Table 4.

Social withdrawal: characteristics of studies meeting inclusion criteria (n = 8).

Author (date) location	Study design sample (number & diagnosis) (gender ratio: M/F) (CHR/controls)	Mean age (SD) ethnicity (CHR/controls)	Diagnosis and manual used & comorbidities (CHR/controls)	Outcome measures	Main findings & clinical implications
Boldrini et al.117	Cross-sectional 58 CHR 60 HC with PD 59 HC without PD 28 M/30 F 30 M/30 F 21 M/38 F	16 (1.6) 16 (1.6) 16 (1.4) Ethnicity not recorded.	Structured Interview for Prodromal Syndromes (SIPS) CHR diagnoses 14 GAD 10 Panic disorder, 6 Dysthymia, 6 Major depressive disorder PD group diagnoses 9 Cluster A 28 Cluster B 23 Cluster C HC comorbidities 14 GAD, 11 Eating disorder, 10 Panic disorder, Dysthymia, 6 Major depressive disorder, 6 ADHD 5 Oppositional defiant disorder	Shedler–Westen Assessment Procedure for Adolescents (SWAP-200-A)	CHR group had significantly higher mean scores in the SWAP- 200-A Schizoid and Schizotypal PD scales than the PD and HC without PD groups. The CHR and PD groups had significantly higher mean scores in the SWAP-200-A Borderline and Avoidant PD scales and lower mean scores in the SWAP-200-A High-Functioning scale than the HC without PD group. The SWAP-200-A items that had the highest mean scores and were most descriptive of personalities of the CHR group included: avoidance of interpersonal relationships, associated with feelings of shame, shyness, embarrassment, and fear of rejection, a tendency to express suspicion toward others, obsessional thoughts, severely impaired mentalization, in both self-oriented and other-oriented dimensions, emotional dysregulation, with dysphoric feelings of anxiety, and depression, odd and anomalous reasoning or perceptual experiences, especially when under stress; dissociative symptoms of depersonalization and derealization, and negative symptoms of avolition, abulia and blunted affect, and impaired role and academic/occupational functioning.
Chudleigh et al.104	Cross-sectional 20 FEP 20 CHR 20 HC 11 M/9 F 13 M/7 F 10 M/10 F	22.05 (3.0) 20.75 (2.7) 22.00 (2.5) Ethnicity not recorded.	Comprehensive Assessment of At-Risk Mental State (CAARMS)	Brief Psychiatric Rating Scale (BPRS) Social Functioning Scale (SFS) World Health Organization Disability Assessment Scale II (WHODAS) Social and Occupational Functioning Assessment Scale (SOFAS) Depression Anxiety Stress Scale (DASS) Brief Social Phobia Scale (BSPS)	CHR and FEP group’s SOFAS scores did not significantly differ from each other, but both groups were rated as functioning at a significantly lower level than HCs. HCs performed significantly better on interpersonal communication than the CHR group, as they were communicating more frequently with others. On the WHODAS, the CHR and FEP groups reported experiencing significantly more difficulty on the following subscales: understanding and communication, self-care, getting along with people, life activities, and participation in society, compared with HCs. The CHR and FEP groups did not differ from each other on any of these subscales. For the CHR group, increased levels of depressive symptoms were associated with decreased levels of both quantitative and qualitative measures of social functioning (i.e., withdrawal/social engagement, interpersonal communication and getting along with people). Significant correlations were found only between positive symptoms and the qualitative measures of disability; three of these four associations were for the CHR group only. Specifically, those at risk who reported more positive symptoms also indicated more difficulty with self-care (r = 0.68, P < 0.001), participating in life activities (r = 0.58, P < 0.01) and participation in society (r = 0.53, P < 0.01). There were no significant correlations observed between positive symptoms and any of quantitative social functioning (SFS) scores for CHR or FEP group.
Dragt et al.65	Longitudinal 36 month follow up 72 CHR 47 M/25 F	19.3 (4.0) 51 Caucasian 21 Other	Structured Interview for Prodromal Syndromes (SIPS) AS + BS: 48.6% AS: 22.2% BLIPS + AS + BS: 8.3% GRRF + AS + BS: 8.3% BLIPS + AS: 4.2% GRRF + AS: 4.2% BLIPS: 1.4% BLIPS + BS: 1.4% GRRF + BS: 1.4% Psychiatric medication: 41 Not on medication 17 Antipsychotic 7 Antidepressants 7 Other	Premorbid Adjustment Scale (PAS)	Over 36 months, 19 (26.4%) of the 72 included participants made the transition to psychosis. Social withdrawal significantly predicted transition to psychosis in CHR individuals (P = 0.001). Poor premorbid adjustment predicts onset of psychosis, as it may be a reflection of neurodevelopmental anomalies.
Hodges et al.118	Cross-sectional 100 CHR 32 HC 52 M/48 F 16 M/16 F	21.6 (2.8) 21.1 (2.2) Ethnicity not recorded.	Present State Examination (PSE) Schedule for Affective Disorders and Schizophrenia - Lifetime Version (SADS-L) CHR Comorbidities Major depressive syndrome: 1%, Minor depressive disorder: 4%, Alcohol dependency: 1%, obsessive-compulsive disorder: 1%, Suicidal behavior: 3%, GAD/Panic: 2% Antisocial personality disorder: 2% No comorbidities reported in HCs	Structured Inventory for Schizotypy (SIS)	Compared to HCs, CHR individuals demonstrated a trend towards significance for the following variables of the SIS: Childhood social isolation P = 0.08), Interpersonal sensitivity (P = 0.09), Social isolation (P = 0.09), Suicidal ideation (P = 0.09), Restricted affect (P = 0.08), Oddness (P = 0.05) and a significant association with Disordered speech (P = 0.04).
Jang et al.131	Longitudinal 12 month follow up 57 CHR 58 HC 37 M/20 F 40 M/18 F	21.3 (3.8) 20.8 (3.6) Ethnicity not recorded.	Comprehensive Assessment of At-Risk Mental State (CAARMS) Positive and Negative Syndrome Scale (PANSS) Psychiatric medication: 10 Antipsychotic (AP) 3 Antidepressants (AD) 2 AP + AD 2 Anxiolytics	Social Functioning Scale (SFS)	During the 12-month follow-up period, 13 of the 57 CHR individuals converted to full psychosis. The number of CHR individuals who converted to psychosis during the first 12 months was 6, between 12 and 24 months was 4, and after 24 months was 3. The mean time to conversion from inclusion in the study was 14.3 months. Both CHR groups, i.e., non-converters and converters, showed significantly lower average scores and significantly lower scores on the subscales addressing: social engagement/withdrawal, interpersonal behavior, independence—performance, independence—competence, and prosocial activities compared with HCs.
Mason et al.135	Longitudinal 12 month follow up 74 CHR 39 M/35 F	17.3 (2.8) Ethnicity not recorded.	PACE criteria APS: 58% GRDS: 26% BLIPS: 31% 20 No diagnosis, 16 Depression	Premorbid Social Adjustment scale (PSA) International Personality Disorder Examination (IPDE) Quality of Life Scale (QLS) Schedule of Recent Experience (SRE) Assessment of Prodromal and Schizotypal Symptoms (APSS) Brief Psychiatric Rating Scale (BPRS) Scales for Assessment of Positive and Negative symptoms (SAPS and SANS) Rating Scales for Depression & Anxiety (HRSD)/HRSA) Global Assessment of Functioning (GAF)	37 individuals (50%) made a transition to psychosis at 12-month follow-up The most reliable scale-based predictor was the degree of presence of schizotypal personality characteristics. Individual items assessing odd beliefs/magical thinking, marked impairment in role functioning, blunted or inappropriate affect, anhedonia/asociality and auditory hallucinations were also highly predictive of transition, yielding good sensitivity (84%) and specificity (86%) and odds ratio of 6.2. These predictors are consistent with a picture of poor premorbid functioning that further declines in the period up to transition.
Shim et al.125	Cross-sectional 32 CHR 30 HC 19 M/13 F 17 M/13 F	20.9 (3.9) 22.8 (2.4) Ethnicity not recorded.	Comprehensive Assessment of At-Risk Mental State (CAARMS) APS: 88% GRDS: 12% BIPS: 0% 13 CHR participants received antipsychotic medication.	Social Functioning Scale (SFS)	CHR group scored significantly lower than HCs on: Social engagement/withdrawal, Interpersonal behavior, and independence performance. Positive and negative symptoms were not significantly associated with social functioning, whereas disorganized and general symptoms were significantly correlated with poor “independence-competence” in CHR individuals.
Wisman van der Teen64	24 CHR 24 HC	21.78 (2.96) 20.27 (2.73)	Comprehensive Assessment of At-Risk Mental State (CAARMS) 16 CHR participants received medication 6 Atypical AP 1 Typical & Atypical AP, 6 SSRI, 3 Benzodiazepines	Experienced Sampling Method: Social context and frequency. Participants reported whether they were alone (i.e., “lone” and “alone with pet”) or they reported with whom they were (i.e., “classmates”, “friends”, “family”, “stranger”). The percentage of time spent alone was calculated and used as a measure of social withdrawal. Positive and Negative Syndrome Scale (PANSS) Green Paranoid Thoughts Scale (GPTS)	Social withdrawal did not significantly differ between CHR and HCs. CHR individuals showed no significant associations between social withdrawal and symptom severity nor with paranoia (PANSS: b = −0.11, P = 0.78; GPTS: b = −0.15, P = 0.47). An overall decrease of emotional distress in CHR individuals when with others was found, as indicated by a decrease in negative affect and an increase in positive affect when with others compared to when alone. Supporting patients to keep engaging in social interactions may alleviate their emotional distress.

AP antipsychotic medication, APS Attenuated Positive Syndrome, AS attenuated symptoms, BS basic symptoms, BIPS Brief intermittent psychotic symptoms syndrome, BLIPS brief limited intermitted psychotic symptoms, CHR Clinical High Risk, GRDS Genetic Risk & Deterioration Syndrome, GRRF genetic risk and reduced functioning, SSRI Selective Serotonin Reuptake Inhibitor.