Abordări psihocomportamentale la pacienții cu tulburare depresivă majoră și comorbidități somatice

Introduction

Major depressive disorder (MDD) represents a leading cause of disability worldwide and has a substantial impact on patients’ quality of life and psychosocial functioning⁽¹⁾. In current clinical practice, MDD rarely occurs in isolation, and it is frequently associated with various chronic medical conditions. Recent studies have highlighted a high prevalence of somatic comorbidities among patients with psychiatric disorders, with cardiovascular diseases, gastrointestinal disorders, diabetes mellitus and oncological conditions being among the most common^(2,3).

The relationship between major depressive disorder and somatic comorbidities is complex and bidirectional. On the one hand, chronic inflammation, neuroendocrine dysregulation and oxidative stress associated with somatic diseases may increase neurobiological vulnerability, thereby triggering or exacerbating depressive episodes⁽⁴⁾. On the other hand, patients with MDD frequently exhibit reduced adherence to medical treatment, unhealthy lifestyle behaviors and ineffective coping mechanisms. Collectively, these factors may adversely affect the prognosis of the underlying physical illness⁽⁵⁾. The concomitant presence of depression has been shown to be associated with an unfavorable clinical course and with an increased mortality among patients with severe somatic conditions⁽⁶⁾.

Although pharmacological interventions are essential in the management of both psychiatric and somatic disorders, their effectiveness may be limited in the absence of an integrated biopsychosocial approach. Recent analyses have demonstrated that psychotherapy represents an effective intervention for these patients. Approaches such as schema therapy and compassion-focused therapy have been shown to play an important role in modifying dysfunctional patterns of thinking and in improving emotional regulation^(7,8). Despite these findings, the available literature indicates that a concerningly small proportion of patients with depression and somatic comorbidities have access to appropriate psychological assessment and psychotherapy⁽⁹⁾.

Pathophysiological mechanism

Current perspectives on major depressive disorder support moving beyond the Cartesian dualistic view that separates mind and body. Contemporary medical literature indicates that affective disorders and chronic physical diseases share important and complex biological mechanisms⁽¹¹⁾. A central mechanism underlying this interrelationship is the persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to psychological and biological stressors⁽¹²⁾.

Chronic hyperactivation of this system results in sustained cortisol release. This phenomenon may subsequently induce glucocorticoid resistance in immune cells, thereby promoting the development of a systemic inflammatory response⁽¹³⁾. Furthermore, current immunological research has directly associated the severity of depressive episodes with elevated serum concentrations of proinflammatory cytokines, particularly interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α)⁽¹⁴⁾. Within the central nervous system, these mediators may disrupt neurotransmitter pathways, thereby reducing serotonin and dopamine availability. In addition, inhibition of brain-derived neurotrophic factor (BDNF) may impair neuroplasticity, potentially contributing to the development of anhedonia and bradyphrenia⁽¹⁵⁾.

From a somatic perspective, chronic low-grade inflammation promotes atherogenesis associated with endothelial dysfunction, thereby significantly increasing the risk of acute cardiovascular events. Concurrently, inflammation may disrupt insulin receptor signaling, contributing to severe glycemic dysregulation and worsening type 2 diabetes mellitus⁽¹⁶⁾. Consequently, physical illness may act simultaneously as a biological trigger and as a factor contributing to the maintenance of the depressive clinical picture.

Theoretic fundaments of third-wave therapies: schema therapy and compassion-focused therapy

The management of these complex clinical interactions has encouraged the adoption of integrative models derived from third-wave cognitive-behavioral approaches, with particular emphasis on schema therapy and compassion-focused therapy. Schema therapy, developed by Jeffrey Young, aims to identify and modify early maladaptive schemas (EMSs). These are rigid cognitive and emotional patterns established during childhood⁽⁷⁾. The onset of a disabling somatic illness may reactivate these latent structures, thereby facilitating the adoption of maladaptive coping strategies. Such strategies may manifest as surrender (self-victimization), avoidance (denial or minimization of the illness) or overcompensation (disregarding the physical limitations imposed by the condition), with potentially adverse consequences for disease progression and medical prognosis⁽⁸⁾.

Complementarily, compassion-focused therapy (CFT), developed by Paul Gilbert, is based on an evolutionary model comprising three emotional regulation systems⁽¹⁷⁾. In patients experiencing both depression and severe physical illness, the threat system is frequently hyperactivated by fear of deterioration in health status, which may inhibit the functioning of the soothing and safety system. Through techniques aimed at cultivating self-compassion and a sense of emotional safety, CFT contributes to reducing self-criticism and attenuating the physiological response associated with stress⁽¹⁸⁾.

Materials and method

A series of three clinical cases from the Psychiatry Clinic of the Mureș County Clinical Hospital, Târgu Mureș, Romania, were evaluated. The assessment of these cases incorporated a psychosomatic approach and included psychological case conceptualization.

Results

The first clinical case

The patient M.O., a 60-year-old man from an urban area (Târgu Mureș), presented for psychiatric evaluation. Medical history revealed a significant psychiatric history dating back to 2009, including two suicide attempts, one of which required hospitalization. This underlying psychiatric vulnerability was accompanied by a complex somatic clinical profile characterized by multiple chronic comorbidities. The patient had inadequately controlled type 2 diabetes mellitus associated with hyperglycemia, grade II obesity and significant cardiovascular disease, including chronic ischemic heart disease following acute myocardial infarction, circumflex coronary artery occlusion, moderate aortic stenosis and left ventricular failure.

Following clinical assessment, the primary diagnosis was major depressive disorder, current severe major depressive episode. Psychological assessment confirmed the severity of the clinical presentation, with a score of 27 on the Hamilton Depression Rating Scale, indicating severe depression, and a score of 25 on the Hamilton Anxiety Rating Scale. Major functional impairment was reflected by a GAFS score of 40. The patient’s clinical presentation was dominated by persistent, depressed mood, anhedonia, hypobulia and frequent crying spells, accompanied by prevalent micromanic delusions of worthlessness and guilt.

Additional symptoms included multisensory hyperesthesia, suicidal ideation without current active intent or plan and mixed insomnia with morning worsening. These manifestations occurred against a structural personality profile characterized by anxious-avoidant traits.

The psychopharmacological management was aimed at controlling affective and anxiety symptoms and sleep disturbances. Continuation of the therapeutic regimen was recommended, including Trittico AC® (trazodone) 150 mg in the evening, sertraline 50 mg in the morning, Rivotril® (clonazepam) 0.5 mg twice daily and zolpidem 10 mg at bedtime.

Regarding long-term evolution, the patient exhibited marked adaptive impairment, reflected by the loss of socio-occupational abilities. Therefore, continued close psychiatric follow-up and maintenance of social protection measures were considered necessary.

Psychological conceptualization of Case 1

According to the clinical conceptualization model, M.O.’s psychopathological profile revealed marked activation of schemas within the Disconnection and Rejection domain, particularly Social Isolation/Alienation and Vulnerability to Harm or Illness^(7,19). The history of suicide attempts and the underlying anxious-avoidant personality structure indicated the presence of a Vulnerable Child mode, profoundly affected by the loss of physical autonomy. The triggering events represented by myocardial infarction and inadequately controlled diabetes mellitus were interpreted through the vulnerability schema, generating a catastrophic level of somatic anxiety and micromanic ideas of devaluation. To manage distress, the patient employed an avoidance and withdrawal coping style, manifested through the loss of socio-occupational functioning and self-imposed isolation. This avoidance limits access to corrective experiences and reduces adherence to somatic treatment, maintaining the patient within an internal Critical Parent mode, which continuously reinforces feelings of guilt and frequent crying episodes.

The second clinical case

The patient J.I., a 71-year-old man (73 years old at the time of psychological reassessment), residing in Mureș County, was evaluated for complex and chronic psychiatric symptomatology. His medical history included childhood meningoencephalitis and a highly chronic psychiatric disorder, with numerous admissions to the psychiatry clinic since 1977. Of particular relevance, the patient had been receiving continuous antidepressant treatment for approximately 45 years. From a psychosomatic perspective, the clinical presentation was additionally characterized by dorsolumbar pain and sensations of heaviness involving the back, head and limbs, associated with pronounced autonomic reactivity, including tremors of the extremities, excessive sweating and tachycardia.

The established clinical diagnosis was major depressive disorder, with the current episode in partial remission and characterized by anxiety and somatization features, associated with major neurocognitive disorder due to Alzheimer’s disease, currently at a moderate clinical stage. Psychometric assessment confirmed a severe level of impairment, with a GAFS score of 40 and a score of 22 on the Hamilton Anxiety Rating Scale, indicating severe anxiety. The Mini-Mental State Examination (MMSE) score was 22, suggesting moderate cognitive dysfunction.

Clinical examination revealed temporal disorientation, motor apraxia and speech dominated by prevalent micromanic delusions of worthlessness and failure. Phobic symptoms, including agoraphobia and acrophobia, were also identified, together with significant motivational retardation and maladaptive coping mechanisms predominantly oriented toward avoidance of anxiety-provoking stimuli.

The therapeutic management was aimed at an integrated approach to affective, anxiety and cognitive symptoms. The current pharmacological regimen included quetiapine 50 mg in the evening, Prozac® (fluoxetine) 20 mg in the morning, Rivotril® (clonazepam) 0.5 mg/day, Anxiar® 1 mg and piracetam 400 mg/day. The overall assessment indicated markedly reduced functioning, with a severe impact on the patient’s quality of life across all areas of activity. Accordingly, the clinical course requires strict continuation of the established treatment, periodic clinical reassessment and sustained implementation of social protection measures in accordance with applicable legislation.

Psychological conceptualization of Case 2

In the context of a psychiatric history characterized by marked chronicity, with more than 45 years of evolution, J.I.’s case presents a complex conceptualization in which organic cerebral deterioration associated with major neurocognitive disorder due to Alzheimer’s disease coexists with Dependence/Incompetence and Subjugation schemas^(7,20). The intense somatoform symptoms represent a bodily expression of severe anxiety, as reflected by a Hamilton Anxiety Rating Scale score of 22. Under these circumstances, the patient has limited cognitive and emotional capacity to conceptualize his distress through alternative mechanisms. His maladaptive behaviors are dominated by an anxious avoidance coping mode, including agoraphobia, acrophobia and social phobia, intended to protect him from stimuli perceived as threatening outside the family environment. Cognitive deterioration further intensifies the patient’s sense of helplessness. Temporal disorientation and motor apraxia activate a Helpless Child mode, controlled by a Punitive Parent mode, which reinforces cognitions of complete failure and existential worthlessness.

The third clinical case

The patient C.A., a 53-year-old woman at the time of the most recent assessment, from a rural area, had an approximately 10-year psychiatric history characterized by multiple hospitalizations. From a somatic perspective, recurrent Cushing's disease secondary to a pituitary adenoma diagnosed in 2005 was particularly relevant. The patient had previously undergone surgical treatment and radiotherapy. This endocrine disorder was accompanied by insulin-requiring type 2 diabetes mellitus, essential hypertension, chronic ischemic heart disease and mitral insufficiency. Her medical history also included a severe SARS-CoV-2 infection complicated by viral pneumonia and acute respiratory failure, requiring admission to the intensive care unit (ICU) and oxygen therapy.

The primary psychiatric diagnosis was depressive affective disorder, recurrent severe depressive episode accompanied by somatization and conversion features. Psychological assessment confirmed the severity of the clinical presentation, with a GAFS score of 40, a score of 26 on the Hamilton Depression Rating Scale, indicating a severe depressive episode, and a score of 25 on the Beck Depression Inventory.

The clinical examination revealed profoundly depressed mood, feelings of self-devaluation and structured suicidal ideation with a specific plan involving medication ingestion. During the assessments, the patient exhibited emotional numbness, reduced frustration tolerance and episodes of psychomotor agitation. The psychiatric symptoms were accompanied by a significant somatic component, expressed through multiple physical complaints, including severe headache, chest pressure, back pain and cenesthopathic sensations described as stabbing sensations localized in the head. The therapeutic management involved a multidisciplinary approach adapted to the complexity of the clinical presentation. Psychiatric treatment was progressively adjusted during repeated hospitalizations and included anxiolytic medication (Rivotril®), antipsychotic treatment (quetiapine), antidepressant treatment (escitalopram) and hypnotic medication (nitrazepam).

The patient’s clinical course remained fluctuating, being characterized by recurrent episodes of agitation, significant difficulties in emotional regulation and a marked reduction in overall functioning. In this context, continued support and social protection measures, together with limitation of exposure to stressors, were recommended.

Psychological conceptualization of Case 3

The clinical presentation of C.A. illustrates a vicious cycle in which the hypothalamic-pituitary-adrenal (HPA) axis is directly affected by an organic disorder. Cushing's disease, characterized by chronic hypercortisolism, acts as a major biological triggering factor for severe depressive symptomatology and emotional lability. At the cognitive-behavioral level, chronic physical illness, including diabetes, cardiovascular disease and a history of ICU admission, strongly activates the Vulnerability to Illness and Threat schema, resulting in an extreme level of anticipatory anxiety and selective hyperprosexia focused almost exclusively on health-related concerns and excessive self-monitoring.

Because of depleted adaptive resources, the patient developed a Surrender coping mechanism, manifested through a Vulnerable/Dependent Child mode, characterized by childlike behavior, an external locus of control and an inability to self-soothe. The intense somatoform complaints reflect the psychological system’s inability to process emotional distress, with intrapsychic tension being converted into additional physical symptoms, including chest pressure and pain.

In this case, psychotherapy should focus on increasing distress tolerance and developing autonomous emotional regulation skills, while reducing dependency and unrealistic expectations within interpersonal relationships.

Discussion

The cases described in this study illustrate the complexity of the clinical management of major depressive disorder (MDD) when it co-occurs with multiple somatic comorbidities and cognitive decline. The interpretation of these cases in the context of recent medical literature supports the view that depression comorbid with chronic somatic conditions represents a major therapeutic challenge, and it is associated with a prolonged clinical course and increased resistance to standard guideline-based psychopharmacological treatment⁽¹⁰⁾.

From a pathophysiological perspective, research conducted in recent years has emphasized the bidirectional relationship between somatic disorders and MDD. Low-grade systemic inflammation, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and oxidative stress, which are commonly observed in conditions such as type 2 diabetes mellitus and cardiovascular disease – particularly evident in Case 1 –, may induce neuroplastic changes that precipitate or contribute to the chronicity of depressive episodes⁽¹¹⁾.

Recent clinical guidelines recommend a transition toward an integrated model of care. Such an approach should simultaneously address biological and psychological factors, as patients with severe comorbidities frequently develop maladaptive coping mechanisms⁽¹²⁾. The evolution of international clinical guidelines, including recommendations issued by the National Institute for Health and Care Excellence (NICE) and the American Psychiatric Association (APA), emphasizes the importance of systematic screening for depressive and anxiety symptoms across internal medicine specialties⁽¹²⁾.

Current epidemiological data indicate that the presence of a major somatic condition triples the risk of developing a major depressive episode, while their co-occurrence increases total healthcare costs by more than 45%, mainly as a consequence of repeated hospitalizations associated with poor treatment adherence⁽²¹⁾. Recent developments in clinical practice guidelines promote the implementation of the Collaborative Care Model, in which the physician managing the somatic condition, such as a cardiologist or diabetologist, works together with the psychiatrist and psychotherapist as an integrated multidisciplinary team⁽²²⁾.

The literature emphasizes that pharmacological treatment optimization alone does not provide long-term improvement when psychological variables, including illness-related cognitive distortions, helplessness schemas and avoidant coping styles, remain unaddressed. Controlled clinical studies published between 2022 and 2026 support the role of interventions based on schema therapy and compassion-focused therapy not only in significantly reducing depression scale scores but also in influencing biological parameters, including reductions in glycated hemoglobin (HbA1c) levels in patients with diabetes and stabilization of heart rate in patients with coronary disease⁽²³⁾.

A comparative analysis of the three cases, considered in relation to the available literature, highlights the important role of social isolation, persistent rumination and feelings of worthlessness in maintaining depressive symptoms and associated somatic manifestations. Previous studies have shown that short-term cognitive-behavioral interventions may have limited outcomes in patients with a chronic clinical course or rigid personality patterns⁽¹³⁾. In this context, schema therapy represents a potentially valuable therapeutic option, because it focuses on identifying and restructuring early maladaptive schemas, such as social isolation or defectiveness, as well as coping strategies based on avoidance or surrender⁽¹⁴⁾.

Furthermore, Cases 2 and 3 highlight the association of depression with cognitive dysfunction and the somatization of anxiety. The prolonged psychiatric course observed in the presented cases illustrates the potential limitations of relying exclusively on pharmacological treatment in the absence of early psychotherapeutic intervention.

In this context, compassion-focused therapy may be particularly useful, as compassion-oriented interventions are intended to develop self-compassion and may contribute to reducing self-criticism, hypervigilance and feelings of failure, which may be particularly relevant in patients experiencing neurocognitive decline⁽¹⁵⁾.

Conclusions

The analysis of the three clinical cases emphasizes the complexity of managing patients with major depressive disorder when it is associated with severe somatic conditions and cognitive decline. The presence of chronic comorbidities – whether metabolic and cardiovascular, as observed in Cases 1 and 3, or neurodegenerative, as observed in Case 2 – was associated with a more severe psychopathological presentation, chronic depressive symptoms, social isolation and with marked anxiety-related distress.

Therefore, the integration of psychological assessment and psychobehavioral interventions into the therapeutic plan is essential. Directly addressing maladaptive cognitive schemas and dysfunctional coping mechanisms may facilitate not only a reduction in the severity of depressive and anxiety symptoms but also improved adherence to medical treatment, ultimately contributing to a better quality of life.

Study limitations

The conclusions derived from this study should be interpreted in the context of the inherent limitations of a descriptive design based on a small case series comprising only three patients. The limited sample size does not allow the findings to be generalized to the broader population of patients with major depressive disorder and somatic comorbidities.

Conflict of interests: none declared

Financial support: none declared

This work is permanently accessible online free of charge and published under the CC-BY.