Neurobiological and pharmacological arguments for customization of cognitive behavioral psychotherapy in the treatment of major depressive disorder

Abstract

Introduction: Depression represents a public health issue because it significantly increases the risk of disabilities and premature mortality, decreases the quality of life, and increases the costs of care. The incomplete remissions favor the aggravation of neurobiological dysfunctions and pathogenesis of severe somatic comorbidities. The etiopathogenic mechanisms of depression are complex and involve multisystemic risk factors (genetic, neuroanatomic, neurobiochemical, neuroendocrine and psychosocial). Cognitive behavioral therapy (CBT) is used in all the stages of depression, as independent therapeutic method or as support of pharmacotherapy.

Patients, materials and methods: This study has evaluated the therapeutic response of depression in M (medication) group with 136 patients under pharmacotherapy, compared with P (psychotherapy and medication) group with 137 patients treated simultaneously with medication and CBT, and the factors that can improve therapeutic management.

Results: Patients with depression had predominantly a reactive onset, recurrent evolution of at least four episodes, and frequent somatic comorbidities. After treatment, a significant improvement of depressive symptomatology was recorded especially in M group (72.06%), compared to P group (88.32%), p<0.01, as well as a significant difference in regaining functional skills (69.12% - M group, 93.43% - P group; p<0.001). The therapeutic response was significantly correlated with age (p<0.01), social-economical involvement and education level.

Conclusions: CBT demonstrated efficiency in the treatment of major depressive disorder in association with pharmacotherapy. The therapeutic approach should rely on the pathogenic biological models that would highlight the prediction indicators for the therapeutic response and for the evolution of depression, as well as considering the psychological profile of each patient.

Figure 1

Neurobiological and pharmacological aspects involved in cognitive impairment from the depressive disorder. Ach: Acetylcholine; CBF: Cerebral blood flow; CSVD: Cerebral small vessel disease; DA: Dopamine; NA: Noradrenaline; HPA: Hypothalamic–pituitary–adrenal; GABA: Gamma-aminobutyric acid; mTBI: Mild traumatic brain injury

Figure 2

Microscopic image of normal cerebral cortex, without lesions of neuronal cytoarchitecture. Hematoxylin–Eosin (HE) staining ×100

Figure 3

Cholinergic blockade: microscopic image of the cerebral cortex showing a reduction in the number of neurons, especially in the superficial layers (molecular, external granular and external pyramidal layers), with neuropil fragmentation in these areas (fragmentation of neuronal prolongation) due to neuronal cell death. In the deep layers, the condensation of neurons with tachychromatic nucleus is observed. HE staining ×100

Figure 4

Ischemia: microscopic image of the cerebral cortex showing a reduction in the number of neurons in the superficial (molecular) layer, with marked perineuronal and perivascular edema. HE staining ×100

Figure 5

Clinical, neuroimaging and pharmacological factors with negative influence on cognitive behavioral psychotherapy. CBF: Cerebral blood flow; CRP: C-reactive protein; EPS: Extrapyramidal symptoms; IL: Interleukin; SSRIs: Selective serotonin reuptake inhibitors; TBI: Traumatic brain injury; TNF-α: Tumor necrosis factor-alpha; WMHs: White matter hyperintensities