Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_205_библиотеки_им_акад_М_И_Перельмана
.pdf
102 The APA Publishing Textbook of Mood Disorders, Second Edition
https://t.me/med1917
Karolewicz B, Maciag D, O’Dwyer G, et al: Reduced level of glutamic acid decarboxylase-67
kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol 13(4):411–
420, 2010 20236554
Kasa K, Otsuki S, Yamamoto M, et al: Cerebrospinal fluid gamma-aminobutyric acid and
homovanillic acid in depressive disorders. Biol Psychiatry 17(8):877–883, 1982 7115838
Kaufman J, DeLorenzo C, Choudhury S, Parsey RV: The 5-HT1A receptor in major depressive
disorder. Eur Neuropsychopharmacol 26(3):397–410, 2016 26851834
Klempan TA, Sequeira A, Canetti L, et al: Altered expression of genes involved in ATP biosyn-
thesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with
and without major depression. Mol Psychiatry 14(2):175–189, 2009 17938633
Knorr U, Simonsen AH, Zetterberg H, et al: Biomarkers in cerebrospinal fluid of patients with
bipolar disorder versus healthy individuals: a systematic review. Eur Neuropsychophar
macol 28(7):783–794, 2018 29802040
Kuhn R: [Treatment of depressive states with an iminodibenzyl derivative (G 22355)]. Schweiz
Med Wochenschr 87(35–36):1135–1140, 1957 13467194
Lapin IP, Oxenkrug GF: Intensification of the central serotoninergic processes as a possible
determinant of the thymoleptic effect. Lancet 1(7586):132–136, 1969 4178247
Lemieux G, Davignon A, Genest J: Depressive states during Rauwolfia therapy for arterial
hypertension; a report of 30 cases. Can Med Assoc J 74(7):522–526, 1956 13304797
Lener MS, Niciu MJ, Ballard ED, et al: Glutamate and gamma-aminobutyric acid systems in the
pathophysiology of major depression and antidepressant response to ketamine. Biol Psychiatry 81(10):886–897, 2017 27449797
Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet sero-
tonin uptake site: identity with the brain serotonin transporter. J Neurochem 60(6):2319–
2322, 1993 7684072
Lester D: The concentration of neurotransmitter metabolites in the cerebrospinal fluid of sui-
cidal individuals: a meta-analysis. Pharmacopsychiatry 28(2):45–50, 1995 7542785
Levinson AJ, Fitzgerald PB, Favalli G, et al: Evidence of cortical inhibitory deficits in major
depressive disorder. Biol Psychiatry 67(5):458–464, 2010 19922906
Li Z, He Y, Tang J, et al: Molecular imaging of striatal dopamine transporters in major depres-
sion—a meta-analysis. J Affect Disord 174:137–143, 2015 25497470
Lin Z, Madras BK: Human genetics and pharmacology of neurotransmitter transporters. Handb
Exp Pharmacol (175):327–371, 2006 16722243
Mann JJ, Stanley M, McBride PA, McEwen BS: Increased serotonin2 and beta-adrenergic recep-
tor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43(10):954–959,
1986 3019268
Merali Z, Du L, Hrdina P, et al: Dysregulation in the suicide brain: mRNA expression of corti-
cotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical
brain region. J Neurosci 24(6):1478–1485, 2004 14960621
Merali Z, Kent P, Du L, et al: Corticotropin-releasing hormone, arginine vasopressin, gastrin-
releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides
and control subjects. Biol Psychiatry 59(7):594–602, 2006 16197926
Meyerson LR, Wennogle LP, Abel MS, et al: Human brain receptor alterations in suicide vic-
tims. Pharmacol Biochem Behav 17(1):159–163, 1982 6289359
Miller AH, Haroon E, Felger JC: Therapeutic implications of brain-immune interactions: treat-
ment in translation. Neuropsychopharmacology 42(1):334–359, 2017 27555382
Moriguchi S, Yamada M, Takano H, et al: Norepinephrine transporter in major depressive dis-
order: a PET study. Am J Psychiatry 174(1):36–41, 2017 27631962
Moriguchi S, Takamiya A, Noda Y, et al: Glutamatergic neurometabolite levels in major depres-
sive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Mol Psychiatry 24(7):952–964, 2019 30315224
Müller-Oerlinghausen B, Roggenbach J, Franke L: Serotonergic platelet markers of suicidal be-
havior—do they really exist? J Affect Disord 79(1–3):13–24, 2004 15023476
Mulvihill KG: Presynaptic regulation of dopamine
porters. Neurochem Int 122:94–105, 2019 30465801
release: role of the DAT and VMAT2 trans-
-
103 Neurochemistry of Mood Disorders
https://t.me/med1917
Murrough JW, Henry S, Hu J, et al: Reduced ventral striatal/ventral pallidal serotonin1B recep-
tor binding potential in major depressive disorder. Psychopharmacology (Berl) 213(2–
3):547–553, 2011 20480149
Nemeroff CB, Widerlöv E, Bissette G, et al: Elevated concentrations of CSF corticotropin-releas-
ing factor-like immunoreactivity in depressed patients. Science 226(4680):1342–1344, 1984
6334362
Nemeroff CB, Knight DL, Krishnan RR, et al: Marked reduction in the number of platelet-triti-
ated imipramine binding sites in geriatric depression. Arch Gen Psychiatry 45(10):919–923,
1988a 2844132
Nemeroff CB, Owens MJ, Bissette G, et al: Reduced corticotropin releasing factor binding sites
in the frontal cortex of suicide victims. Arch Gen Psychiatry 45(6):577–579, 1988b 2837159
Nemeroff CB, Bissette G, Akil H, Fink M: Neuropeptide concentrations in the cerebrospinal
fluid of depressed patients treated with electroconvulsive therapy. Corticotrophin-releas
ing factor, beta-endorphin and somatostatin. Br J Psychiatry 158:59–63, 1991 1673078
Ongür D, Drevets WC, Price JL: Glial reduction in the subgenual prefrontal cortex in mood dis-
orders. Proc Natl Acad Sci USA 95(22):13290–13295, 1998 9789081
Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-
sensitive human noradrenaline transporter. Nature 350(6316):350–354, 1991 2008212
Pandey GN: Biological basis of suicide and suicidal behavior. Bipolar Disord 15(5):524–541,
2013 23773657
Pech J, Forman J, Kessing LV, Knorr U: Poor evidence for putative abnormalities in cerebrospinal
fluid neurotransmitters in patients with depression versus healthy non-psychiatric individ
uals: a systematic review and meta-analyses of 23 studies. J Affect Disord 240:6–16, 2018
30041075
Popoli M, Yan Z, McEwen BS, Sanacora G: The stressed synapse: the impact of stress and glu-
cocorticoids on glutamate transmission. Nat Rev Neurosci 13(1):22–37, 2011 22127301
Prévot T, Sibille E: Altered GABA-mediated information processing and cognitive dysfunc-
tions in depression and other brain disorders. Mol Psychiatry 26(1):151–167, 2021 32346158
Raadsheer FC, Hoogendijk WJ, Stam FC, et al: Increased numbers of corticotropin-releasing
hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed
patients. Neuroendocrinology 60(4):436–444, 1994 7824085
Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, et al: Corticotropin-releasing hormone mRNA
levels in the paraventricular nucleus of patients with Alzheimer’s disease and depression.
Am J Psychiatry 152(9):1372–1376, 1995 7653697
Racagni G, Popoli M: Cellular and molecular mechanisms in the long-term action of antide-
pressants. Dialogues Clin Neurosci 10(4):385–400, 2008 19170396
Radhu N, de Jesus DR, Ravindran LN, et al: A meta-analysis of cortical inhibition and excitabil-
ity using transcranial magnetic stimulation in psychiatric disorders. Clin Neurophysiol
124(7):1309–1320, 2013 23485366
Rajkowska G, Miguel-Hidalgo JJ: Gliogenesis and glial pathology in depression. CNS Neurol
Disord Drug Targets 6(3):219–233, 2007 17511618
Ressler KJ, Nemeroff CB: Role of norepinephrine in the pathophysiology and treatment of
mood disorders. Biol Psychiatry 46(9):1219–1233, 1999 10560027
Ressler KJ, Nemeroff CB: Role of serotonergic and noradrenergic systems in the pathophysiol-
ogy of depression and anxiety disorders. Depress Anxiety 12 (suppl 1):2–19, 2000 11098410
Rivero G, Gabilondo AM, García-Sevilla JA, et al: Increased α2- and β1-adrenoceptor densities
in postmortem brain of subjects with depression: differential effect of antidepressant treat-
ment. J Affect Disord 167:343–350, 2014 25020269
Ruhé HG, Mason NS, Schene AH: Mood is indirectly related to serotonin, norepinephrine and
dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychi-
atry 12(4):331–359, 2007 17389902
Sanacora G, Treccani G, Popoli M: Towards a glutamate hypothesis of depression: an emerging
frontier of neuropsychopharmacology for mood disor
77, 2012 21827775
ders. Neuropharmacology 62(1):63–
-
-
104 The APA Publishing Textbook of Mood Disorders, Second Edition
https://t.me/med1917
Savitz JB, Drevets WC: Neuroreceptor imaging in depression. Neurobiol Dis 52:49–65, 2013
22691454
Schildkraut JJ: The catecholamine hypothesis of affective disorders: a review of supporting evi-
dence. Am J Psychiatry 122(5):509–522, 1965 5319766
Schür RR, Draisma LW, Wijnen JP, et al: Brain GABA levels across psychiatric disorders: a sys-
tematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp
37(9):3337–3352, 2016 27145016
Sequeira A, Klempan T, Canetti L, et al: Patterns of gene expression in the limbic system of sui-
cides with and without major depression. Mol Psychiatry 12(7):640–655, 2007 17353912
Sequeira A, Mamdani F, Ernst C, et al: Global brain gene expression analysis links glutamater-
gic and GABAergic alterations to suicide and major depression. PLoS One 4(8):e6585, 2009
19668376
Stockmeier CA: Involvement of serotonin in depression: evidence from postmortem and imag-
ing studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 37(5):357–
373, 2003 12849929
Svenningsson P, Chergui K, Rachleff I, et al: Alterations in 5-HT1B receptor function by p11 in
depression-like states. Science 311(5757):77–80, 2006 16400147
Svenningsson P, Kim Y, Warner-Schmidt J, et al: p11 and its role in depression and therapeutic
responses to antidepressants. Nat Rev Neurosci 14(10):673–680, 2013 24002251
Tiger M, Farde L, Rück C, et al: Low serotonin1B receptor binding potential in the anterior cin-
gulate cortex in drug-free patients with recurrent major depressive disorder. Psychiatry
Res Neuroimaging 253:36–42, 2016 27269199
Tiger M, Varnäs K, Okubo Y, Lundberg J: The 5-HT1B receptor—a potential target for antide-
pressant treatment. Psychopharmacology (Berl) 235(5):1317–1334, 2018 29546551
Veith RC, Lewis N, Langohr JI, et al: Effect of desipramine on cerebrospinal fluid concentrations
of corticotropin-releasing factor in human subjects. Psychiatry Res 46(1):1–8, 1993 8464952
Walter M, Henning A, Grimm S, et al: The relationship between aberrant neuronal activation
in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in
major depression. Arch Gen Psychiatry 66(5):478–486, 2009 19414707
Wang L, Zhou C, Zhu D, et al: Serotonin-1A receptor alterations in depression: a meta-analysis
of molecular imaging studies. BMC Psychiatry 16(1):319, 2016 27623971
Waters RP, Rivalan M, Bangasser DA, et al: Evidence for the role of corticotropin-releasing fac-
tor in major depressive disorder. Neurosci Biobehav Rev 58:63–78, 2015 26271720
Yatham LN, Sossi V, Ding YS, et al: A positron emission tomography study of norepinephrine
transporter occupancy and its correlation with symptom response in depressed patients
treated with quetiapine XR. Int J Neuropsychopharmacol 21(2):108–113, 2018 29016993
CHAPTER 6
https://t.me/med1917
Psychoneuroendocrinology
of Mood Disorders
Luca Sforzini, M.D.
Maria Antonietta Nettis, M.D., Ph.D.
Frances Isabella Weston, B.Sc.
Carmine Maria Pariante, M.D., Ph.D., FRCPsych
The body and mind are profoundly linked. Underpinning this link is the
neuroendocrine system, which is the major route of communication between body
and mind and results from the interaction between the endocrine system and the nervous system (Toni 2004). The endocrine system comprises several glands throughout
the body; these glands release hormones, which in turn can affect many physiological
processes. The interaction between the endocrine and nervous systems helps to maintain homeostasis—that is, the equilibrium among all organs and systems in the body.
It is therefore conceivable that everything that affects the mind could also affect the
body, and vice versa. In fact, each time homeostasis deviates from its optimal func
tioning, an imbalance is caused, which could result in several pathological signs and
symptoms.
Psychoneuroendocrinology is the study of the relationship between the neuroendocrine system and psychiatric symptoms. Compelling evidence indicates that endocrine dysregulations are frequently associated in a bidirectional link with psychiatric
conditions, including mood disorders. In particular, neuroendocrine alterations are
-
This research was funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), London, United Kingdom. This work was also supported by
the Wellcome Trust strategic award (104025) to the Neuroimmunology of Mood Disorders and
Alzheimer’s Disease (NIMA) Consortium, which is also funded by Janssen, GlaxoSmithKline,
Lundbeck, and Pfizer. Dr. Sforzini and Prof. Pariante report grant funding from the European
Commission (IMI2 853966).
105
106 The APA Publishing Textbook of Mood Disorders, Second Edition
https://t.me/med1917
among the biological alterations most consistently reported in both major depressive
disorder (MDD) and bipolar disorder (Belvederi Murri et al. 2014; Daban et al. 2005;
Delvecchio et al. 2017). In this chapter, we discuss in detail the psychoneuroendocri
nology of mood disorders by describing different neuroendocrine systems, their interactions, and their clinical relevance to the development of psychiatric symptoms.
Physiology of the Neuroendocrine System
Our review focuses on four major components of the neuroendocrine system: the
hypothalamic-pituitary-adrenal (HPA), the hypothalamic-pituitary-thyroid (HPT),
and the hypothalamic-pituitary-gonadal (HPG) axes, and the hypothalamic-neuro
hypophysial system (HNS). The HPA, HPT, and HPG axes show similar functioning.
The coordinating center is the hypothalamus, which receives numerous cortical and
peripheral inputs and communicates directly with the pituitary gland. In particular,
the hypothalamus produces neurohormones—also called releasing hormones because of
their ability to regulate the secretion of hormones from the pituitary gland (also called
the hypophysis). The pituitary gland stimulates production of hormones in peripheral
glands. Notably, within each axis, there is a negative feedback system that self-regu
lates hormonal production: peripheral hormones act upstream in each axis, inhibiting
the release of the respective hypothalamic and pituitary hormones. In contrast, the
HNS involves hypothalamic neurons and their axonal projection to the posterior pituitary (or neurohypophysis), where hormones are then released into the bloodstream. The
physiology of the neuroendocrine system is graphically summarized in Figure 6–1.
-
-
-
Hypothalamic-Pituitary-Adrenal Axis
The HPA axis is pivotal in modulating immune responses and, together with the autonomic system, it is also the main center involved in stress response (Ulrich-Lai and
Herman 2009). Following stressful stimuli, the autonomic sympathetic system rep
resents the most rapid response, whereas the HPA axis is responsible for more complex
and both acute and longer-term biological modifications, modulating homeostasis in
the whole body, including the brain. These biological effects aim to promote the fightor-flight response—that is, the physiological changes that occur in the body in response
to stressful and potentially harmful stimuli.
The final products of the HPA axis are glucocorticoid (GC) hormones, mainly cortisol in humans. The paraventricular nucleus of the hypothalamus produces corticotropin-releasing hormone (CRH), leading to the release of adrenocorticotropic hormone
(ACTH) in the pituitary gland. This stimulates the cortical region of the adrenal
glands, which are two endocrine glands located on top of the kidneys. Finally, the adrenal cortex stimulation induces the discharge of GC hormones.
GC hormones are a class of steroid hormones synthesized from cholesterol and
then capable of passing through lipid membranes and acting on nuclear receptors.
GC hormones act on two different types of receptors: the GC receptor (GR), encoded
by the NR3C1 (nuclear receptor subfamily 3, group C, member 1) gene, and the mineralocorticoid receptor (MR). Cortisol binds with low affinity to GRs and with high
affinity to MRs. This is consistent with the hypothesis that MR binding is mainly in-
-
107 Psychoneuroendocrinology of Mood Disorders
https://t.me/med1917
FIGURE 6–1. Physiology of the neuroendocrine system.
To view this figure in color, see Plate 1 in Color Gallery in middle of book.
Schematic representation of the four major components of the neuroendocrine system: the HPA, HPT, and
HPG axes and the HNS. Hypothalamic neurons produce releasing hormones and HNS hormones. Releasing
hormones act on the anterior pituitary gland, causing the release of stimulating hormones. HNS hormones
are released from hypothalamic axons in the posterior pituitary, also called the neurohypophysis. The stim
ulating hormones produced in the pituitary gland then stimulate peripheral organs (thyroid, gonads, and
adrenal cortex) to produce specific hormones, which in turn exert several biological functions (T
terone, progesterone, estrogens; and cortisol, respectively). These peripheral hormones also act backward
within each axis, self-controlling their production via a negative feedback. The hypothalamic-pituitary
thyroid (HPT) axis is represented in red, the hypothalamic-pituitary-gonadal (HPG) axis in blue, the hypothalamic-pituitary-adrenal (HPA) axis in yellow, the hypothalamus and the hypothalamic-neurohypophysial system (HNS) in black, and the pituitary gland in green. Arrows indicate a stimulation, and dotted lines
an inhibition. Hormone-producing organs are shown in rounded boxes, and hormonal products in rectangles.
ACTH= adrenocorticotropic hormone; AVP=arginine vasopressin; CRH=corticotropin-releasing hormone;
FSH= follicle-stimulating hormone; GnRH= gonadotropin-releasing hormone; LH=luteinizing hormone;
OT= oxytocin; T
stimulating hormone.
=triiodothyronine; T4=thyroxine; TRH=thyrotropin-releasing hormone; TSH=thyroid-
3
, T4; testos-
3
volved in the homeostatic basal function, whereas cortisol-GR binding is more clearly
related to stress response, when cortisol levels are raised (Pariante 2004).
GRs are the main modulators of HPA axis activity; they are necessary for life after
birth and are expressed in nearly every cell of the body. Following GC binding,
through different isoforms and diverse signaling cascades, GRs regulate the transcription of target genes and mediate composite biological actions (Oakley and Cidlowski 2013). Central in GR functioning and sensitivity is the FKBP5 gene, encoding
FK506-binding protein 51 or FKBP51, a co-chaperone protein (Alhajji and Nemeroff
-
-
108 The APA Publishing Textbook of Mood Disorders, Second Edition
https://t.me/med1917
2015) that physiologically binds to the GR complex, reducing the receptor affinity for
GC. The increased transcription and translation of FKBP5 following the activation of
GRs by GC hormones further reduce the GR sensitivity in an overall ultrashort nega
tive feedback loop (Binder 2009; Menke 2019).
Cortisol production is a highly controlled process, optimized to maintain GC hormone levels in the perfect range. As for other neuroendocrine systems, in normal individuals, cortisol regulates the synthesis of CRH by exerting negative feedback that
controls its own production (Zunszain et al. 2013). Interestingly, this negative feed
back is mediated by GR and thus is impaired when GR i s disrupted, such as in chronic
GC stimulation. This phenomenon, called GC resistance, in turn leads to HPA axis
hyperactivity (Pariante and Lightman 2008; Pariante and Miller 2001). The most dif
fused clinical tests for assessing HPA axis function, namely suppression tests, assess
the efficacy of the negative feedback mechanism. In the dexamethasone suppression
test, cortisol levels are measured after the injection of the exogenous steroid dexamethasone, which binds to GR. The prednisolone suppression test has the advantage
of probing both GR and MR (Juruena et al. 2009). Cortisol levels show a marked cir
cadian rhythm; they peak in the morning shortly after a person wakes (around 8
A.M.), in what is defined as the cortisol awakening response (Elder et al. 2014), and
then progressively decline during the day, reaching the nadir in the middle of the
night, about 3–5 hours after a person falls asleep (roughly from midnight to 4
A.M.).
-
-
-
-
Hypothalamic-Pituitary-Thyroid Axis
The HPT axis is pivotal in the regulation of metabolism. Thyroid hormones affect
basal metabolic rate, energy balance, protein synthesis, and cell growth. The hypo
thalamus produces thyrotropin-releasing hormone (TRH), thus stimulating the anterior pituitary to release thyroid-stimulating hormone (TSH). TSH acts on the thyroid,
an endocrine gland located in the anterior part of the neck, to produce the thyroid
hormones, namely triiodothyronine (T
hormone calcitonin. The thyroid mainly releases T
then enzymatically converted to T
) and thyroxine (T4), together with the peptide
3
into the bloodstream, where it is
4
, which has a much higher affinity for the thyroid
3
hormone receptor, a nuclear receptor (Baek et al. 2014). When the HPT axis is bal
anced, a person has a condition of euthyroidism. The HPT axis can be disrupted in
two main directions, resulting in increased or reduced thyroid functioning, referred
to as hyperthyroidism or hypothyroidism, respectively. Moreover, TSH levels may be
altered in the presence of normal thyroid hormones levels, resulting in what is called
subclinical hypo- or hyperthyroidism. T
and T4 inhibit TRH and TSH secretion via a
3
negative feedback similar to the one described in the HPA axis.
Hypothalamic-Pituitary-Gonadal Axis
The HPG axis is the main regulator of reproductive functions. The hormones estrogen,
progesterone, and testosterone are secreted from gonads, and are differently represented according to sex. The hypothalamus secretes gonadotropin-releasing hormone
(GnRH), which stimulates the anterior pituitary to produce luteinizing hormone (LH)
and follicle-stimulating hormone (FSH). These two hormones, each with precise and
different roles, exert their action on the gonads. In females, they act together on the
ovaries to produce estrogen and progesterone, thus regulating menstrual and ovarian
-
-
109 Psychoneuroendocrinology of Mood Disorders
https://t.me/med1917
cycles. In males, they act chiefly on testes to induce the production of testosterone and
regulate spermatogenesis. Sex hormones could inhibit their own production, acting on
the hypothalamus or hypophysis via a negative feedback. Circulating sex hormones
are largely bound to carrier proteins, mainly albumin and sex hormone–binding globulin; thus, only very small percentages of estrogens and testosterone (approximately
1%–2%) are unbound (i.e., free) and bioactive.
Sex hormones exert their function by acting on specific nuclear receptors. There are
two main types of estrogen receptors, alpha (ER-α) and beta (ER-β). Androgens act
primarily on the androgen receptor. Estrogen levels change widely in relation to life
stages and menstrual and ovarian cycles. Testosterone levels can also vary according
to an individual’s age, even if in a less dramatic way. Interestingly, however, andro
gen levels also may vary within the same day, similar to cortisol, with significant diurnal variations (Long et al. 2015). In addition to its obvious function of regulating the
life cycle and reproduction, the HPG axis affects several other biological functions, in
cluding the activity of the immune system, which in turn affects brain development,
structure, and functioning.
Hypothalamic-Neurohypophysial System
In addition to the three main axes discussed above, a fourth part of the neuroendocrine
system that is important for mood disorders is the HNS, which includes projections of
hypothalamic neurons to the posterior pituitary, or neurohypophysis. These neurons
produce two structurally related neurohypophysial hormones, oxytocin (OT) and arginine vasopressin (AVP), which are then released into the bloodstream. OT facilitates
lactation and parturition by acting on mammalian glands and uterus smooth muscles.
It also plays an important and widespread role in social functioning (Jones et al. 2017).
Interestingly, OT promotes affiliation and both mother-child and pair bonding and
modulates fear and anxiety behavior (Zik and Roberts 2015). AVP, also called antidi
uretic hormone (ADH), regulates body water balance and fluid homeostasis by regulating blood pressure, osmotic balance, and kidney function. The release of AVP can be
pathologically increased, as observed in the syndrome of inappropriate ADH secre
tion (SIADH), or decreased, causing diabetes insipidus, with inability to concentrate
urine (Verbalis 2014). AVP acts on three different receptors (V1a, V1b [also known as
V3], and V2), whereas OT has a unique receptor (Surget and Belzung 2008). Of note,
there is cross-reactivity in the binding of AVP and OT with their respective receptors,
with a higher bonding affinity observed for OT (Kimura et al. 1994; Lach et al. 2018;
Surget and Belzung 2008).
-
-
-
-
Cross Talk Between Endocrine
and Immune Systems
In the wide-ranging and multifaceted field of psychoneuroendocrinology, the immune system also plays a central role. Indeed, the neuroendocrine system is firmly
connected to the immune system in a complex neuroimmune-endocrine interaction
(Ashley and Demas 2017), which influences both hormonal functioning and the immune response in order to maintain homeostasis. Immune system cells can produce
110 The APA Publishing Textbook of Mood Disorders, Second Edition
https://t.me/med1917
low levels of different hormones, and neuroendocrine system cells can release cytokines (Verburg-van Kemenade et al. 2017). Remarkably, alterations of the immune
system have been widely linked to several psychiatric diseases, including mood dis
orders (Pariante 2017; Stetler and Miller 2011). The immune system and its response,
inflammation, are therefore important factors in the relationship between the neuro
endocrine system and mood disorders.
Particularly important in the endocrine-immune cross talk is the HPA axis, which
directly controls the immune system, and vice versa. Indeed, immune cells express
both GRs and adrenergic receptors (Ménard et al. 2017). In addition, a number of
proinflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis
factor alpha, can activate the HPA axis. On the other hand, cortisol has an extremely
powerful anti-inflammatory effect. Therefore, the HPA axis acts as a modulator of the
inflammatory responses that occur throughout the whole body, including the CNS
(Otmishi et al. 2008). The hyperactivation of the HPA axis, which is typical under
chronic conditions, can induce persistent GC resistance. The lack of GR-mediated neg
ative feedback leads to HPA axis hyperactivity, and at the same time the lack of GRmediated restraint of inflammation leads to increased inflammation (Pariante 2014).
Finally, an excess of cortisol may activate the kynurenine pathway (Menke 2019). This
catabolic pathway for tryptophan is enhanced both in inflammation and depression;
therefore, it has been proposed as a potential biological shared mechanism for depres
sion comorbid with immune-related diseases (Sforzini et al. 2019).
The HPT axis also is linked to the immune system (Masek et al. 2003). In fact, thyroid function is fundamental for the normal development of the thymus, which is a
specialized organ of the immune system in which hematopoietic precursors from the
bone marrow, called thymocytes, mature into the immune cells, called T-lymphocytes.
Again, this relationship is bidirectional; activated immune cells are able to synthesize
and secrete small quantities of TRH (Masek et al. 2003). Furthermore, the thyroid is the
organ that is most commonly affected by autoimmune diseases (McLeod and Cooper
2012). Autoimmunity is a fascinating concept: it is the process involving the activa
tion of the immune system against the individual’s own healthy cells. Three different
thyroid proteins can be targeted by specific autoantibodies: thyroid peroxidase anti
body (TPOAb), thyroglobulin antibody (TGAb), and TSH receptor antibody (TRAb).
The same bidirectional link with the immune system characterizes both the HPG
axis and the HNS. This is demonstrated by the expression of both estrogen receptors
(ER-α and ER-β) and androgen receptors (Taub 2008) in the immune cells and by the
ability of inflammatory cytokines such as interleukin-1 to stimulate the release of both
AVP and OT (Landgraf et al. 1995). Because this chapter focuses specifically on psy
choneuroendocrinology, we will not explore the function of immune processes further,
and we will mention them only when directly related to the neuroendocrine system.
-
-
-
-
-
-
-
Role of Neuroendocrine and Immune Systems
in Mood Disorders
Just as a disruption at any level within the neuroendocrine and immune systems could
result in severe consequences for a person’s health, including mental health, a person’s
111 Psychoneuroendocrinology of Mood Disorders
https://t.me/med1917
neuroendocrine and immune systems may be altered by different psychiatric diseases.
Disruptions in homeostatic balance could follow both external and internal stressors,
or basically everything that causes stress to an organism. An appropriate response to
stress involves both the immune and the neuroendocrine systems (McEwen et al. 2015;
Ulrich-Lai and Herman 2009). Under physiological conditions, body and mind are
able to face even massive perturbations. Yet, at times, homeostasis is disrupted.
Most research available on mood disorders focuses on unipolar depression. Characteristics intrinsic to bipolar disorder complicate the recognition of specific etiopathogenetic mechanisms. Indeed, the clinical picture, with depressive and manic or hypomanic episodes, is often unstable, and the clinical presentation could be extremely wide
ranging. Misdiagnosis of patients with bipolar disorder is unfortunately a frequent
event (Angst et al. 2003), due to potential overlap with depressive disorders, as well as
with psychotic disorders. Moreover, even in patients diagnosed with bipolar disorder,
most data are collected in depressive episodes, and less evidence is available on manic,
hypomanic, and mixed episodes. Bearing in mind these challenges, we discuss the
available evidence on the relationship between each of the four components of the
neuroendocrine system and depression and bipolar disorder, respectively.
Hypothalamic-Pituitary-Adrenal Axis
Depression
The HPA axis has been demonstrated to be crucial in the pathophysiology of depressive disorders. This is not surprising, given the role of this axis in mediating between
stress responses and brain functioning (Pariante and Lightman 2008). Hyperactivity
of the HPA axis is probably the most prominent and consistent neuroendocrine abnormality found in depression (Min et al. 2012; Pariante and Lightman 2008). Patients
with depression typically exhibit higher baseline cortisol levels, altered responses to
the dexamethasone suppression test, and reduced GR mRNA expression (Palazidou
2012). HPA axis hyperactivity has also been proposed as a biological mechanism explaining the high prevalence of comorbid medical illnesses during depression (Stetler
and Miller 2011). In a large meta-analysis, Stetler and Miller (2011) confirmed this evi
dence of HPA axis hyperactivity in depressed individuals. Specifically, they found increased levels of cortisol and ACTH, but no difference in CRH, in patients with
depression compared with healthy control subjects. They found that the degree of
HPA axis hyperactivity was variable across groups of patients with depression, being
the most marked in older hospitalized individuals and in patients with depression
with melancholic or psychotic features. Therefore, interestingly, HPA biological cor
relates of depression may be different based on clinical features, such as depression
subtype or age.
Consistently, increased cortisol levels have been found in patients who have depression with psychotic features compared with healthy subjects and with patients with
nonpsychotic depression (Cherian et al. 2019). Moreover, Lamers et al. (2013) found
that the HPA axis was hyperactive in patients with depression with melancholic features; they also observed a lower diurnal slope in patients with depression with atypical features compared with subjects without atypical depression. In a recent systematic
review exploring the evidence to date on the HPA axis in depression with seasonal pattern, Agustini et al. (2019) found some evidence of an attenuated cortisol awakening
-
-
Соседние файлы в папке Библиотека им академика М.И. Перельмана