An endogenous opiate mechanism seems to be involved in stress-induced anhedonia

by Zurita A, Murua S, Molina V

Departamento de Farmacologia, Universidad Nacional de Cordoba, Argentina.

Eur J Pharmacol 1996 Mar 28; 299(1-3):1-7

ABSTRACT

This study assessed the effect of an uncontrollable stressor on the preference for a palatable solution (sucrose 1%), and on the preference for a context associated with a single administration of D-amphetamine (3 mg/kg i.p.) by means of the conditioning place preference test. We also evaluated the effect of prior naloxone (2 mg/kg, i.p.) administration on the influence of this stressful stimulus in both tests. Animals previously submitted to a 120-min–but not 60-min–restraint period showed a selective reduction in the preference for sucrose intake as compared to unstressed animals. Similarly, an identical restraint exposure elicited a diminished preference for the place previously paired with amphetamine. Both stress-induced effects were blocked by prior naloxone administration. These data demonstrate that a highly aversive experience decreased the reinforcing efficacy of sucrose and amphetamine, suggesting that uncontrollable stress may lead to an impaired capacity to experience pleasure, which could resemble the anhedonia observed in clinical depression. Furthermore, an endogenous opiate mechanism activated by stress seems to be involved in stress-induced anhedonia since naloxone normalized the reduction of the rewarding induced by both reinforcers.  Depression, stress, and anhedonia : the opioid connection.

To read more go here:  http://opioids.com/depression/index.html

Don’t read more if you are already depressed.    Diane

Today is Dr. day. I have to wait three months to see my Dr. and now I will have a short period of time in which to try to explain how not being severely depressed is not enough. Clinicians seem to think if I can take a shower, comb my hair, get dressed, smear on a little makeup and show up on time I must be okay.  I am much better than I was in April, when I felt suicidal.  Part of my brain was thinking up painless non-intrusive ways to kill me and the other part was saying “Bad idea!  We need more meds.”  I am much better than I was a few weeks ago, when I was getting things done, but walking around in psychic pain all the time, but it is not enough.  There is a huge space between feeling suicidal, entirely cut off, entirely unnecessary and wanting, really wanting to live. I fully appreciate not being in pain but I am so very tired of that huge gray space where I exist but never really get to live.  I exist and provide service to others and I exist and provide service to others-because I do not know how to give up and I do not know how to stay down long enough to die.  The best I can do is find some way to create an adrenaline rush and I have pretty much run out of energy for that, unless I become hypomanic….

Perhaps I can tell the Dr. I am not dead, but I’m not alive.  I can get things done, but I can’t see what I’ve done and I never believe I’ve done enough.  I am a work machine, and I have always been a work machine.  Decades ago I wrote a poem called Imitation “She’s a perfect imitation of a real person, she does her job. Then she turns herself off and goes home alone.” The only difference is now I work at home much of the time.  I could go to a party next Saturday night; part of me wants to go the other part is starting to feel ambivalent and a little sick already, so I avoid thinking about it.  That’s good, that will assure that I am completely unprepared, that I have not made the necessary plans.
The wonderful little aluminum trailer I was going to fix up has been sitting in the yard for over a year now. It’s now a wonderful little aluminum storeroom. I don’t have enough life in me to get started on it. 

I think of Halloween and what a pain it is to put up decorations.  It might however be nice to get in a good disguise and behave really badly…. I think of Christmas and what a pain in the butt it is to put up decorations, go shopping where there are lots of people, go any place where there are lots of people and watch all the cheer and not have access to a bit of it. I do it for the kids, for the neighbors, for my clients, for friends but I can’t do it for myself.  I want to feel what other people feel, I want to stop watching myself all the time.
           I read and I study – to escape ANHEDONIA.  I felt alive and connected once, for a week or so, over 20 years ago.  That’s the only way I know it can happen.  That time the meds were just right and I don’t remember exactly what happened.  Ultimately because of severe hypertensive reactions I had to quit taking that class of medication. I don’t even care if I have hypertensive reactions anymore.  I will try anything or anything again.
I always go to the doctor with my ‘papers’, new meds, new studies, or mood charts.  I’m taking a little lithium to protect and rehabilitate my brain.  I’m taking a little Metformin to protect my brain (I have the study someplace).  The Wellbutrin keeps me moving and producing.  The Buspar keeps me from having so much anxiety I can’t focus or breathe. The levothyroxine should help it all work.  5000u Vitamin D, lots of fish oil, melatonin, therapy, you should’ve seen me before I had all this stuff!!  Can you imagine a severely depressed person who can’t stop moving around but can’t focus or concentrate, who is always afraid “something bad” is about to happen, who is on the edge of a panic attack and trying hard to breathe, who is also trying desperately to look like they are okay-for 40+ years?  That was me.  So of course it’s better, incredibly better – but not good.  From a song, “It’s all very nice, but not very good”.  Later. Diane

 It was, not at all nice, to be seven years old at my house.

My father had to deal with a bipolar disorder and alcoholism.  No doubt this was overwhelming, with a wife and seven kids to take care of.  He probably did an excellent job under the circumstances, but sometimes the best you can do isn’t good. 

 Of course my mother had an alcoholic bipolar husband and seven kids to take care of.  I have no idea how she did it.  Perhaps it was her God connection, but even that couldn’t make things good for any of us.

I had an alcoholic bipolar father and an entirely overwhelmed preoccupied mother, to deal with, as well as the belief that I was supposed to take care of everyone.  I have no idea where that came from.  I did the best I could under the circumstances.  I wish I had been raised by wolves.

I had acquired vast amounts of the ingredients necessary to manifests a significant set of difficulties, including alcoholism, anxiety disorder, panic attacks and bipolar disorder  very early.  That is I was, both genetically and situationally by virtue of constant stress set up to fail at being mentally or emotionally stable.  I imagine, from the same place I got all this, I probably also got incredible strength and resilience, pit bull toughness, appreciable intelligence and a potpourri of skills and talents.  Bottom line, I would not do any of it over, not a day, an hour or an event-nothing.  Everything is nothing.

So, where it comes from, this anhedonia, is no different than were a beautiful trained singing voice comes from, a combination of inherited potential, exposure to favorable circumstances for development and years of training.

If you experience anhedonia, what do you think it came from?   

Anhedonic babies grow up. I go to sleep thinking and I wake up thinking and all day thoughts drop and swirl through my mind like snowflakes, the only difference, some of them are the same over and over. When I woke up this morning the anhedonic children were in my mind. I started to think, to remember, to link.
Do you ever recall being scared by something just because you couldn’t clearly define what it was-some shadow in the dark-some errie noise? Then there are the more subtle forms of alert, confusion, worry, bewilderment, anxiety… all because you are thrown off base, can’t quite get a grasp on what is happening, what you’re seeing, what you’re hearing-the ‘why’ of the moment. For me it’s like this all day long every day every month every year decade after decade. Everyone around me is acting and reacting in ways I don’t understand, don’t have access to, can only imitate-and I do imitate quite well, well enough to fool everyone except my self. To keep from being ‘found out’, I keep all but a few people at a distance.

Christmas doesn’t really mean anything to me except candy canes and bright lights and endless demands on my very limited energy to make things nice for someone else. I watch this thing called joy, merriment, good will toward all and I have no idea what’s going on. Easter doesn’t really mean any thing to me except jellybeans and Easter bunnies. I’ve always liked the jellybeans, but that bunny, he’s always looked rather ridiculous. I don’t understand why people celebrate birthdays or anniversaries. I do not understand what party in general is about or social or Memorial or funeral and the list goes on. I don’t know why anyone gets excited when a baby is born or would want to have anything in particular to do with one.
The thing that makes this anhedonic state rather sticky, much more confusing, something a psychologist could have fun with for years-are all the stories I have made up and incidents and experiences to which I have attributed value to explain to myself how I got this way, why Everything is Nothing.
Tomorrow-or some time soon I will say more-in this 12 part essay on my personal anhedonic experience.

• Making up stories…
• in vivo adrenalin shootups!…
• No dreams, goals, aspirations… 
• how nothing becomes nothing good…
• “I don’t care”
• the value of anger… 
• one saving grace…
• the hug, the touch, other confusing things… 
• furfaced angels for anhedonia…
• Bipolar connection?…
• sex or not…
• creating reasons to live…
• and other STUFF.

Running across this just made me extremely sad. Imagine…
Document title
Characteristics of depressed preschoolers with and without anhedonia: Evidence for a melancholic depressive subtype in young children
Auteur(s) / Author(s)
LUBY Joan L. (1) ; MRAKOTSKY Christine (1) ; HEFFELFINGER Amy (1) ; BROWN Kathy (1) ; SPITZNAGEL Edward (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Psychiatry, Washington University School of Medicine, St Louis MO 63110, ETATS-UNIS

Résumé / Abstract
Objective: This study investigated whether a melancholic subtype similar to that established in depressed adults can be identified in depressed preschool children. Method: A final group total of 156 preschool children between the ages of 3.0 and 5.6 years and their caregivers underwent a comprehensive psychiatric assessment that included a structured psychiatric interview modified for young children. The clinical characteristics of four study groups (N=156) were compared: depressed preschoolers with anhedonia, depressed preschoolers without anhedonia (hedonic), a psychiatric comparison g.oup with DSM-IV attention deficit hyper-activity disorder and/or oppositional defiant disorder, and a healthy comparison group. Results: Fifty-four depressed preschoolers were identified, and 57% of this depressed group was anhedonic, a symptom deemed to be highly developmentally and clinically significant when arising in the preschool period. The anhedonic depressed subgroup identified was characterized by greater depression severity, alterations in stress cortisol reactivity, increased family history of major depressive disorder, and increased frequency of psychomotor retardation as well as other melancholic symptoms, such as a lack of brightening in response to joyful events. Conclusions: The clinical characteristics of this depressed subgroup are consistent with those described in melancholic depressed adults and suggest that a melancholic depressed subtype can be manifest in children as young as age 3.
Revue / Journal Title
The American journal of psychiatry ISSN 0002-953X CODEN AJPSAO
Source / Source
2004, vol. 161, no11, pp. 1998-2004 [7 page(s) (article)] (32 ref.)
http://cat.inist.fr/?aModele=afficheN&cpsidt=16268209… All the little children, just like I used to be, without a chance of feeling good-ever. I’m so depressed I have to go to bed now.

Sometimes I wonder if it’s all about being afraid of feeling good.  I’ve been away for a few days, a few days of trying to have a good time and a few days of trying to get back on track.  I need to overcome some of my reluctance to let anyone in the house hear, what I’m saying, after all they could go online and read it all, but probably wouldn’t.  Some of the turmoil I experience and fast mood swings, accompanied by entirely divergent states of mind are probably much more revealing and interesting ‘fresh’, before I have had the opportunity to try to explain them to myself and adjust them.

I took a friend on a mini vacation to the coast for his birthday.  I found a delightful place to stay called Wild spring, charming cabins set in a forest on a hill above Port Orford, on the Oregon coast. It was an absolutely ideal atmosphere by nearly any standard; rich sumptuous eclectic decor a big bed like a cloud with a thick down comforter, two fat soft upholstered chairs nearly the size of loveseats, candles everywhere, a high A-frame ceiling, lightly embroidered transparent fabric covering the lower half of the Windows only- not to interfere with the view of sunlight streaking down through the forest and in the corner, a small crystal chandelier, the list goes on.  Just out the door to the right a stone lined walking labyrinth had been constructed.  A two-minute walk through the forest and past the main lodge, we enjoyed a huge deep jacuzzi with a wonderful ocean view (which you can’t see in the dark, LOL).  I find I’m enjoying it much more thinking about it than I did when I was there. 

I have to wonder if I enjoyed it as much as anyone would.  I have to wonder if I would be okay if I lived there.  Then I have to come back to reality.  It might be okay to not be able to feel happy, if it didn’t feel like such a huge weight.  I feel like I’m disappointing the whole world, and that’s ridiculous, but I don’t know how to stop feeling that way.

Sometimes I see little glimpses of how I might be afraid to feel good.  It makes it hard to talk, that thought makes me cry a little, like right now.  If I felt good, disappointment, the slide into pain would be longer, the crash harder, the damage more.  Or is that just my rationalization for being stuck in “Everything is nothing”.  However, everything is not nothing, in addition to nothing, all those negative emotions exist and I’m certainly privilege to their full experience.

Many years ago, when I was first in a recovery, from alcoholism, I was involved in a program where everyone was responsible for helping others, as they had been helped.  That was supposed to be one of the keys to feeling well and staying sober.  Under any circumstances, I have always been a great ‘others helper’ and I took the opportunity to help others night and day.  The point of course was to stay sober and I did that.  I followed all the directions to the best of my ability, over and over, but I didn’t feel any better.  Whenever I would try to express some of my distress to other ‘program people’, looking for some kind of direction or help, I would always get the same answer. “Work with a newcomer.”  “Get out of yourself.”  So I worked with newcomers, dozens of them, for years.  As soon as they felt better, I couldn’t relate to them anymore, they had moved on to a different world and I was left behind to find another newcomer with whom to empathize and commiserate.  I stayed sober so I could feel the pain, mine and everyone else’s, with nothing with which to balance it or anesthetize it. After 11 years I became imminently suicidal. I went and got the anti-depressants that were unacceptable in “the program”. The whole thing still makes me feel confused.

I recall having an interview with a psychiatrist at one time.  He asked me if I felt confused.  The question was too confusing for me.  After some time, I said.  “I don’t know.”  I’ll bet he wrote very confused, and he certainly would’ve been correct.  Having everyone around me, appear to be experiencing pleasures and comforts I can’t touch, is a very confusing.

1: Psychol Med. 1993 Nov;23(4):957-66.LinksAnhedonia: a neglected symptom of psychopathology.

Snaith P.

Academic Unit of Psychiatry, University of Leeds, St James’ Hospital.

In the last century psychopathologists attached importance to the concept of anhedonia, the loss of ability to experience pleasure. Its role in the diagnosis of melancholia was considered to be crucial. In the present century attention to anhedonia has faded, possibly because of the focus upon depressed mood as the pathognomonic feature of depressive disorders. Research on the symptomatology of endogenous depression did not include the concept; anhedonia was also lacking from the major instruments of psychiatric research, the depression rating scales, Attention was drawn to anhedonia by two authors: by Meehl in the 1960s and by Klein in the 1970s. Meehl considered anhedonia from the point of view of a personality defect predisposing to mental illness; and Klein regarded anhedonia to be a symptom of depressive illness and probably the best clinical marker predicting response to antidepressant drugs. In 1980 the revised DSM presented the concept of ‘loss of interest or pleasure’ as one of the two cardinal symptoms of major depression. Since then there has been a gradual rec

via Anhedonia: a neglected symptom of psychopathology. [Psychol Med. 1993] – PubMed Result.

Why is this important? Because there has been little to no progress on the causes of, importance of or resolution of Anhedonia in the past 16 years!!

I’m on my case again.  This time it’s that swimming Pool I bought.  I really believed I wanted it, I really believed I would use it, I really believed it would help me feel good.  I put it up in the middle of June, now in late August I can count the times I’ve used it on my fingers.  The last time I was in the pool I stood in the middle of it and told myself this feels good, this really feels good, remember how this feels.  I don’t remember how it felt and now every time I look at the pool or think of the pool I just feel guilty for spending so much money on something I’m not using, again. 

Sometimes I walk around downtown or at the mall and look at all the  junk in the world and I say to myself, there is nothing I can buy that’s going to make it any better.  It’s now been over two years since I felt good, since I wanted to use and did use the pool twice a day.  I had enjoyed a two month reprieve from my harsh life.  Then, my primary care provider decided I was stable on Lamictal and no longer needed my antidepressant.  It took me a little over three weeks to dive completely to the bottom, again.  I was so bad I had to restart the antidepressant myself and be on it for a little over a week before I came up enough to call the primary care provider and make an appointment.  Even though I went back up to the top dose of antidepressant, I never got to feel good again.  Since then I tried Seroquel and quickly gained 35 pounds plus. (I have now lost 15)  I continued with the Lamictal until I couldn’t remember why I had walked from one room to another on a regular basis.  That got very scary.  Then I tried the new improved Effexor, Pristique.  I noted no difference whatsoever with that medication, and I know enough to give them the 4-6 weeks trial they really need.  Then I got angry and threw them all away.  Bad move.  For the first time in 15 years I became suicidally depressed.  One side of my brain was thinking of ways to kill me and telling me about it and the other side was saying “Bad, bad idea, we need more meds.”  “We” restarted the handy dandy Wellbutrin, which always pulls me up somewhat, but never enough or long enough.

Here’s part of a letter I had written to the primary care provider to help her understand the situation;

“Reducing the Wellbutrin has not worked well.  When I reduced from 450 mg to 300 mg I started getting nervous and bit all my fingernails off again.  Soon after reducing to 150 mg I started shaking my leg/ foot and getting unfocused, irritable and losing the will or energy to exercise.  I had no idea how irritable I get until I started monitoring this symptom and looking at some historical incidents.  When I reduced further I quickly became very depressed, tired, anxious, irritable, asocial and sensitive to sound.  I was too depressed and upset to call so I increase to 150 mg for a week, and called a soon as I was able to talk without crying, to get another appointment.  A week later I returned to 300 mg.  I started getting some energy back and I was much less depressed,  however, I was still shaking my foot and crying when I wake up in the morning because I’m upset with my meds or, I think of something sad.  I was also still pretty irritable, easily annoyed (bitchy) and socially disconnected.  Last week I went back to 450 mg of Wellbutrin.  I feel pretty good today and I’m not afraid to go on this week’s business trip.”

I went on to say;  “My experience and research indicated I have a dopamine imbalance, which dwarfs any other neurotransmitter problems I may have.  As you know, Wellbutrin is one of the few antidepressants that primarily target dopamine.” 

So why am I not getting medications that target dopamine, why, why ,why!  I’m going to find out when I see the doctor on September 21.

Lonely is the catalyst for social interaction and avoidance of lonely is the glue that holds people together. I see the lonely people, they are everywhere. Lonely, a word to describe the pain of wanting to be close to other people, of yearning for connection, it is a very positive emotion. That is one double edge, good thing, about having anhedonia. I don’t get lonely, that is I can only recall feeling lonely once in my life, over 30 years ago for a short period of time. That is the only way I know the pain of lonely, that some people live with on a daily basis. I have nearly no craving for social interaction. I don’t understand “chat”. I do not enjoy people -in general. There are only a few people I care to see at all. They are the people who, for some reason I don’t understand, reach out to me, so I imitate them and reach back. For the first time I have a couple precious relationships. For the first time in over 50 years, I know if I went away, as I have dozens of times, I would miss a couple people. Perhaps that’s a step in learning to be lonely.

Donations are very welcome!

50% of donations go to NAMI ( The National Alliance on Mental Illness). 50% of donations go toward my Brain Transplant…It shouldn’t be too hard to find one; there are a lot of people running around who obviously are NOT using theirs…thank you!

Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression
Thomas E Schlaepfer1,2, Michael X Cohen3,4, Caroline Frick1, Markus Kosel1, Daniela Brodesser1, Nikolai Axmacher3, Alexius Young Joe5, Martina Kreft1, Doris Lenartz6 and Volker Sturm

“Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia—the inability to experience pleasure from previously pleasurable activities—and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto–striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system—in which the nucleus accumbens is a key structure—are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.”
Perhaps I don’t need a brain transplant-a little deep brain stimulation may do the trick!   Diane