Autism spectrum disorder and personality disorders: Comorbidity and differential diagnosis

Table 1 Description of the studies included in the systematic review

Ref.	Setting	Aim	Statistical methods	Limitations
Soderstrom et al[50], 2002	NeuropsychiatricClinic in Sweden	To study the personality characteristics of adults with AS	One sample t-test	Small sample size
Anckarsäter et al[47], 2006	Neuropsychiatric Clinic in Sweden	To describe PD in relations to ADHD and ASD symptoms	One sample t - test	Non-specific symptoms may be overselected
Ketelaars et al[43], 2008	Center of Expertise for Autism in Netherlands	To explore difference between patients with mild ASD and patients without ASD in term of AQ scores and psychiatric comorbidity	Χ2 test	Small sample size
Rydén and Bejerot[40], 2008	Psychiatric setting (tertiary unit) in Sweden	To characterize psychiatric patients with ASD in regard to demographical factors, psychiatric comorbidity and personality traits and compare the ASD group with a psychiatric control group; to compare differences of personality traits between females and males in the ASD group.	Fisher exact test; t-test; Kruskal-Wallis test	Not ADOS/ADI-R for assessing ASD; A naturalistic study
Hofvander et al[14], 2009	Neuropsychiatric Hospital in France NeuropsychiatricClinic in Sweden	To describe the clinical presentation and psychosocial outcome of a group of normal intelligence adults with ASD	Χ2 test	Lack of comparison group; Two studies sites; Prevalence of comorbid psychiatric conditions may be overestimated
Sizoo et al[49], 2009	Two diagnostic centers specialized for adult patients with developmental disorders in Netherlands	To test whether adults with ASD or ADHD have distinct personality profiles, to assess how personality profiles in these groups differed by SUD status	One sample t-test	The clinically based diagnostic procedures; The absence of a psychiatric control group; All participants were diagnosed in adulthood
Geurts and Jansen[44], 2011	Tertiary psychiatric unit from diagnosing ASD in Netherlands	To draw the pathway to a diagnosis for adults referred to ASD assessment	Mann-Whitney U tests; Kruskal-Wallis tests; Χ2 test	Retrospective chart study; Not standardized clinical interviews for assessing axis I and axis II diagnosis
Kanai et al[59], 2011	University Hospital in Japan	To examine the clinical characteristics of adults with AS	Spearman’s rank correlation coefficient	Small sample size
Kanai et al[67], 2011	University Hospital in Japan	To examine the clinical characteristics of adults with AS	Mann-Whitney U test	Small sample size
Lugnegård et al[38], 2012	Neuropsychiatric clinics in Sweden	To explore the presence of PD in young adults with AS	Χ2 test	Small sample size
Schriber et al[55], 2014	Local recruitment by physicians, psychologists, speech and language pathologists, occupational therapists, advocacy groups, regional centers, ASD support groups in United States	To compare self-reports of Big Five personality traits in adults with ASD to those of typically developing adults.	Independent sample t-test	Small sample size
Hesselmark et al[62], 2015	Tertiary psychiatric unit for diagnosing ASD; a community based facility for ASD; a website for ASD	To test validity and reliability of self-report data using the NEO-PI-R in adults with ASD	Independent sample t-test	Small sample size
Strunz et al[26], 2015	Department of Psychiatry at a University Hospital in Germany	To identify personality traits in adults with ASD and to differentiate them from patients with NPD, BPD and NCC	MANOVA	Selection bias (BPD and NPD were inpatients, while ASD were outpatients)
Helles et al[52], 2016	Neuropsychiatric Centre in Sweden	To examine temperament and character in males who were diagnosed with AS in childhood and followed prospectively over almost two decades	t-test; Kruskal-Wallis H testDunn’s post hoc test	Only men with AS
Schwartzman et al[56], 2016	On line recruitment United States	To assess and compare personality traits of adults with and without elevated ASD traits using; the Five Factor Model of personality	Independent sample t-test	Online administration of self-report questionnaires; Sample was not representative of adult population with ASD
Vuijk et al[51], 2018	Expertise Centre for Autism in Netherland	To investigated temperament and character dimensions of men with ASD by individual case matching to a comparison group.	t-test	Only men with ASD
Ozonoff et al[65], 2005	University Child and Adolescent specialized clinic in United States	To explore personality and psychopathology in adult with ASD	Independent sample t-test	Small sample size
López-Pérez et al[95], 2017	Four different mental health institutions in Spain	To examine use of different interpersonal ER strategies in BPD and AS compared to normative control participants	ANOVA	Self-reports of interpersonal ER; ToM was not assessed
Dudas et al[92], 2017	CARD, online responders to a website	To compare ASC, BPD, and comorbid patients in terms of autistic traits, empathy, and systemizing	ANOVA	Diagnosis was based on self-report of patients
Murphy[100], 2006	High security psychiatric care in UK	To compare the ToM performance of three forensic patient groups (AS, Schizophrenia and PD patients)	Kruskal-Wallis H test	No control for the potential influence of medication on cognitive functioning
Stanfield et al[87], 2017	Clinical and support services in Scotland; Nonpsychotic people who had previously participated in the EHRS of schizophrenia	To compare Social Cognition in ASD and SPD using functional magnetic resonance imaging (fMRI).	Kruskal- Wallis tests	Small sample size
Booules-Katri et al[84], 2019	Patients and relatives of schizophrenia patients attending psychiatric service at a hospital in Spain; Public advertisements	To compare the ToM performance of a group of HFA and SSPD with a matched HC group	t-test	SSPD sample consisted of non-clinical individuals

ADHD: Attention deficit hyperactivity disorder; ADI-R: Autism diagnostic interview - revised; ADOS: Autism diagnostic observation schedule-generic; AQ: Autism quotient; AS: Asperger Syndrome; ASC: Autism spectrum condition; ASD: Autism spectrum disorder; BPD: Borderline personality disorder; Er: emotion regulation; HC: Health control; HFA: High-functioning autism; NCC: Non-clinical controls; NEO-PI-R: NEO personality inventory revised; NPD: Narcissistic personality disorder; PD: Personality disorder; SPD: Schizotypal personality disorder; SSPD: Schizotypal-schizoid personality disorder; SUD: Substance use disorder; ToM: Theory of mind.

Table 2 Summary of included studies exploring comorbid personality disorders diagnosis (according to DSM-IV) in autism spectrum disorder patients

Ref.	Participants	Measures	PD assessment instrument	PD Prevalence (at least one PD)
Ketelaars et al[43], 2008	n = 15 (4 AS, 10 PDD-NOS, 1 HFA)	AQ, SCAN-2.1	IPDE	> 50%
Rydén and Bejerot[40], 2008	n = 84 (5 autistic disorder, 51 AS, 28 PDD-NOS); 37% comorbid ADHD	SCID-I, WAIS III, ASSQ, ASDI, ASRS, MADRS,Y-BOCS, GAF, CGI-S, WRAADDS	SCID-II screen; SPP	> 40%
Hofvander et al[14], 2009	n = 117 (5 autistic disorder, 62 AS, 50 PDD-NOS)	WAIS-R or WAIS-IIISCID-I, ASDI	SCID-II	62%
Lugnegård et al[38], 2012	n = 54 (AS)	WAIS-III, DISCOS-11AQ	SCID-II or a structured DSM-IV-based clinical interview	48%
Strunz et al[26], 2015	n = 59 (49 AS, 10 HFA)	ADOS, ADI-R, MINI, SCID-I, DAPP-BQ,NEO-PI-R	SCID-II	45%
Geurts and Jansen[44], 2011	n = 105 (27 autistic disorder, 28 AS, 50 PDD- NOS); 34% of sample with intellectual disability	Former DSM-IV Axis I diagnosis reported	Former DSM-IV Axis II diagnosis reported	15%
Anckarsäter et al[47], 2006	n = 174 subjects with childhood onset neuropsychiatric disorder (47 ASD, 27 ASD+ADHD, 81 ADHD, 19 other diagnosis)	SCID-I, ASDI, Y-BOCS; ASHFAQ, TCI	SCID- II	75%

ADHD: Attention deficit hyperactivity disorder; ADI-R: Autism Diagnostic interview-revised; ADOS: Autism diagnostic observation schedule-generic; AS: Asperger syndrome; ASD: Autism spectrum disorder; ASDI: Asperger syndrome diagnostic interview; ASHFAQ: Asperger syndrome and high-functioning autism screening questionnaire; ASRS: Adult ADHD self-report scale; ASSQ: Autism spectrum disorder in adults screening questionnaire; ASDI: Asperger syndrome diagnostic interview; AQ: Autism spectrum quotient; CGI-S: Clinical global impression severity of illness; DAPP-BQ: Dimensional assessment of personality pathology; DISCOS-11: Diagnostic interview for social an communication disorder; GAF: Global assessment of functioning; HFA: High-functioning autism; IPDE: International personality disorder examination; MADRS: Montgomery asberg depression rating scale; MINI: Mini international neuropsychiatric interview; NEO-PI-R: Neo personality inventory revised; PDD-NOS: Pervasive developmental disorder not otherwise specified; SCAN-2.1: Schedules for clinical assessment in neuropsychiatry; SCID-I: Structured clinical interview for DSM-IV axis I disorders; SCID-II: Structured clinical interview for DSM-IV personality disorders; SPP: Swedish universities scales of personality; TCI: Temperament and character inventory; Y-BOCS: Yale -brown obsessive compulsive scale; WAIS-R: Wechsler adult intelligence scale-revised; WAIS-III: Wechsler adult intelligence scale-III; WRAADDS: Wender-reimherr adult attention deficit disorder scale.

Table 3 Specific personality disorders (Structured clinical interview for DSM-IV axis II diagnosis) prevalence in autism spectrum disorder samples

PD	Lugnegård et al[38], 2012	Hofvander et al[14], 2009	Anckarsäter et al[47], 2006	Strunz et al[26], 2015
Paranoid	0%	19%	25.5 % ASD; 25.9% ASD + ADHD	2%
Schizoid	26%	13%	31.9% ASD; 22.2% ASD + ADHD	36%
Schizotypal	2%	21%	23.4% ASD; 11.1% ASD + ADHD	0%
Antisocial	0%	3%	0% ASD; 18.5% ASD + ADHD	0%
Histrionic	0%	0%	0%	0%
Borderline	0%	9%	10.6% ASD; 14.8% ASD + ADHD	0%
Narcissistic	0%	3%	6.4%ASD; 3.7% ASD + ADHD	0%
Avoidant	13%	25%	34% ASD; 11.1% ASD + ADHD	2%
Obsessive-compulsive	19%	32%	42.6% ASD; 29.6% ASD + ADHD	17%
Dependent	0%	5%	8.5% ASD; 22.2% ASD + ADHD	0%

PD: Personality disorders; ASD: Autism spectrum disorder; ADHD: Attention deficit hyperactivity disorder.

Table 4 Summary of studies using temperament character inventory to evaluate personality in adults with autism spectrum disorder

Ref.	Participants	Comparison group	Measures	Personality measures	Results
Anckarsäter et al[47], 2006	n = 113 (6 autistic disorder, 46 AS, 66 Atypical Autism); 47ASD+ADHD 66 ASD	Age and sex matched group	SCID-I; ASDI; Y-BOCS; ASHFAQ; TCI	TCI; SCID-II	Lower NS, RD, SD, C; Higher HA; Cluster A and Cluster C PD were common
Soderstrom et al[50], 2002	n = 31 AS	Age and sex matched group	WAIS-III	TCI	Higher HA ST; Lower NS, RD, SD, C
Sizoo et al[49], 2009	n = 75 (53 without SUD, 8 with past SUD, 14 with current SUD)	n = 657 NC	ADI-R; ADOS; DSM-IV criteria checklists; WAIS-III	VTCI	Higher HA, ST; Lower RD, SD, C; Lower NS and RD for ASD without SUD; Higher P for subgroups with current or past SUD
Vuijk et al[51], 2018	n = 66 (15 ASD, 25 AS, 26 PDD-NOS)	Matched comparison group (age, education, marital status)		TCI	Higher HA, lower NS, RD, SD, C
Helles et al[52], 2016	n = 40 AS	Within comparison group (no longer ASD/ASD pure/ASD plus)	GAFWAIS-IIIASDI; BDI; ASRS	TCI	Higher RD in no longer ASD; Higher HA, lower NS in ASD pure; Higher HA, lower C, SD in ASD plus

C: Cooperativeness; HA: Harm avoidance; NC: Neurotypical controls; NS: Novelty Seeking; P: Persistence; RD: Reward dependence; SD: Self-directedness; ST: Self-transcendence; SUD: Substance use disorder; SUD: No history of SUD; VTCI: Short version of temperament character inventory.

Table 5 Summary of studies measuring big five personality traits in adults with autism spectrum disorder

Ref.	Partecipants	Comparison group	Measures	Personality trait measures	Results
Schwartzman et al[56], 2016	n = 364 adults with elevated ASD traits	n = 464 adults with lower ASD traits	RAADS-R	IPIP-NEO-120	Neuroticism was positively correlated with ASD symptomatology; Extraversion, openness to experience, conscientiousness, and agreeableness were negatively correlated with ASD; About 70% of the variance in RAADS-R scores accounted for by the IPIP-NEO-120 facets. A great variability in personality traits emerged in the elevated ASD traits group with four distinct clusters of FFM personality types
Schriber et al[55], 2014	n = 37 ASD (29% HFA, 57% AS, 14% PDD-NOS)	n = 42 NC	WAIS; ADOS G	BFI	Higher Neuroticism Lower Openness to experience, Conscientiousness, Extraversion, Agreeableness
Kanai et al[67], 2011	n = 64 AS	n = 65 NC	AQ; HADS; L-SAS	NEO-FFI	AQ, HADS, and L-SAS were significantly higher in AS than in control. Higher Neuroticism, Lower Extraversion, Agreeableness, Conscientiousness AQ correlated with the subscale scores of HADS and NEO-FFI in AS
Strunz et al[26], 2015	n = 59 ASD(83% AS, 17% HFA)	n = 62 NPD,80 BPD, 106 NC	SCID-I/MINI	NEO-PI-R; DAPP BQ; SCID-II	On the NEO-PI-R: Conscientiousness: NCC = ASD > BPD and NPD Neuroticism: NCC < ASD = NPD < BPD; Extraversion: ASD < BPD, NPD, NCCOpenness for experience: ASD < NCC, BPD, NPDAgreeableness: ASD = BPD and NPD > NCCOn the DAPP-BQ: Inhibitedness: ASD = BPD > NCC and NPD Dissocial Behaviour: NCC = ASD < BPD and NPD; Emotional dysregulation: NCC < ASD = NPD < BPD Compulsivity: ASD > BPD, NPD, NCC
Hesselmark et al[62], 2015	n = 48 ASD	n = 53 NC	MINI	NEOPI-R	Satisfactory internal consistency of the NEOPI-R. Neuroticism correlated with psychiatric comorbidity in ASD group

BFI: Big five inventory; L-SAS: Liebowitz social anxiety scale; HADS: Hospital anxiety and depression scale; IPIP-NEO-120: International personality item pool representation of the NEO-PI-R; NEO-PI-R: Neo personality inventory revised.

Table 6 Summary of studies using different assessment measures to evaluate personality in adults with autism spectrum disorder

Ref.	Participants	Comparison group	Measures	Personality measures	Results
Ozonoff et al[65], 2005	n = 20 HFA	24 NC (age, intelligence and gender matched college students)	WAIS-R	MMPI-2	Higher Depression, Social Introversion, Social Discomfort, Repression and PSY-5 scale Introversion
Kanai et al[59], 2011	n = 55 AS	57 NC	WAIS-R	SPQEPQ	SPQ: AS>NC; SPQ subscale scores (unusual perceptual experiences, odd behaviour, and suspiciousness) were correlated with total scores of the AQ in the AS group; Higher ‘Neuroticism’ and ‘Psychoticism’; Lower ‘Extraversion’ and ‘Lie’

EPQ: Eysenck personality questionnaire; MMPI-2: Minnesota multiphasic personality inventory; SPQ: Schizotypal personality questionnaire.

Table 7 Studies comparing autism spectrum disorder patients with personality disorders patients on different assessment measures

Ref.	Participants	Comparison group	Measures	Results
Strunz et al[26], 2015	59 ASD (83% AS, 17% HFA)	62 NPD, 80 BPD, 106 NC	NEO-PI-R; DAPP BQ; SCID-I/MINI; SCID-II	On the NEO-PI-R: Conscientiousness: NCC = ASD > BPD and NPD; Neuroticism: NCC < ASD = NPD < BPD; Extraversion: ASD < BPD, NPD, NCC; Openness for experience: ASD < NCC, BPD, NPD; Agreeableness: ASD = BPD and NPD > NCC; on the DAPP-BQ; Inhibitedness: ASD = BPD > NCC and NPD; Dissocial Behaviour: NCC = ASD < BPD and NPD; Emotional dysregulation: NCC < ASD = NPD < BPD; Compulsivity: ASD > BPD, NPD, NCC
López-Pérez et al[95], 2017	30 AS	30 BPD60 matched NC	SCID-ISCID-IIEmotion regulation of others and self (two scales: extrinsic affect improvement, extrinsic affect worsening)Interpersonal emotion management	Affect improvement: BPD = AS < NNC; Affect worsening: BPD = AS = NNC; Affect improvement > affect worsening in BPD e NCC; Affect improvement = affect worsening in ASD; Adaptive interpersonal strategies (attention deployment, cognitive change) ASD < BPD and NNC; Maladaptive interpersonal strategies (expressive suppression) ASD > BPD and control.
Dudas et al[92], 2017	624 ASD	23 BPD; 16 ASD+ BPD; 2081 NC	AQ; EQ; SQR; SCID-II	AQ: NC < BPD = ASC < ASC+BPD; EQ:NC = BPD > ASC = ASC+BPD; SQR NC < BPD = ASC = ASC+BPD
Murphy[100]2006	39 AS; Male forensic patients detained in high security psychiatric care	39 PD (antisocial and/or borderline)39 SC with positive symptoms detained in high security psychiatric care	WAIS-R; ToM measures	IQ PD = AS > SC; AS and SC performed worse on two ToM measures (the Revised Eyes Task and the second order mental representation stories)
Stanfield et al[87], 2017	28 ASD	21 SPD; 10 CM; 33 NC	ADOS-G; SCID-II; PANSS; WAISsocial judgment taskEkmann 60 facies task; fRMI task of social judgement	SPD = CM = ASD < controls on social judgment task and Ekman 60-Faces Test; on positive symptoms: ASD < SPD = CM; on negative symptoms ASD = SPD > CM; fRMI: hyperactivation in SPD and CM group compared to ASD was found in the amygdala and the cerebellum
Booules-Katri et al[84], 2019	35 HFA	SSPD (n = 30) and a NC (n = 36)	O-LIFE questionnaire; SCID-I; SCID-II; ADI-R; ADOS; WAIS-III; ToM test	HFA showed greater impairment and no dissociation between affective and cognitive ToM components; SSPD scored significantly lower on cognitive than affective ToM test

BPD: Borderline personality disorder; CM: Comorbid group (SPD+ASD); EQ: Empathy quotient; NPD: Narcissistic personality disorder; O-LIFE questionnaire: Short version of the Oxford-Liverpool Inventory of Feelings and Experiences questionnaire; PANSS: Positive and negative syndrome scale; NC: Non clinical control group; SQR: Systemizing quotient revised; SSPD: Schizotypal-schizoid personality disorder; ToM: Theory of mind.