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Neurological Changes Associated with Psychotherapy and Pharmacotherapy

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             The brain is a major organ system in the body, having primary control over many of the behavioral and bodily functions of all animals, including humans. Sometimes, human behavior affects an individual’s daily life or ability to perform tasks, and at times these behaviors affect others. These changes in behavior, voluntary or involuntary, can include, and are not limited to, what psychologists diagnose as obsessive-compulsive disorder (OCD) or depression. Diagnosing OCD and depression as “disorders”, violates the great diversity between each individual brain and body, and assumes that these individuals are different than “normal”. The spectrum of what society views as “normal” or “baseline” is intrinsically biased, which limits our understanding of mental “disorders” and adds unnecessary ambiguity. Some “disorders” interfere with an individual’s life and some do not, can this still be considered a “disorder”? If a “disorder” does not affect an individual personally or in their daily life, should it be changed just to fit into the societal definition of “normal”? The behavioral changes associated with OCD and depression can more accurately be referred to as particular brain states.  

             Studies have identified alterations in specific brain regions associated with treatment of depression and OCD through psychotherapy and drug treatment trails.  Do we need drugs to change the brain? Can the brain be altered using psychotherapy? Trials have suggested similar improvements in behavior through both psychotherapy and drug treatment plans, but the benefit of one treatment over the other remains questionable.  

            OCD affects approximately 2.2 million American adults (age 18 and older) and involves an intense mental battle between obsessions tamed by compulsions (1, 3). OCD characteristically involves the plaguing of persistent unwelcome thoughts or images associated with an urgent need to engage in certain rituals (4). The plaguing thoughts and ritualistic behaviors that define OCD can be separated into two categories, obsessions and compulsions. Obsessions involve persistent thoughts, impulses and images, and are felt as intrusive, ultimately leading to feelings of anxiety or distress (2). Individuals attempt to cope with these obsessions by neutralizing unwanted thoughts, impulses or images via other thoughts and actions. Unwanted thoughts or obsessions lead to compulsions or ritualistic behaviors as a way to cope with anxiety producing thoughts (1). Compulsions can include counting, checking, cleaning, and in general ridged application of rules (4).

            People with OCD understand the characteristics of their symptoms as being absurd and ridiculous which sets OCD apart from many other anxiety “disorders”. Many individuals recognize their thoughts, impulses and images as products of the mind (4). Studies have identified neurological structural changes associated with OCD, including less total white matter, and a greater total neocortex (5). Other possible structural abnormalities include blocked or damaged serotonin receptor sites that results in chemical changes within the body (4). Some scientists believe that OCD stems from environmental stimuli that are reinforced and turned into habits (4).

            Depression, on the other hand, involves negative thoughts that dominate and control a person leading them to become self-perpetuating (7). Negative thinking, or cognitive distortions, can include: all or nothing thinking, overgeneralization, disqualifying the positive, jumping to conclusions, and catastrophizing, etc. (8). Aaron Beck, the developer of the Cognitive Theory of Depression, defined depression as an activation of schemas (6). Beck claims, that people with depression develop a negative schema of the world in childhood and adolescence, either through loss of a parent, rejection from peers or criticisms from others (6, 7). According to Beck, negative schemas develop when a person encounters a situation that resembles the condition in which the original schema was learned (7, 9). To reverse the formation of negative schemas, Beck developed the therapy of Cognitive Reconstruction, in which the therapist requires the patient to confront cognitive schemata (6). The therapist also provides the patient with techniques to give them a greater amount of control over their negative thinking by correcting cognitive distortions (9).

            Similar to OCD, people with depression have a decrease in the concentration of neurotransmitters, such as, serotonin and norepinephrine within brain synapses, and decreases in receptor affinity (7). Also, in those individuals with major depression, studies have found patients with a smaller total hippocampal area, a location of the brain associated with motivation, emotion, and memory (10).

            OCD and depression are associated with chemical changes within the body, especially involving the neurotransmitter serotonin. Studies have identified serotonin concentration as one of the major contributors to depression and OCD. From these studies, pharmaceutical companies have developed drug treatments for different “disorders”, known as pharmacotherapy. Pharmacotherapy involves the use of psychoactive drugs that alter the chemical interactions within the brain to treat different “diseases” (13). To treat depression and OCD, many health care providers prescribe selective serotonin reuptake inhibitors (SSRIs), which work in the body to increase the level of serotonin available in the brain (11, 12). The use of pharmacotherapy has been viewed as an easy route to treat complex and not fully understood brain states, such as OCD and depression.

            Evidence supports the biological basis of neurological changes associated with OCD and depression, but is it valid to study brain anatomical and neurochemical changes through a cognitive approach, as presented by Beck? In depression, combinations of both biological and environmental factors (such as schemas and negative cognitions) are affecting a person’s mental state. Beck’s theory focuses primarily on social effects, but can social/environmental influences support the evidence that identifies prominent chemical changes in the brain associated with altered mental states? It has been discussed that the Cognitive Theory of Depression (Aaron Beck) is an oversimplification (14). Perhaps all cognitive theories are an oversimplification for altered mental states, such as depression. Beck’s theory assumes that depression is a diagnosable “disorder”, when in fact, depression might be an altered brain state as a result of a person’s more practical and realistic view of the world (14). Depression could be an evolutionary adaptation to a world that revolves around destruction and violence. Instead of identifying depression as a “disorder”, it can be referred to as an altered brain state from a preconceived definition of mental and biological baseline (14). To fully understand the biological and environmental basis of altered mental states, the following question must be addressed: which came first, the chicken (biological changes/ genetic predisposition) or the egg (social/environmental influences)?

            The problem with the “chicken or egg” is a question that cannot be fully answered and is subject to patient and health care provider bias. To determine the origin of depression is a large endeavor, and answers are biased and dependent on preferred academic disciplines, such as biology versus psychology. Also, patient bias has a large effect on treatment plan, either through a biological approach by taking psychotropic drugs, or environmental/social approach by undergoing “talk therapy” or Cognitive Behavioral Therapy (CBT). The problem with the biological approach to treatment involves the ambiguity of the serotonin pathway and the lack of concrete evidence supporting the biological basis of depression or OCD.  Psychotropic treatment is an option for people diagnosed with depression and OCD, but the biological pathways are not fully understood and therefore these drugs could be working upstream or at another point within the brain (14). Thus, we do not know how many different areas of the brain are being selectively affected by SSRI treatment and the therapeutic effects are uncertain. If these biological pathways have yet to be understood, perhaps a combination of pharmacotherapy and CBT can be a more effective treatment, or CBT alone might be stimulating similar parts of the brain as those seen during drug treatment. Studies show significant evidence linking CBT to biological changes in brain, thus the brain can be altered biologically by environmental stimuli such as talking.

            CBT, a form of psychotherapy, is based on the premise that the patient can become aware of their distorted thoughts and behaviors, and work towards changing them (21). CBT assumes that there are specific stimuli that elicit thoughts that distort reality, reinforce these distortions, and cause distressed emotional states (21). CBT functions by making a patient aware of their maladaptive thoughts and behaviors, and provides patients with the tools to work towards creating a realistic and positive viewpoint of their thoughts (21). For OCD, treatment involves exposure and response prevention to the fear provoking stimuli. A therapist exposes a patient directly or indirectly to the anxiety producing situation or object to lessen subsequent anxiety (22). Through imagining and being in direct contact with the fear producing situation, the patient is learning to refrain from engaging in avoidance behaviors such as compulsions (23). In Depression, patients undergo Cognitive Reconstruction in which they identify and correct distorted thoughts and feelings (24). Therapy also involves an active behavioral approach in which patients are encouraged to engage in pleasurable activities.

            Although CBT has proven to be an effective method of treatment for OCD and depression, how does psychotherapy differ or relate to pharmacotherapy, and how can they work as a simultaneous treatment? In comparing treatment plans, CBT versus pharmacotherapy, brain imaging studies found changes in brain region activity associated with the different treatments. CBT treatment of OCD revealed information supporting a “top down” approach with changes in brain region activity such as, increases in the hippocampus and anterior cingulate, and decreases in the dorsal, ventral, and medial frontal cortices (15,16). Drug treatment or pharmacotherapy utilizes a “bottom up” approach, inducing changes in different brain regions as compared to CBT. The brain regions altered during treatment of patients with OCD were, decreases in brainstem activity, and increases in prefrontal cortex and subgenual cingulate activity (15, 16). Brain imaging studies also emphasize the importance of caudate nucleus activity and functioning in OCD. The caudate nucleus acts as a filter that distinguishes between extraneous thoughts and impulses (17, 18). Thus, CBT works on changing behavioral aspects and distorted thinking associated with OCD, while pharmacotherapy functions by changing the biology, with SSRI drug therapy (17). The brain regions altered by the two forms of therapy show that the pathways of OCD have yet to be fully elucidated. The distinct patterns of brain activity associated with either treatment suggest that these different activations of brain region reflect fundamental differences between treatments. According to brain imaging techniques, there are many neurological structures involved in both forms of treatment indicating that the underlying causes of OCD must involve a complex neuronal network.

            Brain imaging studies comparing treatment plans for patients diagnosed with depression also revealed a “top down”/ “bottom up” approach for CBT versus pharmacotherapy, respectively. Patients enrolled in CBT showed increased activity in brain regions that included the dorsal midsingulate, ventromedial frontal and cingulate gyrus, and decreases in the posterior cingulate (16). Patients taking a prescribed drug treatment had increased activity in the brainstem and cerebellum, and showed decreased activity in the subgenual cingulate and insula (16). The data shows distinct changes in brain region associated with different forms of treatment, but is one method better than the other if both treatments lead to a change in behavior?

            There are distinct differences in brain structure activity associated with CBT and pharmacotherapy which act by stimulating different neuronal networks or pushing at two sides of a neurological circuit. Both treatments affect different structures of the brain because they are distinctly different in approach. Perhaps these differences make the combination treatment of CBT and pharmacotherapy more effective. There is a difference between something happening within the nervous system and no intention of it happening (14). In CBT, there is an intention, an active behavioral decision to seek the help of another. Enrolling in CBT is a conscious activity, and regulation of behavior. In pharmacotherapy, the patient feels something might be wrong and is given a prescription drug that, in OCD and depression, increases serotonin within the brain. The problem with studies showing the neurological differences associated with CBT and pharmacotherapy lies in the artifact of connection (14). If you push a system from any side hard enough, you will get a result. It is difficult to assume that behavioral improvements from OCD and depression are the direct result of these treatments, there could be other factors involved in the treatment process. The two sets of brain systems altered in CBT versus pharmacotherapy are compared at third neuronal loci, but is this again an artifact of connection? If both treatments are working by activating different brain structures then why does a combined treatment of CBT and pharmacotherapy not yield 100% improvement? Instead, CBT or drugs alone result in 48% improvement of symptoms, while a combined treatment leads to 73% improvement (19). Still, the combined treatment is more effective, which supports the complexity of the biological understanding of OCD and depression.

            According to some researchers, psychotherapy alone is an ineffective treatment for schizophrenia, which suggests a correlation between behavioral functioning and structural brain abnormalities (17). From this evidence, CBT is not effective in treating severely disordered brains, but if CBT has been shown to alter brain activity in depression and OCD, why does it not work for schizophrenia? Could people, with OCD and depression, who do not respond to CBT, have severe neurological abnormalities similar to those observed in patients with schizophrenia? The idea is that CBT works by re-teaching a patient’s brain which leads to the formation of new neuronal connections. Work with sea slugs has revealed a doubling of neuronal connections when exposing sea slugs to a controlled learning environment similar to that of CBT (17). The evidence suggests the brain is plastic, and is able to change functionally and structurally through learning.

             One of the major problems with CBT is the self selective nature of the treatment, which implies that the same sample of the population is being treated through CBT (14). The other bias resides in the monetary investment of CBT and the time commitment. For some patients, this form of treatment is expensive, time consuming, and some patients feel drug treatment is a more “potent intervention” and actually changes the chemical levels in the brain (14, 19). While many patients with depression use pharmacotherapy as a main form of treatment, studies show the potential for the placebo effect noticed in patients taking anti-depressants (20). Are these drugs treating the symptoms associated with OCD and depression biologically, or are the drugs making patients more proactive and thus promoting changes in behavior that result in improvements? Further study is required to completely isolate the pathways of these brain states.

            Dr. Elna Yadin, psychologist at the Child Study Institute at Bryn Mawr College, presented a very interesting point of view as a specialist in CBT. Dr. Yadin believes in using plasticity and learning to teach the brain how to heal itself, or to heal a “glitch” in the brain. CBT works with our own bodily mechanisms to change the brain by activating substrates in the brain in the same manner that pharmacotherapy does. According to Dr. Yadin, pharmacotherapy is not specific enough and acts on the periphery which can result in other less desired effects. Dr. Yadin’s approach for treating OCD is through exposure to reduce obsessions, and response prevention to diminish compulsions.  By using what we already have, Dr. Yadin believes that CBT is a very effective form of treatment that relies on learning and behavioral changes associated with the brain.

            As noted in the course blog “Brain, Behavior, and Human Well-Being” (“Psychotherapy and Brain”, Serendip), there is a divide between the efficacy of both CBT and pharmacotherapy. While CBT has proven effective, these improvements could be related to the self selective nature of CBT and the self motivated nature of the treatment (ehinchcl, 2/28/2008). Also, do we even need to work with a therapist that is specialized in “talk therapy”, or can an advisor, mentor, parent, or friend fill the role of a psychologist as effectively? (Rebecca W., 3/2/2008) Many forum participants agree that CBT is a natural form of treatment “working with what we have” as proposed by Dr. Yadin. CBT provides patients with long term benefits by encouraging neuronal plasticity, but as stated in the forum, “the biggest pro-psychotropic drug argument is that taking a pill is a lot easier.” (ebitler, 2/29/2008). Further, “drug treatments can break down the barrier that prevents the patient from enacting change” (krosania, 3/13/2008), which can account for the short term effects associated with pharmacotherapy. The main problem with pharmacotherapy addressed in the forum focused on the lack of drug treatment specifically targeting one structure. There could be a series of undesirable downstream changes associated with pharmacotherapy. Drug treatment could be potentially affecting systems through upregulation or downregulation, but it was proposed that CBT could also be causing similar changes (ebitler, 2/29/2008). Although CBT could lead to other downstream or upstream effects, CBT is more natural and involves a “relationship between a person and their disorder.” (Elliot Rabinowitz, 3/2/2008). CBT allows a person to take control over their OCD and depression, while pharmacotherapy does not (aamen, 3/2/2008).

            There is a significant sociocultural influence in deciding between treatment plans for OCD and depression. Society places many rules and regulation on how a “normal” functioning individual should act in the world. As stated by Dr. Yadin, what is “normal” includes a large spectrum of behaviors and thoughts. People who appear to have depression and OCD do not always feel plagued by their symptoms and many do not seek medical evaluations or treatment. Does society force us to be happy all the time? Perhaps our lack of happiness is adaptive, and trying to “fix” this maladaptiveness is not helping (aamen, 3/2/2008). Also, society focuses on what is “trendy”, “talk therapy” or pharmacotherapy. By attending daily CBT sessions, an individual must actively acknowledge and confront their OCD and depression, and make it known to others. Drug treatment allows a patient to take less of an active role and keep their “disorder” more private. Perhaps the differences in treatment option are related to the level of private versus public a person feels most comfortable with.

            In the future, more studies need to focus on the relationship between specific brain regions and psychological diagnosis, such as in depression and OCD. Drug treatment pathways must be further studied and elucidated to target more specific brain regions associated with OCD and depression to ensure the effectiveness of drug treatment. At present, pharmacotherapy targets the brain as a whole and while scientists understand that SSRI drug treatment increases serotonin concentration within synapses, the downstream effects of pharmacotherapy are not fully understood. By targeting the specific structures involved in OCD and depression onset and activation, drugs can be more effective in treating symptoms.

            While pharmacotherapy targets various parts of the brain, CBT has no additional chemical side effects and requires a personal desire to engage in behavioral modifications. Studies need to focus on showing patients the benefits of CBT and to reduce the negative social stigma associated with “talk therapy”. At present, people still remain skeptical of CBT’s ability to alter specific brain states, such as OCD and depression. For many patients, CBT requires a personal confrontation with the brain, to make behavioral changes which are long lasting. CBT changes the brain, by activating a series of different brain regions as compared to pharmacotherapy, but these differences should not diminish the efficacy of CBT as an effective treatment.

             It is clear that both CBT and pharmacotherapy are changing different brain regions but yielding similar results. Rigorous study of CBT as a treatment plan for both men and women comparatively can help assert CBT as a preferred treatment among patients. Public health work must focus more on publicizing the benefits of CBT as a long term treatment plan with little side effect, which can be tailored to suit a specific patient.



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(4) Obsessive-Compulsive

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(16) Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H. (2008) Modulation of cortical-limbic pathways in major depression. Arch Gen Psychiatry 61:34-41.

(17) Friedman R. 2002 Aug 27. Like Drugs, Talk Therapy Can Change Brain Chemistry. Forensic Psychiatry and Medicine. <>

(18) Goleman D. 1996 Feb 15.Psychotherapy Found to Produce Changes in Brain Functions Similar to Drugs. The New York Times. <>

(19) Bender E. 2004 May 7. Brain Data Reveal Why Psychotherapy Works. The American Psychiatric Association. Psychiatric News. <>

(20) 2008 Feb 26. Anti-depressants ‘little effect’.  BBC News. <>

(21) Warman M., Beck A. 2003. Cognitive-Behavioral Therapy.  National Alliance on Mental Illness.<>

(22) 2007 Dec 12. Factsheet: Obsessive-Compulsive Disorder. Mental Health America. <>

(23) 2002.Obsessive-Compulsive Disorder at Johns Hopkins. Department of Psychiatry and Behavioral Sciences. <>

(24) 2006 Feb 2. Cognitive Behavioral Therapy.University of Michigan Depression Center. <>



jyohthsna's picture



Paul Grobstein's picture

Brain imaging and pharmaco/psycho-therapy

For more on what it may mean that different treatments produce somewhat similar but somewhat different imaging results, see Exploring Depression.