Blood-brain barrier damage as a risk factor for corticosteroid-induced psychiatric disorders in systemic lupus erythematosus

To clarify the incidence of and risk factors for corticosteroid-induced psychiatric disorders (CIPDs) in patients with systemic lupus erythematosus (SLE), we conducted a prospective study of 161 consecutive episodes in 155 inpatients with a SLE flare who were treated with corticosteroids. A subgroup of these patients, those who experienced a total of 22 episodes with current overt central nervous system manifestations of SLE (CNS-SLE), were excluded from follow-up. Results of clinical, laboratory, and neurologic tests (including electroencephalography, magnetic resonance imaging of the brain, and cerebrospinal fluid [CSF] analysis), performed within a week before corticosteroid administration, were assessed with regard to development of CIPDs. Within 8 weeks of corticosteroid administration, a diagnosis of CIPD was made for 14 (10.1%) of 139 episodes in 135 patients with a non-CNS-SLE flare. Using multiple logistic regression analysis, we identified positive Q(albumin) (CSF/serum albumin ratio; an indicator of blood-brain barrier [BBB] damage) (odds ratio [OR], 33.3; 95% confidence interval [CI], 3.64-304; p=0.002) and low serum levels of complements (OR, 0.91; 95% CI, 0.83-1.00; p=0.047) as independent risk factors for CIPDs. Positive Q(albumin) was detected in 45% (5 of 11) of episodes in which CIPDs developed. Compared with episodes in which no psychiatric events occurred, a higher level of Q(albumin) was found in episodes in which CIPDs developed, and an even higher level was noted in episodes with active CNS-SLE (Jonckheere-Terpstra test, p<0.001). Although no causal links have been proven, the results from the present study raise the possibility that BBB damage may be associated with SLE- and corticosteroid-induced behavioral changes.     

Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies

OBJECTIVE: To estimate the prevalence of psychiatric disorders in patients with systemic lupus erythematosus (SLE) and explore their association with anti-ribosomal P (anti-P) antibodies. METHODS: Seventy-one consecutive female SLE patients without neurological manifestations were evaluated for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID). Anti-P antibodies were measured by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis. RESULTS: The mean age of subjects was 34.8 years (SD: 10.1 years), and the mean duration of SLE was 9.8 years (SD: 6.5 years). The 30-day prevalences of psychiatric disorders were: mood disorders 26.8%, anxiety disorders 46.5%, adjustment disorders 8.4%, alcohol abuse 1.4%, and somatoform disorder 1.4%. The lifetime prevalences of psychiatric disorders were: mood disorders 69%, anxiety disorders 52.1%, alcohol abuse 1.4%, and somatoform disorder 1.4%. Subjects with and without psychiatric manifestations did not differ regarding SLE clinical and laboratorial parameters including presence or absence of anti-P antibodies (23.1% vs. 20%, respectively, p=1.0), disease activity, as measured by the Systemic Lupus Erythematosus Disease activity Index (4.08+/-5.7 vs. 4.95+/-6.3 respectively, p=0.60) and cumulated damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (0.7+/-2.3 vs. 0.3+/-0.7 respectively, p=0.33). CONCLUSIONS: Mood and anxiety disorders are the most frequently observed psychiatric disorders in female SLE patients without concomitant neurological manifestations. These mild/moderate forms of psychiatric disorders are not associated with anti-P antibodies in SLE patients. Our findings reinforce the importance of systematic psychiatric evaluation for these patients in order to provide adequate and comprehensive care.     

Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most important manifestations of SLE, and includes a variety of clinical manifestations, classified by the American College of Rheumatology in 19 different neuropsychiatric syndromes. To date, more than 116 antibodies have been reported in SLE and at least 20 of them, including 11 brain-specific and 9 systemic antibodies, have been controversially associated with NPSLE. To systematically review the available evidence, to define the association between the above antibodies and NPSLE as a whole and with the 19 neuropsychiatric syndromes associated with SLE, by strictly applying the American College Rheumatology case definitions. Medline reports published between 1999 and 2013 investigating the association between antibodies and NPSLE were included. Whenever possible, associations between antibodies and both NPSLE as a whole and with the 19 syndromes were analysed. This systematic review is based on available data from more than 8,000 patients and controls from 42 studies analysing antibodies and NPSLE. Nineteen studies analysed the role of antiphospholipid antibodies (aPL), 11 focused on anti-ribosomal-P protein antibodies and 5 on anti-N-Methyl-d-Aspartate receptor antibodies. Two studies analysed, respectively, antibodies to aquaporin-4 and VH4-34 encoded antibodies. Given the multitude of clinical manifestations related to NPSLE, a single biomarker failed to be reliably associated with all neuropsychiatric events. Our findings provide evidence that aPL, mainly the lupus anticoagulant, and anti-ribosomal P antibodies are significantly associated with specific manifestations of neuropsychiatric disease attributed to SLE, namely, cerebrovascular events and psychosis, respectively.     

Case series: neuropsychiatric symptoms with pediatric systemic lupus erythematosus

OBJECTIVE: To describe the psychiatric presentation, serologic findings, and neuroimaging patterns in children and adolescents with central nervous system involvement with systemic lupus erythematosus (CNS-SLE). METHOD: Pediatric patients with psychiatric symptoms who fulfilled the 1997 revised diagnostic American College of Rheumatology criteria for SLE were studied. Complement levels, and anti-double-stranded DNA, anti-Smith, anti-phospholipid, and anti-neuronal antibodies were evaluated. Computed tomography, magnetic resonance imaging, and single photon emission computed tomography (SPECT) neuroimaging studies were reviewed. RESULTS: The 10 patients with CNS-SLE presented with psychosis, mood disturbance, or confusion, and 8 patients had concomitant neurologic symptoms. The 8 girls and 2 boys ranged in age from 7.5 to 17 years. Serum anti-neuronal antibodies were positive with onset of symptoms and declined with improvement. Initial SPECT was abnormal in all 10 patients and remained abnormal. CONCLUSION: SPECT and anti-neuronal antibodies help confirm CNS involvement in patients with SLE and neuropsychiatric symptoms.     

Associations of specific psychiatric disorders with isolated focal dystonia,and monogenic and idiopathic Parkinson’s disease

Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson’s disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of 2.6 [confidence interval (CI) 1.7–4.0] for general axis I disorders in IFD, an OR of 2.5 (CI 1.4–4.7) in monogenic PD, and an OR of 1.4 (CI 0.8–2.6) in idiopathic PD. More specifically, the monogenic PD group showed the highest ORs for affective disorders including depression (OR = 4.9), bipolar disorder (OR = 17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in the PD groups but not in IFD. Our findings underline the notion that psychiatric disorders are part of the phenotypic spectrum of movement disorders. Moreover, they suggest that IFD, monogenic PD, and idiopathic PD are associated with specific psychiatric disorders indicating disturbances in a different neural circuitry for sensorimotor control.     

Cardiovascular disease and psychiatric disorders among Latinos in the United States

Purpose

Cardiovascular disease (CVD) is the leading cause of death among Latinos and disproportionately impacts people with psychiatric disorders. The aim of this study was to examine the relationships between CVD and psychiatric disorders among different Latino subgroups using a nationally representative sample.

Methods

Latinos participants (N = 6359) were drawn from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. A structured diagnostic interview was used to determine psychiatric diagnoses for any past-year mood, anxiety, and substance use disorders. A self-reported measure of physician-confirmed CVD was used. The relationships between CVD and psychiatric disorders among Latino subgroups were examined with logistic regression models adjusting for sociodemographics, CVD-risk factors, and acculturation.

Results

CVD were highest among Puerto Ricans (12%) and Cubans (11%), followed by Other Latinos (7%) and Mexicans (5%). The relationship between psychiatric disorders and CVD differed by Latino subgroups. Significantly increased odds of CVD were found among Mexicans with any past-year mood and anxiety disorders, Puerto Ricans with any past-year psychiatric disorders, Cubans with any past-year mood and substance abuse disorders, and Other Latinos with any past-year mood, anxiety, and lifetime schizophrenia/psychotic disorders.

Conclusions

The associations between CVD and psychiatric disorders are not uniform among Latinos. Efforts to address the need for health and mental health services must carefully consider this heterogeneity.

     

Psychiatric Co-morbidity in Ketamine and Methamphetamine Dependence: a Retrospective Chart Review

Both ketamine and methamphetamine (MA) have become very popular and have been abused worldwide over the past two decades. However, the relationship between dependence on ketamine or MA and psychiatric comorbidities is still unclear. This study aimed to examine the frequency of co-morbid psychiatric disorders in patients dependent on ketamine or methamphetamine who were receiving treatment at three substance abuse treatment clinics (SACs) in Hong Kong. This was a retrospective chart review. The medical records of 183 patients (103 with ketamine and 80 with MA dependence) treated between January 2008 and August 2012 were retrieved. Patients’ demographic data, patterns of substance abuse and comorbid psychiatric diagnoses were recorded. The mean age of onset and duration of substance abuse were 18.1?±?4.7 and 9.2?±?6.2 years for ketamine and 19.9?±?8.8 and 10.5?±?9.8 years for MA users, respectively. Psychotic disorders were more common in MA dependent users (76.2 % vs. 28.2 %, p?<?0.001), whereas mood disorders were more common in ketamine dependent users (27.2 % vs. 11.2 %, p?=?0.008). Ketamine and MA dependence have a notably different profile of psychiatric co-morbidity. Compared with MA dependence, ketamine dependence is more likely to be associated with mood disorders and less likely with psychotic disorders.     

Prevalence of psychiatric disorders among homeless people in Athens area: a cross-sectional study

Purpose

Homelessness is a chronic social phenomenon in European and other Western cities. In the recent years, the number of homeless people in Greece, mainly in Athens, is also increasing.

Method

The aim of this study was to explore the prevalence of psychiatric disorders among a sample of 254 homeless people, using the Mini International Neuropsychiatric Interview (M.I.N.I.). The sample was drawn from the existing shelters, soup kitchens, and the streets.

Results

The sample was predominantly male (74 %) with mean age 51 years, being in their majority homeless for over 25 months, 27 % of them living in the streets. The vast majority of the sample was single or separated with an education level <12 years. Current prevalence of psychiatric disorders was 56.7 % with 20.8 % comorbidity. For psychotic and mood disorders, current prevalence rates were 13 and 16 %, respectively. One year prevalence of alcohol and drug dependence was found to be low. Logistic regression analysis revealed that being older with higher number of months living in the streets and exposed to high frequency of adverse social events, increase the likelihood to become a psychiatric case. Finally, the vast majority of the identified psychiatric cases were lacking any current psychiatric care.

Conclusions

The magnitude of the prevalence of psychiatric morbidity was more than three times higher than that of the general population in Athens. Implications for psychosocial care and the organization of a support network for the homeless people are discussed.     

Central nervous system disease in patients with systemic lupus erythematosus.

Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups.     

Depression with psychotic features in a child with SLE: successful therapy with psychotropic medications—case report

Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease of unknown etiology, which affects multiple organ systems, including the central nervous system (CNS). Neuropsychiatric manifestations are seen in 13–75 % of all SLE patients, with equal frequency in children and adults. Despite a high prevalence of psychiatric manifestations, there is no consensus on the proper treatment of such cases. We report here a case of an 11-year-old girl diagnosed with a severe depressive episode with psychotic features, treated successfully with risperidone and sertraline as an adjunct to immunosuppressive therapy.     

Hippocampal damage and affective disorders after treatment of cerebral aneurysms

Despite good neurological outcome after the treatment of ruptured or incidental cerebral aneurysms, many patients complain about mood disturbances such as anxiety and depression. The present study investigated the nature of these affective disorders, their trigger factors, and corresponding structural brain changes. We assessed 63 patients matched by history of previous subarachnoid hemorrhage (SAH) and treatment modality (clipping vs. coiling) by a test battery including the Hospital Anxiety and Depression Scale (HADS) and beck depression inventory-II (BDI-II). MR imaging for the evaluation of structural changes included H¹-MR spectroscopy, hippocampal volumetry, and diffusion tensor imaging (DTI). The applied multimodal imaging revealed no significant differences between patients with previous SAH and patients with incidental aneurysms; there were also no substantial differences between patients with and without previous SAH with respect to depression and anxiety. However, we observed significantly higher mean HADS scores in patients treated surgically versus patients treated by coiling (p < 0.01). BDI-II tended to be higher in surgically treated patients, but this difference appeared statistically insignificant. Surgically treated patients displayed substantial hippocampal damage in all imaging techniques: reduction in mean concentrations of N-acetylaspartate (p = 0.04), hippocampal volume reduction (p = 0.012), and diffusion disorder (p = 0.02). The structural alterations correlated significantly with the increased HADS scores. In contrast to endovascular treatment, aneurysm surgery seems to be associated with an increased incidence of mood disorders corresponding to hippocampal neuronal loss, independent of preceding SAH.     

Asthma, life events and psychiatric disorders: a population-based study

Purpose

Although asthma and other chronic physical conditions have been shown to be associated with psychiatric symptoms, the relative contributions of negative life events to this association and impaired quality of life (QOL) are not clear.

Methods

This is a cross-sectional study of a nationally representative sample of Singaporean adults aged 20–59 (n = 2,847). Individuals were grouped by asthma, other chronic physical conditions, and no chronic physical conditions. Participants were assessed life events (list of threatening experiences questionnaire), psychiatric disorders [schedule for clinical assessment in neuropsychiatry diagnoses of psychiatric disorder including any psychiatric disorder, major depressive disorder (MDD) and generalized anxiety disorder (GAD)], and QOL (medical outcomes study 12-item short form).

Results

In multivariate analyses controlling for confounding variables, asthma and other chronic physical conditions, compared to no chronic physical conditions, both showed similarly (two- to four-fold) elevated odds ratio (OR) of association with MDD and GAD. However, the asthma group reported more life events as compared to other chronic physical conditions (OR = 4.33, 95 % CI: 2.09–8.95) or no chronic physical conditions (OR = 7.64, 95 % CI: 3.87–15.06). Life events accounted significantly for excess coexistence of psychiatric disorders with asthma over participants without chronic physical conditions. It also contributed significantly to relatively worse QOL observed among individuals with asthma.

Conclusions

In this cross-sectional study, life events among adults in Singapore appeared to mediate the co-occurrence of psychiatric disorders and functional impairment with asthma, more than with other chronic physical conditions. This should be further investigated in longitudinal studies.     

Cumulative life events,traumatic experiences,and psychiatric symptomatology in transition-aged youth with autism spectrum disorder

Background

Co-occurring mood and anxiety symptomatology is commonly observed among youth with autism spectrum disorders (ASD) during adolescence and adulthood. Yet, little is known about the factors that might predispose youth with ASD to mood and anxiety problems. In this study, we focus on the role of cumulative stressful life events and trauma in co-occurring psychopathology among youth with ASD who are preparing to exit high school. Specifically, we examined the distribution of cumulative life events and traumatic experiences and their relations with mood and anxiety symptomatology.

Methods

Participants included 36 youth with ASD, all of whom were in their last year of high school. Cumulative life events and trauma were assessed by parent report. Mood and anxiety symptomatology was determined using a variety of methods (structured interview, questionnaire, self- and informant report). Frequencies were used to examine the distributions of cumulative life events (count of total events) and trauma (coded into any trauma vs. no trauma), as well as mood and anxiety symptomatology (categorized into clinical-level, sub-threshold, or none for each). Bivariate relations between life events/trauma and mood/anxiety symptomatology were assessed using analysis of variance and chi-square. Ordinal logistic regression models were used to test whether significant bivariate relations remained after controlling for the sex of the youth with ASD and his/her IQ.

Results

Over 50 % of youth had experienced at least one trauma. Nearly one half had clinical-level mood or anxiety symptomatology. There was a statistically significant relation between absence/presence of trauma and mood symptomatology; nearly 90 % of the youth with clinical-level mood symptoms had at least one trauma, compared to 40 % of those with no mood symptomatology.

Conclusions

Our findings suggest that contextual factors such as trauma might be important for the development of mood symptomatology in individuals with ASD. Although this idea is well-accepted in typically developing populations, contextual factors are rarely studied in investigations of psychopathology or transition outcomes in ASD. Given the high rates of psychiatric comorbidities in this population, future research should continue to identify the range of possible factors—both behavioral and contextual—that might influence the emergence of these disorders.

     

Prevalence and correlates of disordered eating in a general population sample: the South East London Community Health (SELCoH) study

Purpose

Disordered eating has been shown to be more prevalent than full eating disorders diagnoses. However, research on its prevalence, socio-demographic, psychological correlates, and patterns of service use in multi-ethnic samples is still limited. This paper explores these associations in a South London-based (UK) sample.

Methods

The South East London Community Health (SELCoH) study is a general population survey (N = 1,698) of individuals aged 16+. Disordered eating was defined as ≥2 positive answers at the SCOFF questionnaire. Crude and adjusted logistic and multinomial logistic regression models were fit to investigate associations between socio-demographic characteristics, disordered eating, psychiatric comorbidity, and service use.

Results

A total of 164 (10 %) participants reported disordered eating and the majority were from ethnic minorities. In adjusted models, Asian ethnicity was associated with purging, loss of control eating and preoccupation with food. Individuals with disordered eating had higher odds of screening positive for post-traumatic stress disorder and personality disorders and of having anxiety/mood disorders, suicidal ideation/attempts, hazardous levels of drinking, and used drugs in the previous year. Only 36 % of individuals with disordered eating had sought professional help in the previous 12 months mostly through their general practitioner (27.4 %), followed by psychotherapists (12.8 %) and mental health specialists (5.5 %).

Conclusion

This study found a high prevalence of disordered eating, especially amongst ethnic minorities, and associations with a number of psychiatric conditions. Overall few participants accessed specialist services. These findings suggest that both disordered eating manifestations amongst ethnic minorities and access to care need better investigation.     

The role of life events in onset and recurrent episodes of schizophrenia and schizoaffective disorder

The experience of both positive and negative recent life events has long been recognized as a possible precipitant of episodes of psychiatric illness. Among individuals with recurrent mood disorders, investigators have found that recent life events are more likely to be associated with initial and early episodes of illness, with later episodes less likely to be temporally associated with life events. This study investigated the relationship between recent life events and episodes of illness in schizophrenia (defined as the number of acute episodes of schizophrenia requiring hospitalization). Among 32 male U.S. Military veteran inpatients, those with three or fewer episodes of illness reported significantly more recent life events than those patients with more than three episodes of illness (P = 0.01). Overall, recent life events were negatively correlated with number of episodes (P < 0.05). These data suggest that initial or early episodes of schizophrenic illness are more likely to be associated with recent life events than are later episodes.     

Mood Spectrum Disorders and Perception of Pain

Evaluation of pain perception in chronic pain patients with a concomitant mood-spectrum disorder. Design: The observational retrospective study is based on patient data collected in psychosomatic consultations held at the Gift Institute for Integrative Medicine in Pisa, Italy, from 2002 to 2014. Evoked pain stimulus threshold and tolerance were evaluated using the cold pressor test. Clinical pain intensity and Sensorial, Affective, and Evaluative dimensions were assessed using the Italian Pain Questionnaire, and Anxiety and Depressive symptoms using the Hospital Anxiety Depression Scale. Mood-spectrum disorders were diagnosed via the Mini-International Neuropsychiatric Interview, and affective temperament in accordance with Akiskal and Pinto’s criteria (1999). Of a total of 627 chronic pain clinic patients, 381 were diagnosed with a concomitant mood-spectrum (MS) disorder, unipolar (US) in 61.41%. Pain threshold (t = 2.28; p < 0.05) was lower, and all clinical pain dimensions (t = 2.28; p < 0.05) increased, in MS patients compared to those without psychiatric disorders. Pain intensity (F = 3.5, p < 0.05) and cognitive pain component scores (F = 7.84; p < 0.0001) were higher in US and, to a lesser extent Bipolar Spectrum, than in subjects with other (n.112) or no psychiatric disorders (n. 134). Suicide ideation was highest in US (F = 37.20; p < 0.0001), although in BS major depressive episodes had more melancholic features (F = 46.73; P < 0.0001), and a longer history of psychiatric disorders before the pain onset than US (F = 20.31; p < 0.0001). Pain management should take into account pre-existing psychiatric disorders.     

Suicidality in Non-Treatment Seeking Young Adults with Subsyndromal Gambling Disorder

Gambling Disorder is associated with elevated rates of suicidal thoughts and acts. However, virtually nothing is known about suicidality in people with subsyndromal forms of gambling disorder. A total of 174 non-treatment seeking subjects were recruited for a study of impulsivity and met criteria for a subsyndromal form of DSM-5 gambling disorder (31.0 % females; mean age = 21.7 ± 3.61 years). Subjects were categorized as being ‘at risk of suicide’ or ‘no suicide risk’ based on the Mini-International Neuropsychiatric Interview (MINI). Those with and without suicidality were compared on clinical and cognitive measures. 32 (18.4 %) met MINI criteria for suicidality. Suicidality was significantly associated with mood and anxiety disorders, greater rates of nicotine consumption, and relative impairments in decision-making and cognitive flexibility. These findings suggest that decision-making impairments may be implicated in the development of both gambling problems and suicidality. Future work should address causality, neural correlates, and tailored suicide prevention strategies for people with, or at risk for, disordered forms of gambling.     

Latent class analysis reveals five homogeneous behavioural and developmental profiles in a large Dutch population sample of infants aged 14–15 months

Precursors of child psychiatric disorders are often present in infancy, but little is known about the prevalence and course of general psychopathology in population-based samples of children 0–3 years. We examined whether homogeneous behavioural and developmental profiles could be identified in children aged 14–15 months (M = 14.84; SD = 2.19), and we explored whether or not these profiles corresponded with existing classifications of DSM-IV-TR, ICD-10, and DC 0–3R. Parents of 6,330 children answered 74 items about externalizing, internalizing, and social-communicative behaviour. Exploratory factor analysis revealed nine factors: deviant communication, negative emotionality, deviant reactive behaviour, deviant play behaviour, demanding behaviour, social anxiety/inhibition, advanced social interaction problems, basic social interaction problems, and sleep problems. Latent class analysis yielded five profiles, of which three were associated with increased behavioural and developmental problems. Some infants (5.7 %) had communication and social interaction problems corresponding to multisystem developmental disorders (DC 0–3R) and suggestive of anxiety, mood, or pervasive developmental disorders (DSM-IV-TR, ICD-10). Other infants (16.4 %) had communication problems, possibly precursors of communication, language, or speech disorders (DSM-IV-TR, ICD-10). Yet other infants (10.8 %) showed negative and demanding behaviour suggestive of regulation disorders (DC 0–3R), attention-deficit and disruptive behaviour disorders (DSM-IV-TR), or hyperkinetic and conduct disorders (ICD-10). Thus, even in infancy certain distinct behavioural and developmental profiles can be recognized. This combined approach will enable follow-up research into the stability of factors, classes, and profiles over time, and will facilitate early detection, diagnosis, and treatment of behavioural and developmental problems.