Introduction

Large proportion of the research on anxiety disorders addresses the involvement of genes regulating hypothalamic-pituitary-adrenal axis, neurotransmitter systems and/or neuronal plasticity, in which the disruption of gene expression of these genes through epigenetic mechanisms is believed to contribute to the pathogenesis of anxiety (^{Trancoso, 2022}). Anxiety in schizophrenia usually is studied as a risk factor or residual, and received secondary importance. The major focus is the control of psychotic symptoms, and if persists after an acute state, considered as dependent on residual psychosis, treated with neuroleptics eventually associated with cognitive-behavior interventions focusing on psychosis and fear of consequences of delusions.

This approach misses the point that anxiety is frequent, intense and devastating to people with the diagnosis of schizophrenia, and even if antecedent, concomitant or residual, has important consequences over the lives of patients and relatives. Social anxiety disorder (SAD) or social phobia (SF) is considered the most common anxiety disorder, often without remission, and is usually related to significant functional and psychosocial impairment (^{Levitan et al., 2011}). It refers to the heightened situational discomfort that the individual feels when interacting socially, the fear of feeling embarrassed and humiliated by others (^{Francisco, Toledo & Tavares, 2019}).

Fear and anxiety overlap but also differ, the former being an emotional response to real or perceived imminent threat and most often associated with surges of autonomic arousal necessary for fight or flight, thoughts of immediate danger, and avoidance behaviors, and anxiety the anticipation of a future threat, most often linked to muscle tension and vigilance in preparation for future danger or avoidance behaviors (American Psychiatric Association (^{APA, 2022}).

Fear is a sensation that is related to the emotional process including the amygdala and the hypothalamus, the first being linked in processing information about the potential risk of an event and can generate responses that will result in fear, escape or paralysis, and the second associated with the limbic areas, where it receives information from the internal environment, and can act in a direct way (^{Fuentes et al., 2014}).

SF (F40.1), along with Agoraphobia (F40.0) and Specific/isolated phobias (F40.2), are part of the phobic-anxious disorders group (F40) in ICD-10 and refer to the fear of being exposed to the close observation of others and leading to avoidance of social situations (^{DATASUS, 2008}).

The behavioral pattern of individuals with SF is characterized by a typical fear and a desire to avoid social situations in which they need to expose themselves, because the central fear is to be the center of attention, to expose their weaknesses and, thus, to have their performance negatively evaluated (^{Burato et al., 2009}).

Social phobics usually present hand tremor, blushing, nausea, or an urgent desire to urinate, and sometimes they are convinced that one or more of these secondary manifestations constitutes their primary problem. The symptoms can develop into a panic attack (^{DATASUS, 2008}).

The feared situations can be restricted (such as meeting the opposite sex, eating or public speaking) or diffuse (any situation outside the family environment can cause stress to the patient). Seeking avoidance of the feared occasions, the patient with SAD symptoms shows a behavior of avoidance of social interactions and, in more extreme cases, complete social isolation (^{Francisco, Toledo & Tavares, 2019}).

Avoidance of social occasions is frequent and constant, which characterizes phobic avoidance, but when such situations are unavoidable, important manifestations of anxiety are evidenced that are often accompanied by autonomic symptoms (^{Osório et al., 2005}).

The use of security behavior by people with SF has been pointed out as an important factor in the maintenance of this disorder, by preventing feared situations from being faced (^{Burato et al., 2009}).

SF is not just shyness, since the person with this disorder experiences fears that generate feelings of total discomfort, with a sense of personal inferiority, with dysfunctional thoughts that reduce their motivation, and with a sense of humiliation due to the belief of inability to produce something. These aspects interfere with social relationships, negatively affecting the subject’s life, either individually or socially (^{Da Silva et al., 2019}), where epidemiological studies indicate that FS disorder has a major negative functional impact, socially, educationally and occupationally (^{Peres, 2018}).

Schizophrenia (SZ) is one of the fifteen leading causes of disability due to illness in the world, where approximately half of individuals have concomitant mental and/or behavioral disorders (National Institutes of Health (NIMH) ²⁰⁰⁶). One cause is the greater difficulty in facing social situations due to a high degree of anxiety, which makes patients feel safer away from social gatherings at work, leisure and family (^{Weittenhiller et al., 2021}).

The diagnosis of SZ involves a set of signs and symptoms and impaired professional or social functioning (^{APA, 2022}). Its symptoms affect perception, thought, affect and behavior (^{Ruiz-Iriondo et al., 2019}), without any pathognomonic symptoms (^{APA, 2022}), and involve distortions of perception in relation to oneself and external reality (^{Silva et al., 2016}).

^{Gabbard (2016)} mentions a useful organization of the descriptive symptomatology of SZ into three groups: positive symptoms, negative symptoms and disturbed interpersonal relationships. The latter tends to develop over a long period and includes numerous and varied interpersonal difficulties, such as: withdrawal, inappropriate expressions of aggression and sexuality, lack of awareness of the needs of others, excessive demands and inability to make meaningful contacts with other people.

SF-SZ comorbidity have been described in many studies (^{Aikawa et al., 2018}; ^{Kibru et al., 2020}; ^{Teixeira & Belmonte-De-Abreu, 2022}, ²⁰²³), negatively affecting quality of life, treatment outcomes (^{Nemoto et al., 2019}; ^{Kibru et al., 2020}), medication adherence (^{Kibru et al., 2020}), social cognition, social functioning, with different risk factors such as illness duration (^{Aikawa et al., 2018}), age of onset (^{Aikawa et al., 2018}; ^{Kibru et al., 2020}), gender, poor social support, prior hospitalization, and suicide ideation and attempts (^{Kibru et al., 2020}).

Despite the high morbidity of SF in schizophrenia, only half of the patients throughout their lives will seek specific treatment, with a median delay time of 16 years. With this delay, these people often miss several opportunities for personal and professional growth, developing a negative self-image and becoming more withdrawn in social functioning (^{Levitan et. al, 2011}). Due to this high impact, early and correct identification of this comorbidity is considered extremely important to minimize suffering and to prevent the associated impairment (^{Osório et al., 2005}).

As a result of the above considerations, the study explored SF comorbidity in patients diagnosed with schizophrenia, quantifying the dimensions of fear and avoidance of social situations. The major hypothesis is that SF is significant and must be identified and treated in SZ.

Methods

Results

Of the original 82, fifty-nine patients had comorbid SZ-SF, with 41 of those (69.5%) of male sex and 18 (30.5%) female. The mean age was 46.8 years, and the most frequent education was complete high school (44.1%), followed by complete elementary school (33.9%). The median number of psychiatric hospitalizations was 2 (two), the mean age of onset of schizophrenia was 21.7 years, and the mean duration of illness was 25.1 years.

Regarding clinical comorbidities, 76.3% had an associated condition, the most frequent being obesity (32.2%), dyslipidemia and diabetes (16.9%), and smoking (13.6%). Regarding psychiatric medication, 94.9% of the patients used Clozapine and 42.2% used Clonazepam (table 1).

The comorbidity of social phobia in schizophrenic patients

From 59 patients identified with SF, 17% had mild, 40.7% moderate and 42.4% severe, according to the LSAS scale (figure 1).

Figure 1 Classification of Social Phobia Positive by LSAS According to Severity 

Regarding the fear and avoidance sub-scores of the LSAS (table 2), we noticed significantly higher levels for avoidance in the items “Talking to people in a position of authority”, “Talking to people you don’t know very well”, “Expressing a disagreement or disapproval to people you don’t know well”, “Having a party”, with higher avoidance (28.5 points) than fear (25 points).

Table 2 Comparison of LSAS Items Regarding Fear and Avoidance 

Items	Fear	Avoidance	p
	Median (P25 - P75)	Median (P25 - P75)
1. Making phone calls in public.	0 (0 - 2)	1 (0 - 3)	0,068
2. Participation in small groups.	1 (0 - 2)	1 (0 - 3)	0,838
3. Eating in public places.	0 (0 - 2)	0 (0 - 2)	0,660
4. Drinking with others in public places.	0 (0 - 2)	0 (0 - 2)	0,115
5. Talking to people in a position of authority.	1 (0 - 2)	2 (0 - 3)	0,030
6. Acting, performing or speaking in front of an audience.	2 (1 - 3)	2 (1 - 3)	0,948
7. Going to a party.	1 (0 - 2)	1 (0 - 2)	0,657
8. Work being observed.	1 (0 - 2)	1 (0 - 2)	0,946
9. Write being observed.	1 (0 - 2)	1 (0 - 2)	0,451
10. Call someone you don't know very well.	1 (0 - 2)	1 (0 - 2)	0,128
11. Talking to people you don't know very well.	1 (0 - 2)	2 (0 - 2)	0,033
12. Meeting with strangers.	2 (0 - 3)	2 (0 - 3)	0,783
13. Urinating in a public bathroom.	0 (0 - 2)	0 (0 - 2)	0,484
14. Enter a room where others are already seated.	1 (0 - 2)	1 (0 - 2)	0,831
15. Being the center of attention.	2 (0 - 3)	2 (0 - 3)	0,537
16. Speaking in a meeting.	2 (0 - 2)	2 (0 - 2)	0,349
17. Taking a test.	1 (0 - 2)	1 (0 - 2)	0,765
18. Expressing a disagreement or disapproval to people you don't know well.	0 (0 - 2)	1 (0 - 2)	0,040
19. Looking into the eyes of people you don't know well.	0 (0 - 2)	0 (0 - 2)	0,851
20. Report something to a group.	1 (0 - 2)	1 (0 - 2)	0,450
21. Try to flirt with someone.	1 (0 - 2)	1 (0 - 3)	0,090
22. Returning goods to a store.	1 (0 - 2)	0,5 (0 - 2)	0,614
23. Throw a party.	0 (0 - 2)	1 (0 - 3)	0,009
24. Resist the pressures of a salesperson.	1 (0 - 2)	1 (0 - 2)	0,684
Total Score	25 (12,5 - 42,3)	28,5 (14 - 43)	0,013
Performance Anxiety	13 (6,8 - 23)	14,5 (7 - 23)	0,073
Social Anxiety/Social Phobia	14 (6 - 21)	15 (7 - 21)	0,005

The highest scores of fear were “Acting, performing or speaking in front of an audience,” “Meeting strangers,” “Being the center of attention,” and “Speaking at a meeting.” Additionally the highest avoidance scores were: “Talking to people in a position of authority”, “Acting, performing, or speaking in front of an audience”, “Talking to people you don’t know very well”, “Meeting strangers”, “Being the center of attention”, and “Speaking at a meeting”.

It is noticeable that there are four items that stand out in both sub-scores, these are “Acting, performing or speaking in front of an audience”, “Meeting with strangers”, “Being the center of attention” and “Speaking at a meeting”, referring to sentence numbers six, twelve, fifteen and sixteen of LSAS.

Discussion

Avoidance of social situations was identified with high frequency and intensity in the patients in the sample, with a greater intensity than fear itself. In other words, from 82 schizophrenic patients with stable conditions 59 (72%) had comorbid SF. And from those, more than 80% had moderate to severe SF. Additionally the subjects avoided more social situations than directly feared it. The subject avoided feared situations more than experienced it. What’s more, it is possible to consider that avoidance is associated with increased social harm, with consequent reduced detachment from social interactions.

These findings bring attention to the need to reevaluate the usual assessment and treatment guidelines (medication, psychological and psychosocial) for patients diagnosed with schizophrenia including the possibility of comorbid SZ-SF.

Although it may be premature to assemble treatment guidelines for FS in schizophrenia, the study shows the opportunity to include pharmacological, psychological, and environmental strategies in controlling these symptoms and possibly expanding the repertoire of drugs for FS control further than antipsychotics.

Besides medications, several strategies already used separately in SZ and SF, have not yet been tested in SZ-SF comorbidity, despite potential effects, such as rehabilitation programs, cognitive-behavioral psychotherapy (CBP), virtual reality (VR), augmented reality (AR), and mindfulness.

Some rehabilitation programs that usually train social living skills, independence, work, and romantic interpersonal relationships (^{Vasconcelos et al., 2021}) may be modified and tested in the management of SF. Additionally, individual or group psychotherapy can focus on fear and avoidance reduction with further gains on social integration, communication, and thought coordination (Zacharias, 2019 cited by ^{Vasconcelos et al., 2021}).

A large array of CBT techniques, ranging from the classical in vivo exposure cognitive therapy, to new modalities like third wave therapies such as internet-delivered therapy, virtual reality exposure, cognitive bias modification can be tested for identification and management of predisposing factors, search for appropriate responses in the face of stressful situations beyond the control of delusions and hallucinations. AR in particular had a greater potential, by combining real and virtual worlds in the search for systematic desensitization and social interaction of the patient (^{Mauro & Mauro, 2021}).

Other interventions with evidence of efficacy in SF like mindfulness addressing moment awareness without judgment, emotional and behavioral self-regulation, and meditation based on mindfulness (^{Crane et al., 2017}; ^{Liu et al., 2021}), may be modified and tested to increase awareness of social anxiety and include curiosity and experimentation in place of fear and avoidance, further expanding different meditation exercises and techniques in SZ-SF comorbidity (^{Goldin et al., 2021}).

Final Considerations

This study sought to carefully evaluate patients with schizophrenia for the presence of FS as comorbidity. Among the 82 patients studied, close to ¾ (59) had SZ-FS, with only 23 without any level for this comorbidity. We also found that these patients who shared some of the items on the two scales are more likely to display avoidance behaviors than fear behaviors.

The study demonstrates additional evidence of significant frequency and probably negative impact of SF in SZ individuals. It is conceivable that avoidance may have negative personal and professional consequences for these patients leading to increased social isolation. The majority of post-acute patients appear to fear situations, fail to experience them and end up withdrawing from the outside world.

Psychotherapies, particularly CBP alone or associated with pharmacotherapy with evidence in the treatment of isolated SF (^{Alomari et al., 2022}; ^{Pelissolo et al., 2019}) may be tested in SZ-SF comorbidity, and checked for possible effect on different outcomes like distress and suffering, relapse, and family and environment integration (^{Soares, 2019}).

Despite the initial evidence, there is a need for further investigation regarding neurophysiological and biochemical mechanisms of this frequent comorbidity, and the potential -effect of medications and psychological interventions to reduce social phobia in patients with the diagnosis of schizophrenia.