Dag Neckelmann

The validity of the Hospital Anxiety and Depression Scale - An updated literature review

OBJECTIVE To review the literature of the validity of the Hospital Anxiety and Depression Scale (HADS). METHOD A review of the 747 identified papers that used HADS was performed to address the following questions: (I) How are the factor structure, discriminant validity and the internal consistency of HADS? (II) How does HADS perform as a case finder for anxiety disorders and depression? (III) How does HADS agree with other self-rating instruments used to rate anxiety and depression? RESULTS Most factor analyses demonstrated a two-factor solution in good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS-D), respectively. The correlations between the two subscales varied from.40 to.74 (mean.56). Cronbachs alpha for HADS-A varied from.68 to.93 (mean.83) and for HADS-D from.67 to.90 (mean.82). In most studies an optimal balance between sensitivity and specificity was achieved when caseness was defined by a score of 8 or above on both HADS-A and HADS-D. The sensitivity and specificity for both HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and specificity achieved by the General Health Questionnaire (GHQ). Correlations between HADS and other commonly used questionnaires were in the range.49 to.83. CONCLUSIONS HADS was found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population.

Mr morphometry analysis of grey matter volume reduction in schizophrenia: association with hallucinations.

The authors used voxel-based morphometry (VBM) to study GM volume differences in the whole brain volume between a group of patients with schizophrenia and a healthy control group. There were 12 patients and 12 control subjects. The subjects were scanned in a 1.5 T MR scanner. The patients had all been evaluated by a senior psychiatrist on the brief psychiatric rating scale (BPRS). The VBM data was correlated with reports of rate and frequency of hallucinations based on their scores on the BPRS hallucination item. There were significant grey matter volume reductions in the schizophrenia patient group in the left superior (transverse) temporal gyrus, the left middle frontal gyrus, and in the right cuneus. Areas of grey matter volume reduction that correlated negatively with hallucinations were found in the left superior (transverse) temporal gyrus, left thalamus, and left and right cerebellum. This article proposes that significant reductions in grey matter volume may be instrumental in generating spontaneous neuronal activity that is associated with speech perception experiences in the absence of an external acoustic stimulus that may cause hallucinations.

Migraine with and without aura: association with depression and anxiety disorder in a population-based study. The HUNT Study

Some data indicate that migraine with aura (MA) is more strongly associated with anxiety disorder and depression than migraine without aura (MoA), but the evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total of 49 205 (75% of the participants) subjects gave valid answers to both HADS (Hospital Anxiety and Depression Scale) and a validated headache questionnaire. Associations between anxiety disorder/depression and MA/MoA were evaluated by multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder (COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in prevalence of depression and anxiety disorders between MA and MoA. This is a new finding that might have relevance for both research and clinical treatment.

Efficacy of repetitive transcranial magnetic stimulation in depression: A review of the evidence

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment in psychiatry. We reviewed all published evidence on the efficacy of this treatment option in depressive disorders. An extensive electronic and manual search for eligible research reports identified only 12 studies that met the predetermined criteria for inclusion. rTMS was administered differently in most studies, and patient characteristics varied widely. A formal meta-analysis of the studies was thus not possible. Instead, we conducted a qualitative evaluation of the included studies. The antidepressive efficacy was not consistent, and where efficacy was demonstrated, it was modest in most studies. Some patients had good but transient responses to rTMS. Treatment gains were not maintained beyond the treatment period. Comparisons with electroconvulsive therapy (ECT) indicated the superiority of ECT. More, larger and more carefully designed studies are needed to demonstrate convincingly a clinically relevant effect of rTMS. We conclude that there is insufficient evidence for rTMS as a valid treatment for depression at present.

Citalopram: differential sleep/wake and EEG power spectrum effects after single dose and chronic administration.

The sleep/wake effects of the selective serotonin re-uptake inhibitor citalopram were studied in both a single-dose study with three dose levels (0.5, 2.0 and 5.0 mg/kg), and a 5-week chronic administration study (15 mg/kg/24 h). Single doses of citalopram resulted in a dose-dependent inhibition of rapid eye movement (REM) sleep. After chronic citalopram treatment there was a sustained REM sleep inhibition. Single doses of citalopram resulted in only minor changes in non-REM (NREM) sleep as well as in NREM EEG power spectral density. Chronic administration resulted in a major shift from SWS-2 to SWS-1. The observed corresponding changes in EEG power density were regional. A 30 to 40 percent reduction of power density in the 0.5-15 Hz range in the fronto-parietal EEG derivation was seen for the whole 8-h registration period. In the fronto-frontal EEG derivation only minor changes were seen. A decreasing trend in NREM sleep power density between 0.5 and 7 Hz, usually seen during the course of the light period, was not observed in the chronic condition, but was seen in control and single-dose condition, suggesting altered diurnal distribution of slow wave activity in the chronic condition. The data indicate that acute and chronic administration of citalopram shows clear differences in sleep effect, which may be caused by alteration of serotonergic transmission, and may be related to the antidepressant effect.

Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram

The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG.

Migraine aura without headache compared to migraine with aura in patients with affective disorders.

The characteristics of psychiatric comorbidity in migraine have been studied in migraine with aura (MA) and migraine without aura (MO). Little information is available concerning patients with migraine aura without headache. In a study of 201 patients with major affective disorders (DSM–IV) we have described the clinical characteristics of patients with these three sub–types of migraine (IHS criteria) and compared the MA and migraine aura without headache groups. Compared to patients having MA (n=57), the group with migraine aura without headache (n=18) had a higher age of onset of migraine (28.5 vs. 19.2, p=0.001), significantly lower prevalences of affective temperaments (28% vs. 56%, p=0.036), suicide attempts (17% vs. 53%, p=0.013) and Raynaud’s syndrome (0% vs. 25%, p=0.017). These results indicate that there seem to be differences in the clinical characteristics found in patients with migraine with aura when compared to those having the migraine subtype without a headache phase. This may convey new information concerning the comorbid expression of migraine and affective disorders or concerning the processes that differentiates the migraine types with and without a subsequent pain attack.

The 5-HT1A antagonist (-)-alprenolol fails to modify sleep or zimeldine-induced sleep-waking effects in rats.

Sleep and waking in rats were studied for 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a putative 5-HT1A antagonist (L(-)-alprenolol hydrogene tartrate monohydrate [(-)-alprenolol]) and a combination of (-)-alprenolol and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased during the first 3 h, followed by a small decrease. Deep slow-wave sleep (SWS-2) showed the opposite trend. An initial decrease in SWS-2 was followed by an increase after around 3 h. Rapid eye movement sleep was markedly suppressed and latencies to sleep increased after zimeldine. (-)-Alprenolol had no effects on the different sleep and waking stages or latencies to sleep. The 5-HT1A antagonist also failed to modify the effects of zimeldine administration. The behavioral syndrome induced by a selective 5-HT1A agonist [8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT)] was clearly antagonized by administration of (-)-alprenolol, indicating that (-)-alprenolol was an efficient 5-HT1A blocker. The data indicate that the sleep-waking effects of zimeldine cannot easily be explained by stimulation of 5-HT1A receptors.

Diurnal differences in L-tryptophan sleep and temperature effects in the rat

Sleep/waking and EEG power spectra were investigated for 6 h periods in rats following administration of the essential amino acid L-tryptophan (40 mg/kg), the selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a combination of L-tryptophan and zimeldine. In contrast to earlier studies, L-tryptophan decreased waking and increased total slow wave sleep when administered late in the light phase (8 1/2 h after light onset). No sleep effects were seen after early light phase injections (2 h after lights on). In agreement with earlier studies, zimeldine initially increased wakefulness, followed by an increase in slow wave sleep-2. REM sleep was abolished after zimeldine treatment. Zimeldine increased EEG delta activity and decreased EEG activity above 7 Hz. L-Tryptophan potentiated the zimeldine induced increase in waking only when given early in the light phase. In a separate experiment, body temperature was monitored after L-tryptophan injections in both early and late light phase. A thermogenic effect of L-tryptophan was seen in the early light phase, while the opposite was seen in the late light phase. The data indicate diurnal differences in sleep/waking and temperature effects of a physiological dose of L-tryptophan.

Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT and the NMDA antagonist AP-5 in rats

The modulating effect of an intrathecally (i.t.) administered 5-HT1A agonist and an NMDA antagonist on sleep, waking and EEG power spectra was investigated in rats. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5-phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but TSWS was not changed. An increase in REM sleep was seen during the last part of the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and increased TSWS. No change in REM sleep was seen. There were no systematic changes in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments. The results suggest that in the spinal cord stimulation of 5-HT1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased possibilities for sleep induction. Blockade of the NMDA receptors may also lead to a small dampening of sensory transmission with similar consequences.