Immersive Virtual Reality Applications in Schizophrenia Spectrum Therapy: A Systematic Review

(1) Background: Virtual Reality (VR) is a fully immersive computer simulated experience consisting of a three-dimensional interactive virtual environment, through a head-mounted display (HMD) and controller. The use of virtual reality has recently been proposed for the treatment of various psychiatric conditions, including the spectrum of schizophrenia. Our review aims to investigate the current available evidence regarding the use of immersive virtual reality in the treatment of psychotic symptoms. (2) Methods: From April 2019 to June 2020, we conducted a systematic review aimed at identifying therapeutic applications in immersive virtual reality for the spectrum of schizophrenia, searching for relevant studies on Web of Science, EMBASE, PsycINFO and CINHAL. (3) Results: We identified a total of 2601 unique records. Of these, 64 full-text articles were assessed for eligibility, and six out of these met the inclusion criteria and were included in the final systematic review. (4) Conclusions: The available data on immersive virtual reality are currently limited due to the few studies carried out on the topic; however, it has demonstrated its effectiveness and versatility in successfully treating various psychotic symptoms including delusions, hallucinations, or cognitive and social skills. Existing literature agrees on safe, tolerable, and long-term persistence of the therapeutic effects obtained by immersive VR. No serious side effects have been reported. In some specific cases, VR therapy was found to be very effective compared to usual treatment, allowing effective drug free interventions, and therefore without side effects for patients, even in those resistant to normal drug therapies.


Introduction
Virtual Reality (VR) is a fully immersive computer simulated experience consisting of the development of a three-dimensional virtual environment, around an individual through a head-mounted display (HMD). Such an environment is built to let the user look around him and move in every direction. It is also possible to interact with the environment through inputs given via a controller or keyboard or, in the most advanced VR headsets, through tactile gloves or body motion and six out of these met the inclusion criteria and were included in the systematic review, 58 were excluded because they did not deal with VR therapy or immersive VR (flow diagram, Figure 1). The included studies are summarized in Table 1, while in Table 2 we reported the various types of VR interventions. Risk of bias assessment for included studies is shown in Table 3. In La Paglia et al. (2016) the experimental and control group were not homogeneous in numerosity (n = 9 vs. n = 6) sex and age difference, as the control group is made up exclusively of males with an average age higher than the experimental group, these make the randomization process marked as high risk (Table 3).
they compared the effect of VR exposure therapy to VR exposure modified with cognitive therapy elements across six VR scenarios, on a group of 30 patients affected by persecutory delusions, testing their effectiveness and confirming the initial idea about inconsistent threat beliefs. Their findings showed significative reduction in delusion's conviction in both groups. VR CBT, however, has proved itself 22% more effective than VR exposure. They also demonstrated how these VR therapeutic results were still consistent after therapy in dealing with real-world situations, too. These results are further confirmed by Pot-Kolder et al. [26] that demonstrated how VR CBT can reduce significantly paranoid ideation in schizophrenic patients. Even in this case the results obtained with VR therapy were maintained in daily life and was recorded a decrease of safety behaviors and social cognitive problems specifically targeted by the authors. We have to conclude that the aforementioned trials support the effectiveness of VR CBT and VR exposure in the treatment of delusions and paranoia in schizophrenic patients, although in our opinion, it is necessary to expand the samples and make a trial confronting VR CBT with classic CBT.

Authors
Year Title Target

Principal Findings
Treatment effects on paranoid ideation were significant: at the post-treatment and follow-up assessments, levels of ideas of persecution and social reference were lower in the VR-CBT group than in the ontrol group. The VR-CBT group had improvements in self-stigmatisation and social functioning at follow-up whereas the control group did not. Table 2. Classification of VR intervention types.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity.
VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and re challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic S intervention, thought conversation training and role-plays focused on interper communication. It aimed at enhancing verbal, non-verbal skills and social cogn detecting and correcting the errors committed by the patient on multiple comm levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and digital simulation (avatar) of one of his hallucinated voices, made by patients h representation of the entity to which he attributes his auditory hallucinations. T therapist's voice is transformed through speech transformation software to coi the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatme delusional disorders and paranoia, taking advantage of the immersive environ offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situ stimulus that usually causes anxiety and fear in the subject, in order to induce progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patie digital simulation (avatar) of one of his hallucinated voices, made by pa representation of the entity to which he attributes his auditory hallucin therapist's voice is transformed through speech transformation softwar the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the delusional disorders and paranoia, taking advantage of the immersive offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment stimulus that usually causes anxiety and fear in the subject, in order to progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and re challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic S intervention, thought conversation training and role-plays focused on interper communication. It aimed at enhancing verbal, non-verbal skills and social cogn detecting and correcting the errors committed by the patient on multiple comm levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and digital simulation (avatar) of one of his hallucinated voices, made by patients h representation of the entity to which he attributes his auditory hallucinations. T therapist's voice is transformed through speech transformation software to coi the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatme delusional disorders and paranoia, taking advantage of the immersive environ offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situ stimulus that usually causes anxiety and fear in the subject, in order to induce progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily lif challenges, to training and improve cognitive skills of schizophrenic su VR SST Virtual reality social skill training (VR SST), consist of a VR version of c intervention, thought conversation training and role-plays focused on i communication. It aimed at enhancing verbal, non-verbal skills and soc detecting and correcting the errors committed by the patient on multip levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patie digital simulation (avatar) of one of his hallucinated voices, made by pa representation of the entity to which he attributes his auditory hallucin therapist's voice is transformed through speech transformation softwar the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the delusional disorders and paranoia, taking advantage of the immersive offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment stimulus that usually causes anxiety and fear in the subject, in order to progressive desensitization towards it.   ar The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. e r ) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.
ure Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

R Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation. exposure Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and re challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic S intervention, thought conversation training and role-plays focused on interper communication. It aimed at enhancing verbal, non-verbal skills and social cogn detecting and correcting the errors committed by the patient on multiple comm levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and digital simulation (avatar) of one of his hallucinated voices, made by patients h representation of the entity to which he attributes his auditory hallucinations. T therapist's voice is transformed through speech transformation software to coi the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatme delusional disorders and paranoia, taking advantage of the immersive environ offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situ stimulus that usually causes anxiety and fear in the subject, in order to induce progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between the digital simulation (avatar) of one of his hallucinated voices, representation of the entity to which he attributes his audito therapist's voice is transformed through speech transformat the vocal characteristics attributed by the patient to the entit VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (C delusional disorders and paranoia, taking advantage of the offered by VR, that allows a controlled exposure to social sit VR exposure Therapy based on controlled exposure in a virtual reality en stimulus that usually causes anxiety and fear in the subject, progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and re challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic S intervention, thought conversation training and role-plays focused on interper communication. It aimed at enhancing verbal, non-verbal skills and social cogn detecting and correcting the errors committed by the patient on multiple comm levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and digital simulation (avatar) of one of his hallucinated voices, made by patients h representation of the entity to which he attributes his auditory hallucinations. T therapist's voice is transformed through speech transformation software to coi the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatme delusional disorders and paranoia, taking advantage of the immersive environ offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situ stimulus that usually causes anxiety and fear in the subject, in order to induce progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily lif challenges, to training and improve cognitive skills of schizophrenic su VR SST Virtual reality social skill training (VR SST), consist of a VR version of c intervention, thought conversation training and role-plays focused on i communication. It aimed at enhancing verbal, non-verbal skills and soc detecting and correcting the errors committed by the patient on multip levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patie digital simulation (avatar) of one of his hallucinated voices, made by pa representation of the entity to which he attributes his auditory hallucin therapist's voice is transformed through speech transformation softwar the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the delusional disorders and paranoia, taking advantage of the immersive offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment stimulus that usually causes anxiety and fear in the subject, in order to progressive desensitization towards it.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

VR training
Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communication levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself as a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide with the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation or a stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and related challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic SST intervention, thought conversation training and role-plays focused on interpersonal communication. It aimed at enhancing verbal, non-verbal skills and social cognition, detecting and correcting the errors committed by the patient on multiple communicati levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and a VR digital simulation (avatar) of one of his hallucinated voices, made by patients himself a representation of the entity to which he attributes his auditory hallucinations. The therapist's voice is transformed through speech transformation software to coincide w the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatment of delusional disorders and paranoia, taking advantage of the immersive environment offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situation o stimulus that usually causes anxiety and fear in the subject, in order to induce a progressive desensitization towards it.   Table 2. Classification of VR intervention types.

Type of VR Intervention Description
VR training Training consisting of a series of 3D-VR scenarios reproducing daily life and re challenges, to training and improve cognitive skills of schizophrenic subjects.

VR SST
Virtual reality social skill training (VR SST), consist of a VR version of classic S intervention, thought conversation training and role-plays focused on interper communication. It aimed at enhancing verbal, non-verbal skills and social cogn detecting and correcting the errors committed by the patient on multiple comm levels.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patient and digital simulation (avatar) of one of his hallucinated voices, made by patients h representation of the entity to which he attributes his auditory hallucinations. T therapist's voice is transformed through speech transformation software to coi the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the treatme delusional disorders and paranoia, taking advantage of the immersive environ offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment to a situ stimulus that usually causes anxiety and fear in the subject, in order to induce progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between therapist, patie digital simulation (avatar) of one of his hallucinated voices, made by pa representation of the entity to which he attributes his auditory hallucin therapist's voice is transformed through speech transformation softwar the vocal characteristics attributed by the patient to the entity. VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (CBT) for the delusional disorders and paranoia, taking advantage of the immersive offered by VR, that allows a controlled exposure to social situation.

VR exposure
Therapy based on controlled exposure in a virtual reality environment stimulus that usually causes anxiety and fear in the subject, in order to progressive desensitization towards it.

VR Avatar therapy
The therapy involves a three-way conversation between the digital simulation (avatar) of one of his hallucinated voices, representation of the entity to which he attributes his audito therapist's voice is transformed through speech transformat the vocal characteristics attributed by the patient to the entit VR CBT (cognitive behavior therapy) Use of techniques of cognitive behavioral psychotherapy (C delusional disorders and paranoia, taking advantage of the offered by VR, that allows a controlled exposure to social sit VR exposure Therapy based on controlled exposure in a virtual reality en stimulus that usually causes anxiety and fear in the subject, progressive desensitization towards it.

. Delusions and Paranoia
We identified two randomized controlled trials on the treatment for delusions and paranoia: one based on VR exposure and VR (cognitive behavior therapy) CBT by Freeman et al. [15], the second one on VR CBT only, by Pot-Kolder et al. [26]. Freeman et al. starting from the idea that persecutory delusions derive from inconsistent threat beliefs that activate safety-seeking behaviors aimed to avoid anxiogenic situations [27], introducing virtual reality-controlled exposure as a possible therapy [14]. They developed these ideas in a subsequent trial that was included in this review [15]; in particular, they borrowed the controlled exposure already employed to treat phobias and anxiety, proposing for the first time the use of a VR version exposure therapy and CBT to treat delusions. In their pilot study, they compared the effect of VR exposure therapy to VR exposure modified with cognitive therapy elements across six VR scenarios, on a group of 30 patients affected by persecutory delusions, testing their effectiveness and confirming the initial idea about inconsistent threat beliefs. Their findings showed significative reduction in delusion's conviction in both groups. VR CBT, however, has proved itself 22% more effective than VR exposure. They also demonstrated how these VR therapeutic results were still consistent after therapy in dealing with real-world situations, too. These results are further confirmed by Pot-Kolder et al. [26] that demonstrated how VR CBT can reduce significantly paranoid ideation in schizophrenic patients. Even in this case the results obtained with VR therapy were maintained in daily life and was recorded a decrease of safety behaviors and social cognitive problems specifically targeted by the authors. We have to conclude that the aforementioned trials support the effectiveness of VR CBT and VR exposure in the treatment of delusions and paranoia in schizophrenic patients, although in our opinion, it is necessary to expand the samples and make a trial confronting VR CBT with classic CBT.

Auditory Verbal Hallucinations
We found a single RCT by du Sert et al. [28] regarding the treatment of auditory verbal hallucinations (AVH) through the VR Avatar therapy. The auditory verbal hallucinations represent one of the most frequent and disabling symptoms associated with psychosis. Avatar therapy was first introduced by Leff et al. [29] as non-pharmacological intervention method for AVH treatment. Leff et al. [29], however, did not make use of virtual reality but employed standard monitor visualization instead, so to administer "computer assisted therapy" without immersive characteristics. Avatar therapy with the implementation of immersive virtual reality, was successively introduced by du Sert et al. in 2018 [28] that, to our knowledge, is the only clinical trial conducted on treatment of AVH thought immersive VR to date. In this randomized partial cross-over trial, patients affected by pharmacologically resistant schizophrenia treated with VR showed significant improvements in AVH severity, depressive symptoms, and life quality with respect to those in the TAU control group. The sample consisted of 15 patients, including interventional and TAU groups. Patients' improvements remained stable overtime and even got better at the 3-month follow-up, showing that the coping strategies learned during VR therapy applied to everyday life brought further improvements and enhanced life quality of these patients, even after the end of the therapy itself. The effectiveness of VR avatar therapy on AVH was supposed to be linked to the immersive VR environment capacity to induce feelings of presence, activating emotional arousal according to Diemer et al. [30], so that it is possible to work therapeutically on emotional dysregulation improving patients' self-esteem and self-image. Emotional dysregulation was in fact recently identified as central principle in the treatment of psychotic symptoms by Trémeau [31], Khoury and Lecomte [32], and Craig et al. [33]. Through immersive VR, the patients can explore and experiment emotions in a safe controlled environment and learning how to better regulate them modifying their relationship with persecutory voices. These results, although preliminary, indicate how VR Avatar therapy could represent an innovative and useful non-pharmacological therapeutic intervention tool for hallucinations, especially in case of drug-resistant schizophrenia, which is otherwise poorly treatable.

Cognitive Deficits
Two clinical trials by La Paglia et al. [34,35] were focused on treatment of cognitive deficits thought VR training. It consists in training the patient through targeted exercises performed in VR scenarios that reproduce everyday life situations (see Table 2). The cognitive functions in schizophrenic patients are often compromised, and this heavily impacts subject's functioning, especially in relation to social activities and self-sufficiency, and more generally in carrying out targeted activities.
In their first clinical trial (2013), La Paglia et al. [34] performed VR trainings for cognitive rehabilitation in schizophrenic patients, targeting attention and executive functions. It was based on tasks execution in four VR environments including a park, a supermarket, a beach and a valley. It should be noted that the type of VR equipment used was not specified in this article, although it looks reasonable to assume immersive virtual reality was used. They confronted a VR-exposed group with a control group treated with IPT (integrated psychological therapy) only. After 10 sessions, similar improvements marked both groups out, although they were more significant in the VR one, which showed better reduction of number of errors and tasks execution time, combined with an increased rules' compliance and sustained attention. These results were confirmed by a second trial in 2016 [35], in which the same experiment was carried out using three VR environments (park, supermarket, and beach). In addition to what was recorded during the first trial, patients treated with VR training showed better improvements in sustained attention, general cognitive functioning and planning than those of the control group treated with IPT only. In conclusion, current findings suggest the effectiveness of such therapy, but results look only slightly better in VR-treated groups than what was recorded in the control groups; therefore, in our opinion, a bigger generalization on larger population samples is needed in order to validate VR treatments.

Social Skills
We identified a single randomized controlled trial on the use of immersive virtual reality in the treatment of social skills by Park et al. [36], in which the effectiveness of social skill training intervention in VR (VR SST, see Table 1) versus traditional SST (TR-SST) was compared on a sample of 91 schizophrenic patients diagnosed according to DSM 4 criteria. The VR SST is based on social training and role-play interventions in an immersive virtual environment with avatars reproducing social interactions, while TR-SST is based on interactions with actors and audio-video material. According to the findings of this paper, VR SST demonstrated greater improvements in the conversational skills and also induced greater assertiveness and motivation to treatment than TR-SST. On the other hand, VR SST was less effective in improving vocal and non-verbal skills than classical TR-SST. Interactions with avatars instead of with real people, as in the TR-SST, and difficulties of the therapist in being able to observe and correct patient's non-verbal language while wearing the VR viewer are the reasons why such a result was obtained.

Discussions
It is remarkable that among authors there is no general agreement and uniqueness on the use of the term "virtual reality", but often a general confusion, probably due to its recent introduction in medical research. Many authors in fact generically refer to "virtual reality" implying both the immersive and non-immersive types without clear distinctions, whereby "immersive" we mean the VR that is administered through head mounted display (HMD), characterized by total and natural immersion of the patient in the virtual environment, while by "non-immersive" we mean that is administered through a panoramic or classic screen and interactive commands so, unlike the first one, not to allow a real and total immersion. The latter should not be defined in our opinion as real "virtual reality" because it lacks the characteristic of total immersion that specifically differentiates this novel medium. The concept of non-immersive virtual reality gets too close to the experience of a classic video game played on a console or PC. In fact, such a concept has the defect of excluding immersivity. Immersive VR with adequate equipment allows a greater sense of reality in a virtual environment, since virtual scenes through HMD follow the head movements, while in non-immersive VR, it is possible to simply move the camera on a flat screen like in any video game. Immersivity helps to reproduce and elicit through VR the same emotions and reactions that the subject would experience in the real world. In this sense, as mentioned in the introduction, VR proved to be an ecologically valid environment, giving the possibility to develop new perspectives of assessment and therapy, as well as standardizable and repeatable environments and situations, difficult or impossible to be recreated in the real world. What, in fact, identifies specifically and represents the novelty of VR is the union of full immersivity and interactivity in a single instrument. By exploiting the union of the two, new scenarios and possibilities can be considered in the treatment of mental disorders and schizophrenia, exploiting a virtual malleable "alternative reality". For all these reasons, in order to avoid vagueness in the literature, in our opinion the term "virtual reality" should exclusively imply "immersive virtual reality".
Just the highly standardization and reproducibility of virtual environments (not possible during a classical face-to-face patient visit) offers the key for a possible use of VR in the assessment of mental disorders. For example, as underlined by Freeman [14], it is possible recording the physiological correlates of symptoms during the exposition to a particular environment or social situation reproduced in VR, such as participant's movement, eye movements, signs of arousal like skin conductance, heart rate and blood pressure, etc., or also studying brain activation thought magnetic resonance imaging during a VR session. Moreover, some parameters can be directly measured during the session, mapping the interactions between controlled virtual social environments in relation to symptom domains, physiological responses and behavior, allowing a more personalized and contextual diagnostic assessment to be made [20]. In the same way it is potentially possible to identify any environmental triggers that can induce or worsen the psychopathological symptoms.
According to our findings, immersive VR has some obvious advantages compared to conventional treatments: first, it allows effective and brief interventions without the use of drugs and, therefore, the pharmacological side effects; second, it is highly customizable on the needs of the individual patient; third in some cases, it allows treatments of pharmacological resistance psychotic symptoms, too. We noticed that, in some case, the sample size is too small, and the trial was conducted with per-protocol approaches instead of intention-to-threat and, therefore, this may introduce bias. Looking at the future of immersive VR treatments, it is necessary to develop a greater degree of interactivity in order to make virtual environments and social interactions more and more complex, plausible and adherent to reality, at the same time these interactions must adapt and react to the behavior of the patient dynamically. In this sense, some protocols for future trials have already been published about forms of automated psychological VR therapy [37,38]. This involves automating the provision of cognitive therapy within VR using an avatar coach, so that a therapist is not needed [38]. New intervention protocols have also been proposed regarding social cognition and social functioning (DISCoVR) [39] and cognitive deficit [40]. Preliminary results were presented at the SIRS 2020 congress concerning the use of VR for the improvement of physical health [41] and social functioning [42] in schizophrenic patients. It is desirable to aim for greater diffusion of these technologies in hospital and outpatient settings thanks to the progressive decrease in costs, to meet the patient's needs with increasingly scalable and personalized VR therapies. The future of VR treatments is currently promising and will face new challenges in the coming years. There is a general need to understand how new technologies, given their transformative potential, can find a place within the therapeutic practice [43].

Conclusions
In conclusion, the available data on immersive virtual reality are currently limited due to the few studies carried out on the topic and more research is needed to better evaluate their effectiveness as a treatment. However, the available evidence seems to suggest its effectiveness and versatility in successfully treating various psychotic symptoms including delusions, hallucinations, or cognitive and social skills, proposing itself as a promising new branch of research and therapy. The existing literature agrees on the safety, tolerability, and long-term persistence of the therapeutic effects obtained by immersive VR. No serious side effects have been reported, apart from temporary motion sickness or rare annoyance wearing VR equipment by Du Sert et al. [26].
Current evidence does not yet allow to establish whether VR treatments are better than conventional ones since, in some cases, results were similar or slightly better for VR. In some specific cases, VR therapy was found to be very effective compared to usual treatment, such in improving conversational skills. In VR-based treatment of AVH, results showed improvement at follow-up after the end of VR therapy as a result of the acquisition and real-life reinforcement of the behavioral patterns learned during the treatment. The fact that virtual reality is not necessarily better but has similar effectiveness, does not mean that it is not useful, since it has undoubted advantages that may make it the chosen therapy compared to conventional treatments, such as versatility, reproducibility, standardization of treatments, adaptability on patients' needs, rapidity, effectiveness, long-term persistent results even after a few sessions, greater patient motivation and therefore it is characterized by an excellent cost-effectiveness ratio.
It should also be emphasized that immersive VR allows effective drug-free interventions and, therefore, without side effects for patients, even in those resistant to normal drug therapies, such as in the case of persistent AVH or negative symptoms. Today's wide and growing availability of VR devices (like Oculus Rift or HTC Vive series) and their diffusion on the market make them potentially a powerful, cheap, and versatile tool of therapy for schizophrenia spectrum disorders. We must conclude that applications of immersive VR for treatment of psychotic disorders are very promising at present. However, in our opinion, due to the lack of studies on the argument, new ones on larger samples are needed to confirm the promising results obtained so far.