Wolfgang P. Kaschka

Are affective disorders associated with alterations of heart rate variability

A standardized heart rate analysis was carried out in unmedicated patients with major depression, melancholic type (n = 16), panic disorder (n = 16), reactive depression with suicide attempts during the preceding 24 h (n = 16) and in 16 normal control subjects. The investigations included time- and frequency-derived measurements of heart rate variability. In the patients with reactive depression, no differences could be detected as compared with the control group. The patients with panic disorder showed a significantly increased low-frequency band of spectral analysis (P < 0.01) and a marginally significant increment of heart rate (P = 0.05), probably indicating predominance of sympathetic control of heart rate. In the patients with major depression, we found significantly lower values of hearts beat-to-beat intervals and of the high-frequency peak of spectral analysis than in the other groups (P < 0.025), indicating decreased parasympathetic activity.

Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation : preliminary results

The antidepressant properties of total sleep deprivation (TSD) have been well established. There is some evidence that TSD may improve depression by altering central dopamine (DA) function. We therefore studied five depressed TSD responders and five TSD nonresponders after sleep and after TSD and five controls after sleep with IBZM single photon emission computerized tomography (SPECT). Responders showed a significant decrease (Wilcoxon--test p < 0.05) of relative basal ganglia D2 receptor occupancy after TSD compared to nonresponders (change score responders versus nonresponders p < 0.05, U-test). The data are interpreted as a sign of an enhanced DA release in responders. The results confirm previous hypotheses of dopaminergic involvement in the therapeutic action of TSD and indirectly support a dopamine hypotheses of depression.

Increased limbic blood flow and total sleep deprivation in major depression with melancholia.

Single photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO) was carried out in 20 melancholic patients before and after total sleep deprivation. Findings in 11 responders to total sleep deprivation (defined by > or = 40% improvement on the Hamilton Rating Scale for Depression) were compared with findings in nine nonresponders. On the basis of a semiquantitative evaluation of SPECT findings, responders showed relative hyperperfusion before sleep deprivation in the right anterior cingulate cortex and in the right and left fronto-orbital cortex and basal cingulate gyrus. Responders who showed > or = 50% improvement also showed hippocampal overactivation before sleep deprivation. It is possible that limbic overactivation may characterize depressed responders to total sleep deprivation as a distinct subtype. Another possibility is that the pattern of limbic hyperactivation reflects the increased number of bipolar patients in the responder group, with response to total sleep deprivation being only a covariate of this bipolar-unipolar distinction.

Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil spect

We compared a group of nine patients with panic disorder (DSM-III-R) and depression with a matched control group of nine dysthymic patients without a previous or actual history of panic attacks or anxiety with iomazenil SPECT (single photon emission computed tomography) to evaluate panic-related abnormalities of the benzodiazepine receptor complex. The panic group had a significant decrease (p < .05, U-tests) in the regional activity index (RAI) in the following regions after 2 h: lateral inferior temporal lobes, right and left, medial inferior temporal lobes, left, inferior frontal lobes, right and left. All other regions investigated were not significantly different. The findings may be due to either regional blood flow differences or benzodiazepine receptor effects. The hypothesis that the effects are due to altered blood flow is confirmed to some extent by similar findings in the scans acquired after 10 min. Only the hypoactivity in the left lateral temporal region seemed to be independent of reduced blood flow in panic disorders.

Autonomic cardiac abnormalities in alcohol-dependent patients admitted to a psychiatric department

Standardized heart rate analyses were performed in 60 drug-free patients with alcohol dependence, who were admitted consecutively to a psychiatric department, and in 60 healthy normal matched subjects. The procedure included time and frequency derived measurements of heart rate variability (HRV). The investigations were carried out 3 weeks after admission and treatment on a closed ward to avoid autonomic hyperexcitability during withdrawal or relapse.The patients showed a significantly increased heart rate (p<0.05), a significant reduction in the coefficient of variation while resting (p<0.01) and a significant decrease of the high frequency power of spectral analysis (p<0.01) compared with the normal subjects. Cardiovascular autonomic dysfunction was found in 12 of the patients, but in only one of the normal subjects (p<0.01). The results indicated moderate parasympathetic (vagal) alteration in alcohol-dependent patients treated in a psychiatric department. This may have implications for psychotherapeutic or psychopharmacological treatment strategies and prognosis in such patients with alcohol dependence.

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients.

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.

A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression

SummarySix depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network.

Prolactin Response to Sulpiride Before and After Sleep Deprivation in Depression

Total sleep deprivation (TSD) has a well-established nonpharmacological antidepressant effect in depressed patients (Wu and Bunney 1990); however, the mechanisms of therapeutic action have not been fully characterized, We addressed the question whether dopaminergic pathways are involved in the antidepressant response to TSD by comparing the response of pmlactin (PRL) to sulpiride injection in TSD responders and nonrespond-

Correlation between plasma clozapine concentration and heart rate variability in schizophrenic patients

Abstractu2002Forty schizophrenic patients treated with 50–600u2005mg/day of clozapine as monotherapy and 40 normal control subjects were tested for heart rate variability (HRV) which is mediated by the vagus nerve using acetylcholine as neurotransmitter. As compared to the control subjects, the patients showed essentially reduced HRV parameters which were negatively correlated with the plasma clozapine levels. Therefore, clozapine’s anticholinergic effect is correlated to the plasma clozapine level when measured by the decrease of HRV. We suggest that HRV data might be useful as a predictor for plasma clozapine levels.

Is diurnal variation of mood associated with parasympathetic activity

18 patients with distinct improvement of mood in the evening and 18 patients without, both suffering from major depression and equally treated with tricyclic antidepressants (TCA), and an age- and sex-matched group of 18 normal control subjects underwent a standardized heart-rate (HR) analysis (HRA) in the morning (08:00) and 12 h later in the evening (20:00). The battery of cardiovascular reflex tests included the determination of HR variability (HRV) while resting and during deep breathing, and a spectral HRA. The depressed patients with diurnal variation of mood showed significantly decreased HR and significantly increased HRV parameters while resting and during deep respiration in the evening. On the contrary, patients without diurnal changes of mood just showed a significant HRV increase during deep respiration in the evening. No statistically significant changes of these parameters were detected in the healthy subjects. It is not known if the observed changes of HR parameters representing increment of parasympathetic tone are intrinsically related to the mood swings or if this rhythm just becomes visible under the circumstances of depression. Also, the impact of TCA treatment upon the results remains to be elucidated.