Pineal Gland Volume in Major Depressive and Bipolar Disorders

Abstract

Abnormal melatonin secretion has been demonstrated in patients with affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). However, magnetic resonance imaging (MRI) studies that previously investigated the volume of the pineal gland, which regulates circadian rhythms by secreting melatonin, in these patients reported inconsistent findings. The present study employed MRI to examine pineal gland volumes and pineal cyst prevalence in 56 MDD patients (29 currently depressed and 27 remitted patients), 26 BD patients, and matched controls (33 for MDD and 24 for BD). Pineal volumes and cyst prevalence in the current MDD, remitted MDD, and BD groups did not significantly differ from those of the healthy controls. However, pineal gland volumes were significantly smaller in the current MDD subgroup of non-melancholic depression than in the melancholic MDD subgroup. Interestingly, pineal volumes correlated negatively with the severity of loss of interest in the current MDD group. Medication and the number of affective episodes were not associated with pineal volumes in the MDD or BD group. While these results do not suggest that pineal volumes reflect abnormal melatonin secretion in affective disorders, they do point to the possibility that pineal abnormalities are associated with clinical subtypes of MDD and its symptomatology.

Potential contribution of pineal atrophy and pineal cysts toward vulnerability and clinical characteristics of psychosis

“…In the present study, the prevalence of pineal cysts in the control group (18.0% for cysts ≥2 mm, 29.5% for small cystic changes <2 mm) was consistent with that in high-resolution MRI studies that differentiated a cyst ≥2 mm (16.1 to 29.1%) and small cystic changes (8.9 to 21.2%) ( Pu et al, 2007 , Sun et al, 2009 , Takahashi et al, 2019a , Takahashi et al, 2020 ). The prevalence of pineal cysts or small cystic changes did not significantly differ between the groups examined herein; however, schizophrenia patients with pineal cysts, particularly large cysts (≥2 mm), exhibited severe positive and mild negative symptoms.…”

“…Moreover, alterations have been reported in melatonin secretory patterns in various neuropsychiatric disorders, including affective disorders ( Pacchierotti et al, 2001 ), autism spectrum disorders ( Rossignol and Frye, 2014 ), and Alzheimer’s disease ( Wu and Swaab, 2005 ). In addition, patients with major depression, particularly the non-melancholic subtype ( Takahashi et al, 2020 ), may have smaller pineal volumes and a higher prevalence of pineal cysts than controls ( Zhao et al, 2019 ). Therefore, further studies on the disease specificity of pineal abnormalities are warranted.…”

“…As previously described in detail ( Takahashi et al, 2019a , Takahashi et al, 2020 ), one rater (TT), who was blinded to the identities of subjects, manually traced the pineal gland on consecutive 1-mm coronal images ( Fig. 1 ).…”

Circadian and Sleep Modulation of Dreaming in Women with Major Depression

“…Accordingly, alterations of circadian gene networks may influence mood disorders, particularly (moderate-to-severe) MDD, through the disruption of monoamines and dopamine transmission [29]. Furthermore, magnetic resonance imaging (MRI) assessments of the pineal gland (a major site of melatonin synthesis) in current MDD, remitted MDD, bipolar depression and (age and sex-matched) healthy controls indicated smaller pineal volume in individuals experiencing current MDD, which was associated with the severity of their depression symptoms [30]. While that study did not include melatonin assessments, pineal abnormalities may be associated with specific subtypes of MDD and symptom severity.…”

Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression

“…Circadian gene polymorphisms have been associated with affective disorders, including depression, through the modulation of MAO-A and dopamine neurotransmission [143]. Moreover, pineal abnormalities lead to altered melatonin secretion and circadian disruptions, which are related with clinical subtypes of MDD and its symptomatology [144]. Therefore, the evaluation of circadian rhythm differences in depressed-like mice before and after antidepressant treatments is of utmost importance.…”