Editorial: Towards causal models – a developmental perspective


Decomposition of psychiatric diagnoses into their underlying genetic, neuroanatomical, biochemical, neurophysiological, and neuropsychological processes may not only provide alternative ways of classification but may also suggest simpler clues to aetiology than behavioural symptoms. Therefore, the concept of endophenotypes or intermediate phenotypes has emerged as a strategic tool in neuropsychiatric research (Gottesman & Gould, 2003). Conceptual reintegration of these processes into causal models of child psychiatric disorders will require taking into account environmental influences and developmental changes of these component processes over time (Coghill et al., 2005). Identifying underlying processing deficits and their causal links can inform treatment targets. In this issue of the Journal, several articles address these challenges. The first seven papers focus on underlying processes in pediatric bipolar disorder, ADHD, and specific learning impairments, and the second section comprises four contributions on the topic of assessment and screening issues.

In the first article, Gogtay and colleagues report the first prospective study of cortical development before and after the onset of paediatric bipolar illness, using a novel mapping technique on longitudinal obtained MRI scans. Results provide a clear quantitative depiction of the system level changes in the brain that occur as bipolar illness begins. In this study, cortical developmental trajectories in children who became bipolar were compared with cortical changes in an age- and gender-matched contrast group who shared similar clinical presentation features at initial screening (characterized by mood dysregulation and transient psychosis) and those in a control group. The authors were able to identify subtle, regionally specific, bilaterally asymmetrical cortical changes. Cortical gray matter increased over the left temporal cortex and decreased bilaterally in the anterior cingulated cortex. This was seen most strikingly after the illness onset, and showed a pattern distinct from what is seen in childhood onset schizophrenia. The bipolar neurodevelopmental trajectory was generally shared by the children who remained with a diagnosis of mood dysregulation and transient psychosis without converting to bipolar I, suggesting that this pattern of cortical development may reflect affective dysregulation in general.

In the next paper, Guyer and colleagues report on the ‘‘Specificity of facial expression labelling deficits in childhood psychopathology’’. These deficits are common to both the narrow-defined bipolar disorder and broader phenotypes characterized by severe mood dysregulation, and differentiate those patients from patients with anxiety/depression or ADHD/conduct disorder and controls. Thus, social skill training with a facial affect labelling component may be an important part of treatment of these patients.

Working memory (WM) deficits, particularly in visual-spatial storage and manipulation, have been considered by many to be core cognitive risk factors for ADHD possibly underlying academic underachievement. Investigating the effects of methylphenidate on working memory, Bedard and colleagues demonstrate selective effects of methylphenidate on working memory components. While methylphenidate enhances the ability to store visual-spatial information, effects on the storage of auditory-verbal information were not detected. By contrast, methylphenidate enhanced the ability to manipulate both auditory-verbal and visual-spatial information. The differential effect of methylphenidate on the storage of auditory-verbal and visual-spatial information suggests selective methylphenidate effects on right neural networks. The differential effect on storage, coupled with methylphenidate effects on the manipulation of auditory-verbal and visual-spatial information, are more consistent with Baddeley's tri-partite framework of WM than with a two-modality component model. This paper illustrates how a theoretical-grounded study-design can address relevant clinical issues but also re-inform causal model building.

Temporal processing deficits, motivational deficits, and impaired performance monitoring mechanisms are involved in ADHD. Whether these impairments may impact on the development of working memory, is still unknown. Knowing what to expect and when to expect it are important cognitive processes and adjusting behaviour when predictions are violated is an essential element of cognitive control. An impaired ability to predict temporal and contextual cues in the environment may hinder the ability to adapt behaviour to changing contexts. Durston and colleagues examine how well individuals with ADHD can anticipate predictable events and consequently modify behaviour when these predictions are violated. The paper convincingly depicts that processing of temporal unpredictable events is paralleled by lower performance accuracy and reduced cerebellar activations, while attenuation in prefrontal regions was found in response to violations of stimulus type.

Allocation of attentional effort as a result of challenging circumstances, and as a function of the motivation to maintain attentional performance, represents an everyday experience and is closely linked to performance monitoring and motivational mechanisms. Psychophysiological variables can provide insight into these processes that are not easily detectable using performance measures. By measuring short-term changes in heart rate following reinforcement feedback and heart rate variability during a time production paradigm under different reinforcement conditions, Luman and colleagues provide convincing psychophysiological evidence for abnormal reinforcement sensitivity and motivational deficits in ADHD. Results highlight the importance to separate performance and ability in ADHD. A key concluding point the authors make is that appropriate reinforcement may increase the ability of children with ADHD to perform well. Thus, further analysis of feedback and its biological underpinnings may open a window for developing therapeutical strategies.

In the next article Epstein and colleagues report developmental effects on functional brain abnormalities and their response to stimulant medication. In their study, concordantly diagnosed ADHD parent-child dyads were compared to a matched sample of normal parent-child dyads. While both youths and adults with ADHD showed attenuated activity in fronto-striatal regions, only adults with ADHD appeared to activate non-fronto-striatal regions more than controls. While stimulants increased activation in fronto-striatal and cerebellar regions in youths, adults increased their activation only in striatal and cerebellar regions but, in contrast to youths, not in prefrontal regions. These important results extend findings of fronto-striatal dysfunctions to adults and highlight the importance of the involvement of both fronto-striatal and fronto-cerebellar circuitries in ADHD, and underline the need to take developmental aspects seriously when studying correlates of ADHD.

In the last paper in this section focusing on underlying processes and causes, Kovas and colleagues examine the mathematical and reading abilities in 2596 pairs of 10-year-old twins. The authors found both disabilities being moderately heritable and largely influenced by the same set of genes. The influence of shared environmental influences was modest and the dissociation between disabilities was largely due to independent non-shared environmental influences. This may open up the development of effective means of environmental interventions in prevention and treatment, i.e. better strategies for teaching mathematics and reading.

The second section of this issue is focused on effective screening and assessment procedures. Decisions about screening for a disorder are not as straightforward as picking a well-researched instrument. Key issues for clinical screening practice are whether it is possible to determine the critical ages and indices for an individual child's risk for a disorder and whether a parsimonious assessment procedure is possible.

Early identification and intervention offered to children with reading disability (RD) is important in order to prevent these children from developing more severe academic problems. Multiple studies have explored group level predictors but hardly any of them have applied findings into screening of individual child's risk for RD. Based on logistic regression modelling, Puolakanaho and colleagues convincingly demonstrate that an individual child's risk for RD can be determined at a reasonable level of classification accuracy as early as 3.5 years by a rough screening procedure taking into account familial risk status and very early phonological and language skills. Identifying these high-risk children about 5 years before their later reading achievement can be reliably assessed may pave the way for future preventive interventions. This is a promising example of the identification of early predictors that may lead to the development of clinically useful screening procedures.

Investigating the diagnostic discrimination of the social communication questionnaire (SCQ) for screening for autism spectrum disorder in a clinical and research-referred sample, Corsello and colleagues detected lower absolute scores, lower sensitivity in younger children and lower specificity for all ages groups than previously reported. Their results point out that age, referral and recruitment biases may influence test specificity and sensitivity. These findings underline that the choice of measures should be determined by the intended purpose (diagnosis or screening) and the targeted population (clinic sample, general population, research sample).

The accurate assessment of children and adolescents exposed to traumatic events requires particular clinical expertise. While the severity of posttraumatic stress symptoms is related to the level of exposure, specific symptoms manifested may vary according to the developmental stage of the child and the nature of the stressor; several factors seem to mediate the development of symptoms. Investigating young children's responses to the experience of an earthquake, Proctor and colleagues highlight that children's vulnerability to serious adverse life events is critically influenced by the quality of the parent-child-relationship prior to the event as well as the responses that parents exhibit following the event. Family context can provide either protective or exacerbating influences; in planning interventions after a natural disaster it is highly important to take the role of parents into account.

The use of an effective screening and assessment procedure for emotional problems is particularly important in deaf children as pointed out by van Gent and colleagues using a multi-method and multi-informant assessment approach. Their study suggests a high prevalence of significant emotional and behavioural problems in deaf children, which are often not recognized, both in mainstreaming and in special schools; low agreement was found between the teacher ratings of emotional problems and the clinical expert rating of emotional disorder. Results argue for special focus on the early detection as well as for the crucial importance of a multi-informant approach to the assessment of strengths and weaknesses of both the deaf child and its hearing environment. Likewise the effect of traumatic effects; it is not deafness per se, as noted by Van Gent and colleagues, but additional factors that mediate the risk of psychiatric symptoms in these children.

This issue of JCPP includes innovative high quality papers dealing with timely issues of general importance. Writing my first editorial, I am intrigued by the close links between clinical and fundamental science developed in most articles. I am sure that there is much of interest, both for researchers and clinicians, and hope that readers may share my enthusiasm.