Psychotherapy and Neuroscience

Psychopharmacology & CBT

Current popular therapies that help provide individuals relief from symptoms of, for example, anxiety, depression, anxiety-driven obsessive compulsive cognition, cognitive looseness of association, cyclical mania and depression, and symptoms of substance abuse, are psychopharmacological and cognitive behavioral therapies (CBT). Psychopharmacological treatment helps to normalize neural activity at certain synapses in discrete areas of the brain and CNS to reduce symptomology. According to findings from Positron Emission Tomography (P.E.T.) paroxetine (most notably known as Paxil), for example, has been found to be efficacious at reducing major depressive symptoms, i.e. anxiety, somatization, psychomotor retardation, etc. (Brody et al., 2001b) as well as anxiety related symptoms in obsessive-compulsive disorder (Saxena et al., 2003). Paroxetine increases basal state glucose metabolism in the perigenual anterior cingulate and dorsolateral prefrontal cortices, caudate, and thalamus as well as decreasing metabolism in the insula, hippocampal formation (Brody et al., 2001a; Kennedy et al., 2001) and amygdala (Saxena et al., 2003). Though Paroxetine is an SSRI, selective serotonin reuptake inhibitor, it functions as a dual serotonin-norephinephrine reuptake inhibitor (Tatsumi et al., 1997) and bicyclic antidepressant (Pariante et al., 2001) that targets the presynaptic 5HT-1A membrane receptor transporter to enhance serotonin binding to this receptor in discrete regions of the brain. Paroxetine’s actions on the 5-HT1A receptor, along with a few other tricyclic antidepressants noted below, regulate membrane steroid transporters by increasing glucocorticoid receptor (GR) function and potentiating GR-mediated (glucocorticoid receptor-mediated) negative feedback on the HPA (hypothalamic-pituitary-adrenal axis). This increases GR binding (Pariante et al., 2001) and regulates cortisol secretion in the plasma, saliva, urine, etc. that is associated with depressed state. Amitriptyline (Elavil), a tertiary amine and tricyclic antidepressant, is a serotonin and norepinephrine reuptake inhibitor that targets serotonin and noradrenergic receptors (Potter et al., 1998; Feighner, 1999). It is also effective at resolving depressive symptoms (Reynolds et al., 1996; Thase, 2003) by increasing GR binding (Okugawa et al., 1999) and mineralocorticoid receptor (MR) binding in the hippocampus (Reul et al., 1993), and in reducing the secretion of cortisol, evidenced in reductions in salivary cortisol concentrations (Deuschle et al., 2003). Imipramine, has been found to be effective at resolving depressive symptoms (Kocsis et al., 1997; Mueller et al., 1999; McGrath et al., 2000) and self-harming behaviors (Hellerstein et al., 2000) by, in part, decreasing hypothalamic-pituitary-adrenal (HPA) axis sensitivity, as evidenced in reduced ACTH and cortisol responsivity to CRH challenge (Michelson et al., 1997). Sertraline (Zoloft), another SSRI, is a serotonin and dopamine reuptake inhibitor (Tatsumi et al., 1997) that targets to slow the receptor’s presynaptic transport of 5-HT1A (to contain it in the receptor and synapse longer) and to increase the availablity of 5-HT1A serotonin by blocking the cascade of dopamine in the D2 receptor and serotonin in the 5-HT2A membranes (Tatsumi et al., 1999). Sertraline’s effects on 5-HT1A receptors are also associated with decreased plasma secretion of norepinephrine (Shores et al., 2001) and decreased activity of the sympathetic nervous system. Decreases in plasma norepinephrine are suggestive of Sertraline’s indirect ability to bind norepinephrine to specific receptors in the brain. Increased receptor binding facilitates regional functional expression that can inhibit the activity of stress neurocircuitry. Sertraline has been shown to be efficacious at treating depressive symptoms in women (Kornstein et al., 2000) as well as anxiety symptoms associated with obsessive-compulsive disorder (Koran et al., 2002; Bergeron et al., 2002). Post-traumatic symptoms of numbing, avoidance, hyperarousal (Davidson et al., 2001), sensitivity to trauma triggers and hypervigilence (Davidson et al., 2002) have also been resolved with therapeutic doses of sertraline; patients demonstrate overall improvements in quality of life (Rapaport et al., 2002).

Psychotropic medications do not totally reverse or treat the underlying cause of affective and cognitive symptoms, as untreated and treated, remitted depressives do not stimulate the same brain regions during P.E.T imaging as healthy controls during an event-related task that required recall of sad memory for prior personal loss (Liotti et al., 2002). Unlike healthy controls, untreated and remitted depressives fail to activate one particular cortical region, the perigenual anterior cingulate cortex or medial prefrontal cortex. This region is one of many brain areas, including the orbitofrontal cortex and structures in the anterior temporal lobe, that have been associated with the processing of emotional memory, i.e. in refining it to make it more amenable for its later retrieval (further detail will be provided in a future section of this web site). In addition, this region’s involvement in memory processing ultimately leads to the eventual extinction of the chronic stress response (also to be noted in a future section). The disparity of responses between healthy controls and remitted and untreated depressives suggests that psychotropic medication works to modulate a limited neural component of the depressive disorder, i.e. that associated with chronic and persistent arousal. An analysis on emotion demonstrated that healthy people tend to activate the ventral perigenual anterior cingulate cortex in response to sadness-induced script driven imagery and facial expressions (Vogt et al., 2003). Because healthy controls also tend to experience and express all emotion in their ongoing experience, their responses to sadness-inducing reminders are probably reflective of their experience of sadness.

As observed in my clinical psychotherapy practice unmedicated patient populations typically attempt to defend against experiencing pain-associated negative emotion. They experience greater autonomic arousal in response to, for example, fear-producing script driven imagery that has been a simulation of previously experienced trauma (See J.D. Bremner et al., 1999ab). In summary psychopharmacology has proven to be very effective and reliable at reducing troubling affective and cognitive symptoms that interfere in one’s quality of life. As will be discussed in later sections of this web site, this normalization is actually a reduction in the neural components that underlie the chronic stress response.

CBT seeks to help an individual to gain awareness of and alter the thought that immediately precedes the experience of a negative emotion, such as anxiety, depression, or anger in response to an arousing event or stress-inducing stimulus. When comparing the efficacy of either modality, psychopharmacological therapy has been shown to be slightly more effective at resolving symptoms relating to social phobia (Heimberg et al., 1998), bulimia nervosa (Mitchell et al., 1990), and major depression (Thase et al., 2000). CBT was found to be superior for reducing depressive symptoms over tricyclic antidepressant therapy (Murphy et al., 1995; DeRubeis et al., 1999). Simultaneous use of both methods has been proven to be quite efficacious at reducing anxiety symptoms associated with bulimia nervosa (Agras et al., 1992; Walsh et al., 1997) and panic disorder (Brown and Barlow, 1995; Stein et al., 2000); however, discontinuation of either therapy method (de Jonghe et al., 2001; Foa et al., 2002) results in later relapse. Many clinicians have observed and it has been demonstrated in research findings that various psychotropic medications and brief cognitive-behavioral therapy, in combination, consistently eliminate affective and psychiatric symptoms; however, symptoms often return with discontinuation of either or both respective treatments (Melfi et al., 1998; Parker et al., 2003).


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