**1. Introduction**

Most researchers agree on the presence of an increased risk of aggressive behavior in patients with schizophrenia, but there is considerable heterogeneity in the reported rates of such aggression and uncertainty as to the causes of this heterogeneity [1,2]. Predisposing factors—namely genotype; prenatal and perinatal insults; early adversity as in childhood maltreatment; conduct disorders; comorbid antisocial personality disorder/psychopathy; and precipitating factors, in particular emergence of psychotic symptoms, neurocognitive impairment, substance abuse, nonadherence to treatment and stressful experiences in adult life—can result in risk interactions, increasing the likelihood for the emergence of aggressive behavior [3–5]. In particular, comorbidity with substance abuse increases the incidence of aggressive behavior in patients with schizophrenia with personality traits and social factors probably mediating the relationship between substance abuse and aggressive behavior in these patients [6–9]. Medication nonadherence may also serve as a contributing factor, particularly if it precedes substance abuse [10].

The literature reports differences in brain structure and function associated with aggression in schizophrenia, particularly in areas involved in the formation of psychosis

**Citation:** Pachi, A.; Tselebis, A.; Ilias, I.; Tsomaka, E.; Papageorgiou, S.M.; Baras, S.; Kavouria, E.; Giotakis, K. Aggression, Alexithymia and Sense of Coherence in a Sample of Schizophrenic Outpatients. *Healthcare* **2022**, *10*, 1078. https://doi.org/ 10.3390/healthcare10061078

Academic Editor: David Crompton

Received: 28 April 2022 Accepted: 8 June 2022 Published: 10 June 2022

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symptoms and affective regulation. The most consistent findings from the structural studies were reduced volumes of the hippocampus and the frontal lobe (i.e., the orbitofrontal and anterior cingulate cortex), and functional studies mainly showed variations in the frontal lobe and amygdala [11,12]. As hypothesized, volume reductions in the hippocampus may predispose individuals with schizophrenia to be less sensitive to social and emotional cues, which might give rise to conflicts and the inability to perceive signals for solutions, leading to conflict escalation [13]. Additionally, functional and neurophysiological studies evidenced an inefficient integration of the information by the dorsal anterior cingulate, between the frontal and limbic regions, in schizophrenia patients with a history of violence during negative emotion processing [14,15]. The anterior cingulate plays a central role in processes that are critical to successful emotion regulation, conflict and performance monitoring, as well as emotional awareness [16,17]. Aberrant dorsal anterior cingulate functional connectivity patterns are consistent with impaired cognitive control over emotions [14]. Aggressive patients display strong reactivity to negative stimuli, which may interfere with response inhibition and lead to impulsive aggression. Relevant research suggested that psychotic symptoms in schizophrenia patients preceded a violent incident only in a small percentage of cases, supporting the idea that behavioral disinhibition and emotional dysregulation are important factors for aggressive behavior in patients with schizophrenia [18].

Aggression in schizophrenia can occur at any time during the disease's course, has significant implications for patient care and treatment and raises the risk of harm. In search for a potential biological signal for early assessing aggressive risk in schizophrenic patients, recent studies identified increased inflammation (CRP levels, leukocyte count and neutrophil to lymphocyte ratio) as a potential biological correlate of aggression [19,20]. The presence of aggressive behavior in schizophrenic patients indicates the severity of the disorder to some degree, and the level of inflammation decreases as the disease goes into remission. The disruptive effect of early-life stress on the immune system is partly involved in brain mechanisms that regulate aggressive behavior in schizophrenia patients, suggesting a link of clinical significance.

A more dynamic feature which has been posited as having an important role in the pathway to aggression is alexithymia [21,22]. Alexithymia is a mental condition characterized by difficulties identifying and describing one's own feelings, externally oriented thinking, and limited imaginative capacity [23]. The majority of research has approached alexithymia as a stable personality trait, thought to be developmental in nature, reflecting a lack in emotion regulation and cognitive processing [24]. Awareness of one's own emotions can prevent us from primitive, uncontrolled emotional responses when facing negative events. Given their inability to identify, manage and express their true emotions, individuals who are alexithymic exhibit high levels of anger and more aggressive behavior. Research indicates that it was primarily the difficulties with identifying feelings aspect of alexithymia that was related to aggression [25]. Brain imaging studies on alexithymia displayed impaired cognitive emotional processing, and—owing to this impairment—alexithymics experience inflexible cognitive regulation. Additionally, they showed weak responses in structures necessary for the representation of emotion used in conscious cognition and stronger responses at levels focused on action [26].

Meta-analyses of functional and structural brain imaging studies have identified the amygdala, the insula, the anterior cingulate cortex and regions of the prefrontal cortex as key correlates of alexithymia in the brain [27–29]. Interestingly, alexithymia is commonly associated with abnormalities of both the anterior cingulate cortex and the insula [30], and impairments in these regions—as suggested—may contribute to aggression, particularly reactive aggression [31]. Contemplating the nature of the alexithymia–aggression relationship, other research evidenced increased right amygdala volume as a common neurobiological denominator for both alexithymia and reactive aggression [31]. Another possible explanation for the association between alexithymia and aggression concerns difficulty labeling emotions. In neuroimaging studies, when labeling emotions, the prefrontal

cortex is engaged, while activity in the amygdala is simultaneously reduced, indicating that the cognitive act of labeling emotions dampens the emotional response [32].

Studies have described a variety of deficits in emotion processing in individuals with schizophrenia and identified dysfunction in the domains of emotion expression, emotion experience and emotion recognition [33,34]. Consequently, individuals with schizophrenia who are unable to accurately recognize emotional expressions face problems of adaptability in social life. Inability to decode the social cues projected by others, in which emotions are contained, can lead to misinterpretation of the ambiguous signals received, violation of personal boundaries and possible manifestation of inappropriate or even aggressive behavior. In addition, people with schizophrenia also experience problems in identifying and expressing their own emotions. One of the key areas in which they fall short which is directly related to the expression of their emotional state is that of communication. Although they experience emotions, they often find it difficult to describe and express them in words, sometimes giving the impression that they feel nothing. Emotional dysregulation is closely linked to aggression. Individuals who are unable to express their emotional state experience an uncomfortable, unpleasant and uncontrollable situation that is difficult to tolerate, and thus resort to the use of aggression more easily in order to either communicate this unpleasant experience or to avoid it.

Over recent years, research has indicated that schizophrenia patients are also likely to have reduced empathic ability when interacting with others in everyday life and are less accurate at tracking the positive and negative affective state of another person [35]. These deficits tend to cover every aspect of empathy, from the cognitive to the emotional dimension [36]. Two other concepts closely related to empathy that are compromised in schizophrenia are theory of mind and insight. People with schizophrenia have difficulty processing both their own mental state and those of others, with the result that they are less able to interpret and predict others' behavior. Deficits in the above characteristics can lead to socially dysfunctional and aggressive behaviors. Conversely, understanding another person's emotional and mental state can act as a deterrent to the occurrence of dysfunctional behavior.

Scientific studies support that alexithymia is highly prevalent among schizophrenic patients [37–39]. Whether it is a trait characteristic in deficit patients and a state related to many symptoms, such as flattening of affect, poverty of speech, depression and anxiety in nondeficit patients, or being a separate construct related to dysfunctions in both cognitive and affective processes remains a matter of controversy. Several authors suggested that alexithymia may be a vulnerability factor for the development of schizophrenia and, more specifically, may be an underlying cause of social dysfunction [40,41]. Various core aspects of social cognition have been found to be disrupted in schizophrenia, including emotion recognition [42] and theory of mind [43,44]. Much of the broader social cognitive literature in schizophrenia has focused on the ability to understand the affective states of others, such as via emotion recognition (the ability to decode affective cues) or theory of mind (the ability to understand another's beliefs and desires). In contrast, alexithymia primarily refers to the ability to understand one's own affective experience and therefore seems conceptually closer not only to the construct of emotion regulation, but also to affective empathy (one's emotional response to the cognitive or affective state of another). Neuroimaging studies investigating pathology underlying alexithymia in schizophrenia report gray matter alterations of the left supramarginal gyrus and reduced white matter integrity within the corpus callosum, mostly in the left part of the superior and inferior longitudinal fasciculi, the inferior occipitofrontal fasciculus, the anterior and posterior thalamic radiation and the precuneus white matter [45,46].

Alexithymia has been shown to be associated with both detachment from the self and inadequate differentiation between self and other [47], both of which are included in schizophrenia-spectrum psychopathology. In the same way that the fragmentation of the self may lead to psychotic phenomena, it may also result in impaired ability to differentiate and express one's own emotional experience. Phenomenologically-oriented researchers propose that a disturbance of the basic sense of self is at the clinical core of the schizophrenia spectrum [48]. These abnormal experiences, possibly driven by neurocognitive disturbances, may evolve into first-rank psychotic symptoms [49]. Low baseline levels of basic self-disturbances and further reductions over time independently predict recovery [50]. Significant association between basic self-disturbances and sense of coherence, not mediated by other clinical symptoms, was reported, identifying high levels of basic self-disturbances as independent contributors to poor sense of coherence [51].

Sense of coherence (SOC) was proposed by Antononsky as a construct that expresses the degree to which a person has a diffuse and dynamic, but lasting sense that the internal and external stimuli and stressors in their environment are understandable (i.e., predictable, structured and explicable), manageable (i.e., there are resources available to meet the requirements of these stimuli) and meaningful (i.e., the requirements are challenges that are worth committing to and addressing) [52]. The SOC is often considered to be a stable entity that develops in young adulthood and stabilizes around the age of 30, and as a personality trait it, is more likely to be a predictor of behavior [53,54]. In searching for a relationship between sense of coherence and aggression, a low level of coherence (perceiving stimuli as threatening accompanied by a lack of sufficient internal and external resources to effectively solve problems) may manifest in aggressiveness in the affective and cognitive dimensions (anger, hostility) and also in the instrumental parts of aggressive behavior (verbal, physical aggression) [55].

Sense of coherence and alexithymia exert opposite influences as to the treatment of psychological and physiological disorders, effectuating positive and negative consequences, respectively [56,57]. With reference to relevant evidence, alexithymia may lead to adverse health outcomes as a result of emotion dysregulation and unsuccessful stress and anxiety management, while sense of coherence is regarded as a protective factor that promotes recovery, allowing a person to be resilient in the face of challenges [58,59]. Individuals with a high sense of coherence are likely to perceive stressors as explicable, have confidence in their coping abilities, and feel engaged and motivated to cope with stressors [60]. Inversely, individuals with alexithymia have lower levels of physical functioning, less energy, poorer emotional wellbeing, poorer social functioning and poorer general health [61]. The salutogenesis theory recognizes sense of coherence as a key component of health, whereas alexithymia is presumed to play an important predisposing role in the pathogenesis of diseases. Strengthening the sense of coherence and coping is conducive to recovery [62,63].

According to the salutogenetic approach to the problem of health and disease, higher sense of coherence protects people from the onset of disorders and, if they emerge, aids in accelerating the recovery of health [64,65]. Major mental illnesses, like schizophrenia, are usually expected to run a chronic course with varying trajectories, sometimes in the form of a steady or gradual deterioration and other times with improvements and acute exacerbations with unpredictable effects on outcome. Prognosis varies on a continuum between satisfactory recovery and total disability; although, according to follow-up studies, several schizophrenic patients have a more favorable course outcome [66,67]. Research indicates that people with schizophrenia with a high sense of coherence experienced less severe psychopathological symptoms and a higher overall level of function while also obtaining better results in treatment [68,69].

Over the past decades, evidence of the association between schizophrenia and aggression has accumulated, thereby identifying a multitude of relevant risk factors [70–72]. The presence of alexithymia among patients with schizophrenia has been extensively studied, and heightened levels of alexithymia in a number of different schizophrenia samples have been evidenced [38,41,73,74]. However, studies focused on how alexithymia may give rise to aggression in patients with schizophrenia are scarce [21,75]. The relationship between alexithymia and aggression has also been investigated mostly in community samples, mixed psychiatric and substance dependence inpatients, adolescents, violent offenders and forensic patients [29,76–85]. The association between sense of coherence and aggression has been investigated among juveniles from reformatories, but also among female employees

and coronary heart disease patients, as predictors of health-related quality of life [55,86–88]. Sense of coherence in schizophrenia and among delusional patients has been studied in relation to psychopathology and in order to predict remission and risk of relapse [68,89–92]. Finally, the relationship between alexithymia and sense of coherence has been investigated among university students, patients suffering from fibromyalgia and among attention deficit hyperactivity disorder patients [56,58,93].

Schizophrenia-related aggression poses a severe threat to the patient's and society's safety and necessitates the development of interventions with specific or nonspecific antiaggressive properties. There are various treatment choices apart from pharmacological treatments for addressing aggression in schizophrenia patients. Psychological treatments and other nonpharmacological interventions may be of interest when the etiology of aggression is not a target for pharmacological agents. Elucidating the role of alexithymia on aggression in schizophrenia suggests new modes of treatment which would target these specific underlying impairments. A review examining the effects of psychological interventions on alexithymia concluded that it is partly modifiable with these therapeutic interventions, offering suggestions for future research [94]. Similarly, salutogenic-based approaches offer promising results, strengthening sense of coherence and effectuating positive outcomes in key variables for personal recovery in people with schizophrenia [95,96].

The exploratory purpose of this study was to investigate the possible association between aggression, alexithymia and sense of coherence in a sample of schizophrenic outpatients since there is no study in the literature that simultaneously examines the relationship of these variables. We argue that specific components of sense of coherence, as well as alexithymic traits involving emotional dysregulation, offer insight into schizophrenic outpatients' aggressiveness influencing their self-reported levels of aggression.

The specific aim of this study is to verify whether certain alexithymia and sense of coherence dimensions serve as mediators predicting various aspects of aggression. Differently, considering that sense of coherence is related to the ability to regulate and manage emotions appropriately [87], counterbalancing the limited ability of alexithymic individuals, we aimed to investigate the intervening role of sense of coherence in the relation between alexithymia and aggression. Results would provide a rationale for the development of psychological interventions [75,97] specifically targeted at improving alexithymia and sense of coherence in outpatients with schizophrenia in order to control their aggressive tendencies and cope with their aggressive feelings themselves.

### **2. Subjects and Methods**

#### *2.1. Research Design*

In this study, a correlational research design was used. It was conducted with outpatients treated at the Outpatient Psychiatric Department of Sotiria General Hospital between September 2021 and February 2022 after approval from the Clinical Research Ethics Committee of Sotiria General Hospital (Number 24252/27-9-21). According to ethical considerations, participation in the survey was completely voluntary. First, the researchers explained the research objectives and patients were assured that the information would remain confidential. After each participant was informed about the study, they provided written and verbal informed consent. Once recruited, all participants were asked to answer to a semi-structured form designed by research staff to collect demographic data and to fill a battery of self-report questionnaires to assess their self-reported levels of aggression, alexithymia and sense of coherence. At the end, all of the responses were collected anonymously.

#### *2.2. Study Participants*

Adopting purposive sampling, the study involved 100 consecutive outpatients with confirmed psychiatric diagnoses of schizophrenia, using the International Classification of Diseases-10 (ICD-10) coding system, who attended the Psychiatry Outpatients Department for maintenance treatment. Eligibility criteria included: (i) aged between 18 and

65 years old; (ii) being in clinical remission in a post-acute phase of illness as defined by no hospitalizations and no changes in psychotropic medication or psychosocial status within 30 days prior to enrollment; (iii) with a history of at least two prior psychiatric hospitalizations (greater diagnostic confidence in confirming schizophrenic disorders), but not more than five hospitalizations (to exclude patients with residual schizophrenia); (iv) coherent verbal contact during the filling of data collection form. Exclusion criteria for participants were psychotic disorders related to clinical medical conditions or substance use; substance addiction and history of substance use in the last six months; uncorrected visual or hearing impairments; neurological disorders or damage to the central nervous system; developmental disability; and signs of intellectual disability, severe cognitive and neuropsychological impairment, personality disorders or schizoid and schizotypal personality traits, other psychiatric comorbidities, namely social anxiety disorder and a record of current substance or alcohol abuse. The majority of participants (68%) were on atypical antipsychotic monotherapy with confirmed antiaggressive properties, while the rest of them were additionally treated with a combination of adjunctive anticonvulsants. A comprehensive health assessment and clinical evaluation of substance abuse were conducted upon study enrollment.

#### *2.3. Minimal Sample Size Calculation*

A sample size of 100 was deemed adequate given five independent variables (IVs) to be included in the hierarchical linear regression analysis (N > 50 + 8 m, N = number of Participants and m = number of IVs) [98]. To confirm sample size adequacy, a post hoc power analysis was carried out using G-Power software [99]. The calculation indicated that with a sample size of 100, effect size f<sup>2</sup> = 0.8116 (derived from the R<sup>2</sup> = 0.448), an alpha of 0.05 and five predictors, an excellent power of 1.00 was identified. The same procedure was followed to verify sample adequacy for the other hierarchical linear regression analyses models built with six predictors. Additionally, a Monte Carlo power analysis for indirect effects was performed through an online application [100]. The results show that a power of 0.95 with a confidence level of 99% is reached with only 60 participants in a simple mediation model. Finally, according to the rule of thumb recommended by Kline [101], an adequate sample size should be 10 times the number of the parameters in path analysis (six parameters were involved in the research path analysis).

### *2.4. Measurement Tools*

Demographic and social data from study participants included age, gender and years of education.

#### *2.5. Brief Aggression Questionnaire*

The brief aggression questionnaire (BAQ) is a 12-item self-report measure of aggression. The questionnaire asks participants to rate on a scale from 1 (strongly agree) to 5 (strongly disagree) the degree to which statements describing behaviors and emotions, are characteristic of themselves. The BAQ measures aggression in the domains of physical aggression, verbal aggression, anger, and hostility. The total aggression score was calculated by summing these four factors' scores. Higher scores indicate higher levels of aggression. The questionnaire was translated and back translated, from English to Greek and vice versa, by three bilingual translators and adapted in Greek population [102]. BAQ has been proposed as a valid and reliable instrument (Webster et al., 2014) with adequate temporal stability and convergent validity with other behavioral measures of aggression [103]. Cronbach's alpha in this study was 0.731.

#### *2.6. Sense of Coherence Questionnaire*

To measure sense of coherence, we used the short version of a self-rating scale, the sense of coherence questionnaire (SOC-13), developed by Antonovsky [52]. SOC-13 comprises of three components (a) a cognitive component, labeled comprehensibility, repre-

senting the ability to understand and integrate internal and external experiences, (b) an instrumental component, labeled manageability, representing the ability to handle challenges and cope with stressful situations and (c) a motivational component, labeled meaningfulness, representing the ability to make sense of experiences and view them as worthy challenges [52,104]. Responses to each question are given using a 7-point Likert scale ranging from 1 ("very common") to 7 ("very rare or never"). Scores range from 13 to 91, with higher numeric values representing a higher degree of SOC. The short version of SOC-13 has been standardized in the Greek population and seems to be a reliable and valid instrument with a Cronbach alpha of 0.83 [104].

### *2.7. Toronto Alexithymia Scale*

The Toronto Alexithymia Scale (TAS-20) is one of the most commonly used self-report measures of alexithymia [105]. It consists of 20 sentences and includes 3 subscales: emotion recognition, which measures the extent to which people report difficulty in identifying their own feelings (DIF); emotion expression, which measures the extent to which people report difficulty in describing feelings to others (DDF); and externally-oriented thinking (EOT), which measures the extent to which people report a tendency to focus on the concrete details of external events rather than of their own inner experience. The sentences are scored using a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree) with total scores ranging from 20 to 100. The scale has good reliability and validity in both its original version and in the Greek adaptation [106] that was used in the present study. The distinctive cutoff scores to indicate the degree of alexithymic characteristics were as follows: ≤50 indicated no alexithymia, 51–60 indicated borderline alexithymia, and ≥61 indicated alexithymia [105]. The Cronbach's alpha for the scale in this study was 0.809.
