In healthy individuals during No REM sleep the
In healthy individuals, during No REM sleep, the metabolic activity decreases on the frontal, temporal and parietal cortices, in contrast with waking levels; individuals with MD do show a non-significant decrease in activity in the same areas of waking during the beginning of sleep. It is possible that this reduction may reflect a deficit in the processes related to sleep–wake cycle, present in MD as a decreased synaptic potentiation. Other brain areas involved in emotional regulation (anterior cingulate cortex, amygdala, thalamus) also had a smaller decline in metabolic level from waking to No REM sleep. Compared with normal individuals, these structures have an increase in metabolism during sleep. Depressed subjects can also present an increase in metabolic activity within these cortical and subcortical structures during REM sleep, due to the fact that these alterations reflect imbalance of the monoaminergic-cholinergic systems in MD [10,22].
The habenula consists of a pair of small adjacent nuclei to the medium dorsal thalamus. It is divided between medial and lateral portions .The lateral habenula (LHb) receives stimuli from several structures such as the internal segment of the globus pallidus. On the other hand, LHb stimulation inhibits the activity of serotonergic and dopaminergic neurons of the brain stem and this, in turn, stimulates the selective inhibitors of serotonin reuptake, which act upon the axon pre-synaptic terminals to suppress LHb hyperactivation. Dopamine has also an excitatory effect on the activity of LHb, upon which the chronic activation of the dopaminergic inputs of LHb contributes to the hyperactivation of the LHb in MD. Although during sleep, some studies demonstrated that the lesion in LHb reduces the REM sleep, due to the fact that the activity of the LHb neurons is indispensible for the maintenance of the REM sleep, this maintenance being obtained by means of the modulation of the serotonergic activity . Considering the regulation of LHb in serotonergic system, it is reasonable to think that LHb is involved in the regulation of sleep and mood, since, in accordance with the obtained evidences, the hyperactivity of LHb causes heterogeneous symptoms such as reduced motor activity and alteration in REM sleep, which are typical of MD. .
Comorbidity of the primary sleep disorders and MD Certain primary sleep disorders, such as obstructive sleep selective estrogen receptor modulators (OSA) and restless legs syndrome (RLS), are more common in patients with MD than in the general population. OSA is defined by frequent episodes of partial (hypopnea) or complete (apnea) obstruction of the superior airway during sleep . It is associated with MD in an odds ratio of 2.4 in men and 5.2 in women . The high comorbidity of OSA with depression indicates that both disorders share a common neurobiological risk factor . The former is demonstrated by studies of cerebral images which suggest that the hypoxemia from OSA has an impact on mood . In addition, MD and OSA have been associated with metabolic syndrome. It has been postulated that the reduction of serotonin levels in MD worsens the function of the superior airway dilating muscles, a factor that could contribute to OSA; however, this is not demonstrated properly since antidepressants do not improve OSA; besides, the first treatment option for this pathology is the continuous positive airway pressure (CPAP) . As far as RLS is concerned, this is a neurological disorder characterized by an irresistible urgency in moving the legs, especially during rest. This symptom worsens during the night and improves when walking . In an additional study, it has been demonstrated that 26% of patients with MD presented symptoms of RLS, concluding that MD is a risk factor for RLS (with an odds ratio of 1.64). Ohayon, in a telephonic survey, found out that psychiatric disorders have a 50% risk factor to develop RLS [31,32]. The elevated comorbidity of RLS and MD is explained in part by dopamine hypofunction in patients with RLS who also suffer from chronic insomnia, because they have also a risk factor to develop MD [31,33]. Narcolepsy is a neurological disease characterized by irresistible sleep episodes, besides alterations on the REM sleep, caused by hypocretin deficiency. Neuroanatomical studies indicated that hypocretin projections are widespread, including limbic structures, the locus ceruleus and the raphe nucleus. Due to the latter, it regulates mood and several neuroendocrinal functions . According to Ohayon׳s investigation, 19.2% of all narcoleptic patients demonstrated MD, in comparison with only 6.4% of the general population . Some of the additional mechanisms which could also explain the comorbidity of MD in narcolepsy are obesity or overweight, physical inactivity, excessive daytime sleepiness, involvement of quality of life of the patient as well as subjacent medical and sleep disorders.