Free from depression

SAMHSA’s National Helpline | SAMHSA

Your browser is not supported

Switch to Chrome, Edge, Firefox or Safari

Main page content

  • SAMHSA’s National Helpline is a free, confidential, 24/7, 365-day-a-year treatment referral and information service (in English and Spanish) for individuals and families facing mental and/or substance use disorders.

    Also visit the online treatment locator.

SAMHSA’s National Helpline, 1-800-662-HELP (4357) (also known as the Treatment Referral Routing Service), or TTY: 1-800-487-4889 is a confidential, free, 24-hour-a-day, 365-day-a-year, information service, in English and Spanish, for individuals and family members facing mental and/or substance use disorders. This service provides referrals to local treatment facilities, support groups, and community-based organizations.

Also visit the online treatment locator, or send your zip code via text message: 435748 (HELP4U) to find help near you. Read more about the HELP4U text messaging service.

The service is open 24/7, 365 days a year.

English and Spanish are available if you select the option to speak with a national representative. Currently, the 435748 (HELP4U) text messaging service is only available in English.

In 2020, the Helpline received 833,598 calls. This is a 27 percent increase from 2019, when the Helpline received a total of 656,953 calls for the year.

The referral service is free of charge. If you have no insurance or are underinsured, we will refer you to your state office, which is responsible for state-funded treatment programs. In addition, we can often refer you to facilities that charge on a sliding fee scale or accept Medicare or Medicaid. If you have health insurance, you are encouraged to contact your insurer for a list of participating health care providers and facilities.

The service is confidential. We will not ask you for any personal information. We may ask for your zip code or other pertinent geographic information in order to track calls being routed to other offices or to accurately identify the local resources appropriate to your needs.

No, we do not provide counseling. Trained information specialists answer calls, transfer callers to state services or other appropriate intake centers in their states, and connect them with local assistance and support.

  • Suggested Resources

    What Is Substance Abuse Treatment? A Booklet for Families
    Created for family members of people with alcohol abuse or drug abuse problems. Answers questions about substance abuse, its symptoms, different types of treatment, and recovery. Addresses concerns of children of parents with substance use/abuse problems.

    It's Not Your Fault (NACoA) (PDF | 12 KB)
    Assures teens with parents who abuse alcohol or drugs that, "It's not your fault!" and that they are not alone. Encourages teens to seek emotional support from other adults, school counselors, and youth support groups such as Alateen, and provides a resource list.

    After an Attempt: A Guide for Taking Care of Your Family Member After Treatment in the Emergency Department
    Aids family members in coping with the aftermath of a relative's suicide attempt. Describes the emergency department treatment process, lists questions to ask about follow-up treatment, and describes how to reduce risk and ensure safety at home.

    Family Therapy Can Help: For People in Recovery From Mental Illness or Addiction
    Explores the role of family therapy in recovery from mental illness or substance abuse. Explains how family therapy sessions are run and who conducts them, describes a typical session, and provides information on its effectiveness in recovery.

    For additional resources, please visit the SAMHSA Store.

Last Updated: 08/30/2022

SAMHSA Behavioral Health Treatment Services Locator


Welcome to the Behavioral Health Treatment Services Locator, a confidential and anonymous source of information for persons seeking treatment facilities in the United States or U.S. Territories for substance use/addiction and/or mental health problems.

PLEASE NOTE: Your personal information and the search criteria you enter into the Locator is secure and anonymous. SAMHSA does not collect or maintain any information you provide.

Please enter a valid location.

please type your address

  • FindTreatment.


    Millions of Americans have a substance use disorder. Find a treatment facility near you.

  • 988 Suicide & Crisis Lifeline

    Call or text 988

    Free and confidential support for people in distress, 24/7.

  • National Helpline

    1-800-662-HELP (4357)

    Treatment referral and information, 24/7.

  • Disaster Distress Helpline


    Immediate crisis counseling related to disasters, 24/7.

  • Overview
  • Locator OverviewLocator Overview
  • Locator OverviewLocator Overview
  • Finding Treatment
  • Find Facilities for VeteransFind Facilities for Veterans
  • Find Facilities for VeteransFind Facilities for Veterans
  • Facility Directors
  • Register a New FacilityRegister a New Facility
  • Register a New FacilityRegister a New Facility
  • Other Locator Functionalities
  • Download Search ResultsDownload Search Results
  • Use Google MapsUse Google Maps
  • Print Search ResultsPrint Search Results
  • Use Google MapsUse Google Maps
  • Icon from Find practitioners and treatment programs providing buprenorphine for opioid addiction (heroin or pain relievers). Find practitioners and treatment programs providing buprenorphine for opioid addiction (heroin or pain relievers).
  • Icon from Find practitioners and treatment programs providing buprenorphine for opioid addiction (heroin or pain relievers). Find programs providing methadone for the treatment of opioid addiction (heroin or pain relievers).

The Locator is authorized by the 21st Century Cures Act (Public Law 114-255, Section 9006; 42 U.S.C. 290bb-36d). SAMHSA endeavors to keep the Locator current. All information in the Locator is updated annually from facility responses to SAMHSA’s National Substance Use and Mental Health Services Survey (N-SUMHSS). New facilities that have completed an abbreviated survey and met all the qualifications are added monthly. Updates to facility names, addresses, telephone numbers, and services are made weekly for facilities informing SAMHSA of changes. Facilities may request additions or changes to their information by sending an e-mail to [email protected], by calling the BHSIS Project Office at 1-833-888-1553 (Mon-Fri 8-6 ET), or by electronic form submission using the Locator online application form (intended for additions of new facilities).

Free from depression - Andrey SAMOKHIN

Andrey SAMOKHIN, Amur Region


Federal newspapers and TV channels hardly talk about this construction site of the century. As well as about the town of Svobodny, near which the Amur Gas Processing Plant (Amur Gas Processing Plant) is being built - perhaps the largest of its kind in the world.
Soon the famous "Power of Siberia" will reach here. However, not a transshipment point for export raw materials is being built, but a modern gas processing and gas chemical cluster that can become a key growth factor for the entire region. "Culture" visited the Zeya River, the birthplace of director Leonid Gaidai, the "capital" of the former BAMlag and, perhaps, the main center of today's Far Eastern optimism. nine0009

From Moscow to Blagoveshchensk (Blagi - this is what the locals often say) - about 8000 km. Svobodny is still about a hundred and fifty. The route is generally quite good. The plain is gradually replaced by low picturesque hills, covered with crooked trees and yellow grass, slightly powdered with snow. A pheasant slipping off the side of the road, like a large long-tailed chicken, makes you slow down sharply. “They often rush around here,” the driver calmly explains, “they can even go head-on if they’re not lucky. Foxes, too, by the way, are not afraid of cars, look at both! nine0005

We look: a wonderful view of the Zeya, a tributary of the Amur, opens up from the turn. The driver, as if reading my thoughts, drives onto the Hill of Love, hung with colored ribbons, as the newlyweds called it. However, you can’t admire the majestic landscape for a long time - the morning minus forty with a piercing wind is not conducive to contemplation.

On distant shores

The Amur region... Our distant box full of treasures - from coal and titanium to gold and diamonds, once opened by the Cossacks of Poyarkov and Khabarov. nine0005

Ever since the Amur region became part of the Russian Empire in 1858, rumors about the local arable freemen have not ceased to excite the peasants of Central Russia, squeezed by land shortages and extortions. The tsarist government willingly helped the brave settlers - after all, they had to travel with all their belongings, cattle, children and household members over a gigantic distance of several thousand miles. In addition to the "Far Eastern hectare" provided generous lifting.

So the village of Surazhevka (now a district of the city of Svobodny) arose in 1899 year on the high bank of the Zeya thanks to several dozen families of immigrants from the region of the same name in the Chernihiv province. Two factors gave Surazhevka an unusual fate: nearby gold mines and a branch of the Amur railway that passed through it, which later became part of the BAM.

- By 1911, 2368 people lived in the village, branches of large Annunciation supermarkets opened, schools and a temple, drinking yards and hotels operated, as many as 124 enterprises, - says the guide of the Museum of Local Lore Svetlana Yurchenko. - It was then that the Amur Governor-General Nikolai Gondatti began to seek to give the settlement the status of a city with the name Alekseevsk, as a "gift" to the Emperor and Tsarevich for the 300th anniversary of the Romanov dynasty. Before his death, Prime Minister Pyotr Stolypin managed to support the initiative. nine0005

In April 1917 Alekseevsk was renamed Svobodny. The city survived a lot: Japanese and American invaders, armored trains, "dashing squadrons of the Amur partisans" and several years of limitrophe formation - the Far Eastern Republic. Its abbreviation - DVR - was translated by jokers as "Quite a cheerful republic. "

In 1932, by topographical irony, the administration of one of the largest correctional labor institutions in the Gulag, the BAMlag, was located in Svobodny. From here, the management of numerous camps was carried out, the prisoners of which built the Baikal-Amur railway line and the second tracks on the Trans-Siberian. Actually, the city was always familiar with convicts and exiles. The father of director Leonid Gaidai, for example, is from the exiled political prisoners of the pre-revolutionary era. nine0005

From the end of the 1950s, Svobodny lived a measured progressive life. Remaining somewhat in the shadow of Blaga, he was far from living in misery. Various enterprises worked - a railway and lemonade factories, textile and furniture factories, a meat processing plant.

Speaking, Svetlana Yurchenko complains that there is no "mandatory regional component" in the curricula of Svobodny schools, so visitors to the local history museum often visit. People like me.

What is good for a German

A migrant from Central Russia has a hard time even in the south of the region. The city of Svobodny is even though it is on the Voronezh parallel: in July, the heat is over thirty, and in winter with little snow it drops to minus 50 at night. It is recommended to warm up cars with automatic start regularly, otherwise you may not start in the morning. A strong wind often blows here, although the sky is blue and the sun is dazzling. Paradoxically, in brief moments of calm, it warms hands and face even in cold weather. In summer - an abundance of berries and mushrooms, fish and game all year round. Live - I don't want to! nine0005

However, not everyone wants to. Until recently, such desolation and oblivion reigned in the Amur Region, which often happens on the outskirts of a huge power: survive, dear people, as best you can. And they survived, like other Far Eastern neighbors, by reselling Chinese clothes and right-hand drive “Japanese”, hunting, subsistence farming. Who was lucky - he served the border units at the "high banks of the Amur".

Free is no exception. Soviet enterprises closed in the 90s, leaving epic ruins of workshops. The townspeople were leaving, the city was quietly slipping into oblivion. Svobodny did not save and its main attraction is the longest children's railway in Russia (11.6 km) to the village of Bardagon. After all, there were fewer and fewer children who wanted to study as railway workers, as well as children in general. Tourists - and even more so. The general depressiveness was aggravated by the stealth of a number of local officials. The penultimate mayor was arrested on charges of abuse, his predecessor was also under investigation. nine0005

However, in recent years, the Amur region has blossomed right before our eyes. The main reason is Eastern. Our first civilian cosmodrome has been commissioned and is working as intended. It is only fifty kilometers from Svobodny. The second key facility, the Amur GPP, is just under construction. The first stage should be launched at the beginning of 2021, it will reach its full capacity in 2025. The customer of the project is OOO Gazprom Pererabotka Blagoveshchensk, the general contractor is NIPIGAZ (part of the Sibur group). The economic condition for the construction was the signing in 2014, without exaggeration, of a historic document between Gazprom and China National Petroleum Corporation (CNPC) on the supply of Russian blue fuel through the Power of Siberia gas pipeline. nine0005

In October 2015, the starting symbolic pile was driven in at the Amur GPP - the head of state watched this process via a teleconference. And on August 3, 2017, Vladimir Putin was already personally present at the pouring of the first concrete into the foundation of the complex.

In June 2017, the territory of advanced socio-economic development (TOR) "Svobodny" was created. In terms of the number of emergency housing, the city was known as the regional champion. Now it has become a leader in terms of the rate of resettlement of dilapidated houses, often wooden barracks from the BAMlag era with "amenities" on the street. Today, construction cranes have become a sign of Svobodny. Today, 54 thousand people are registered here, and with visitors, probably, there will be a couple of thousand more. This is for now... The influx in the foreseeable future is expected to be very large - there are no longer enough free apartments for rent and in new buildings. Shift workers of Asian guise flit in groups along the central Lenin Street. Specialists are the main streams of profit and continue to arrive from Tyumen, Moscow, Nizhny Novgorod, St. Petersburg, Krasnodar. Of course, there are a lot of Amur residents at the construction site. Germans, Dutch, Japanese and even Indians are increasingly found on the streets, amazing the townspeople: about three dozen countries participate in the project as subcontractors. It is no coincidence that Svobodny schools introduced additional lessons of tolerance, designed to make it easier for children to communicate with representatives of other peoples and states. nine0005

We will come to the ends of the earth. ..

I am talking to a young NIPIGAZ specialist, Nikita S., who came here under a contract from Moscow. Together with him, his wife and son are settling in a new place.

“Terrible broken roads, faded signs, an abandoned, overgrown city park — this is how I found Svobodny three years ago during my first business trip,” he says. “Now there are clear changes in the city: construction is in full swing, replacement of heating mains; a cinema and large chain hypermarkets were opened, playgrounds appeared, green spaces were put in order. nine0005

“At first, the Svobodnen people reacted negatively to the construction site,” my interlocutor continues, “they were afraid of the very words “gas”, “chemistry”. They imagined clouds of toxic substances, fires and explosions... All employees of NIPIGAZ, Gazprom and even builders are called "gas workers" here. So, after several city meetings held by the gas workers, meetings with local entrepreneurs, clarifications in the press, public opinion calmed down. This, by the way, was greatly facilitated by the new economic opportunities opening up for the old-timers. nine0005

I'm interested in how the relations between "newcomers" and "locals" developed.

“Personally, I have no problems,” Nikita replies. Not a single sideways glance or rude word.

I am telling a “hurt” I heard in passing. They say that the Gazprom workers put up an apartment building for their own people, built a playground for the children, and took the yard and took it away with a high fence. The townspeople are annoyed: they always went for a walk - and suddenly you're in a closed zone for the elite...

- I heard a different version, - Nikita grins. - Drunken locals began to turn into the playground and senselessly “vandalize”. I had to fence. Although these are the little things in life, it will resolve and get used. Better ask why I decided to move to such a distance? Of course, by no means the last motivation is a decent salary, which includes Far Eastern allowances; as well as a decent furnished apartment in a new building. But this, of course, is not all. I was attracted by the scale of the construction, which gives a second life to the whole region, to which I am now directly involved. You can probably consider it romantic...

Customs approves

We leave the city. Ahead, several kilometers away, there are sites, roads and interchanges related to the future of the AGPP, and a residential microdistrict for 5,000 people is being built right on the border of Svobodny. Workers of the plant, including those who wished to settle down, will be accommodated in it.

And everything started, as usual, shift workers. “Under the wing of an airplane” the virgin taiga did not sing here to those who arrived from the mainland; they did not set up romantic tent cities, like volunteer Komsomol members. Immediately neat plastic houses with heating from their boiler room. Three shift camps - the largest one can accommodate up to 16,500 people - are collected by Turks, Slovenes, Croats. It has its own artesian wells, canteens, even sports grounds. On the other side of the highway there are cylinders of RBU (mortar-concrete units) going into a cone. These are erected in a couple of months right in the field and are easily transferred to a new place. nine0005

At the entrance to the construction site of the plant, towering above the tops of the trees are the columns of methane and nitrogen emission of the first technological line, the booms of giant cranes. All this is fenced with a thorn, at the gate there is a serious guard. Secrecy has nothing to do with it - just a special customs zone, the equipment comes duty-free.

Work is in full swing in two shifts, sometimes they introduce a third, night shift. They work on holidays and in frost, down to minus forty. At temperatures below, objects under construction must be covered with special shelters according to the standards. nine0005

The scale of what has already been done is impressive. Whole hills were dug up on hundreds of hectares, dumps were leveled and reclaimed; highways were poured, together with Russian Railways they dragged a branch from the Amur "piece of iron" more than 20 kilometers long, put up railway bridges and stations. The Ministry of Natural Resources arranged for a significant deepening of the channel of the Zeya River, built a pier and ordered a small river fleet from Holland and China: ten barges and about the same number of low draft tugboats. Otherwise, it would not have been possible to deliver here such cargoes as a ninety-meter gas column with a diameter of about six meters and a weight of about 900 tons.

These colossus, made abroad, are brought to the Far East port of De-Kastri. There, right in the roadstead, they are loaded with floating cranes onto a barge, which, in replaceable tugboats, goes through the Amur to Zeya.

— The navigational period is short, — Nikita explains, going to the pier along the bank of the river, sparkling in the sun with a diamond scattering of rearing ice floes — from mid-May to the end of September, when the ice rises. It is necessary to have time to bring in the equipment, otherwise the construction site will freeze for a long time. The logistics are exceptionally tough! And in each such window - from 30 to 100 units (depending on the logic of the assembly), at least die, but deliver. So far, such navigations are planned until 2022. nine0005

National Treasure

Natural "wet" gas, which will come from the Chayandinskoye and Kovyktinskoye fields, will undergo deep processing on the equipment of the German company Linde AG (there are no Russian analogues). The lightest hydrocarbon, methane, will fly through a pipeline to China. The remaining fractions - ethane, propane, butane, pentane - will be isolated here and will be useful for gasification of the region, as well as for the domestic chemical industry. In particular, the supply of ethane to the Amur Gas Chemical Complex (AGCC) of Sibur, which is likely to appear next to the GPP (the final decision will be made this year), can reach two million tons per year, forming the largest ethylene producer in Russia. nine0005

We should also mention helium. It will also begin to be extracted from Siberian raw materials, and on a scale that is significant not only for the All-Russian, but also for the world market. It is indispensable in astronautics, nuclear and laser technology, aviation and shipbuilding, electronics and medicine. Without it, for example, magnetic resonance imaging machines will not be able to work.

All valuable components, which are no longer pure raw materials, but the product of the second redistribution of "blue gold", will be monetized in Russia. The total gas processing capacity has been determined at 42 billion cubic meters per year - we have not yet built anything like this! nine0005

What else is unique about the future giant? It would seem that after the collapse of the USSR, objects were erected that were comparable in complexity to the AGPZ. And the neighbor - the Vostochny cosmodrome is also by no means simple. And yet, the local undertaking is not in vain led by experts to the construction sites of the century. Too many heterogeneous participants with their standards, organizational thinking, customs from almost five continents converged at one point. Once in the Union they were able to build mega-objects on their own, even if they bought part of the equipment abroad. Well, having lost Soviet managerial competencies, today we are learning from advanced Western experience. We are talking about the so-called EPC - the English abbreviation stands for "design, supply, construction" and indicates that under such a contract it is possible to implement a large and complex turnkey industrial facility - from site preparation to start-up. nine0005

NIPIGAZ, for the first time in its history, being in the role of the main coordinator at such a large-scale facility, obviously has every chance to master the competence that until recently had to be delegated to Western companies. The main asset is not deposits, buildings and machines, but people - specialists and practitioners. And, it seems, as a result of this construction, Russia will finally have its own full-fledged "turnkey creator" in the oil and gas sector. The experience of such mega-coordination can hardly be overestimated, it is precisely this experience that will be needed during the mobilization breakthrough of the entire Russian economy. ..

Skepticism and even sarcasm of some metropolitan wits about any large-scale state undertaking here, in the Amur region, looks pale - after all, you see with your own eyes the creation of the future. And the Freemen, gradually moving away from the haze of decadent decades, cautiously, but with great hopes, are trying on for a new era. Someone taking advantage of the moment will rent housing that has risen sharply in price. For others, stable income opportunities will come true - for themselves and their children. It is already known that about 25,000 employees will be needed during the peak period of the AGPZ construction. And then thousands of qualified specialists will be required - for a long time. With this in mind, training for the needs of the facility in the region is in full swing: from secondary education to universities. So, on the basis of school No. 1 of Svobodny, the Gazprom-class was created. Amur Technical College has been training process pump and compressor operators, oil refining operators, environmental laboratory assistants for the third year already. Amur State University in Blagoveshchensk began to train future process engineers for the GPP and AGCC in several areas. Quite recently, with a clear expectation of a science-intensive future, the first children's technopark "Quantorium" was opened in the capital of the region. This year, a branch will also appear in Svobodny. nine0005

Past dilapidated barracks and fresh high-rise buildings, bright shops with brisk signboards, past the Leonid Gaidai cinema with a monument to the director and the first artificial skating rink in the region, locomotives periodically whistle, trains tap for miles. The Amur Railway is the historical core of the city. The Amur Gas Processing Plant promises to be its new heart. Several times a year, residents of Svobodny indiscriminately, both old and gas workers, drive out in car cavalcades towards Tsiolkovsky (aka old Uglegorsk) to watch from the roadside the launch of another rocket from the Vostochny cosmodrome. They say it's impressive. nine0005

Announcement photo: Yuri Smityuk/TASS

Monoamino-hormonal connections in the pathogenesis of anxious depression

Depression has now become a major medical and social problem [1, 2]. A comprehensive study of depression and the pathogenetic mechanisms of this disease is becoming one of the main tasks of medical science.

Currently, there are several hypotheses of the pathogenesis of depression [3], among which two are most widely used. One of them is the monoaminergic hypothesis, according to which the pathogenetic mechanisms of depression and anxiety are associated with a deficiency of serotonin and norepinephrine in brain structures [4, 5]. Another theory is hormonal, according to which the main manifestations of these two pathological conditions are associated with a violation of the hypothalamic-pituitary-adrenal axis [6, 7]. It can be assumed that ultimately all these and many other factors are involved in one way or another in the pathogenetic mechanisms of depression. nine0005

The presence of different hypotheses of the pathogenesis of depression also indicates that many aspects of this complex problem have not been resolved and require further in-depth study.

According to the World Health Organization [8], depression and anxiety are the most commonly coexisting disorders in primary care [9]. These two conditions largely overlap each other in terms of clinical symptoms and a number of pathophysiological mechanisms. So, M. Hamilton [9] notes that anxiety in recurrent depression is detected in 96% of cases. J. Rodney et al. [10] indicate that anxiety can be detected in 42-100% of patients with depression.

As part of the studies of anxious depression [11, 12], some biochemical aspects of the relationship between the monoaminergic and hormonal systems were studied. Before proceeding to the presentation of literature data, let us briefly dwell on our own previously published data.

Psychopathological analysis of the structural features of depression was carried out in 61 patients (41 women and 20 men, the average age of which was 33.0±9.0 years). In these cases, the type of the leading affect was taken into account, which made it possible to identify a pronounced predominance of the anxious affect over the melancholy one. When analyzing the structure of depression according to the clinical card with ranked signs of examination in the entire group of patients, it was also found that anxiety was the most pronounced. This made it possible to diagnose anxious depression in patients (category F3 according to ICD-10) [13]. According to the Hamilton Scale (HAM-D), the total score was 21.83, which corresponds to severe depressive disorder. According to the HAM-A scale, the total score was 30.0, which also corresponds to severe anxiety. According to the results of this scale, mental anxiety was more pronounced than somatic anxiety (18.43 and 11.60 points, respectively). Before the start of treatment, 43 out of 61 examined patients had a significant, almost 2-fold (by 94.8%), platelet monoamine oxidase (MAO) activity is increased, and the functional properties of blood serum albumin are significantly impaired. Compared with the control values, the indicators of the functional activity of albumin - the values ​​of the effective concentration of albumin (ECA) and the albumin binding reserve (PCA) - were significantly reduced by 30 and 38%, respectively [11, 12]. Patients with anxious depression also had a violation of the hormonal status. Thus, the level of cortisol in the blood serum of patients before the start of treatment was increased by more than 10 times compared with the upper limit of the norm [14]. The study showed that patients with anxiety depression are characterized by significant disturbances in the metabolism of biogenic monoamines and changes in hormonal status, which is a reflection of disturbed homeostasis in general. nine0005

Over the past three decades, there has been a strong opinion that endogenous depression in the vast majority of cases (up to 90%) is accompanied by a violation of the state of the hypothalamic-pituitary-adrenal axis [6, 7, 15]. This is expressed in the fact that in patients in the blood serum the concentration of corticotropin-releasing factor increases and the secretion of adrenocorticotropic hormone increases. It is noted that in patients with depression, the level of cortisol in the blood is increased [6]. Our study confirmed these results [11, 12]. nine0005

In the early 2000s, a hypothesis was put forward [4], according to which depression and anxiety are controlled not by the absolute levels of serotonin and norepinephrine, but by the balance in their content and the activity of these systems. The concept of "balance" has already been formulated and experimentally substantiated by prof. E.A. Gromov in the mid-70s of the XX century. E.A. Gromova [16] pointed out that emotional reactivity is largely determined by the balance of activity of the serotonergic and noradrenergic systems. Serotonin and norepinephrine play a special role in the pathogenetic mechanisms of anxiety and depression due to their modulating functions. At the same time, the activity of these monoaminergic systems is controlled by other neurotransmitter systems, such as GABAergic [17]. Moreover, any of these neurotransmitters initiates a cascade of processes that causes anxiety in patients and gradually forms a depressive state in them [18]. nine0005

In depression and anxiety, there is a deficiency of serotonergic and noradrenergic activity [4, 6, 15]. At the same time, a deficiency of norepinephrine leads to an increase in the level of corticosteroids (cortisol), while a deficiency of serotonin causes a violation of the regulation of cortisol secretion. Deficiency of both monoamines leads to disruption of circadian rhythms in the secretion of this hormone. Against the background of an increased level of cortisol in the morning, its decrease is not observed in the evening and at night. The elevated level of cortisol persists throughout the entire 24-hour period and, therefore, various enzyme systems are under the constant influence of glucocorticoids [6]. Thus, chronic hypercortisolism, which is characteristic of both depression and anxiety, can be considered as a state of chronic stress. nine0005

Of theoretical and practical interest is the question of what biochemical mechanisms are involved in the imbalance between the serotonergic and noradrenergic systems. An analysis of the data of clinical, biochemical and experimental studies, carried out on models of depression [19, 20], in combination with the results of our studies [11, 12], made it possible to propose a possible neurochemical mechanism for these disorders in anxious depression.

It is known that the main route of tryptophan metabolism in brain cells of humans and other mammals is kynurenine: about 90% of tryptophan molecules are metabolized via this pathway and no more than 10% of tryptophan is used for the synthesis of serotonin [21]. The main enzyme that transfers tryptophan metabolism to the kynurenine pathway is tryptophan pyrrolase [21, 22]. An increase in cortisol levels in anxious depression is a consequence of a weakening of monoaminergic control over the functioning of the hypothalamic-pituitary-adrenal system [23] (see figure). It can be assumed that an increased level of cortisol activates tryptophan pyrrolase, which even more actively transfers tryptophan metabolism to the kynurenine pathway, thereby further reducing the percentage of tryptophan used for serotonin synthesis [21, 22, 24]. It should be noted that the kynurenine pathway of tryptophan metabolism produces numerous metabolites that have both neurotoxic (kynurenine, quinoline acid) and neuroprotective (kynurenic acid) properties [21, 24, 25]. It is assumed that during depression, the level of neurotoxic kynurenins prevails over neuroprotective metabolites, which makes a negative contribution to the pathogenetic mechanisms of this disease [25]. nine0005

A possible mechanism for the relationship between monoaminergic and hormonal systems in anxious depression. MAO - monoamine oxidase, ↑ - increase in activity or concentration, ↓ - decrease in activity or concentration.

A significant role in the disruption of serotonin metabolism in depression is assigned to a decrease in the availability of its precursor, tryptophan, to the brain, which is associated with a decrease in the concentration of albumin, which carries up to 90% of blood tryptophan [25, 26]. However, our data do not confirm these results: the concentration of albumin in the blood of patients with anxiety depression was within the normal range [11, 12]. We believe that the decrease in the availability of tryptophan to the brain is not associated with a decrease in the concentration of albumin, but with a violation of its physicochemical properties, namely, with a violation of its conformation. Thus, using the methods of stationary fluorescence spectroscopy [11, 12], as well as subnanosecond laser fluorescence spectroscopy [27], it was shown that the conformation of the albumin molecule is disturbed in patients with anxious depression. This changes its binding capacity, which is reflected in the damage to the transport function of this protein, which naturally reduces the availability of tryptophan to the brain. nine0005

At the same time, increased cortisol secretion increases the activity of the enzyme tyrosine transaminase, which can lead to a decrease in the volume of the tyrosine fraction used for the biosynthesis of catecholamines, and a decrease in the content of the latter, including the level of norepinephrine [28].

MAO also makes a significant contribution to the decrease in the level of serotonin and norepinephrine in the brain. In recent years, evidence has emerged that platelet monoamine oxidase reflects the activity of this enzyme in the brain [29]. MAO activity may be increased under the influence of high levels of cortisol, which was confirmed by the results of this study. It should be noted that MAO deaminates serotonin and norepinephrine at different rates [30]. In a pathological condition, the rates of deamination of monoamines can change, which can disrupt their concentration in tissues and the balance in their content. A sharp increase in MAO activity is accompanied by an increase in the content of monoamine deamination products - hydrogen peroxide, aldehydes and ammonia. Hydrogen peroxide itself is not a free radical. However, in the cell in the presence of metals with variable valence (Fe 2+ /Fe 3+ ; Cu + / Cu 2+ ), especially iron ions, hydrogen peroxide in the Fenton reaction immediately turns into an extremely aggressive free hydroxyl radical (HO - ) with all the ensuing negative consequences for enzymes, receptors, proteins, nucleic acids and lipoprotein complexes.

Learn more