Marijke Gordijn

Depressed patients' perceptions of facial emotions in depressed and remitted states are associated with relapse - A longitudinal study

Within the framework of interpersonal and cognitive theories of depression, we investigated whether the perception of facial emotions was associated with subsequent relapse into depression. The 23 inpatients with major depression who remitted (65 admitted patients) were studied at admission (T0), at discharge (T1), and 6 months thereafter to assess relapse. They judged schematic faces with respect to the expression of positive and negative emotions. Six patients (26.1%) relapsed. High levels of perception of negative emotions in faces, either assessed at T0 or at T1, were associated with relapse. Moreover, subjects saw more negative emotions in depressed than in remitted state. Significant results were confined to ambiguous faces, i.e., faces expressing equal amounts of positive and negative emotions. Our data support the hypothesis that a bias toward the perception of others facial emotions as negative is an enduring vulnerability factor to depression relapse and depressed mood amplifies this negative bias in perception.

A longitudinal study of diurnal mood variation in depression; characteristics and significance

The course of 39 depressed in-patients daily mood was recorded by means of frequent self-ratings during their entire stay (in total 3718 days). The frequency of diurnal variations largely varies between subjects without clear dichotomy in diurnal and non-diurnal subjects and the occurrence of diurnal variations is rather irregular. Mood variability measures rather than average daily mood improvement correlate with the response to sleep deprivation. These observations do not support theories of chronobiological rhythm disturbances in depression. It is argued that depressed subjects largely vary in susceptibility to stimuli. Signals generated by the biological clock or by processes related to the sleep-wake cycle are considered examples of such stimuli.

Gender-specific mechanisms associated with outcome of depression : perception of emotions, coping and interpersonal functioning

We proposed that a negative bias in the perception of facial expressions would affect the way in which deficient coping and interpersonal functioning influenced the risk of persistent depression. Furthermore, we hypothesised that cognitions, coping strategies, and interpersonal functioning would be more likely to contribute to the prediction of outcome of depression among women than among men. At admission, 60 in-patients with major depression judged 12 schematic faces with respect to the emotions that they expressed (fear, happiness, anger, sadness, disgust, surprise, rejection and invitation). In addition, difficulty in assertiveness and social distress, and coping strategies for dealing with stressful events were measured with self-report questionnaires. At admission and 6 weeks later, the severity of depression was evaluated with the Beck Depression Inventory. Women who were inclined to perceive high levels of negative emotions from facial expressions and who reported high levels of social distress at admission were less likely to be improved after 6 weeks. Among women, these high levels of perception of negative emotions and high levels of social distress tended to predict the persistence of depression independently. A propensity to perceive negative facial expressions may underlie the unfavourable course of depression, especially among women.

Effects of light exposure and sleep displacement on dim light melatonin onset

The purpose of the study was to induce in two different ways, a phase‐angle difference between the circadian pacemaker and the imposed sleep–wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep–wake cycle fixed; and (ii) keep the timing of the circadian pacemaker fixed by a constant light–dark cycle and displace sleep. We monitored dim light melatonin onset (DLMO), core body temperature and sleep. DLMO was delayed significantly after 3 days of a 3‐h delayed sleep‐phase when compared with 3 days of sleep at a normal or 3‐h advanced sleep‐phase. The shifts in DLMO were not accompanied by shifts in body temperature, changes in waking‐up time or by a change in the duration of the first rapid eye movement (REM) sleep episode. Three days of light exposure in the morning or evening resulted in shifts in DLMO of similar magnitude, but this was accompanied by shifts in the rhythm of body temperature, changes in waking‐up time and in the duration of the first REM sleep episode. We conclude that the changes observed after light exposure reflect shifts in the circadian pacemaker. In contrast, we propose that the changes observed in DLMO after sleep displacement are not mediated by the circadian pacemaker. These results raise some doubts about the reliability of DLMO as a marker of circadian phase in cases of sleep disturbances. Finally, we initiate a search for changes in sleep that might be responsible for the unexpected effects on DLMO.

Extraocular light therapy in winter depression: a double-blind placebo-controlled study

BACKGROUNDnIt has been hypothesized that the circadian pacemaker is phase delayed in seasonal affective disorder, (SAD) winter type, and that the phase advance resulting from morning ocular light accounts for the efficacy of light therapy. Extraocular light has been reported to produce phase-shifts of the human circadian pacemaker. This allows a double-blind, placebo-controlled study of light therapy in SAD.nnnMETHODSnTwenty-nine SAD patients participated. Clinical state was measured on days 1, 8, and 15 of the protocol. From days 4 through 8, 15 patients (4 M, 11 F) received extraocular light by fiberoptic illumination, and 14 (4 M, 10 F) placebo (no light) in the popliteal fossae, from 8 AM to 11 AM. In the evenings of days 3 and 8, the salivary dim light melatonin onset (DLMO) was assessed. Patients completed daily self-ratings on mood, alertness, and sleep.nnnRESULTSnBoth conditions showed a progressive improvement of clinical state over time. Between conditions, no significant differences were observed in clinical scores, the self-ratings on mood and alertness, and in timing of the DLMO before and directly after treatment.nnnCONCLUSIONSnThe response to extraocular light therapy in SAD patients did not exceed its placebo effect. Extraocular light did not induce a phase shift of the circadian pacemaker.

The eye of the african mole-rat Cryptomys anselli: to see or not to see?

In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located superficially and display all features typical of sighted animals: iris, pupil and well‐developed lens, separating the anterior chamber and the vitreous. The retina shows a well stratified organization and the folds described in blind subterranean or nocturnal mammals were not observed. The major population of the photoreceptor cells in the Cryptomys retina consists of rod cells, again with a morphology quite similar to that found in sighted animals. The relatively short outer segments contain numerous well‐stacked disks and show a strong rod‐opsin as well as transducin immunoreaction. Synapses were evident in the spherules, the round basal processes of the rod cell, but they lacked the precise organization reported for sighted mammals. Cone cells were present as well, as indicated by peanut lectin staining, but no immunolabelling with polyclonal M/L‐opsin antisera was detectable. The presence of cone cells was also suggested by some basal processes at the outer plexiform layer which displayed several synaptic active sites and irregular contours. While the other retinal layers also showed an organization typical of sighted mammals, there were signs of less tightly preserved morphology as well. Displaced rods and amacrine and/or ganglion cells were observed, and some sparse rod spherules penetrated into the inner nuclear layer. A major reduction was observed in the number of ganglion cells, estimated from the number of axons in the optic nerve, that was very low (≈1000 per retina on average) relative to sighted mammals. The data we have suggest a slow, ongoing loss of cells with ageing. Apoptotic nuclei, mainly corresponding to photoreceptor cells and ganglion cells, were detected in young individuals, and an overall reduction in the thickness of the retina was observed in older animals. The morphological data presented here allow some first speculations on the physiological role of the Cryptomys eye and will hopefully trigger detailed studies on the chronobiology and the anatomy of the retinal projections and of the visual cortex of this remarkable species.

Prediction of the antidepressant response to total sleep deprivation of depressed patients : longitudinal versus single day assessment of diurnal mood variation

The relationship between diurnal variation of mood and the clinical response to total sleep deprivation (TSD) was investigated in 43 depressed patients. The question asked was whether the propensity to produce diurnal variations of mood or the actual mood course on the day before TSD determines the clinical response to TSD. Patients rated their mood three times daily during an experimental period of 56 days. The frequency as well as the amplitude of daily mood changes were assessed during this period. For each patient six TSDs were scheduled: two after days with a positive mood course, two after a negative mood course, and two after days without a diurnal change of mood. This strategy allowed comparisons of TSD responses within patients. Moreover, longitudinally and retrospectively assessed diurnal variation were compared with each other. It was found that patients vary largely in the occurrence of diurnal variations of mood. The propensity to produce diurnal variations either in terms of frequency or amplitude was positively correlated with the response to TSD. Within patients no differences were found in responses to TSDs applied after days with diurnal variations (positive or negative) or without diurnal variations. A second aim was to get more insight into the mechanism relating diurnal variations of mood and the TSD response. Therefore, the interrelatedness of various measures of diurnal variations, such as amplitudes and frequencies of positive or negative diurnal mood changes, was studied, as well as the relationships of these variables with TSD responses. On the basis of the strong interrelatedness it is suggested that they all reflect the same underlying mechanism, to be symbolized by an oscillator, producing positive daily fluctuations of mood.

Testing the Hypothesis of a Circadian Phase Disturbance Underlying Depressive Mood in Nonseasonal Depression

In a crossover design, 8 nonseasonal depressed subjects, selected on the presence of diurnal mood variations, and 8 sex and age-matched controls were exposed to dim light (< 10 lux) in the evening (18:00-21:00 h) and bright light (2500 lux) in the morning (ML, 6:00-9:00 h), to dim light in the morning and bright light in the evening (EL), or to dim light both in the evening and in the morning (DL) during 3 consecutive days in each of these conditions. There were no initial phase differences between depressed and healthy subjects in the timing of dim light melatonin onset, sleep termination, and body temperature. The phase shifts after EL and ML in both healthy and depressed subjects were as expected on the basis of a human phase response curve. On average, there was no therapeutic effect of the light exposure in the depressed patients. Two patients improved, but these effects do not seem to be related to shifts in the circadian system.

A LONGITUDINAL-STUDY OF SLEEP-DEPRIVATION RESPONSES IN DEPRESSION - THE VARIABILITY IS HIGHLY RELATED TO DIURNAL MOOD VARIABILITY

Unequivocal results demonstrating a causal relationship between a disturbance in circadian rhythms and depression have not yet been reported (reviews). However, acute mood changes, such as the antidepressive effect of sleep deprivation, diurnal variations of mood and their interrelationship, are commonly put forward as evidence of the importance of circadian dysregulations in affective disorders. The purpose of the present study is to obtain more insight in the mechanisms underlying these mood changes. The results will be discussed in the context of a recently postulated non-chronobiological explanation. Earlier studies have suggested that the relationship between diurnal variation of mood and the response to total sleep deprivation (TSD) is clear and unambiguous: improvement of mood during the day prior to TSD (a positive diurnal variation) is followed by a positive response (mood improvement) to TSD, while no improvement or deterioration of mood during the day prior to TSD (a negative diurnal variation) may result in no, or even a negative, TSD response (for references see Van den Hoofdakker). However, these conclusions were based on the results from cross-sectional studies, comparing single TSD effects across individuals. Comparison of sleep deprivation effects within individuals, however, revealed that the course of mood during the day prior to TSD is irrelevant for the TSD response. Accordingly, a favourable response to TSD appeared to be related to the patients propensity to show diurnal mood variations per se, irrespective of their direction.

The eye of the African mole-rat Cryptomys anselli

In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located superficially and display all features typical of sighted animals: iris, pupil and well‐developed lens, separating the anterior chamber and the vitreous. The retina shows a well stratified organization and the folds described in blind subterranean or nocturnal mammals were not observed. The major population of the photoreceptor cells in the Cryptomys retina consists of rod cells, again with a morphology quite similar to that found in sighted animals. The relatively short outer segments contain numerous well‐stacked disks and show a strong rod‐opsin as well as transducin immunoreaction. Synapses were evident in the spherules, the round basal processes of the rod cell, but they lacked the precise organization reported for sighted mammals. Cone cells were present as well, as indicated by peanut lectin staining, but no immunolabelling with polyclonal M/L‐opsin antisera was detectable. The presence of cone cells was also suggested by some basal processes at the outer plexiform layer which displayed several synaptic active sites and irregular contours. While the other retinal layers also showed an organization typical of sighted mammals, there were signs of less tightly preserved morphology as well. Displaced rods and amacrine and/or ganglion cells were observed, and some sparse rod spherules penetrated into the inner nuclear layer. A major reduction was observed in the number of ganglion cells, estimated from the number of axons in the optic nerve, that was very low (≈1000 per retina on average) relative to sighted mammals. The data we have suggest a slow, ongoing loss of cells with ageing. Apoptotic nuclei, mainly corresponding to photoreceptor cells and ganglion cells, were detected in young individuals, and an overall reduction in the thickness of the retina was observed in older animals. The morphological data presented here allow some first speculations on the physiological role of the Cryptomys eye and will hopefully trigger detailed studies on the chronobiology and the anatomy of the retinal projections and of the visual cortex of this remarkable species.