“Not Dead Yet!” – Confronting the Legacy of Dualism in Modern Psychiatry

Mind versus body. What we see versus what we feel. What we can measure versus what can never be quantified. For millennia, philosophers, religious leaders, and scientists have wrestled with the tension between our physical existence and the intangible nature of consciousness.

It wasn’t until the 17th century that the brain was recognized as a key player and the debate began to focus: is it possible that the richness of human experience can be contained within this extraordinary organ? In the mid-1800s, a new era of science began to take root, with pioneers such as Broca and Charcot leading early efforts to understand brain function. Sigmund Freud himself was one of the first to try reconciling his training as a neurologist with evolving models of the mind. But the tools of the time were not yet powered to accommodate his vision. Lamenting the lack of scientific sophistication of his day, Freud ultimately turned his efforts toward understanding the depths of the psyche. Through this work he eventually came to believe that psychiatric illness could not only be understood through a psychological lens but could also be treated in this way. Over the ensuing decades, psychodynamic psychotherapy became the gold standard treatment. More streamlined forms of “the talking cure” would follow, from Aaron Beck’s introduction of cognitive behavioral therapy (CBT) in the 1960s to a range of newer, evidence-based therapies. All were rooted in the premise that psychiatric illnesses could be treated as “diseases of the mind.”

There was good reason that psychological interventions dominated the first half of the 20th century: biological models of the time had limited value for both understanding and treating patients. (One need only to think of insulin comas, lobotomies, and treating syphilis with malarial fevers to conjure up the problematic nature of available options.) But a powerful shift was waiting in the wings.

Starting in the 1950s, psychopharmacology took the world by storm. In rapid succession, antipsychotics, antidepressants, and mood stabilizers emerged as real treatment options. The change was revolutionary: a pill a day could lead to improvements in feelings, thoughts, and behaviors. And the kicker? They seemed to work without the need to do any deep (or even shallow) psychological work. Theories of mental illness that explained psychopathology as a “chemical imbalance” began to spread—disease could be seen as something of the body, rather than of the mind.

One might have hoped that the psychological and biological camps would come together to create a new, unified psychiatry. Alas, the split only widened. Proponents of biological models (rightfully) balked at some of the extreme psychosocial hypotheses (e.g., the “schizophrenogenic mother” as a childhood cause for psychosis). Those in the psychological camp were equally critical of what would come to be termed “neuromania”—the exaggerated belief in the ability of neuroscience to explain the complexity not only of individual human experience but of broad sociocultural phenomena. With so much tension and animosity, could the two worlds ever find a way to converse?

Unbeknownst to many, the conversation had already begun. On September 11, 1947, at the Book-Cadillac Hotel in Detroit, Donald Hebb presented the results of a simple but unorthodox experiment. The genius of the study was that it questioned the very frame of how research was conducted: whereas the scientific method encourages researchers to isolate a specific process in a focused laboratory setting (by controlling as many variables as possible), Hebb asked the opposite—what is the impact of the experience of engaging with a complex world? To answer this, he raised two groups of rats: one set was raised in his laboratory, according to current standards; a second set was raised in his home and treated as pets (1). The pet rats had greater opportunity for social interaction and innumerable novel experiences as they explored a complex space. And Hebb found that they performed much better on tests of learning and memory.

Over the following decades, study after study demonstrated that the effects were not just behavioral: engaging with an enriched environment had a profound neurobiological impact (2). Animals developed larger cerebral cortexes, larger hippocampi, and had increased numbers of synapses. Moreover, they also showed evidence of improved “mental health” with fewer anxiety-like behaviors, a decreased tendency to self-administer drugs of abuse, and a greater ability to recover from mild stressors. Even rodents with a genetic risk for illness were shown to benefit from enriched settings.

How could such a seemingly simple intervention have such a profound impact on neurobiological development? One model was that, paradoxically, the enriched environment might actually constitute a mild form of stress. Novelty, play, and exercise all result in activation of the hypothalamic-pituitary-adrenal (HPA) axis. By experiencing mild stress in a safe and rewarding environment, the rats were essentially being inoculated. When subsequently exposed to severe stressors, the animals showed more adaptive HPA axis activation, with an enhanced ability of the prefrontal cortex (PFC) to regulate the amygdala (3). In effect, the experience of safe exploration seemed to prepare these rats to better navigate environments that were dangerous or unpredictable. What Hebb’s study—and decades of subsequent research—had demonstrated was that experience shaped neurodevelopment.

But how was this work relevant to humans? And, more specifically, to what extent might it inform the longstanding debate on dualism? The idea that lived experiences (such as exercise and an enriched environment) shape neurodevelopment begins to address this tension—but the bigger question is whether psychological processes themselves might have a similar impact. More directly: could it be that mind- and brain-based interventions are one and the same?

The proof was in the PET scan. In 1992, using positron emission tomography, the world received its first neuroimaging evidence that response to psychotherapy (specifically, CBT for obsessive-compulsive disorder) was associated with changes in brain metabolism (4). Subsequent neuroimaging studies of successful psychotherapy showed that the improvement in an individual’s abilities to cope with life stressors correlated with increased PFC function and enhanced limbic regulation. More recent data have demonstrated more widespread and complex biological effects of psychotherapy—from epigenetic changes in BDNF regulation (possibly leading to increased neurogenesis), to similar changes in FKBP5 expression (thereby modulating circulating stress hormone levels), to reconfiguring serotonin transporter and receptor density in areas of the PFC (correlating with improvement in coping skills and social functioning) (Table 1) (5).

Table 1.

Selected Studies Highlighting the Biological Impact of Successful Psychotherapy^a

Author, Year	Diagnosis	No. of Patients (Intervention Group)	Study Design	Biological Effect in Responders
Viinamäki et al., 1998 (9)	MDD	1	PD PTx for 1 year	SPECT imaging showed SERT density normalization within the mPFC
Koch et al., 2009 (10)	MDD	30	IPT for 6 weeks (12–16 sessions)	Western blot analysis showed increase in CREB phosphorylation in T lymphocytes (associated with increase in BDNF expression). No change found in circulating BDNF levels
Karlsson et al., 2010 (11)	MDD	8	PD PTx for 16 weeks	PET imaging showed greater binding of 5-HT1A in the medial PFC and in the OFC
Lueken et al.,2013 (12)	PD	49	CBT for 6 weeks (12 sessions)	fMRI showed increased hippocampal activation with stimulus processing, as well as enhanced ACC-amygdala coupling
Perroud et al., 2013 (13)	BPD	115	DBT for 4 weeks	Decrease in BDNF methylation in direct proportion to clinical improvement
Yehuda et al.,2013 (14)	PTSD	16	PE for 12 weeks	Decrease in FKBP5 methylation—this correlates with increased circulating cortisol and improved modulation of norepinephrine release by the locus coeruleus
Fonzo et al., 2014 (15)	GAD	21	CBT for 10 sessions	fMRI showed a decrease in maladaptive activation to angry and fearful tasks in the sgACC and amygdala
Paret et al., 2016 (16)	BPD	8	DBT for 12 weeks (in 4 sessions, amygdala NF incorporated)	fMRI showed increased connectivity between the vmPFC and the amygdala (did not persist without NF component)
Ziegler et al., 2019 (17)	PD	57	CBT for 6 weeks	Epigenome-wide association study revealed increased methylation at IL1R1—lower levels of IL-1 have been associated with improved resilience for anxiety symptoms

5-HT, 5-hydroxytryptamine (serotonin); ACC, anterior cingulate cortex; BDNF, brain-derived neurotrophic factor; BPD, borderline personality disorder; CBT, cognitive behavioral therapy; CREB, cyclic adenosine monophosphate response element-binding protein; DBT, dialectical behavior therapy; fMRI, functional magnetic resonance imaging; GAD, generalized anxiety disorder; IL-1, interleukin 1; IPT, interpersonal psychotherapy; m, medial; MDD, major depressive disorder; NF, neurofeedback; OFC, orbitofrontal cortex; PD, panic disorder; PD PTx, psychodynamic psychotherapy; PE, prolonged exposure; PET, positron emission tomography; PFC, prefrontal cortex; PTSD, posttraumatic stress disorder; SERT, serotonin transporter; sg, subgenual; SPECT, single photon emission computed tomography; vm, ventromedial.

^aAdapted from Miller (5).

Ironically, it is now clear that the intervention that has historically been viewed as quintessentially “psychological” is just as biological as medications, and often acts through similar mechanisms. (Interestingly, one contemporary line of thought is that psychotherapy itself may be akin to an enriched environment: patients are offered the opportunity to explore novel or challenging content—both inside and outside of session—with the support of a caring provider.)

One might think that such data would quickly reshape the conversation about psychiatric illness. But, sadly, they seem to have had little impact on the pervasive influence of dualism. As substance use disorders ravage our country and suicide rates increase, public dialogue is all too often infused with a moral model in which sickness is attributed to weakness of character. Across medicine, differential diagnoses routinely seek to distinguish “organic” from “nonorganic” etiology. The very structures of mental health care are designed to segregate types of treatment, with most systems assigning clinicians to specific roles as either prescribers or therapists—healers of body or of mind.

This is not merely an academic question. Colluding with dualism may compound stigma and undermine effective treatment today. Moreover, it may hinder our ability to move forward as a field.

Acknowledging the interconnectivity of mind and body opens up a range of novel treatment options. Recent studies have explored how to strategically use medications and noninvasive brain stimulation to augment the effect of psychotherapy: to hasten exposure therapy, to enhance the impact of cognitive interventions, or to disrupt reconsolidation of fear memories (6,7). Thus, it is not necessarily that combining medications and therapy works better because two good things are better than one. Rather, the art of modern psychiatry may be to appreciate how seemingly distinct interventions may synergistically impact the same underlying process.

One of the most prescient voices in the debate of mind–brain dualism in psychiatry was George Engel. In 1977, he offered the biopsychosocial model as a roadmap for thinking in an integrated way about our patients (8). Though the model has been misconstrued and criticized simultaneously from both sides (for being unscientifically holistic and for being overly reductionistic), the central message is clear—these realms are inseparable, and one cannot be conceptualized in the absence of the other.

The tension between our physical existence and the intangible nature of consciousness will continue to defy ready understanding. Deep philosophical and spiritual questions will persist and be unanswerable. But these should not be confused with scientific insights that emphasize psychobiological unity in the cause and treatment of psychiatric illness. And a first step is clear: to make a commitment to notice and vocally refute the dualistic assumptions that pervade and undermine our field.