Year: 2017
Type: article
Abstract: Some twenty years ago, the onset of psychosis was seen as the first sign of a schizophrenia spectrum disorder. Large scale epidemiological studies have since shown that, before the first psychotic episode, several deviations of normal development take place in (at least part of) the youngsters who later develop schizophrenia. While in childhood there is an average delay in reaching milestones such as walking, talking and reading, the most salient deviation during the teens is the decreased interaction with peers and decreased academic performance1. Children who later develop a psychotic disorder may have some deviant behavior, with schizotypal or schizoid features, which is expressed as few (or no) close friends and fewer social connections in sports, teams or hobbies. Occasional perceptual aberrations and magical beliefs are experienced by some 40% of children who later develop schizophrenia2, 3. In the second decade, cognitive decreases become apparent, which can be observed as lower school level than that of sibs and parents, doubling of classes or even quitting school4, 5. Finally, after puberty, subclinical psychotic symptoms emerge (or increase), which indicates the ultra high risk (UHR) period. Of course there are many exceptions, and some youngsters will develop a first psychosis out of the blue, with perfect social and cognitive skills antedating it. Yet, at least half of psychotic patients show a trajectory which provides clues for early recognition and interventions. All larger cohorts of UHR individuals show that cognitive decline is the clearest predictor of transition to psychosis5-7, together with severity of subclinical psychotic complaints. Animal models, genetic information, imaging studies in high risk groups, studies in children with 22q11 deletion syndrome, and post-mortem studies have shed light on neurobiological deviations that take place in these early phases, before the so-called first psychotic episode. Decreases in GABA functioning, especially of Chandelier cells, reduced NMDA receptor activity, increased oxidative stress and insufficient scavengers (especially glutathione), increased pro-inflammatory status of the brain and lower mitochondrial functioning add to varying degree to an individual's susceptibility towards developing schizophrenia. Some of these neurobiological deviations can be measured in vivo (i.e., glutathione and GABA concentrations by magnetic resonance spectroscopy; inflammatory status by positron emission tomography), whilst others cannot (density of Chandelier cells). This knowledge provides a basis for potential targeted treatment of specific susceptible subgroups of individuals with the same phenotype, but is not yet ready for clinical use. Epidemiology, cohort and case-control studies provide evidence of several risk factors occurring in the teenage period that can further increase risk of onset of psychosis. Among them are drug abuse, bullying, social exclusion, sleep deprivation, stressful events, inflammatory conditions and immigration. At the same time, pilot studies on interventions in the preclinical period have been performed, that showed efficacy of cognitive behavioural therapy (CBT) (although not compared to an active control condition)8 and of nutritional supply of omega-3 fatty acids (although not replicated in a larger group)9. At present, we do not know everything we would like to know to act early to prevent transition to psychosis in vulnerable youngsters, but we do have some basic clues on which we can act already. Each year we wait to complete our knowledge, many youngsters go on to develop a schizophrenia spectrum disorder. This topic should be a high priority in psychiatric research, as even UHR individuals who do not develop psychosis tend to manifest (other) severe psychiatric problems. A psychiatric disease affecting an adolescent or young adult has a large impact on the person himself, but also on his family, surrounding and society at large. There are several ways forward, both for researchers and for health care workers. For the latter, schools are the most important partners for collaboration, since cognition is such an important risk factor. Cognitive decline is first detected at school, and lower functioning than in previous years, with a prominent deviation from sibs, should be a reason to contact health care workers who can screen for (subclinical) psychotic features. When these are present, a working alliance between mental care workers, family and school should be made to prevent further hits, i.e. prevent the youngster from starting to abuse drugs, actively avoid (or stop) being bullied and socially isolated, regulate exposure to stress and sleep. For researchers, individual neurobiological deviations at the UHR stage need to be tested for correction with specific interventions, such as supplementation with n-acetylcysteine to restore glutathione function, glutamatergic or GABA-ergic agents to improve signaling of the inhibitory interneurons, and omega-3 fatty acids or anti-inflammatory agents to restore optimal brain condition. In addition, CBT for UHR needs to be compared to other psychosocial interventions, and efficacy has to be tested at group level and in specific patient groups. In short, there is much work to do for all of us in order to prevent transition to psychosis of vulnerable youngsters, and we need to make haste. Iris E. Sommer1, Celso Arango2 1Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; 2Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM; IiSGM, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
Source: World Psychiatry
DOI: 10.1002/wps.20454
Authors: Iris E. Sommer, Celso Arango
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2759599561