Anxiety and Depression Scale and the Wakefield Depression Inventory. The SADQ was also administered to 17 aphasic patients on two occasions at a four-week interval. RESULTS: Results indicated that scores on the SADQ were significantly related to other measures of depression (r(s) = 0.22-0.52, p <0.05). A shortened 10-item version showed higher validity (r(s) = 0.32-0.67, p <0.01). Test-retest analysis indicated the SADQ is reliable over a four-week interval (r(s) = 0.72, p <0.001). CONCLUSIONS: The SADQ may be used for assessing depressed mood in aphasic patients in the community though further validation is required.     

Magnetic resonance imaging correlates of depression in early- and late-onset Alzheimer''s disease

Even today psychotic depression is connected to a lot of unanswered questions. A self-questionnaire (BFD) was developed in order to evaluate cognitions corresponding to mood congruent depressive delusions. They were assumed to indicate psychotic depression and to be related to severity of the depressive syndrome. 42 depressed inpatients were examined by the BFD, the Hamilton Depression Scale (HAMD) and the Beck Depression Inventory (BDI). BFD scores were found increased in psychotic depression (p = 0.009) and correlated to BDI scores (p = 0.002). 19 re-examined patients showed a significant improvement in HAMD and BDI scores but not concerning the delusion indicating cognitions (BFD), which were significantly correlated to suicidality items of BDI and HAMD (p = 0.005). The results prove the delusion indicating nature of cognitions measured by the BFD and their correlation to severe depression. Differences in treatment response are indicated and persisting or increasing BFD scores seem to be accompanied by more severe suicidal tendency.     

An investigation of cognition and affect in the depressive experiences of normal men.

Administered the Depression Adjective Check List and a projective story completion test as measures of depression to 30 male undergraduates 5 times over a 2-mo period. Data demonstrate the existence of a unified, negative content that is associated with depressed mood among normal Ss and suggest a similarity in the depressive processes of pathological depression and depressed mood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

Evolution in coronary stenting: use of ticlopidine with and without oral anticoagulants

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.     

A meta-analysis of the effect of hormone replacement therapy upon depressed mood

This meta-analysis had two objectives: (a) to aggregate data from studies that used hormone replacement therapy (HRT) and a quantitative measure of depressed mood in order to examine the effectiveness of HRT upon menopausal depressed mood; and (b) to review the methodologies of this literature base. The overall effect size for HRT was 0.68. This indicated that the average treatment patient had lower levels of depressed mood than 76% of the control patients. Analyses of specific hormone treatments suggested that (a) estrogen significantly reduced depressed mood (ES = 0.69); (b) progesterone alone, and in combination with estrogen, was associated with smaller reductions in depressed mood (ES = 0.39, ES = 0.45, respectively); and (c) androgen alone and in combination with estrogen was associated with greater reductions in depressed mood (ES = 1.37; ES = 0.90, respectively). In summary, HRT appeared to be effective in reducing depressed mood among menopausal women. The methodological review indicated that most studies used adequate sample sizes, controlled research designs, random assignment, double-blind treatment manipulations, and valid and reliable measures of depression. Limitations in the interpretation of these results are discussed and recommendations for improved methodology are provided.     

Issues in mapping genes for eating disorders

The purpose of this study was to obtain information about the prevalence of depressive symptoms in a representative sample of elderly subjects aged 85 years and over. The study was carried out as a population-based interview study in the City of Vantaa in Finland. The Zung Depression Status Inventory (DSI) was used to evaluate various depressive symptoms in this study population. The DSI scores range from 20 to 80; the higher the score, the more severe the disturbance. In subjects interviewed (n = 467, 362 women, 105 men), the prevalence estimates of depression with cutoff scores used in earlier studies (40 and 48) were very low: 5.2% and 1.1%. Also, the mean DSI score (SD) was very low, 27.9 (6.4). The scores tended to decrease with age, although the differences were not statistically significant. The DSI means were 28.0 (6.1) for women and 27.3 (7.2) for men (p = .0349). Women had a greater risk of being classified as depressed on the DSI (odds ratio: 1.60, 95% confidence interval: 1.00-2.57, p = .049). Feelings of emptiness, personal devaluation, and depressive mood were the most common depressive symptoms. In conclusion, the present population-based study shows that subjective experience of depression is very rare in Finnish people aged 85+. Our results suggest that optimistic mood might give some protection against death.     

An attempt to reverse performance deficits associated with depression and experimentally induced helplessness.

The learned helplessness model of depression predicts that any effective treatment for reactive depression should also reverse performance deficits associated with experimentally induced helplessness, and vice versa. A study was conducted to test this prediction. Ss were 62 college students who were exposed to experimental manipulations designed to induce helplessness or who scored above a group mean on the Beck Depression Inventory. Depressed and helpless Ss were randomly assigned to 4 groups. The 2 treatment groups received either E. Velten's (1968) mood statements for the induction of elation or a set of simple anagrams to solve. The 2 remaining groups were exposed to no-treatment conditions. All Ss were tested for helplessness on a series of concept formation problems. Results fail to confirm the predictions of the learned helplessness model of depression. Although treatment was effective with helpless Ss, the performance of treated depressed Ss was not enhanced. Also, depressed Ss given anagrams performed more poorly than depressed Ss given mood statements. Several possible explanations for the findings are considered. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Left ventricular contractile performance, ventriculoarterial coupling, and left ventricular efficiency in hypertensive patients with left ventricular hypertrophy

Contractile performance of hypertrophied left ventricle may be depressed in arterial hypertension. Ventriculoarterial coupling is impaired when myocardial contractile performance is reduced and when afterload is increased. The left ventricular contractile performance and the ventriculoarterial coupling were evaluated in 30 hypertensive patients with moderate left ventricular hypertrophy and 20 control subjects. Left ventricular angiography coupled with the simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress/volume index, the slope of end-systolic pressure-volume relationship, ie, end-systolic elastance, effective arterial elastance, external work, and pressure-volume area. In hypertensive patients, left ventricular contractile performance, as assessed by end-systolic elastance/ 100 g myocardial mass, was depressed (4.35 +/- 1.13 v 5.21 +/- 1.89 mm Hg/mL/100 g in control subjects P < .02), when end-systolic stress-to-volume ratio was comparable in the two groups (3.85 +/- 0.99 g/cm2/mL in hypertensive patients versus 3.51 +/- 0.77 g/cm2/mL in control subjects). Ventriculoarterial coupling, evaluated through effective arterial elastance/end-systolic elastance ratio, was slightly higher in hypertensive patients (0.53 +/- 0.08 v 0.48 +/- 0.09 mm Hg/mL in control subjects, P < .05), and work efficiency (external work/pressure-volume area) was similar in the two groups (0.78 +/- 0.04 mm Hg/mL in hypertensive patients versus 0.80 +/- 0.03 mm Hg/mL in control subjects). This study shows that despite a slight depression of left ventricular contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with left ventricular hypertrophy. Thus, it appears that left ventricular hypertrophy might be a useful means of preserving the match between left ventricle and arterial receptor with minimal energy cost.     

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)     

Facial muscle patterning and lateralization during elation and depression imagery.

26 18–30 yr old female Ss read a standard set of self-referent statements and imagined scenes with elated, depressed, and neutral content. The dependent measures were subjective mood ratings (Self-Rating Depression Scale) and left and right zygomatic- and corrugator-muscle activity. The self-statements elicited feelings of elation and depression in approximately 70% of Ss. Among these Ss, elation was accompanied by immediate increases in zygomatic activity, especially on the right side of the face in pure right-handed Ss. Depression was accompanied by bilateral increases in corrugator activity that grew over time. In the remaining 30% of Ss who reported experiencing little or no subjective differences between the elation and depression self-statements, similar though smaller facial patterns of zygomatic and corrugator activity were found that reliably differentiated the affective conditions. Data support the hypothesis that facial EMG patterning is a sensitive psychophysiological indicator of mood. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The prediction of suicidal intent in depressed patients

The aim of the present study was to examine the relationships between suicidal ideation or suicidal attempts and severity of depression, presence of personality disorders, and sociodemographic factors in a population of depressed in-patients. A total of 338 adult depressed psychiatric in-patients were examined and classified according to DSM-III criteria as having major depression with or without melancholic or psychotic features, adjustment disorder with depressed mood or dysthymic disorder. Scores on the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and Zung Self-Rating Depression and Anxiety Scales (SDS and SAS) were measured. We found that suicidal ideation was significantly related to severity of depression (according to the HDRS and all self-rating scales), a lower global assessment of functioning the year before hospitalization, and previous psychiatric hospitalizations. The items with the strongest predictive value for suicidal ideation were hopelessness, depressed mood, feelings of guilt, loss of interest and low self-esteem. These symptoms predicted 43% of the variance in suicidal ideation. None of the above predictors of suicidal ideation was related to suicidal attempts. Depressed patients with a personality disorder attempted significantly more suicidal attempts and showed more suicidal ideation than depressed patients without personality disorder. No significant correlations were found between suicidal ideation or suicide attempts and gender, marital status, employment status or psychosocial stressors during the previous 6 months.     

A review of functional neuroimaging in mood disorders: positron emission tomography and depression

OBJECTIVE: To examine the progress of positron emission tomography (PET) as a tool for understanding the psychobiology of mood disorders, particularly major depression and bipolar disorder. METHOD: Review of the literature on functional imaging of mood disorders. RESULTS: Functional imaging techniques have been used in psychiatric research as a noninvasive method to study the behaviour and function of the brain. Techniques used so far have involved the manipulation of emotion in healthy volunteers, the evaluation of depressed (unipolar and bipolar as well as secondary depression), manic, and normal subjects under resting and various activation conditions, such as cognitive activation, acute pharmacological challenge, and chronic thymoleptic treatments. As a result, functional imaging studies tend to support abnormalities in specific frontal and limbic regions. CONCLUSION: Different PET methods demonstrate consistent abnormalities in the prefrontal, cingulate, and amygdala regions. These findings are in agreement with past animal and clinical anatomical correlates of mood and emotions.     

An examination of depression in the spouses of stroke patients.

Examined the prevalence and correlates of depression in the spouses (SPs [mean age 61.8 yrs]) of 41 stroke patients (SPTs [mean age 65.6 yrs]). SPs reported their own mood on the Beck Depression Inventory (BDI) and rated their partners' (the SPTs') mood using the Hamilton Rating Scale for Depression (HRSD). A clinician evaluated the SPTs' mood using the HRSD and their cognitive/language and physical impairments using a battery of neuropsychological tests. Results indicated that 44% of the SPs were depressed. SP depression was not correlated with the severity of the SPTs' physical, cognitive, or language impairments. However, the SPs' perception of the SPTs' mood was a better predictor of the SPs' mood than was the clinicians' evaluation of the SPTs' mood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of depressed mood on eating among obese and nonobese dieting and nondieting persons.

Induced a depressed or nondepressed mood in obese and nonobese dieters and nondieters (18 male and 38 female undergraduates). Ss were administered a battery of measures, including the Beck Depression Inventory and Depression Adjective Check List. As predicted, dieters ate more when depressed than when nondepressed, and nondieters ate less when depressed than when nondepressed. That is, both groups reversed their typical eating patterns when depressed. Also as predicted, among depressed Ss, dieters ate more than nondieters; among nondepressed Ss dieters ate less that nondieters. This pattern of results was found for both obese and nonobese Ss. Dieting habits were highlighted as a more salient variable than obesity in predicting eating responses to depressed mood. Findings are discussed with respect to the psychosomatic theory of obesity, the stimulus-binding theory of obesity, previous investigations of clinical depression, and the theory of restrained eating. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-schemas and risk for depression: A prospective study.

Two longitudinal experiments with 375 undergraduates investigated the role of depressive self-schemas in vulnerability to depression. Ss were divided into 5 groups hypothesized to be at differential risk for depression according to a schema model: depressed schematic, depressed nonschematic, nondepressed schematic, nondepressed nonschematic, and psychopathology control. In Exp I, Ss were followed regularly for 4 mo with self-report and clinical interview measures of depression (e.g., Beck Depression Inventory). There was no evidence of risk for depression associated with schema status apart from initial mood and no interaction of life stress events and schemas. In Exp II, links among self-schemas, information processing, and mood status were investigated. It was shown that depressive self-schemas did not exert an ongoing, active influence on everyday information processing; instead, current mood affected information processing. Remitted depressed Ss resembled nondepressed rather than depressed Ss. Findings support the distinction between concomitant and vulnerability schemas noted by N. Kuiper et al (in press) and help to clarify differences between cognitions that are symptoms of depression and those that may play a causal role under certain conditions. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides

Suicide and depression are associated with an increased density of alpha2-adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein-coupled receptor kinases, GRKs), which work in concert with the receptors. In this study we quantitated in parallel the levels of immunolabeled alpha2A-adrenoceptors and associated regulatory proteins in brains of suicide and depressed suicide victims. Specimens of the prefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and 31 control subjects. Levels of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 were assessed by immunoblotting techniques by using specific polyclonal antisera and the immunoreactive proteins were quantitated by densitometry. Increased levels of alpha2A-adrenoceptors (31-40%), Galphai1/2 proteins (42-63%), and membrane-associated GRK 2/3 (24-32%) were found in the prefrontal cortex of suicide victims and antidepressant-free depressed suicide victims. There were significant correlations between the levels of GRK 2/3 (dependent variable) and those of alpha2A-adrenoceptors and Galphai1/2 proteins (independent variables) in the same brain samples of suicide victims (r = 0.56, p = 0.008) and depressed suicide victims (r = 0.54, p = 0.041). Antemortem antidepressant treatment was associated with a significant reduction in the levels of Galphai1/2 proteins (32%), but with modest decreases in the levels of alpha2A-adrenoceptors (6%) and GRK 2/3 (18%) in brains of depressed suicide victims. The increased levels in concert of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 in brains of depressed suicide victims support the existence of supersensitive alpha2A-adrenoceptors in subjects with major depression.     

Treatment of refractory depression with high-dose thyroxine

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.