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Chronobiology perspectives in psychiatry/Perspective ale cronobiologiei in psihiatrie.

INTRODUCTION

Chronobiology is the science that studies the circadian, monthly and seasonal rhythms; it has developed exponentially in the past decade and it has recorded discoveries at the major molecular and neuroanatomic level. Circadian rhythm manifests itself at each hierarchical level: from the general population (e.g., most traffic accidents occur at night) to the individual (sleep/ wake cycle), to every organ, cell and molecule. Changes in rhythm provide the temporal organization necessary for the right function at the right time (1, 2).

Biological rhythm is no a new notion for psychiatry; as early as the 19th century, more and more data have proven the importance of periodicity in psychopathology. In the '60s, Menninger-Lerchenthal proposed a hypothalamic neuroendocrine mechanism--to explain the astonishing precision of circadian and seasonal rhythms in close connection with clinical symptoms and behaviour--confirmed and detailed by numerous modern studies (1, 2).

The main synchronizing agent or zeitgeber for the central nervous system is light transmitted directly from the retina via the retinohypothalamic tract. The photic input to the central nervous system is nonvisual; thus, classic cone and rod photoreceptors--important for vision of colour, movement, shape and edges--play a secondary role to circadian photoreceptors at the level of retinal ganglion cells. They contain the photopigment melanopsin, which is sensitive to blue light. One important pathway from the central nervous system leads to the pineal gland, where melatonin is synthesized at night. The secretion of this hormone is inhibited by light (4, 9).

The main characteristic of a zeitgeber is that it can alter the direction of circadian rhythms, depending on the time of day. Both light and melatonin are zeitgebers. Favouring factors for oscillations of the circadian rhythm are found in every organ and in every cell. Moreover, each organ has its own zeitgeber. Adequate temporal organization is crucial for coordinating functions that occur at the same time and for separating antagonistic functions (1).

Therefore, the clocks of both, brain and body are dependent on daily exposure to specific Zeitbergers, for a good coordination. The desynchronization of the circadian rhythm perpetuates and exacerbates clinical symptoms and it can even cause psychopathology.

The study conducted by Bromundt on patients with schizophrenia found that the cognitive functioning of these patients depends on the degree of consolidated circadian rhythms.

At the same time, biological clocks are influenced by nonphotic zeitbergers, such as physical exercise, sleep and food (3). Social factors, such as jobs and other such demands, act indirectly on the central nervous system, because they determine the timing of meals, sleep, physical exercise and light exposure. They have been considered as therapeutic options (1, 4, 5).

Biological rhythms and affective disorders

Periodicity has an important role in the evolution of affective disorders; illness recurrence ranges from seasonal depressive episodes to rapid-cycling manic/depressive episodes. The symptoms related to diurnal and early morning variations of mood suggest rhythmic dysfunction. Circadian rhythms--including hormonal secretion, neurotransmitter function and body temperature--are impaired. Furthermore, hypnic disturbances represent another core element of bipolar disorder, and insomnia often predicts the onset of mood disorder symptomatology (1, 4, 5). At the same time, sleep disturbances are frequent residual symptoms of depression, thus marking an increased risk of relapse. Any disturbance of sleep and circadian rhythms brings along the risk of mood fluctuation, especially in individuals prone to it (6, 7).

Chronotherapy

The biological rhythms of each individual are vulnerable, and their misalignment entangles mood and sleep variations; the last two are closely connected. A series of methods based on light exposure /deprivation and on the modulation of zeitgeber in the central nervous system were created, all meant to resynchronize internal clocks.

These therapies--almost all involving no drugs--targeting the zeitbegers in the central nervous system are chronotherapies. They take various forms, adapted to the nature of mental symptomatology: light therapy, dark therapy, and sleep restriction therapy (1, 2, 28).

Light therapy

The first studies on seasonal affective disorder were initiated three decades ago (8). As it debuted under the influence of environmental triggers like shortened days, the light stimulating a summer day seemed the logical treatment -- and it worked, eventually.

Light therapy was the first successful treatment in psychiatry based on neurobiological principles. It is currently the treatment of choice for seasonal affective disorders (9). Light is also an efficient "antidepressant" in nonseasonal depression (10, 11). Studies have found that light potentiates the effect of antidepressants in unipolar depression and of lithium in bipolar depression (1, 10, 11).

Light therapy is a viable alternative for patients who refuse or cannot tolerate psychotropic medication, as well as for ante partum depression. This form of therapy has been proven successful even for patients with chronic depression (two years or more) and for geriatric patients with hyperthymic negative symptomatology. Light therapy has also been used successfully in other psychiatric and neurological illnesses, including bulimia nervosa, childhood and adult ADHD, Parkinson's disease and Alzheimer dementia (13, 14).

In sleep medicine, light is used as peitgeber to resynchronize the sleep schedule. The light box is the standard, most tested and used device in light therapy: it comprises a diffusion screen with a UV filter and 10,000 lux, at a distance of approximately 30-35 centimetres (recommended distance) (1, 9). Long-term exposure to wavelengths between 400 and 500 nm may induce photochemical retinal injury or it can precipitate age-related macular degeneration. Hence, the light box uses white illumination, with wavelengths lower than 450 nm (15). Though the circadian photoreceptors are more sensitive to lower wavelengths, there are no long-term safety or efficiency studies to allow blue light devices for the time being. In the treatment of seasonal affective disorders, the timing of light therapy is fundamental. It must be individually defined, considering the personal particularities of the internal body clock and of the sleep--wake cycles. The patients' sleeping habits provide an indirect estimate of internal body clocks.

The Horne--Ostberg Morningness--Eveningness Questionnaire can be used to choose the best time to begin light therapy. It comprises 19 questions concerning the daily sleeping--waking patterns (12).

The side effects of this kind of therapy are rare; they include hypomania in patients with bipolar depression, mild visual complaints, irritability, headache and nausea, which usually disappear within a few days of treatment (9). Sleep disturbances may emerge that are usually associated with bad timing for light therapy (e.g., light therapy administered in the evening can determine difficulties in falling asleep and light therapy administered in the morning may lead to premature wakening).

Dawn simulation is a more recent alternative to the light box, which involves a stimulation with medium intensity signal that gradually increases over 45 minutes, from about 0.001 lux to approximately 300 lux during the last period of the sleep episode (up to two hours before awakening). This technique shortens the time spent by the patient considering that the patient, sleeps the entire time, but the effectiveness of dawn simulation is still an open matter (1, 27, 28).

Light therapy is often prescribed for the aforementioned pathology, especially for seasonal affective disorder (1).

Wake Therapy/Sleep Restriction

The slow response to most antidepressants is a major issue when it comes to treating patients with depression. In contrast, there is the paradoxical effect of sleep deprivation for one night and the following day. This form of therapy was first studied four decades ago. Approximately 60% of the patients respond with significant improvement of depressive symptomatology (13). The therapeutic effects are noticeable mostly when the patient is sleep deprived in the second half of the night (after 1 a.m.). When it is associated with light therapy and/or pharmacological therapies, it has been proven more effective and inducing long-term remission. It has proven effective in both bipolar and unipolar depression (16, 17). Sleep deprivation therapy includes 1-3 cycles of complete sleep deprivation separated by nights destined for recovery sleep. It has been shown that most patients can undergo various easy activities and even moderately complex activities (chores, on-line working) in the morning following sleep deprivation. This form of therapy is the most rapid antidepressant treatment in current practice (21). Compared to standard antidepressant treatment, which requires two--eight weeks for improving symptomatology, sleep deprivation therapy is effective within a matter of hours. Light therapy takes a little more time: one--three weeks (1, 6, 18), but it is still efficient.

Sleep phase advance is a form of chronotherapy that shifts progressively the sleeping and waking patterns of the patient and it is often associated with antidepressant treatment. After one day and one night of sleep derivation, the patient starts a sleep from 6 p.m. to 1 a.m. (seven hours), while the following day, from 8 p.m. to 3 a.m. (seven hours) and the last day, from 10 pm to 5 am, in an attempt to regulate the circadian rhythm, almost always impaired in disorders of the depression spectrum (1, 6).

The three forms of chronotherapy can be associated as a triple therapy (6).

Dark therapy

Another form of chronotherapy focuses on exposure to darkness, and it is particularly useful in bipolar disorder, mostly in manic patients. Keeping them in dark rooms has been shown to improve hyperthymic positive symptomatology and to stop rapid cycling (19, 20).

This form of therapy is interesting because of its immediate response, but it is not very practical. Another alternative is currently under investigation--blue-blocking-sunglasses--, to induce "circadian darkness" without impairing the patient's vision.

Chronobiotics--melatonin

Melatonin, secreted by the pineal gland, rises in serum levels in the evening, thus preparing the body for sleep. If its secretion is impaired, as in depressive spectrum, sleep disturbances occur. Not a sedative per se, exogenous administration of melatonin acts as a genuine zeitgeber, to synchronize circadian rhythm and induce sleep. Melatonin has not been shown to have notable effects on mood in persons without affective disorders, but it may worsen depressive symptoms (22). A great deal of research exists on this therapy for persons who are blind or visually impaired and suffering from sleep disturbances, since it provides the synchronizing agent that they lack. However, there are limitations in prescribing melatonin in sleep disturbances, considering the limited data on its safety. An exception is two melatonin antagonists, approved by the Food and Drug Administration, Rozerem and Tasimelteon, strictly used for insomnia (23, 24, 25). Unlike them, the melatonin agonist agomelatine--approved in the European Union--has additional antidepressant properties provided by its serotonergic component, besides its role of Zeitgeber in sleep regulation (19, 26).

CONCLUSIONS

Chronobiology is a revolutionary perspective when it comes to explain affective symptomatology and sleep disturbances. In exchange, chronotherapy is an approach still open to research, which has already started to prove its efficacy; furthermore, it has a great safety profile and minimum side effects. In monotherapy, combined or associated to classic medication, chronotherapies are therapeutic forms worth to consider for the remission of affective disorders and sleep disturbances; there is a close, bidirectional relation between the two therapies.

ACKNOWLEDGMENTS AND DISCLOSURES

Authors state that there are no declared conflicts of interest regarding this paper.

REFERENCES

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(7.) Wirz-Justice, A., Bromundt, V, Cajochen, C., Circadian disruption and psychiatric disorders: the importance of entrainment, Sleep Med. Clin., 2009; 4:273-284

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(13.) www.cet.org

(14.) Wirz-Justice, A., Benedetti, F., Terman, M., Chronotherapeutics for Affective Disorders: A Clinician's Manual for Light and Wake Therapy, Basel, Switzerland: S Karger AG; 2009

(15.) Riemersma-van der Lek, R. F., Swaab, D. F., Twisk, J. et al., Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial, JAMA. 2008; 299:2642-2655

(16.) MD Support: The Eyes of the Macular Degeneration Community. http://www.mdsupport.org. Accessed August 18, 2011

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(22.) Wehr, T. A., Turner, E.H., Shimada, J. M., Lowe, C. H., Barker, C., Leibenluft, E., Treatment of rapidly cycling bipolar patient by using extended bed rest and darkness to stabilize the timing and duration of sleep, Biol Psychiatry, 1998; 43:822-828

(23.) Wehr, T. A., Goodwin, F. K., Biological rhythms in manic-depressive illness, in: Wehr, T. A., Goodwin, F. K. (eds.), Circadian Rhythms in Psychiatry, Pacific Grove, Calif: The Boxwood Press; 1983: 129-184

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(27.) Krauss, S. S., Depue, R. A., Arbisi, P. A., Spoont, M., Behavioral engagement level, variability, and diurnal rhythm as a function of bright light in bipolar II seasonal affective disorder: an exploratory study, Psychiatry Res., 1992; 43:147-160

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Ilinca Untu--M. D., Ph. D. Student, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Resident in Psychiatry, "Socola" Clinical Psychiatric Hospital, Iasi, Romania

Diana Bulgaru Iliescu--M. D., Ph. D., Postdoctoral Researcher, Assistant Professor, Department of Forensic Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Senior Coroner, Institute of Forensic Medicine, Iasi, Romania

Anton Knieling--M. D., Ph. D., Assistant Professor, Postdoctoral Researcher, Department of Forensic Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Senior Coroner, Institute of Forensic Medicine, Iasi, Romania

Dania Andreea Radu--M. D., Ph. D. Student, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Resident in Psychiatry, "Socola" Clinical Psychiatric Hospital, Iasi, Romania

Lucian Stefan Burlea--M. D., Ph. D., Assistant Professor, Postdoctoral Researcher, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania

Anamaria Ciubara--M. D., Ph. D., Assistant Professor, Postdoctoral Researcher, Department of Psychiatry, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Junior Psychiatrist, "Socola" Clinical Psychiatric Hospital, Iasi, Romania

Roxana Chirita--M. D., Ph. D., Postdoctoral Researcher, Professor Department of Psychiatry, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi; Senior Psychiatrist, "Socola" Clinical Psychiatric Hospital, Iasi, Romania

Correspondence:

ANAMARIA CIUBARA

"Socola" Clinical Psychiatric Hospital Iasi, Sos. Bucium nr. 34-36, code 700282, Iasi, Romania

Tel./fax: +40 232 430 920, int.142

E-mail: anamburlea@yahoo.com

Date of submission: June, 13, 2014 / Acceptance: August, 29, 2014

INTRODUCERE

Cronobiologia este stiinta care studiaza ritmurile circadian, lunar si sezonier, cunoscand o dezvoltare exponentiala in ultimul deceniu si inregistrand descoperiri majore la nivel molecular si neuroanatomic. Ritmul circadian se manifesta la fiecare nivel ierarhic, de la populatia generala (de exemplu: majoritatea accidentelor de circulatie se petrec noaptea) pana la individ (ciclul somn--veghe), la fiecare organ, celula si molecula. Schimbarile ritmice determina organizarea temporala necesara pentru functionarea optima, la momentul oportun (1, 2).

Ritmul biologic nu este o notiune noua pentru psihiatrie, inca din secolul al XIX-lea, colectandu-se un numar crescut de date care demonstreaza importanta periodicitatii in psihopatologie. In anii '60, Menninger-Lerchenthal a propus un mecanism hipotalamic neuroendocrin, care sa explice precizia uimitoare a ritmului circadian, cat si a celui sezonier in stransa relatie cu simptomele clinice comportamentale, ce s-a confirmat si detaliat de-a lungul timpului, prin numeroase cercetari (1, 2).

Principalul agent de sincronizare pentru sistemul nervos central sau zeitgeber-ul este lumina transmisa direct de la retina catre tractul retinohipotalamic. Input-ul fotonic asupra sistemului nervos central este non-vizual, astfel clasicii receptori luminosi cu bastonase si conuri, importanti pentru vederea colorata, perceperea miscarii, formelor si marginilor, joaca un rol secundar fata de fotoreceptorii circadieni de la nivelul celulelor ganglionare retiniene. Acestia contin fotopigmentul melanopsina, sensibil la lumina albastra. O cale importanta transmite semnalul de la sistemul nervos central la glanda pineala, acolo unde melatonina este sintetizata pe durata noptii. Secretia acestui hormon este inhibata de lumina (4, 9).

Caracteristica principala a unui zeitgeber este aceea ca poate modifica directia ritmului circadian in functie de momentul zilei. Atat lumina, cat si melatonina sunt zeitgeberi. Factori care sa favorizeze oscilatiile ritmului circadian se gasesc la nivelul fiecarui organ si in fiecare celula. Mai mult, fiecare organ are propriul zeitgeber. Organizarea temporala adecvata este fundamentala pentru coordonarea functiilor, care se impun a fi sincrone, si pentru a separa acele functii antagoniste (1).

Astfel, atat ceasul cerebral, cat si cel al organelor interne este dependent de expunerea zilnica la agentii de sincronizare specifici, in vederea obtinerii unei bune coordonari. Desincronizarea ritmului circadian perpetueaza si accentueaza simptome clinice, putandu-se ajunge pana in sfera psihopatologicului.

In urma studiului realizat de Bromundt pe pacienti cu diagnostic de schizofrenie, s-a constatat ca functionarea cognitiva a acestora este dependenta de consolidarea ritmului circadian. Totodata, ceasurile biologice sunt influentate si de agenti de sincronizare nonfotonici, precum exercitiul fizic, somnul si alimentele (3). Factorii sociali, incluzand locul de munca sau alte exigente din aceasta sfera, actioneaza indirect asupra sistemului nervos central prin faptul ca determina temporizarea meselor, a somnului, a activitatilor fizice si a expunerii la lumina. Acestia sunt luati in considerare in cadrul conduitei terapeutice (1, 4, 5).

Ritmurile biologice si tulburarile afective

Periodicitatea are un rol important in evolutia tulburarilor afective, recurentele bolii variind de la episoade depresive sezoniere la episoade maniacale/depresive cu ciclare rapida. Simptomele legate de variatiile dispozitionale diurne si matinale (la primele ore ale diminetii) sugereaza disfunctia ritmica. Ritmurile circadiene incluzand secretia hormonala, functia neurotransmitatorilor si temperatura corporala sunt destabilizate. In plus, tulburarile hipnice constituie un alt element central al tulburarii bipolare, insomnia aparand frecvent ca un predictor al debutului simptomatologiei afective (1, 4, 5). Totodata, tulburarile de somn sunt, frecvent, simptome reziduale ale depresiei, marcand si un risc crescut de recadere. Orice tulburare a somnului si, implicit, a ritmului circadian, aduce cu sine riscul fluctuatiilor dispozitiei, mai ales in cazul indivizilor susceptibili la acestea (6, 7).

Cronoterapia

Ritmurile biologice ale fiecarui individ sunt vulnerabile, dezechilibrele lor determinand tulburari ale dispozitiei si ale somnului, acestea din urma fiind intim interconectate. S-a creat astfel o serie de metode bazate pe expunerea/privarea de lumina si pe modularea peitgeber-ilor sistemului nervos central in vederea resincronizarii ceasurilor interne.

Aceste terapii, preponderent non-medicamentoase, care vizeaza agentii de sincronizare ai sistemului nervos central, poarta numele de cronoterapii, imbracand diverse forme adaptate la natura simptomatologiei de factura psihica: fototerapia, terapia cu intuneric, terapia prin deprivare de somn (1, 2, 28).

Fototerapia

Primele studii privind tulburarea afectiva sezoniera au fost initiate in urma cu trei decenii (8). Cum aceasta debuta sub influenta unor factori trigger de mediu, precum scurtarea zilelor, atunci stimularea cu lumina care sa simuleze o zi de vara parea tratamentul cel mai logic, care, pana in final, a functionat.

Fototerapia a fost primul tratament psihiatric bazat pe principii neurobiologice care a avut succes. In prezent, constituie tratamentul de electie al tulburarilor afective sezoniere (9). Totodata, lumina reprezinta un "antidepresiv" eficace pentru depresia nonsezoniera (10, 11). Studiile au aratat ca lumina potenteaza efectul antidepresivelor in depresia unipolara si cel al litiului, in depresia bipolara (1, 10, 11).

Fototerapia este o alternativa viabila pentru pacientii care refuza sau nu pot tolera tratamentul medicamentos psihotrop, precum si in cazurile de depresie la gravide. S-a demonstrat inclusiv ca aceasta forma de terapie este benefica chiar si pentru pacientii cu depresie cronica (evolutie mai indelungata de doi ani) si pentru pacientii geriatrici cu simptomatologie de alura hipertimic negativa. Terapia luminoasa a fost folosita cu succes si in alte boli psihiatrice si neurologice, incluzand bulimia nervoasa, ADHD-ul la copil si adult, boala Parkinson si dementa Alzheimer (13, 14).

In medicina somnului, lumina este folosita ca zeitgeber pentru a resincroniza programul de somn. Cutia cu lumina este dispozitivul standard, cel mai testat si folosit in fototerapie, prezentandu-se sub forma unui ecran de difuzie cu filtru UV si avand 10 000 de lucsi, plasat la o distanta de aproximativ 30-35 de centimetri (distanta recomandata) (1, 9). Expunerea pe termen lung la lungimi de unda intre 400 si 500 nm poate induce leziuni retiniene fotochimice sau poate precipita degenerescenta maculara legata de varsta. Astfel, cutia cu lumina utilizeaza lumina alba, cu lungimi de unda sub 450 nm (15). Cu toate ca fotoreceptorii circadieni sunt mai sensibili la lungimi de unda mai scazute, nu exista studii de siguranta sau de eficacitate realizate pe termen lung, care sa permita recomandarea utilizarii dispozitivelor cu lumina albastra. In tratarea tulburarilor afective sezoniere, este fundamentala temporizarea fototerapiei. Aceasta trebuie definita individual, date fiind particularitatile personale ale ceasurilor biologice si ale ciclurilor somn--veghe. Obiceiurile legate de somn ale pacientilor ofera o estimare indirecta a ceasurilor interne.

Chestionarul Horne--Ostberg, Morningness-Eveningness Questionnaire, poate fi utilizat pentru a alege momentul optim de initiere a terapiei. Acesta cuprinde 19 intrebari privind obiceiurile zilnice de culcare/trezire (12).

Efectele adverse ale acestei forme de terapie sunt rare, printre ele numarandu-se hipomania la pacientii cu depresie bipolara, acuze vizuale moderate, iritabilitate, cefalee, greturi care, de regula, se diminueaza pana la disparitie intr-un interval de cateva zile de la initierea tratamentului (9). Pot aparea tulburari ale somnului asociate cel mai frecvent cu inadecvarea timing-ului administrarii terapiei luminoase (de exemplu: fototerapia administrata seara poate determina insomnii de adormire, iar administrarea la ore matinale poate duce la insomnii de trezire).

Simularea Dawn este o alternativa mai recenta la cutia cu lumina, care presupune o stimulare cu semnal de intensitate medie ce creste gradual pe durata a 45 de minute, pornind de la 0,001 lucsi si ajungand pana la aproximativ 300 de lucsi in ultima perioada a somnului (cu pana la doua ore inainte de trezire). Aceasta tehnica economiseste timpul pacientului, dat fiind faptul ca aplicarea sa se face integral in timpul somnului, eficacitatea sa ramanand insa controversata (1, 27, 28).

Fototerapia este frecvent prescrisa pentru patologia mai sus-mentionata, in special pentru tulburarea afectiva sezoniera (1).

Terapia prin deprivare de somn (Wake Therapy/Sleep Restriction)

Raspunsul lent la majoritatea antidepresivelor este o problema majora in tratarea pacientilor cu depresie. In contrast, se afla efectul paradoxal al deprivarii de somn pe timpul noptii si apoi, pe parcursul zilei urmatoare. Aceasta forma de terapie a fost studiata pentru prima data in urma cu patru decenii. Aproximativ 60% dintre pacienti inregistreaza ameliorari rapide ale simptomatologiei depresive (13). Efectele terapeutice apar mai ales atunci cand pacientul este deprivat de somn in a doua jumatate a noptii (dupa ora 1 a.m.). Atunci cand este asociata cu fototerapii si/sau cu terapii farmacologice, are o eficacitate superioara, putand duce la remisiuni de durata. S-a demonstrat ca este eficienta atat in depresia bipolara, cat si in cea unipolara (16, 17). Terapia prin deprivare de somn se constituie din unu--trei cicluri cu deprivare completa de somn, separate de nopti destinate somnului de recuperare. S-a demonstrat ca majoritatea pacientilor pot intreprinde diverse activitati facile pana la activitati de complexitate moderata (activitati casnice, lucru online) in diminetile consecutive noptilor cu deprivare de somn. Aceasta forma de terapie este cel mai rapid tratament antidepresiv in practica curenta (21). In comparatie cu tratamentul antidepresiv standard care necesita doua--opt saptamani pentru ameliorarea simptomatologiei, terapia prin deprivare de somn isi face efectul in cateva ore. Mai putin rapida decat aceasta, dar eficienta totusi in una--trei saptamani este fototerapia (1, 6, 18).

Terapia prin trezire (Sleep phase advance) este o forma de cronoterapie care decaleaza progresiv timpul de adormire si de trezire a pacientului, fiind frecvent asociata tratamentului antidepresiv. Dupa o noapte si o zi in care pacientul este deprivat de somn, acesta doarme de la ora 18 pana la 1 (7 ore), in ziua urmatoare, doarme de la 20 la 3 (7 ore) si in ultima zi, de la 22 la 5, urmarindu-se astfel reglarea ritmului circadian, aproape mereu afectat in tulburarile din spectrul depresiei (1, 6).

Cele trei forme de cronoterapie descrise pot fi asociate sub forma unei triple terapii (6).

Terapia cu intuneric (Dark therapy)

O alta forma de cronoterapie se centreaza pe expunerea la intuneric, fiind utila mai ales pentru tulburarea bipolara, in speta pentru pacientii aflati in episod maniacal. Postarea acestora in camere obscure amelioreaza simptomatologia hipertimic pozitiva si stopeaza ciclarea rapida (19, 20). Aceasta forma de terapie este interesanta datorita raspunsului sau imediat, insa nu este fezabila. In prezent, se investigheaza o alternativa--blue -blocking-sunglasses--care sa induca "intunericul circadian" fara a obtura vederea pacientului.

Cronobioticele: melatonina

Melatonina, secretata de glanda pineala, isi creste concentratia serica vesperal, pregatind organismul pentru somn. Daca se produc dezechilibre in secretia sa, asa cum se intampla in spectrul depresiv, apar si tulburarile hipnice. Nefiind sedativa per se, administrarea exogena de melatonina actioneaza ca un veritabil agent de sincronizare a ritmului circadian si induce somnul. Melatonina nu si-a demonstrat efectul notabil asupra dispozitiei la persoanele fara tulburari afective, insa poate agrava simptomatologia depresiva (22). Ca tratament al tulburarilor hipnice la persoanele cu cecitate sau cu acuitate vizuala foarte scazuta, se afla in ample cercetari, deoarece le poate oferi acestora agentul de sincronizare de care au nevoie. Cu toate acestea exista limitari in prescrierea melatoninei in tulburarile de somn, date fiind informatiile insuficiente privind profilul de siguranta al acesteia. Exceptie fac doi agonisti ai melatoninei, aprobati de Food and Drug Administration, Rozerem si Tasimelteon, utilizate strict pentru insomnie (23, 24, 25). Spre deosebire de acestia, agonistul melatoninei, agomelatina, aprobat in Uniunea Europeana, are si proprietati antidepresive date de componenta de antagonist serotoninergic, pe langa rolul de ytgeber in reglarea somnului (19, 26).

CONCLUZII

Cronobiologia constituie o perspectiva revolutionara in explicarea simptomatologiei afective si in tulburarile somnului. In replica, cronoterapiile reprezinta o forma de abordare deschisa cercetarii, care a inceput sa-si demonstreze eficacitatea si, in plus, foarte bunul profil de siguranta cu efecte adverse minime. In monoterapie, combinate sau asociate cu tratamentul medicamentos clasic, cronoterapiile sunt forme terapeutice demne de luat in considerare atat in obtinerea si mentinerea remisiunii tulburarilor afective, cat si a celor hipnice, strans relationate bidirectional cu primele.

MULTUMIRI SI DEVOALARI

Autorii declara ca nu au potentiale conflicte de interese declarate in legatura cu acest articol.

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Ilinca Untu--M. D., Drd., Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic Rezident Psihiatru, Spitalul Clinic de Psihiatrie Socola, Iasi, Romania

Diana Bulgaru Iliescu--M. D., Ph. D., Conf. univ., Departamentul de Medicina Legala, Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic Primar Legist, Institutul de Medicina Legala, Iasi, Romania

Anton Knieling--M. D., Ph. D., Sef de Lucrari, Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic

Primar Legist, Institutul de Medicina Legala, Iasi, Romania

Dania Andreea Radu--M. D., Drd., Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic Rezident Psihiatru, Spitalul Clinic de Psihiatrie "Socola", Iasi, Romania

Lucian Stefan Burlea--M. D., Ph. D., Asist. univ., Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi, Romania

Anamaria Ciubara--M. D., Ph. D., Sef de Lucrari, Departamentul de Psihiatrie, Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic specialist Psihiatru, Spitalul Clinic de Psihiatrie "Socola", Iasi, Romania

Roxana Chirita--M. D., Ph. D., Prof. univ., Departamentul de Psihiatrie, Universitatea de Medicina si Farmacie "Grigore T. Popa", Iasi; Medic primar Psihiatru, Spitalul Clinic de Psihiatrie "Socola", Iasi, Romania

Corespondenta:

ANAMARIA CIUBARA

Spitalul Clinic de Psihiatrie "Socola" Iasi, Sos. Bucium nr. 34-36, cod 700282, Iasi, Romania

Tel./fax: +40 232 430 920, int. 142

E-mail: anamburlea@yahoo.com

Trimis: 13 iunie 2014 / Acceptat: 29 August 2014
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Author:Untu, Ilinca; Iliescu, Diana Bulgaru; Knieling, Anton; Radu, Dania Andreea; Burlea, Lucian Stefan; C
Publication:Bulletin of Integrative Psychiatry
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Date:Sep 1, 2014
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