(This is a guest post written by Dr. Douglas Watt, Ph.D. His bio is included at the end of the piece.)

 Depression: It’s Not a Chemical Imbalance:

In Part I on depression, I talked about the uncritical acceptance of a cultural meme propagated by big Pharma and by mainstream Psychiatry that depression can be meaningfully conceptualized as a ‘chemical imbalance’. We have argued instead that depression is best conceptualized as a conserved biological vulnerability in social brains. Our vulnerability to depression may reflect one of the major downsides of having a social brain that requires social support and emotional connection.

To see depression instead as a ‘chemical imbalance’ that has nothing to do with personal stressors or the state of one’s social or intrapsychic world obfuscates its real neurobiology and fragments the deep and profound connections between the psychology and the biology of depression; between the state of one’s social and psychic world and the enormous complexity of the brain’s signaling systems. Depression is a complex N-dimensional ‘shutdown mechanism’ orchestrated by many signaling systems in the brain, but intimately related to chronic psychic pain, physical pain (which has deep evolutionary connections to separation distress and psychic pain), and to various forms of ‘social defeat’ (such as losing in a dominance competition, or being fired from a job). Psychic pain, physical pain, and these various forms of separation distress and social defeat are far and away the most common stressors precipitating entry into depression. The conjoining of these factors- seen in individuals dealing with severe social stress who also have acute or chronic pain – predicts a very high risk for depression. In what way does it help any of us (treaters, family members or patients) to conceptualize these problems as mere ‘chemical imbalances’? Well, it helps big Pharma sell drugs, but other than that, it has no real heuristic or scientific utility.

Why Conventional Views & Psychiatric Medication Misses the Target:

One of the difficulties with the conventional psychiatric view of depression is that critical etiologic roles in depression are played by neural signaling systems that mainline psychiatric drugs simply do not directly impact, including the classic prosocial peptides such as oxytocin and opioids (both mu and kappa), as well as pro-inflammatory and stress molecules. These various neural signaling systems form a complex recursion that certainly interacts with the classic monoamines (serotonin, norepinephrine and dopamine) that psychiatry can manipulate, but we believe that it is this entire and deeply interactive signaling matrix that regulates both entry into and exit from depression. Indeed the fact that so many pro-social and stress peptides are implicated in the neurobiology of depression is an unambiguous clue that the current mainstream treatment climate – with psychopharmacology and antidepressants first while psychotherapy and other forms of social support are generally severely neglected – is simply inconsistent with what we know about the real neurobiology of depression.

How to Treat the Depressed Social Brain:

Drugs: 

What are the implications of such a social brain ‘meme’ for depression for those seeking treatment from this all-too-common condition?  Unfortunately, for those with the most common form of depression – mild to moderate – mainline psychiatric drugs (typically SSRIs, SNRIs, or mixed serotonin/norepinephrine reuptake inhibitors) do not separate from placebo, if you combine both the positive published studies with the negative ones that were not published. These drugs only separate from placebo in moderate and worse depressions,  not necessarily because they are more effective in this case, but because the placebo mechanism with which they are competing – positive expectancy itself – is falling apart as depression deepens. This suggests that the primary treatment meme for the most common form of this condition (mild to moderate depression), which is to place people on popular drugs like Celexa, Prozac, Zoloft, etc., does not have a solid empirical basis.

This is not to say that these drugs are not effective for some people, but their effectiveness has been oversold, and their side effects and risks minimized. For those with more serious depression, psychopharmacology should be considered, but not by itself. Where depressions are akinetic/abulic (slowed movement often conjoined with serious motivational deficits), stimulants can be useful. In serious depressions that have been refractory to multiple courses of psychopharmacology and psychotherapy, and where lifestyle changes are either impossible to achieve or ineffective, there are options for Ketamine, for rTMS (magnetic stimulation of the cortex), and if those are unsuccessful, for ECT ( Electroconvulsive therapy). Buprenorphine may also be useful in refractory depression due to its unique combination of kappa opioid antagonism (which counters depressive shutdown) and partial mu agonism (which may help promote prosocial emotions), but it is very hard to get this prescribed for depression instead of for opioid addiction. The current and growing angst over opioid abuse and addiction has also blocked this unique compound from being even adequately studied in depression. Such psychopharmacology decision trees should not be seen as synonymous with the treatment space of depression – an unfortunate equivalence again driven by the ‘chemical imbalance’ meme.

Therapy and Social Interaction:

Psychotherapy and the reduction of social isolation should be the first line of treatment for most mild to moderate depression, along with consideration to various lifestyle changes, as outlined below. Psychotherapy can profitably explore traumatic losses and social defeats that may have precipitated the depression, underlying chronic vulnerabilities in self-esteem, and defensive operations against these forms of psychic pain that are maladaptive and that may in the end only unwittingly reinforce disconnection and loss. This can help socially isolated individuals reconnect, and thereby recover a basic hopefulness. Recovering and rebuilding the sense that basic social rewards are not all lost, and are still potentially available to the depressed individual is an absolutely critical achievement in the treatment of depression.

Our Lifestyle: Depression as a Modern World Disease:

Depression is now the single most common and most costly condition affecting Western societies. This cannot be a coincidence, suggesting that there is likely to be an intrinsic tie between lifestyles in Western technological societies and risk for depression. I believe that this elevated risk is directly related to our multiple and profound lifestyle alterations when compared to our ancient hunter-gatherer societies. Significant alterations include: Our chronic loneliness and social isolation, now ubiquitous in Western societies; our pro-inflammatory Western dietary patterns; our sedentary behavior and lack of aerobic exercise; and last but not least, our fragmented and disrupted sleep. Each of these lifestyle alterations increases systemic inflammatory tone and several promote the stress axis. All of these alterations from an ancient hunter-gatherer lifestyle, one that was both socially intimate and highly aerobic, reflect a deep ‘evolutionary discordance’ between genes and environment.

Fighting Depression in the Modern World: 

This list of profoundly altered lifestyle factors in modern societies suggests, first of all, that if you want to reduce your risk for depression you should try to do the following or at the least try one of the following:

1) Eat a largely Paleolithic or Mediterranean or at least ‘non-Western’ diet pattern minimizing grains, refined sugars and dairy products while maximizing fruits and vegetables

2) Exercise regularly

3) Be in long-term stable attachments and intimate groups (These are hugely antidepressant and affectively mobilizing/energizing)

4) Get a good night’s sleep

5) Get decent amounts of sunlight during the daytime if possible (or supplement this with a lightbox), as stabilization of our circadian rhythms is also antidepressant.

If you notice that you check few or none of these desirable boxes, even if you are not depressed currently, you are at elevated risk for depression, and also at risk for other major chronic diseases, including type II diabetes, heart disease, cancers, and down the road, neurodegenerative disorders.

Correction of these risk factors is not easy, particularly the mitigation of social isolation, which is a growing and deeply pervasive problem in Western societies across virtually all age and socioeconomic groups. Many individuals find themselves trapped in a reliance on addictive online social media, while face-to-face socializing and real social attachment is shrinking, and for some, virtually disappearing. Indeed recent studies have suggested that one’s quality of life is rated to be roughly inversely proportional to how much time you spend on social media sites.

The Importance of Intimate Relationships: Your Most Essential Task for Recovery: 

One of the most critical of these five lifestyle factors, namely positive and stable social attachments and intimate workgroups or family groups is clearly not an easy achievement – indeed probably less than 40-50% of our society can claim even reasonable success in these critical social tasks. Many people simply suffer from this lack of social support and involvement as a primary and even chronic depressogenic stressor on to which additional pro-depressive stressors can fall. Additionally, a classic precipitant for depression is loss of a primary attachment, either through death, or a break-up of a relationship. These can be particularly challenging depressogenic events, particularly when a loss is genuinely catastrophic in quality, such as the death of the child or a beloved spouse. Some degree of depression is almost universal after these kinds of losses, even for those who are exceptionally resilient and with strong social supports.

As someone once said, “hope springs eternal.” But perhaps it’s really longing and need that spring eternal – longing for social connection, love and social support. These are fundamental drivers for much of our motivation, and with a steady supply of social rewards constituting the most important support for a euthymic, non-depressive mood. Hope comes from the deeply felt but potentially even largely unconscious conviction that despite inevitable frustrations and failures, the joys of social connection, affection, play, and sexual intimacy are never completely lost and are available . . . or at least can be recovered. Hope in that sense is simply the willingness to struggle, and the resilience of social motivation in the face of the inevitable obstacles, frustrations and the intrinsic uncertainties of the social space. Depression however blunts and in some cases even virtually extinguishes this basic motivation to seek connection. Its recovery is the essential task in the treatment of depression. Obviously how to do this is a unique and individualized equation for each individual, but with one’s eye on the real target and not on some mythical chemical imbalance, those suffering from this ubiquitous emotional condition have a much better chance of achieving real success.

Author’s Bio:

Dr. Douglas Watt was trained in psychology and neuropsychology at Harvard College and Boston College, completing his PhD studies in 1985.  He did his postdoctoral internship at Human Resource Institute, specializing in projective psychological and neurocognitive assessment of hospitalized inpatients. Over 30 years of clinical practice, he has served as Director of Clinical Psychology/Clinical Neuropsychology in two Boston teaching hospitals. He was on the faculty of the Boston University School of Medicine for 15 years. He was a faculty member at the Boston Graduate School of Psychoanalysis and Institute for the Study of Violence for four years, where he has taught doctoral level courses on affective neuroscience and its implications. He is a prolific scientific author and educator. His current clinical and research interests center on Alzheimer’s disease, its relationship to delirium, and how basic lifestyle factors contribute to or prevent it.