. 2023 Jun 17;9(1):38. doi: 10.1038/s41537-023-00362-z

Table 3.

Psychosocial stress: characteristics of studies meeting inclusion criteria (n = 16).

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 and clinical implications
Addington et al.¹¹⁶	Cross-sectional 360 CHR 180 HC 210 M/150 F 100 M/80 F	18.98 (SD = 4.18) 19.54 (SD = 4.78) Caucasian 55%/58.9%	Structured Interview for Prodromal Symptoms (SIPS) No comorbidities reported	Calgary Depression Scale (CDS) Brief Core Schema Scale (BCSS) Social Interaction Anxiety Scale (SIAS) Social Anxiety Scale (SAS) Perceived Discrimination Scale (PDS) Alcohol and Drug Use Scale Global Assessment of Functioning Scale: Social and Role (GAF)	CHR participants experienced significantly more types of trauma (z = −8.68, P < 0.05) and bullying (z = −4.89, P < 0.05) compared to controls. CHR females reported significantly more trauma than CHR males. Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self. These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms.
Bentley et al.³⁷	Cross-sectional 36 CHR 60 HC (Help-seeking) 10 M/26 F 23 M/37 F	15.17 (2.44) 15.69 (3.18) African American 55%/49% Caucasian 30%/34% Multiracial or other 15%/17%	Structured Interview for Prodromal Symptoms (SIPS) APS: 78% GRDS: 14% BIPS: 8% Mood disorder: 45%/55% Anxiety Disorder: 12%/11% PTSD: 15%/11% AD/HD: 15%/10%	Behavior Assessment System for Children, Second Edition (BASC-2)	For CHR participants, parent–child relationships had a significant negative effect on social stress (b = −0.73, t[92] = − 3.77, P < 0.001, f2 = 0.15); no significant relation was evident for the help-seeking control participants (b = −0.15, t[92] = −0.94, P = 0.35, f2 = 0.01). These findings suggest that a positive parent–child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent–child relationships might be relevant for adolescents and young adults at clinical high risk for psychosis.
Carol¹²⁷	Longitudinal 57 CHR 66 HC 34 M/23 F 30 M/36 F	19.04 (1.63) 18.42 (2.46) Hispanic 11/17 Asian 3/7 Black 1/2 Caucasian 40/38 Interracial 2/2	Structured Interview for Prodromal Symptoms (SIPS) Mood disorders: 30% Anxiety Disorders: 33% PTSD: 7% ADHD: 12% No comorbidities reported in HCs	Daily Stress Inventory (DSI)	CHR individuals reported significantly higher frequency of stressful events [t(117) = 3.01, P = 0.003] and significantly higher levels of overall distress [t(117) = 4.47, P < 0.001] compared to HCs. CHR group showed significantly more positive [t(63) = 17.62, P < 0.001] and negative [t(58.19) = 11.08, P < 0.001] symptoms compared to HCs. CHR group showed significantly elevated resting cortisol levels compared with matched HC adolescents when controlling for age, [F(1,100) = 2.99, P = 0.044].
De Vos et al.¹²⁸	Longitudinal 12 month follow up 81 CHR 32 M/49 F	18 (3.3) Ethnicity not recorded.	Comprehensive Assessment of At-Risk Mental State (CAARMS) APS: 82.7% GRDS: 7.4% BIPS: 0% Major Depressive Disorder: 64.2% Anxiety Disorder: 42% Dysthymic Disorder: 3.7% Eating Disorder: 1.2% Substance Use Disorder: 16% Other diagnoses: 2.5% Schizotypal Personality Disorder: 1.2% Borderline Personality Disorder: 6.2%	Childhood Trauma Questionnaire (CTQ) Brief Psychiatric Rating Scale (BPRS) Scale for the Assessment of Negative Symptoms (SANS) Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) for Axis I & Axis II disorders (SCID-I, SCID-II) Social and Occupational Functioning Scale (SOFAS) Global Functioning Scale (GFS) Social & Role	The majority of CHR sample (82.7%) experienced at least one form of early trauma. No significant correlations emerged between the CTQ total score and baseline levels of APS severity, distress associated with APS and functional outcomes. However, there was a significant positive correlation (r = 0.23, P = 0.044) between the CTQ total score and the CAARMS suicidality and self-harm baseline score. The high prevalence of Childhood Trauma (CT) in CHR individuals and its association with suicidality and self-harm underlines the importance of inquiring about CT during clinical assessments.
Freitas et al.¹³⁰	Longitudinal 87 CHR 115 HC 29 M/58 F 50 M/65 F	24.78 (4.11) 25.09 (4.31) Ethnicity not recorded.	The Prodromal Questionnaire (PQ) Structured Interview for Prodromal Syndromes (SIPS) Scale of Prodromal Symptoms (SOPS) No comorbidities reported in HCs	Childhood Trauma Questionnaire (CTQ)	Compared to HCs, CHR individuals scored significantly higher on: physical abuse (mean rank: controls = 93.81, CHR = 111.67; P = 0.027), sexual abuse (mean rank: controls = 94.67, CHR = 110.52; P = 0.007) and emotional abuse (mean rank: controls = 85.93, CHR = 122.09; P < 0.001). No differences were found for physical and emotional neglect. Childhood trauma such as emotional, physical, and sexual abuse, and physical and emotional neglect appear to be associated with CHR status. In CHR individuals, physical abuse correlated with perceptual abnormalities, and physical neglect correlated with disorganized speech/thought, whereas physical and emotional neglect negatively correlated with grandiosity symptoms.
Huang et al.¹¹⁹	Cross-sectional 56 FEP 83 CHR 61 HC 37 M/19 F 44 M/39 F 32 M/29 F	26.5 (8.5) 28.8 (8.4) 31.3 (7.9) 55 Han Chinese/ 82 Han Chinese/ 60 Han Chinese	Structured Interview for Prodromal Syndromes (SIPS) No comorbidities reported in HCs	Positive and negative syndrome scale (PANSS) Global Assessment Function (GAF) Montgomery–Asberg Depression Rating Scale (MADRS) Childhood Trauma Questionnaire-Short Form (CTQ-SF) Life Events Scale (LES) Perceived Social Support Scale (PSSS)	In terms of the CTQ Total, FEP and CHR groups scored significantly higher than HCs (P = 0.002 and P < 0.001, respectively). CHR individuals scored significantly higher on emotional neglect and physical neglect compared than HCs (P < 0.001 and P = 0.009, respectively). CHR group experienced a significantly more total life events compared with HCs (P = 0.004). FEP and CHR groups scored lower on PSSS Total than HCs (P = 0.03 and P = 0.01, respectively). In Family Support (FS) sub-domain, CHR possessed poorer family support than HCs (P = 0.03). In the CHR group, CTQ Total showed positive correlation with SIPS Total (P < 0.05), while LES Total showed a positive correlation with SIPS Positive (P < 0.05), SIPS Total (P < 0.01) and GAF (P < 0.05). CHR individuals had more childhood trauma, more recent life events and less social support than HCs. There was no significant difference on childhood trauma, life events and social support between CHR and FEP groups. Emotional and physical neglect were more frequently prevalent in CHR group than HCs.
Kline et al.³⁸	Longitudinal 60 CHR 65 HC Total sample (n = 125) 48 M/77 F	15.3 (2.58) 16.46 (3.13) Total sample (n = 125) African American 46.4% Caucasian 34.4% Native American 1.6% Asian 0.8% Multiracial/other 14.4 %	Structured Interview for Prodromal Syndromes (SIPS) Mood Disorder: 61%/49.2% Anxiety Disorder: 50.8%/35.4%, PTSD: 31.7%/24.6%, ADHD: 45.8%/46.2%, Substance use disorder: 8.5%/7.7%, other disorder: 3.4% /18.5%	Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (KSADS-PL)	The proportion of individuals reporting at least one event was higher in CHR (85%) relative to HCs (64.5%; χ²[1] = 6.75), P = 0.01). The CHR group endorsed significantly more lifetime trauma exposures than the HC group (mean exposures for CHR = 2.02, SD = 1.63; mean exposures for HC = 1.45, SD = 1.52; t[12] = −1.98, P = 0.05) For CHR individuals non-violent traumas were significantly associated with grandiose thinking (P < 0.05).
Kraan et al.¹³²	Longitudinal 4 Year follow up 113 CHR 50 M/63 F	23.5 (5.4) Dutch 54% Minority 46%	Comprehensive Assessment of At-Risk Mental State (CAARMS)	Childhood Trauma Questionnaire-Short Form (CTQ-SF) Beck Depression Inventory-II (BDI-II) Social Interaction Anxiety Scale (SIAS) Social and Occupational Functioning Scale (SOFAS)	The percentage of CHR individuals reporting childhood adversity was as follows: emotional abuse (46.7%), physical abuse (20.9%), sexual abuse (24.8%), emotional neglect (66.7%) and physical neglect (41.9%). No significant association was found between childhood adversity subscales and the severity of positive symptoms at baseline and at 4-year follow-up. No significant association was found between total childhood adversity scores and any of the childhood adversity subscales (emotional abuse, physical abuse, sexual abuse, emotional and physical neglect) and transition to psychosis at 4-year follow-up.
Kraan et al.¹³³	Longitudinal 24 month follow up 259 CHR 48 HC 139 M/120 F 26 M/22 F	22.7 (4.5) 23.98 (4.33) Ethnicity not reported	Comprehensive Assessment of At-Risk Mental State (CAARMS) APS: 78.7% GRDS: 8.4% BLIPS: 5.7% APS & Genetic risk: 7.2% No comorbidities reported in HCs	Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) for Axis I & Axis II disorders (SCID-I) Childhood Trauma Questionnaire (CTQ) Cannabis Experience Questionnaire (CEQ)	The number of CHR individuals that transitioned to psychosis was 31 (11.9%): 11 transitioned within the first 6 months, 13 at 12 months, and 7 at 24 months). 54% of the CHR individuals had experienced at least one form of childhood maltreatment compared to 17.4% of HCs (P < 0.001). This difference was apparent for each form of child maltreatment: emotional abuse; cases = 62.5%, controls = 27.1% (P < 0.001); emotional neglect; cases = 76.4%, controls = 33.3% (P < 0.001); physical abuse; cases = 24.3%, controls = 8.3% (P = 0.014); None of the univariate odds ratios for the association between each individual subtype of maltreatment and transition to psychosis was statistically significant. In addition, total child maltreatment did not increase the risk for transition to psychosis (OR = 2.46, 95% CI = 0.95 to 6.41, P = 0.065). Examination of the adjusted odds ratios showed that, after controlling for the other subtypes, a history of emotional abuse significantly contributed to transition (OR = 3.78, 95% CI = 1.17–12.39, P = 0.027)
Loewy et al.¹²⁰	Cross-sectional 103 CHR 49 M/54 F	18 (4.2) Caucasian 52% Asian 18% Black/African-American 5% Native American/Other Pacific islander 1% Multiracial 16% Unknown or unreported 7%	Structured Interview for Prodromal Syndromes (SIPS)	Scale for Assessment of Psychosis Risk Symptoms (SOPS) Traumatic Events Screening Inventory for Children (TESI-C) Global Functioning: Role and Social Scales,	61% of CHR individuals reported lifetime exposure to traumatic events CHR individuals with a trauma history had significantly more severe perceptual disturbances and general/affective symptoms on the SOPS, as well as lower functioning ratings than CHRs without trauma. The number of traumatic events was significantly correlated with more severe perceptual disturbances, general/affective symptoms and lower functioning ratings. The number of interpersonal traumatic events was significantly correlated with more severe suspiciousness, perceptual abnormalities, general/affective symptoms and lower functioning scores.
Magaud et al.¹²¹	Cross-sectional 50 CHR 25 M/25 F	16.7 (3.3)	Structured Interview for Prodromal Syndromes (SIPS)	Childhood Trauma Questionnaire (CTQ) with added questions on cyberbullying	38% of CHR participants reported having experienced cyberbullying. The most frequent types reported were bullying via text messages, Facebook and instant messages (‘chat’). Bullying via texts and Facebook was associated with a past history of sexual abuse and physical neglect; Facebook with a past history of emotional neglect; and texts were more frequent in those who reported past physical abuse.
Pruessner et al.¹⁰	Cross-sectional 32 FEP 30 CHR 30 HC 16 M/14 F 15 M/15 F	20.33 (3.24) 22.47 (3.79) 80% Caucasian in both groups.	Comprehensive Assessment of At-Risk Mental State (CAARMS) CHR comorbidities Depression: 50% Dysthymia: 1% Anxiety: 37% Obsessive-compulsive disorder: 1% PTSD: 1% No comorbidities reported in HCs	Trier Inventory for the Assessment of Chronic Stress (TICS) Brief Psychiatric Rating Scale (BPRS) Global Assessment Function (GAF) Self-esteem Rating Scale (SERS) Brief COPE scale Multidimensional Scale of Perceived Social Support (MSPSS)	CHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the CHR group reported lower social support and active coping than controls. In the CHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. These findings show that CHR individuals experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes.
Stowkowy et al.⁶²	Longitudinal 2 year follow up 764 CHR 280 HC 436 M/328 F 141 M/139 F	18.50 (4.23) 19.73 (4.67) Caucasian 57.3%/54.3%	Structured Interview for Prodromal Syndromes (SIPS) No comorbidities reported in HCs	Childhood Trauma and Abuse scale	CHR individuals reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis. Over the 2-year follow-up period, 86 participants transitioned to psychosis. More than half of CHR participants reported experiencing at least one type of bullying (53.3 versus 28.5 % for controls). Nearly half of the CHR participants reported experiencing at least one type of trauma (46.2 versus 11.4 % for controls), and more than half reported experiencing at least one type of discrimination (72.4 versus 57.5% for controls).
Trotman et al.²¹	Longitudinal 24 month follow up 314 CHR 162 HC 184 M/130 F 78 M/84 F	18.99 (4.18) 19.54 (4.77) Ethnicity not recorded.	Structured Interview for Prodromal Syndromes (SIPS) Scale of Prodromal Symptoms (SOPS) No comorbidities reported in HCs	Daily Stress Inventory (DSI) Life Events Scale (LES)	CHR individuals reported exposure to more Life Events (LE) compared to HCs. CHR individuals rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted. There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current Daily Hassles (DH) as more stressful. The results indicate that the “prodromal” phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors.
Vargas et al.¹²⁶	Cross-sectional 35 CHR 28 HC 17 M/18 F 6 M/22 F	20.63 (1.91) 20.04 (2.12) East Asian 8.6%/14.3% South Asian 5.7% Black 28.6%/14.3% Central/South American 8.6%/3.6% Caucasian 40%/39.3% Interracial 8.6%/10.7%	Structured Interview for Prodromal Syndromes (SIPS) No comorbidities reported in HCs	The Individual and Structural Exposure to Stress in Psychosis-risk states (ISESP) scale	Significant group differences were not observed for lifetime cumulative events, though CHR trended toward endorsing more events and greater stress severity. For stress severity across development, there were trending group differences for the 11–13 age range, and significant group differences for the 14–18 age range; notably, comparisons for earlier time points did not approach statistical significance. Associations between negative symptoms and cumulative severity of exposure were observed. These results suggest exploring exposure to cumulative environmental risk factors/stressors and stress severity across developmental periods and may inform predictive models and diathesis-stress psychosis-risk conceptualizations.
De Vylder et al.¹²⁹	Cross-sectional and Longitudinal 4 year follow up 65 CHR 24 HC 50 M/15 F 14 M/10 F	19.5 (3.7) 20.4 (3.4) Caucasian 46.2%/66.7% African American 29.2%/20.8% Asian American 6.2%/4.2% More than one race 18.5%/8.3% Hispanic 33.9%/29.2%	Structured Interview for Prodromal Syndromes (SIPS) Scale of Prodromal Symptoms (SOPS) CHR individuals: 14% receiving antipsychotics 19% receiving antidepressants	Coddington’s Life Events Record The modified global assessment of function (GAF-m)	CHR individuals demonstrated impaired stress tolerance, which was associated over time with positive and negative symptoms, in addition to depression, anxiety, and poor function. By contrast, life events were comparable in CHR and HCs, and bore no association with symptoms. In this treated cohort, there was a trajectory of improvement in stress tolerance, symptoms and function over time. Impaired stress tolerance was associated with a wide range of “prodromal” symptoms, consistent with it being a core feature of the psychosis-risk state. Self-reported life events were not relevant as a correlate of clinical status. As in other treated CHR cohorts, most patients improved over time across symptom domains.

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 and clinical implications

Addington et al.¹¹⁶

Cross-sectional

360 CHR

180 HC

210 M/150 F

100 M/80 F

18.98 (SD = 4.18)

19.54 (SD = 4.78)

Caucasian

55%/58.9%

Structured Interview for Prodromal Symptoms (SIPS)

No comorbidities reported

Calgary Depression Scale (CDS)

Brief Core Schema Scale (BCSS)

Social Interaction Anxiety Scale (SIAS)

Social Anxiety Scale (SAS)

Perceived Discrimination Scale (PDS)

Alcohol and Drug Use Scale

Global Assessment of Functioning Scale: Social and Role (GAF)

CHR participants experienced significantly more types of trauma

(z = −8.68, P < 0.05) and bullying (z = −4.89, P < 0.05) compared to controls. CHR females reported significantly more trauma than CHR males.

Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self.

These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms.

Bentley et al.³⁷

Cross-sectional

36 CHR

60 HC

(Help-seeking)

10 M/26 F

23 M/37 F

15.17 (2.44)

15.69 (3.18)

African American

55%/49%

Caucasian

30%/34%

Multiracial or other

15%/17%

Structured Interview for Prodromal Symptoms (SIPS)

APS: 78%

GRDS: 14%

BIPS: 8%

Mood disorder: 45%/55%

Anxiety Disorder: 12%/11%

PTSD:

15%/11%

AD/HD:

15%/10%

Behavior Assessment System for Children, Second Edition (BASC-2)

For CHR participants, parent–child relationships had a significant negative effect on social stress (b = −0.73,

t[92] = − 3.77, P < 0.001, f2 = 0.15); no significant relation was evident for the help-seeking control participants (b = −0.15, t[92] = −0.94, P = 0.35, f2 = 0.01).

These findings suggest that a positive parent–child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent–child relationships might be relevant for adolescents and young adults at clinical high risk for psychosis.

Carol¹²⁷

Longitudinal

57 CHR

66 HC

34 M/23 F

30 M/36 F

19.04 (1.63)

18.42 (2.46)

Hispanic

11/17

Asian

3/7

Black

1/2

Caucasian

40/38

Interracial

2/2

Structured Interview for Prodromal Symptoms (SIPS)

Mood disorders:

30%

Anxiety Disorders: 33%

PTSD: 7%

ADHD: 12%

No comorbidities reported in HCs

Daily Stress Inventory (DSI)

CHR individuals reported significantly higher frequency of stressful events [t(117) = 3.01, P = 0.003] and significantly higher levels of overall distress [t(117) = 4.47, P < 0.001] compared to HCs.

CHR group showed significantly more positive [t(63) = 17.62, P < 0.001] and negative [t(58.19) = 11.08, P < 0.001] symptoms compared to HCs.

CHR group showed significantly elevated resting cortisol levels compared with matched HC adolescents when controlling for age, [F(1,100) = 2.99,

P = 0.044].

De Vos et al.¹²⁸

Longitudinal

12 month follow up

81 CHR

32 M/49 F

18 (3.3)

Ethnicity not recorded.

Comprehensive Assessment of At-Risk Mental State (CAARMS)

APS: 82.7%

GRDS: 7.4%

BIPS: 0%

Major Depressive Disorder: 64.2%

Anxiety Disorder: 42%

Dysthymic Disorder: 3.7%

Eating Disorder: 1.2%

Substance Use Disorder: 16%

Other diagnoses: 2.5%

Schizotypal Personality Disorder: 1.2%

Borderline Personality Disorder: 6.2%

Childhood Trauma Questionnaire (CTQ)

Brief Psychiatric Rating Scale (BPRS)

Scale for the Assessment of Negative Symptoms

(SANS)

Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental

Disorders-IV (DSM-IV) for Axis I & Axis II disorders (SCID-I, SCID-II)

Social and Occupational Functioning Scale (SOFAS)

Global Functioning Scale (GFS) Social & Role

The majority of CHR sample (82.7%) experienced at least one form of early trauma.

No significant correlations emerged between the CTQ total score and baseline levels of APS severity, distress associated with APS and functional outcomes. However, there was a significant positive correlation (r = 0.23, P = 0.044) between the CTQ total score and the CAARMS suicidality and self-harm baseline score.

The high prevalence of Childhood Trauma (CT) in CHR individuals and its association with suicidality and self-harm underlines the importance of inquiring about CT during clinical assessments.

Freitas et al.¹³⁰

Longitudinal

87 CHR

115 HC

29 M/58 F

50 M/65 F

24.78 (4.11)

25.09 (4.31)

Ethnicity not recorded.

The Prodromal Questionnaire (PQ)

Structured Interview for Prodromal Syndromes (SIPS)

Scale of Prodromal Symptoms

(SOPS)

No comorbidities reported in HCs

Childhood Trauma Questionnaire (CTQ)

Compared to HCs, CHR individuals scored significantly higher on:

physical abuse

(mean rank: controls = 93.81, CHR = 111.67; P = 0.027),

sexual abuse

(mean rank: controls = 94.67, CHR = 110.52; P = 0.007) and emotional abuse (mean rank: controls = 85.93, CHR = 122.09; P < 0.001).

No differences were found for physical and emotional neglect.

Childhood trauma such as emotional, physical, and sexual abuse, and physical and emotional neglect appear to be associated with CHR status.

In CHR individuals, physical abuse correlated with perceptual abnormalities, and physical neglect correlated with disorganized speech/thought, whereas physical and emotional neglect negatively correlated with grandiosity symptoms.

Huang et al.¹¹⁹

Cross-sectional

56 FEP

83 CHR

61 HC

37 M/19 F

44 M/39 F

32 M/29 F

26.5 (8.5)

28.8 (8.4)

31.3 (7.9)

55 Han Chinese/

82 Han Chinese/

60 Han Chinese

Structured Interview for Prodromal Syndromes (SIPS)

No comorbidities reported in HCs

Positive and negative syndrome scale

(PANSS)

Global Assessment Function (GAF)

Montgomery–Asberg

Depression Rating Scale (MADRS)

Childhood Trauma Questionnaire-Short Form (CTQ-SF)

Life Events Scale (LES)

Perceived Social Support Scale (PSSS)

In terms of the CTQ Total, FEP and CHR groups scored significantly higher than HCs (P = 0.002 and P < 0.001, respectively).

CHR individuals scored significantly higher on emotional neglect and physical neglect compared than HCs (P < 0.001 and P = 0.009, respectively).

CHR group experienced a significantly more total life events compared with HCs (P = 0.004).

FEP and CHR groups scored lower on PSSS Total than HCs (P = 0.03 and P = 0.01, respectively). In Family Support (FS) sub-domain, CHR possessed poorer family support than HCs (P = 0.03).

In the CHR group, CTQ Total showed positive correlation with SIPS Total (P < 0.05), while LES Total showed a positive correlation with SIPS Positive

(P < 0.05), SIPS Total (P < 0.01) and GAF (P < 0.05).

CHR individuals had more childhood trauma, more recent life events and less social support than HCs.

There was no significant difference on childhood trauma, life events and social support between CHR and FEP groups. Emotional and physical neglect were more frequently prevalent in CHR group than HCs.

Kline et al.³⁸

Longitudinal

60 CHR

65 HC

Total sample

(n = 125)

48 M/77 F

15.3 (2.58)

16.46 (3.13)

Total sample (n = 125)

African American 46.4%

Caucasian 34.4%

Native American 1.6%

Asian 0.8%

Multiracial/other 14.4 %

Structured Interview for Prodromal Syndromes (SIPS)

Mood Disorder: 61%/49.2%

Anxiety Disorder: 50.8%/35.4%,

PTSD: 31.7%/24.6%,

ADHD: 45.8%/46.2%,

Substance use disorder: 8.5%/7.7%,

other disorder: 3.4% /18.5%

Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (KSADS-PL)

The proportion of individuals reporting at least one event was higher in CHR (85%) relative to HCs (64.5%; χ²[1] = 6.75), P = 0.01).

The CHR group endorsed significantly more lifetime trauma exposures than the HC group (mean exposures for CHR = 2.02, SD = 1.63; mean exposures for HC = 1.45, SD = 1.52; t[12] = −1.98, P = 0.05)

For CHR individuals non-violent traumas were significantly associated with grandiose thinking (P < 0.05).

Kraan et al.¹³²

Longitudinal

4 Year follow up

113 CHR

50 M/63 F

23.5 (5.4)

Dutch 54%

Minority 46%

Comprehensive Assessment of At-Risk Mental State (CAARMS)

Childhood Trauma Questionnaire-Short Form (CTQ-SF)

Beck Depression Inventory-II (BDI-II)

Social Interaction Anxiety Scale

(SIAS)

Social and Occupational Functioning Scale (SOFAS)

The percentage of CHR individuals reporting childhood adversity was as follows: emotional abuse (46.7%), physical abuse (20.9%), sexual abuse (24.8%), emotional neglect (66.7%) and physical neglect (41.9%).

No significant association was found between childhood adversity subscales and the severity of positive symptoms at baseline and at 4-year follow-up.

No significant association was found between total childhood adversity scores and any of the childhood adversity subscales (emotional abuse, physical abuse, sexual abuse, emotional and physical neglect) and transition to psychosis at 4-year follow-up.

Kraan et al.¹³³

Longitudinal

24 month follow up

259 CHR

48 HC

139 M/120 F

26 M/22 F

22.7 (4.5)

23.98 (4.33)

Ethnicity not reported

Comprehensive Assessment of At-Risk Mental State (CAARMS)

APS: 78.7%

GRDS: 8.4%

BLIPS: 5.7%

APS & Genetic risk: 7.2%

No comorbidities reported in HCs

Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) for Axis I & Axis II disorders (SCID-I)

Childhood Trauma Questionnaire (CTQ)

Cannabis Experience Questionnaire (CEQ)

The number of CHR individuals that transitioned to psychosis was 31 (11.9%): 11 transitioned within the first 6 months, 13 at 12 months, and 7 at 24 months).

54% of the CHR individuals had experienced at least one form of childhood maltreatment compared to 17.4% of HCs (P < 0.001). This difference was apparent for each form of child maltreatment:

emotional abuse; cases = 62.5%,

controls = 27.1% (P < 0.001);

emotional neglect; cases = 76.4%, controls = 33.3% (P < 0.001);

physical abuse; cases = 24.3%,

controls = 8.3% (P = 0.014);

None of the univariate odds ratios for the association between each individual subtype of maltreatment and transition to psychosis was statistically significant. In addition, total child maltreatment did not increase the risk for transition to psychosis (OR = 2.46, 95% CI = 0.95 to 6.41, P = 0.065).

Examination of the adjusted odds ratios showed that, after controlling for the other subtypes, a history of emotional abuse significantly contributed to transition (OR = 3.78, 95% CI = 1.17–12.39, P = 0.027)

Loewy et al.¹²⁰

Cross-sectional

103 CHR

49 M/54 F

18 (4.2)

Caucasian 52%

Asian 18% Black/African-American 5%

Native American/Other Pacific islander 1%

Multiracial 16%

Unknown or unreported 7%

Structured Interview for Prodromal Syndromes (SIPS)

Scale for Assessment of Psychosis Risk Symptoms (SOPS)

Traumatic Events Screening Inventory for

Children (TESI-C)

Global Functioning: Role and Social Scales,

61% of CHR individuals reported lifetime exposure to traumatic events

CHR individuals with a trauma history had significantly more severe perceptual disturbances and general/affective symptoms on the SOPS, as well as lower functioning ratings than CHRs without trauma.

The number of traumatic events was significantly correlated with more severe perceptual disturbances, general/affective symptoms and lower functioning ratings.

The number of interpersonal traumatic events was significantly correlated with more severe suspiciousness, perceptual abnormalities, general/affective symptoms and lower functioning scores.

Magaud et al.¹²¹

Cross-sectional

50 CHR

25 M/25 F

16.7 (3.3)

Structured Interview for Prodromal Syndromes (SIPS)

Childhood Trauma Questionnaire (CTQ) with added questions on cyberbullying

38% of CHR participants reported having experienced cyberbullying. The most frequent types reported were bullying via text messages, Facebook and instant messages (‘chat’). Bullying via texts and Facebook was associated with a past history of sexual abuse and physical neglect; Facebook with a past history of emotional neglect; and texts were more frequent in those who reported past physical abuse.

Pruessner et al.¹⁰

Cross-sectional

32 FEP

30 CHR

30 HC

16 M/14 F

15 M/15 F

20.33 (3.24)

22.47 (3.79)

80% Caucasian in both groups.

Comprehensive Assessment of At-Risk Mental State (CAARMS)

CHR comorbidities

Depression: 50% Dysthymia: 1%

Anxiety: 37% Obsessive-compulsive disorder: 1%

PTSD: 1%

No comorbidities reported in HCs

Trier Inventory for the Assessment

of Chronic Stress (TICS)

Brief Psychiatric Rating Scale (BPRS)

Global Assessment Function (GAF)

Self-esteem Rating Scale (SERS)

Brief COPE scale

Multidimensional Scale of Perceived Social Support (MSPSS)

CHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the CHR group reported lower social support and active coping than controls.

In the CHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship

was not moderated by self-esteem.

These findings show that CHR individuals experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes.

Stowkowy et al.⁶²

Longitudinal

2 year follow up

764 CHR

280 HC

436 M/328 F

141 M/139 F

18.50 (4.23)

19.73 (4.67)

Caucasian

57.3%/54.3%

Structured Interview for Prodromal Syndromes (SIPS)

No comorbidities reported in HCs

Childhood Trauma and Abuse scale

CHR individuals reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis.

Over the 2-year follow-up period, 86 participants transitioned to psychosis.

More than half of CHR participants reported experiencing at least one type of bullying (53.3 versus 28.5 % for controls). Nearly half of the CHR participants reported experiencing at least one type of trauma (46.2 versus 11.4 % for controls), and more than half reported experiencing at least one type of discrimination (72.4 versus 57.5% for controls).

Trotman et al.²¹

Longitudinal

24 month follow up

314 CHR

162 HC

184 M/130 F

78 M/84 F

18.99 (4.18)

19.54 (4.77)

Ethnicity not recorded.

Structured Interview for Prodromal Syndromes (SIPS)

Scale of Prodromal Symptoms

(SOPS)

No comorbidities reported in HCs

Daily Stress Inventory (DSI)

Life Events Scale (LES)

CHR individuals reported exposure to more Life Events (LE) compared to HCs. CHR individuals rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted.

There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current

Daily Hassles (DH) as more stressful. The results indicate that the “prodromal” phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors.

Vargas et al.¹²⁶

Cross-sectional

35 CHR

28 HC

17 M/18 F

6 M/22 F

20.63 (1.91)

20.04 (2.12)

East Asian

8.6%/14.3%

South Asian

5.7%

Black

28.6%/14.3%

Central/South American

8.6%/3.6%

Caucasian

40%/39.3%

Interracial

8.6%/10.7%

Structured Interview for Prodromal Syndromes (SIPS)

No comorbidities reported in HCs

The Individual and Structural Exposure

to Stress in Psychosis-risk states (ISESP) scale

Significant group differences were not observed for lifetime cumulative events, though CHR trended toward endorsing more events and greater stress severity.

For stress severity across development, there were trending group differences for the 11–13 age range, and significant group differences for the 14–18 age range; notably, comparisons for earlier time points did not approach statistical significance.

Associations between negative symptoms and cumulative severity of exposure were observed.

These results suggest exploring exposure to cumulative environmental risk factors/stressors and stress severity across developmental periods and may inform predictive models and diathesis-stress psychosis-risk conceptualizations.

De Vylder et al.¹²⁹

Cross-sectional and Longitudinal

4 year follow up

65 CHR

24 HC

50 M/15 F

14 M/10 F

19.5 (3.7)

20.4 (3.4)

Caucasian

46.2%/66.7%

African American

29.2%/20.8%

Asian American

6.2%/4.2%

More than one race

18.5%/8.3%

Hispanic

33.9%/29.2%

Structured Interview for Prodromal Syndromes (SIPS)

Scale of Prodromal Symptoms

(SOPS)

CHR individuals:

14% receiving antipsychotics

19% receiving antidepressants

Coddington’s Life Events Record

The modified global assessment of function (GAF-m)

CHR individuals demonstrated impaired stress tolerance, which was associated over time with positive and negative symptoms, in addition to depression, anxiety, and poor function. By contrast, life events were comparable in CHR and HCs, and bore no association with symptoms. In this treated cohort, there was a trajectory of improvement in stress tolerance, symptoms and function over time.

Impaired stress tolerance was associated with a wide range of “prodromal” symptoms, consistent with it being a core feature of the psychosis-risk state. Self-reported life events were not relevant as a correlate of clinical status. As in other treated CHR cohorts, most patients improved over time across symptom domains.

APS Attenuated Positive Syndrome, BIPS Brief intermittent psychotic symptoms syndrome, BLIPS brief limited intermitted psychotic symptoms, CHR Clinical High Risk, FEP First Episode Psychosis, GRDS Genetic Risk & Deterioration Syndrome.