Twenty psychiatric patients on lithium medication were examined with 7-Li-magnetic resonance spectroscopy of the brain. Patients on long-term lithium treatment (>6 months) were compared with a short-term group who had been taking lithium for between 4 and 8 weeks. Patients met DSM-III-R criteria for either recurrent unipolar depressive disorder (DSM-III-R 296.3x) or schizoaffective disorder, depressive type (DSM-III-R 295.70). The brain:serum lithium ratio was 0.76 +/- 0.26; there was no significant difference between short-term and long-term treatment In the group of long-term treatment patients there was a positive correlation between lithium dose per day and brain lithium concentration (R = .72, p < .01), and between lithium plasma concentration and brain lithium concentration (R = .65, p < .05). In the short-term group, however, there was no significant correlation for these parameters. No differences between unipolar and schizoaffective disorder were found. (C) 1997 Society of Biological Psychiatry.

A series of studies demonstrated a possible correlation between eye-blink rate and central dopamine activity. The hypothesis has been put forward that the antidepressant effect of sleep deprivation (SD) is mediated by an enhanced dopamine release resulting in an amphetaminelike action of SD. Therefore, the blink rates of 12 drug-naive patients with major depression and 12 healthy controls were compared before and after SD and before and after 2.5 mg bromocriptine as a dopaminergic challenge. The main result of the study was that the depressed patients had a significantly higher increase of blinking after SD both with and without a dopaminergic challenge. Basal eye-blink rate was not different in nonretarded major depression patients compared to controls. Sleep deprivation increased blink rate in depression patients but not in controls, and the increase was proportional to improvements in depressive state after sleep deprivation. Bromocriptine did not increase blink rate 1 hour after application. This result is consistent with the hypothesis that antidepressant SD acts through dopamine release, although it is not conclusive, because other neurotransmitters like acetylcholine may be involved in the regulation of blinking.

In der folgenden Studie werden mittels der magnetresonanzspektroskopischen Methode in vivo Hirnlithiumsignalen bzw. -konzentrationen bestimmt. Es wurde ein Kollektiv von Patienten, die Lithium über sechs bis acht Wochen einnahmen, mit einer Gruppe, der Lithium sechs Monate oder länger verabreicht wurde, verglichen.

Dopaminverarmung im N. caudatus und N. accumbens bei Versuchstieren mit erlernter Hilflosigkeit (Anisman et al. 1979 a, b).

The psychopathology of 183 patients with melancholic depression first admitted to our department in 1969 and 1970 was compared with that of 184 patients first admitted in 1989 and 1990. A multivariate statistical analysis was performed. The main results were as follows: A socioculturally invariable core syndrome of melancholia comprising psychomotor inhibition and vegetative disturbances can be identified. The contents of depressive thinking are, at least in part, culturally determined and vary with value changes in society. Paralleles to social change could be shown in particular for feelings of guilt and a concern with self-realization.

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.

Eighteen patients with refractory depression (dysthymia with superimposed major depression) were treated with a combination of fluvoxamine and moclobemide for 6 weeks and compared with 18 patients treated with fluvoxamine only. Both groups had improved only slightly after 8 weeks of TCA treatment and 6 weeks of SSRI treatment. Two main observations can be made concerning safety and efficacy. Firstly, side effects in the SSRI-RIMA group were minimal. Secondly, the SSRI-RIMA combination treatment significantly improved depression in refractory depressed patients, with a decrease in depression of about 40%. The SSRI monotherapy group also significantly improved, though only by about 20%, indicating that positive effects of SSRI treatment may still develop even after 12 weeks of treatment. In conclusion, the study gives further support to the hypothesis that SSRI-RIMA combinations may be safe and well tolerated. This treatment may also offer some therapeutic advantages in at least some patients who have not responded to conventional pharmacological treatment.

The effects of an antidepressant sleep deprivation on humoral systems and neurotransmitter systems are reviewed (cortisol, endorphins, thyroidea, growth hormone, prolactin, catecholamines, sexual hormones, melatonin, serotonin). The main results are: Depressed patients have a physiological response similar to controls with some differences between responders and nonresponders (responders are more similar to controls). TSH is more activated in responders than in nonresponders. The dopamine system is more activated in responders than in nonresponders and less activated in responders before sleep deprivation. The glucocorticoid-axis in more activated in responders after sleep deprivation. In conclusion, patients who profit from sleep deprivation can activate systems correlated with arousal or stress.

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.

The study questions whether different types of somatization may be a core symptom of melancholia, thus, being invariable across cultures and being a candidate for neurobiological research and diagnostic criteria. 51 Turkish patients and 51 education-matched German patients with melancholic depression were compared for two types of somatization. Turkish patients had higher frequencies of somatic preoccupation and hypochondriasis but they were not different in the perception and experience of somatic symptoms. It is concluded that: (1) somatization has to be differentiated psychopathologically; (2) it may be a neurobiological core symptom of melancholia in the well-defined sense of ‘perceiving abnormal somatic symptoms’; and (3) it may be a culture-bound symptom in the sense of ‘being abnormally concerned with somatic symptoms or hypochondical fears’.

To test theories that response to sleep deprivation in depression is the result of either stress reactions or down-regulation of hyperarousal, the early morning cortisol and beta-endorphin levels of depressed sleep deprivation responders and nonresponders before and after sleep deprivation were compared (areas under the curve of 8 blood samples between 7.30 and 10 a.m.). The beta-endorphin response was significantly different in responders and nonresponders, whereas all other comparisons remained nonsignificant. The results do not support theories that sleep deprivation acts as a stressor, but are not contradictory to the hyperarousal hypothesis of sleep deprivation.

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 compaired to nonresponders (change score responders versus nonresponders p < 0.5 U-test). The data are interpretated as a sign of an enhanced DA release in responders. The results confirm previous hypothesis of dopaminergic involvement in the therapeutic action of TSD and indirectly support a dopamine hypothesis of depression.

The parietal lobes have only infrequently been implicated as being important in schizophrenia or affective disorders. However, in recent years, there has been some evidence that they might be considered as a possible site of damage or dysfunction, especially in schizophrenia but also in affective disorders. First, some positron emission tomography (PET) studies showed abnormalities in the parietal lobes in schizophrenia, especially a hypoparietal pattern on the right (Kishimoto et al. 1987; Cleghorn et al. 1989; Buchsbaum et al. 1990). Second, the right inferior parietal lobe may play an important role in the mediation of selective attention, which is thought to be impaired in schizophrenia (Buchsbaum et al. 1990). Third, the inferior parietal lobe has direct and reciprocal connections to most regions which have been found to play a role in schizophrenia, for example, the dorsolateral prefrontal cortex.

Six 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.

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-

Erste Untersuchungen mit funktionsbildgebenden Verfahren zum therapeutischen Schlafentzug (SE) bei Depressionen erbrachten bereits Unterschiede zwischen Se-Respondern und Nonrespondern und Hinweise auf mögliche therapeutische Wirkmechanismen (Ebert et al. 1991, Kasper et al. 1992, Wu et al. 1992). In PET (Wu et al. 1992) und SPECT Studien (Ebert et al. 1991) waren nur die Responder vor SE hyperaktiv in limbischen Arealen mit Suppression dieses Hypermetabolismus durch SE. Diese Unterschiede zu Nonrespondern und Kontrollen zeigten sich vor allem im frontoorbitalen Cortex und Gyrus cingularis, weniger deutlich im Hippocampus und infratemporalen Cortex.

Benzodiazepine sind bei verschiedenen mit Angst einhergehenden Erkrankungen therapeutisch wirksam. Sie werden an den GABA A/Benzodiazepin-Rezeptor gebunden, der mit einem Chloridkanal gekoppelt ist (Übersicht bei Möhler 1992). Dieser Rezeptor kann heute mit Iomazenil, einem J123-markierten partiellen inversen Agonisten am Benzodiazepin-Rezeptor (Derivat des Flumazenils), in der Single Photon Emission Computed Tomography (SPECT) dargestellt werden (Höll et al. 1989, Beer et al. 1990). In der vorliegenden Pilotstudie sollte geprüft werden, ob Angsterkrankungen mit einer veränderten Verteilung zerebraler GABA A/Benzodiazepin-Rezeptoren einhergehen, die geeignet wäre, ein Benzodiazepin- Rezeptor-bezogenes Modell der Angst zu stützen (vgl. Insel et al. 1984).