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Breaking Through Depression: A Guide to the Next Generation of Promising Research and Revolutionary New Treatments

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“A thorough, up-to-date, and upbeat introduction to current scientific thinking about mood disorders and their treatment. An important resource for patients and their families—and for anyone curious about progress in psychiatric research."― Peter D. Kramer, Listening to Prozac

This inspiring exploration of the recent advances in depression research and treatment shares new methods that offer promising paths to wellness. 

Breaking Through Depression explores how the anatomy of the brain and the biochemistry of nerve impulses play a major role in how we view ourselves and the world. Drawing from his long-term research, Dr. Philip W. Gold makes the case for depression arising at the intersection of genetic vulnerability with stressful, disturbing life experiences that get encoded in our emotional memory. Breaking Through Depression will delve into the interplay between our anatomy and our lived experiences as the key to understanding why there are such individual differences in how we make connections with others, deal with adversity, or recover from trauma. More importantly, Dr. Gold reveals the latest breakthroughs that can heal people struggling with depression, The FDA has fast-tracked Psilocybin and Ketamine as anti-depressant treatments, which cause immediate improvement in depressive symptoms. Low-energy lasers have been developed that can stimulate these areas directly and painlessly to relieve symptoms in treatment-resistant patients suffering from major depression. Scientists are developing genetically ‘thumbprinted' antidepressants that can be individually tailored to match a person's DNA increasing their effectiveness.   Inflammation in the body and the brain is a prominent component of depressive illness, to the point that anti-inflammatory agents are useful in the treatment of depression.  Incredible progress with gene therapy including a treatment overcoming the BDNF gene mutation that interferes with resiliency, promotes vulnerability to depression, and inhibits the capacity of antidepressants to work effectively.  These are just a few of the fascinating new developments explored in Breaking Through Depression and the many reasons for hope that Dr. Gold shares in this groundbreaking book.

293 pages, Kindle Edition

Published August 15, 2023

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Philip William Gold

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Displaying 1 - 5 of 5 reviews
Profile Image for Camelia Rose.
889 reviews112 followers
December 26, 2023
I picked up the book from our local library without knowing the author. For many years Dr Gold worked at the National Institutes of Health Clinical Center where he served as Chief of Neuroendocrine Research. He is an expert in major depression and still a practicing psychiatrist. Breaking Through Depression is quite different from medical science books written by journalists I’ve read. The language is dry and plain in a no-nonsense way, with a lot of medical words. The content is rich.

A few years ago I read an article that pharmaceutical companies had stopped researching medicines to treat mental illness. I am surprised to learn from Dr. Gold that there are new antidepressants being developed and new medical research being conducted. Not only psilocybin and ketamine, but also medicine to stabilize hormones, to correct circadian rhythms, to target various new neuro receptors and genes. Even old antidepressents have generated new understandings.

Another surprise is that as a practicing psychiatrist, Dr. Gold stresses the importance of psychoanalytic therapy. Medicine alone is not enough for many patients.

Chapter 5 The Art of Therapy is worth reading on its own. Do I know a psychoanalyst should be analyzed before treating patients?

Quotes:
P62
“Patients who have a hard time dealing with anger also frequently develop the means to deny or shield themselves from assertiveness and competitiveness…The purpose of these defenses is relatively similar to those defending against anger: to avoid hatred and abandonment. In this case, the envy of others would be an instrument that could potentially injure them.”

P63

“We also learned that it was critical to help our patients diminish the impact of their shame over being imperfect. Perfectionism impedes the patient's task enormously. Patients sadly feel ashamed because they are depressed, a state they feel they could have avoided if only they were not so grievously imperfect. They develop this equation: “If you are not perfect, you are worthless.” Hence, they feel humiliated by their depression. ”
Profile Image for madison.
129 reviews2 followers
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November 17, 2023
a rundown of the current state of research into the neuroscience of depression. so good. goes into where neuroscience is at in understanding depression today, how it works in the brain, and where we can hopefully be in a few years as the science progresses.

this is not a self help book, rather, it lays out where the study of depression has been and where it might go next.
156 reviews2 followers
July 8, 2025
Peter Kramer of Listening to Prozac by Peter D. Kramer recommendation on the dust jacket convinced me this might be worthwhile read !. Gold begins with his own familial history as if taken by a psychologist (which it was), but in addition to the various case studies (similar to Kramers') the book does delve more into the psycho - pharmacology aspect of depression stressing the biologistics of the brain and what role that plays in long term treatment resistant depression.

The NIH [310 acre Bethesda campus] makes an interesting back drop for the study of depression (he took over the lab from Julie Axelrod. Dr Gold's thesis begins with the 2 major groupings of depressives. As Freud might have quipped you sleep too much you're depressed (Atypical) ; sleep too little your depressed (Melancholic). From this vantage he builds the neuro-endocrine model(s) of depression based on Stress (chapter 3) ie. the over production of cortisol (CRH overproduction by the sympathetic nervous system) involved in early morning awakening, and conversely the underproduction of norepinephrine (because the hypothalmus is releasing too little CRH) as seen in Atypical depressives.

The story of how impramine was the first attempt (1951) to control over stimulation by inhibiting nor-adrenalin in depressives is an old one, but Gold does a credible job at expanding the discussion to include the progression towards MAOI inhibitors and later SSRI's which was the focus of Kramer's book. The middle chapters become something of a plethora of Biological Dysfunction [metabolic] and Hormonal deregulation [including insulin] factors that may (or not) cause (affect) depressive individuals.

Chapters 10 on is where the book begins to pull together the clinical aspect leaving more questions than answers. i. are children more susceptible to biologic or environmental causation ? ii. is the depressive portion of Bipolar disorder both melancholic and Atypical ?. iii. do so called advance treatments ie. hallucinogens, electrical stim, or even lithium provide any more relief than so called psychopharmacology ?.

The later chapters bring one more up to date on several treatment modalities that had previously been abandoned (or never tried) i. ECT ii rTMS iii. Hallucinogens ( sic Roland Griffiths John Hopkins ). Overall Dr GoLd does a really good job putting the development of clinical psychiatry onto the chronological plane.

In chapter 15 he reexamines the role of older anti depressants and their mechanisms. In particular he mentions how WellButrin, Cymbalta, and Effexor bind to the BDNF receptor. IN furtherance of Seratonin's 2a receptor; he points out that ALL immune cells contain this. In chapter 16 he moves into Ketamine's role in glutamate production which in turn activates the AMPA receptor. This also promises BDNF production. Ketamine not just being more fast acting, but more potent in countering the GABA deficiency often present in depressives highlights the role of BDNF in emotional memory amelioration within the amygdala.

This unblocking of seratonin 2A receptors by psychodelics (or even MDNA) therapies is seen to allow more effective use of antidepressants later in therapy. The final chapter deals with the idea of resilience. In fact why 2 children of "Adverse Child Events" One(1) will recover, and Two(2) hardly ever does seems to be the great mystery. One better addressed by psychology perhaps in this book What Happened To You? Conversations on Trauma, Resilience, and Healing by Bruce D. Perry

Over all a good read for those deciding to study pharmacological psychology OR therapeutic psychiatry !
Profile Image for Erin Dennis.
43 reviews1 follower
July 13, 2024
I would only recommend this book to patients who have been newly diagnosed or families that have a loved one recently diagnosed with depression. It covers the biological basics and general medical history of therapies. But for those suffering from depression for decades due to repeated traumas there's not a whole lot of new information or wisdom on navigating the complications of accessing breakthrough treatments. I did not find it insightful or useful.
Profile Image for Geoffrey Weiss.
52 reviews3 followers
January 6, 2024
This volume provides an excellent review of the progress made in identifying the causes and addressing the management of depression and its variants. Dr. Philip Gold, a recognized research authority from the NIMH, has led a career uniting neurobiology and psychotherapy to the control of this extremely common and debilitating disease. The key revelations include, the application of neuroimaging, biochemistry and genetics to the recognition of the anatomic and metabolic changes occurring in depression, the development of therapies targeted to the seminal molecular disorders operative in the disease, and the proposition of a working hypothesis for the cause of depression based on the physiological stress response gone awry. The absence of diagrams and the use of arcane scientific nomenclature detracts from the reader's ability to acquire a unified understanding depression, but the book is nevertheless a worthy addition to the lay literature.
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