Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset
Abstract
:1. Introduction
2. Methods
- (i)
- they were very recent and were not cited in second literature publications;
- (ii)
- They discussed topics never included into second literature works, mainly regarding protective factors or preventive programs that have a less wide literature.
3. Results
3.1. Risk Factors for Primary Psychosis
3.1.1. Individual Risk Factors
Familiar and Parental Risk Factors
Sociodemographic Risk Factors
Personal Pre-Morbid Characteristics Associated with a Higher Risk of Developing Primary Psychosis
Comorbidities Associated with a Higher Risk of Developing Primary Psychosis
Genetic Factors Associated with a Higher Risk of Developing Primary Psychosis
3.1.2. Environmental Risk Factors
Prenatal and Perinatal Risk Factors
Childhood-Related Environmental Risk Factors
Adolescence-Related Environmental Risk Factors
Continuous Risk Factors and Factors That Can Play a Role at Any Time in Life
3.2. Protective Factors for Primary Psychosis
3.2.1. Individual Protective Factors
Parental, Socio-Demographic, and Personal Protective Factors
Autoimmune Comorbidities Associated with a Reduced Risk of Developing Primary Psychosis
3.2.2. Environmental Protective Factors
Prenatal Protective Factors
Childhood and Adolescence-Related Environmental Protective Factors
3.3. Early Detection of the Onset
3.3.1. Help Seekers and Populations at Risk of Developing Primary Psychosis
3.3.2. Screening Tools for Stratification of the Risk of Developing Primary Psychosis
3.3.3. Models and Levels of Preventive Interventions and their Limitation
3.3.4. Integrated Model of Prevention and Early Detection of the Onset in Primary Psychosis
- (i)
- a first part, the ERIraos-Check List, which is used for screening purposes, contains questions on generic and psychotic psychiatric symptoms, on global functioning, with importance given to self-perception of functioning, and on the evaluation of some well-known risk factors for primary psychosis such as obstetric complications, neurodevelopment delays or alterations, family history, and substance abuse;
- (ii)
- a second part, the ERIraos-Symptom List, which is administered to people evaluated at least at modest risk of transition to psychosis in the ERIraos-Check List. This second-level evaluation is carried out in specialized centers and aims to carefully detect imminent transition [115]. Thereafter, the ERIraos has been successfully employed as a tool for the early recognition of psychosis risk in several further German studies [116,117,118] and subsequently translated and validated into different languages and populations [115,119]. This instrument proved to be suitable for routine use as a scale for the identification of the at-risk subjects.
- (i)
- subjects at early (pre-psychotic) prodromal stage and
- (ii)
- subjects at late (early psychotic) prodromal stage.
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Gene Loci | Corresponding Transcript/Protein and Localization | Principal Known Functions | ||||
---|---|---|---|---|---|---|
General Description of the Function(s) | Central Nervous System (CNS) Development | Neuronal Morphology Regulation | Signal Transmission | |||
NEUROTRANSMITTER RECEPTORS | DRD2 (Dopamine Receptor D2) | G protein-coupled membrane receptor | Dopamine signaling | Dopaminergic system | ||
DRD1, 3, 4 (Dopamine Receptors D1, D3, D4) | G protein-coupled membrane receptor | Dopamine signaling | Dopaminergic system | |||
HTR2A (5-Hydroxytryptamine -5-HT- Receptor 2A) [44] | G protein-coupled membrane receptor | Regulation of dopamine and glutamate release in the mesolimbic and mesocortical systems | Serotoninergic system Dopaminergic system Glutamatergic system | |||
GRM3 (Glutamate Metabotropic Receptor 3) | G protein-coupled membrane receptor | Glutamate signaling | Glutamatergic system | |||
GRIN2B (Glutamate Ionotropic Receptor N-methyl-D-aspartate—NMDA—Type Subunit 2B) | Subunit of the NMDA membrane receptor—ion channel (NMDAR) | Neurodevelopment, circuit formation, synaptic plasticity, and cellular migration and differentiation | Neurogenesis Differentiation of neural progenitors | Glutamatergic system | ||
GABRB2 (Gamma-Aminobutyric Acid -GABA- Type A Receptor Subunit Beta2) | Subunit of the GABA-A membrane receptor—ion channel | Balance in excitatory/inhibitory signaling in the CNS | GABAergic system | |||
NEUROTRASMITTER METABOLISM AND SIGNAL REGULATION | PDE4B (Phosphodiesterase 4B) | Intracellular enzyme | Cyclic AMP (cAMP)-specific phosphodiesterase (PDE), family IV. It modulates cAMP second messenger concentration in the transduction of the signal process | Signal transmission in different systems | ||
COMT (Catechol-O-Methyl-transferase) | Intracellular enzyme | Dopamine and noradrenaline metabolism | Dopaminergic system Noradrenergic system | |||
RGS-4 (Regulator of G Protein Signaling 4) [45] | Intracellular enzyme activator | Activate GTPase activity of G alpha subunits of heterotrimeric G proteins, thus deactivating them | Differentiation of neural progenitors—Axonogenesis in embryogenesis | Glutamatergic system (signal transduction) | ||
SLC18A2 (Solute Carrier Family 18 Member A2) | ATP-dependent transmembrane transporter | ATP-dependent transporter of monoamines | Dopaminergic system Serotoninergic system Noradrenergic system | |||
DAOA (D-Amino Acid Oxidase Activator) and DAOA-AS1 (Antisense RNA 1) | Intracellular enzyme activator and corresponding long non-coding RNA | Metabolism of glial D-serine that regulates neuronal NDMAR signaling, mitochondrial function, dendritic arborization | Dendritic regulation | Glia-neuron communication Glutamatergic system | ||
DTNBP1 (Dystrobrevin Binding Protein 1) and CMYA5 (Cardiomyopathy Associated 5) | Intracellular proteins that participate in the formation of the lysosome-related organelles complex 1 (BLOC-1) | Synaptic vesicle trafficking and neurotransmitter release, in particular regulation of cell surface exposure of DRD2 and glutamatergic release. Actin cytoskeleton reorganization and neurite outgrowth. | Neurite regulation | Dopaminergic system Glutamatergic system Synaptic regulation | ||
CELL-CELL CONTACT AND NEURODEVELOPMENT | DISC1 (Disrupted In Schizophrenia 1) | Scaffold intracellular protein | Involved in neurogenesis (neural progenitor proliferation, neuron positioning), dendritic development, and synapse formation | Neurogenesis | Dendritic regulation | Synaptic regulation |
NRXN1 (Neurexin 1) | Membrane receptor | Binds neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the CNS | Synaptic regulation | |||
ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) | Membrane receptor tyrosine kinases, epidermal growth factor subfamily. | Binds neuroregulins NMDAR pathway | Regulation of CNS development | Glutamatergic system | ||
NRG1 (Neuregulin 1) | Membrane glycoprotein | Mediates cell–cell signaling. Binds to ERBB receptors NMDAR pathway | Neurogenesis Gliogenesis Differentiation of neural progenitors | Glutamatergic system | ||
AKT1 (AKT-8 retrovirus Serine/Threonine Kinase 1) [46] | Intracellular Serine/Threonine kinase | Known oncogene involved PI3K and mTOR signaling pathways Placentar and CNS development and functioning | Neurogenesis | Dendritic regulation | Synaptic regulation | |
RELN (Reelin) | Large extracellular matrix serine protease | Enzymatic activity modulates cell adhesion | CNS development (cellular migration) | Neuronal morphology regulation (microtubule functioning) | ||
IMMUNE SYSTEM | IL1B (Interleukin 1 Beta) | Cytokine (extracellular messenger) | Potent proinflammatory cytokine, involved in neuroinflammation during neurodevelopment and adult life | Altered by neuroinflammation |
Factors Associated with the Development of Primary Psychosis | Prenatal | Perinatal | Childhood | Adolescence | Strength of Evidence of the Association | References | Modifiable Factor | Level(s) of Preventive Intervention | |
---|---|---|---|---|---|---|---|---|---|
RISK | Family history of primary psychosis | ● | +++ | [13,16,17,19,20,21] | No | - | |||
Paternal characteristics (e.g., age <20 or >45, low socio-economic status) | ● | +++ | [13,15,23,24] | No | - | ||||
Maternal characteristics (e.g., age <20 or >35, any severe psychiatric condition, pre-pregnancy obesity) | ● | +++ | [15,23] | Only obesity | Primary | ||||
Diabetes and hypertension during pregnancy | ● | ++ | [15] | Yes | Primary | ||||
Maternal infections during pregnancy | ● | +++ | [13,23,48] | Yes | Primary | ||||
Suboptimal number of antenatal care visits | ● | ++ | [23] | Yes | Primary | ||||
Maternal stress during pregnancy | ● | +++ | [13,23] | Yes | Primordial a | ||||
Maternal nutritional deficits during pregnancy | ● | +++ | [13,23] | Yes | Primary | ||||
Obstetric complications (e.g., maternal or fetal hypoxia during delivery, preterm ruptured membranes) | ● | +++ | [15,23] | No | - | ||||
Neonatal factors (e.g., premature birth, incubator or resuscitation) | ● | +++ | [13,15,23] | No | - | ||||
Minor physical anomalies | ● | ++++ | [15,16,24,28] | No | - | ||||
Genetic factors (cf. Table 2) | ● | ● | ● | +++ | [17,18,22,42,43] | No | - | ||
Socio-demographic (e.g., male gender, ethnic minority, birth in winter, disadvantaged groups) | ● | ● | ● | ● | ++++ | [13,15,20,23,24] | Only social part | Primordial b | |
Childhood adversities and traumas (e.g., physical, psychological, and sexual abuse, bullying) | ● | +++ | [13,15,24,51,52,53,55] | Yes | Primordial b | ||||
Difficult parental relationship (e.g., parental communication deviance, separation or death, neglect) | ● | +++ | [15,52,53,55] | Only some | Primordial c | ||||
Childhood infections (mostly CNS infections) | ● | +++ | [15,24,28,31,58] | Yes | Primary | ||||
Traumatic brain injury | ● | ● | ++ | [13,15] | Yes | Primary | |||
Exposure to traffic | ● | ● | ++ | [15] | Yes | Primordial | |||
Exposure to benzene | ● | ● | ++ | [15] | Yes | Primary | |||
Tobacco use | ● | ++ | [13,15,24,62] | Yes | Primary/Secondary | ||||
Cannabis use | ● | +++ | [13,20,24,56,59,60] | Yes | Primary/Secondary | ||||
Psychostimulants use | ● | ++ | [13,20] | Yes | Primary/Secondary | ||||
Autoimmune diseases (e.g., celiac disease, pernicious anemia) | ● | ● | ++ | [29,30] | No | - | |||
Psychological characteristics (e.g., trait anhedonia; premorbid low IQ) | ● | ● | ++++ | [15,24] | No | - | |||
Other psychiatric disorders (e.g., obsessive compulsive disorder, schizotypal personality) | ● | ++ | [32,33,34,35,36,37] | Yes | Primary | ||||
Urbanicity * | ● | ● | +++ | [13,15,20,24,26] | No | - | |||
Ethnicity (migration and specific ethnic minorities) * | ● | ● | ++++ | [15,24] | No | - | |||
PROTECTIVE | Prenatal dietary supplementation (vitamin D, iron, folates, phosphatidyl-choline) | ● | ++ | [80,81] | Yes | Primary d | |||
Socio-demographic (e.g., elevated socio-economic status and an economic well-being) | ● | ● | ● | ● | +++ | [15] | Yes | Primordial | |
Physical characteristics (e.g.,: olfactory identification abilities) | ● | ● | ++ | [15,24] | No | - | |||
Psychological characteristics (e.g., extraversion, openness; high premorbid IQ; resilience) | ● | ● | ++ | [16,24,28] | No | - | |||
Positive family environment (e.g., good parental system, healthy relationships with relatives) | ● | ● | ++ | [16,83,84] | Yes | Primordial | |||
Autoimmune diseases (e.g., ankylosing spondylitis) | ● | + | [29,30,79] | No | - | ||||
Physical activity | ● | + | [87] | Yes | Primordial/Primary |
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Brasso, C.; Giordano, B.; Badino, C.; Bellino, S.; Bozzatello, P.; Montemagni, C.; Rocca, P. Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset. Diagnostics 2021, 11, 2146. https://doi.org/10.3390/diagnostics11112146
Brasso C, Giordano B, Badino C, Bellino S, Bozzatello P, Montemagni C, Rocca P. Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset. Diagnostics. 2021; 11(11):2146. https://doi.org/10.3390/diagnostics11112146
Chicago/Turabian StyleBrasso, Claudio, Benedetta Giordano, Cristina Badino, Silvio Bellino, Paola Bozzatello, Cristiana Montemagni, and Paola Rocca. 2021. "Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset" Diagnostics 11, no. 11: 2146. https://doi.org/10.3390/diagnostics11112146
APA StyleBrasso, C., Giordano, B., Badino, C., Bellino, S., Bozzatello, P., Montemagni, C., & Rocca, P. (2021). Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset. Diagnostics, 11(11), 2146. https://doi.org/10.3390/diagnostics11112146