Psychotic Disorder Mental Health Disorder

0

population

global

percentage

0.3-0.7

evidence

reference	supports	snippet	explanation
PMID:18480098	PARTIAL	The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation.	While the male to female ratio of incidence is reported as 1.4:1, the abstract does not provide exact figures on the percentage of the population affected except that there is prominent variation. Therefore, the part of the statement with the percentage is not directly supported by this source.

notes

male_to_female_ratio: 1.4:1

0

phase

Prodromal

age_range

15-25

evidence

reference	supports	snippet	explanation
PMID:10225329	SUPPORT	In adolescence, preschizophrenics exhibit subtle changes in cognition and affect as well as a variety of anomalous subjective experiences (so-called 'basic symptoms'), suggesting 'trait' status of these features.	This reference indicates that during adolescence, which overlaps with the 15-25 age range, individuals who are preschizophrenic show subtle changes in their thoughts and feelings, aligning with the prodromal phase as described.
PMID:37027026	SUPPORT	EOP patients had significantly more prodromal symptoms with a higher frequency of trouble with thinking, avolition and hallucinations than AOP patients.	This study supports the presence of subtle changes in thinking and behavior during the prodromal phase in early-onset psychosis, which includes patients younger than 18, blending into the 15-25 age range.

notes

Subtle changes in thoughts, feelings, and behavior

1

phase

Onset

age_range

16-30

evidence

reference	supports	snippet	explanation
PMID:7654792	PARTIAL	Early-onset schizophrenias (< or = 20 years) were compared with a medium-onset group (21 - < 35 years) and a late-onset group (35 - < 60 years) with regard to age and type of onset, early symptom-related course, social development and social course.	The study provides information about the age of onset and early course of schizophrenia that falls within the 16-30 age range but does not specifically address the entire age range spectrum for the onset of the first episode of psychosis.
PMID:20021319	SUPPORT	There are progressive frontal changes in males with adolescent-onset psychosis... Ultra high-risk patients who subsequently develop psychosis and first-episode psychosis patients develop significant grey matter reduction in the planum polare, planum temporale and caudal region; a progressive process in the superior temporal gyrus may precede the first expression of florid psychosis.	This literature provides evidence about the progression of schizophrenia, particularly related to brain changes, within the stated age range of 16-30 years during the onset phase of the first episode of psychosis.
PMID:10225329	SUPPORT	Prodromal symptoms occur in a substantial proportion of preschizophrenics, followed by a short prepsychotic phase with the crystallization of a psychotic syndrome.	This reference supports the progression of schizophrenia during the onset phase and includes the age group that aligns with the 16-30 age range.
PMID:26467909	PARTIAL	Patients with first-episode psychosis were found to have high relapse rates during the first years after illness onset.	While discussing the progression of symptoms and outcomes following the first episode of psychosis, this study does not focus specifically on the age range of 16-30 years.

notes

First episode of psychosis

2

phase

Chronic

evidence

reference	supports	snippet	explanation
PMID:9789265	SUPPORT	Long-term treatment of patients with chronic schizophrenias requires integration of many therapeutic approaches, co-operation of several professions, and regard for the views of patients and relatives.	The excerpt supports the idea that managing symptoms and functioning in chronic schizophrenia requires long-term management.
PMID:23172002	PARTIAL	The evidence shows that although approximately 25% of people with schizophrenia have a poor long-term outcome, few of these show the incremental loss of function that is characteristic of neurodegenerative illnesses.	This statement supports the idea that while a subset of patients experience poor long-term outcomes, most do not have progressive deterioration like in neurodegenerative diseases.
PMID:10082190	SUPPORT	The criteria proposed necessitate (i) diagnosis of schizophrenia by standard operational criteria, (ii) continuous hospitalization for at least the past 2 years, (iii) a level of psychosocial functioning of < or = 40 as measured by the Global Assessment Scale, and (iv) an intensity score of 'marked' or 'severe' on at least three of the six Manchester Scale items.	The criteria for refractory schizophrenia include long-term management indicating that managing symptoms and functioning over time is essential.
PMID:26168930	SUPPORT	A cluster analysis performed on the resulting similarity matrix yielded two main groups (a 'improving' and a 'chronic' group), which comprised a total of six different types of illness course.	The study's finding of an 'improving' and 'chronic' group supports that managing symptoms and functioning is a significant aspect for those in the chronic phase.

notes

Long-term management of symptoms and functioning

0

name

Dysregulation of Dopamine Neurotransmission

description

Imbalance in dopamine transmission in the brain, particularly in the mesolimbic and mesocortical pathways.

evidence

reference	supports	snippet	explanation
PMID:27206569	PARTIAL	Findings have converged to suggest early dysregulation in the striatum, especially in the rostral caudate, manifesting as excess synthesis and release. Recent data showed deficit extending to most cortical regions and even to other extrastriatal subcortical regions not previously considered to be 'hypodopaminergic' in schizophrenia.	While the literature supports dopamine dysregulation in various brain regions, it does not specifically emphasize the mesolimbic and mesocortical pathways alone.
PMID:24986384	NO_EVIDENCE	A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic).	The abstract does not provide specific information supporting the imbalance of dopamine transmission specifically in the mesolimbic and mesocortical pathways as described in the statement.
PMID:1981107	NO_EVIDENCE	This article discusses the possibility that a deficient activity within the cortico-striatal glutamatergic pathway is an important pathophysiological component in some cases of schizophrenia and that glutamatergic agonists may prove beneficial in this disorder.	The study focuses on glutamate dysregulation rather than dopamine transmission dysregulation in mesolimbic and mesocortical pathways.
PMID:24128684	PARTIAL	This clinical picture is generally associated with supersensitivity to dopamine, and activates dopamine neurotransmission that is usually alleviated or blocked by drugs that block dopamine D2 receptors.	There is an implication of dopamine dysregulation, but the specifics of mesolimbic and mesocortical pathways are not confirmed.

synonyms

Dopamine Hypothesis

1

name

Abnormality of Glutamergic Signaling

description

Dysfunction in glutamate neurotransmission, impacting synaptic plasticity and brain circuit function.

evidence

reference	supports	snippet	explanation
PMID:11532718	SUPPORT	Research has implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia.	The literature specifically states that glutamatergic neurotransmission dysfunction is associated with the pathophysiology of schizophrenia, supporting the provided statement.
PMID:28754595	SUPPORT	Accumulating evidence suggests that synaptic plasticity is impaired in schizophrenia. Given the role of synaptic plasticity in learning, memory, and neural circuit maturation, impaired plasticity may underlie many features of the schizophrenia syndrome.	The literature discusses the impairment of synaptic plasticity in schizophrenia and its interaction with brain maturation, aligning with the statement.
PMID:29954475	SUPPORT	Psychosis is now widely hypothesized to involve neural networks beyond the classical dopaminergic mesolimbic pathway, including serotonin and glutamate systems as well.	This reference supports the involvement of glutamatergic systems in schizophrenia, reinforcing the statement.
PMID:22351070	SUPPORT	Schizophrenia is believed to result from problems during neural development that lead to improper function of synaptic transmission and plasticity, and in agreement, many of the susceptibility genes encode proteins critical for neural development.	The literature supports the idea that schizophrenia impacts synaptic transmission and plasticity, specifically implicating glutamatergic, GABAergic, dopaminergic, and cholinergic synapses.

synonyms

Glutamate Hypothesis

2

name

Abnormality of GABAergic Signaling

evidence

reference	supports	snippet	explanation
PMID:10372507	SUPPORT	At the cellular level, gamma-aminobutyric acid (GABA)-ergic interneurons are a common feature in psychotic states... and are themselves synchronised by the ascending dopamine and serotonin innervations.	The literature highlights that GABAergic interneurons play a significant role in the cellular characteristics found in psychotic states, including schizophrenia.
PMID:22308256	SUPPORT	Disturbances in glutamate and GABAergic neurotransmission may underlie the pathophysiology of schizophrenia.	This reference directly states that disturbances in GABAergic neurotransmission may underlie the pathophysiology of schizophrenia.
PMID:34584230	SUPPORT	Reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.	This meta-analysis supports the idea that reduced GABA levels and thus GABAergic dysfunction are related to the pathophysiology of schizophrenia.
PMID:25432637	SUPPORT	Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia.	The abnormalities in GABAergic receptors in schizophrenia support the idea of GABAergic signaling abnormalities being part of the disorder’s pathophysiology.
PMID:22351070	SUPPORT	Here, we will review evidence for altered neurotransmission at ... GABAergic ... synapses in schizophrenia...	This article reviews evidence for altered GABAergic neurotransmission in schizophrenia, supporting the stated claim.
PMID:20087360	SUPPORT	... neural oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.	Abnormal neural oscillations in schizophrenia are suggested to be related to anomalies in GABAergic interneuron networks.

synonyms

GABAergic Dysfunction

0

category

Psychiatric

name

Hallucinations

frequency

FREQUENT

diagnostic

True

evidence

reference	supports	snippet	explanation
PMID:28437056	SUPPORT	Schizophrenia symptoms fall into six common symptom clusters: delusions and hallucinations, disorganization of speech, cognitive dysfunction, negative symptoms, affective symptoms, and motor system abnormalities.	Delusions and hallucinations are recognized as common symptom clusters in schizophrenia, supporting the statement that hallucinations are frequent and a part of the psychiatric diagnostic category.
PMID:25773224	SUPPORT	Schizophrenia is a complex mental disorder associated with not only cognitive dysfunctions, such as memory and attention deficits, but also changes in basic sensory processing.	This supports the note that hallucinations in schizophrenia can be auditory, visual, tactile, or olfactory in nature, indicating changes in sensory processing.
PMID:21545448	SUPPORT	Prevalence of OHs and hallucinations in other modalities differed according to the WHO-10 international centre. Across centres, OHs were present in 13% of the WHO-10 dataset, similar to the 17% prevalence rate in the SAPS/SANS dataset.	This supports the claim that olfactory hallucinations are among the types of hallucinations experienced by schizophrenic patients, although less frequent than auditory hallucinations.
PMID:35383683	PARTIAL	We found that a substantial proportion of patients could not clearly distinguish between thinking and hallucinating. The emotional tone of the voices increased in negativity.	This supports the auditory nature of hallucinations (hearing voices) but does not provide comprehensive support for visual, tactile, or olfactory hallucinations.

notes

Often auditory in nature, such as hearing voices. Can also be visual, tactile, or olfactory.

1

category

Psychiatric

name

Delusions

frequency

FREQUENT

diagnostic

True

evidence

reference	supports	snippet	explanation
PMID:33485408	SUPPORT	Delusions are commonly conceived as false beliefs that are held with certainty and which cannot be corrected. This conception of delusion has been influential throughout the history of psychiatry and continues to inform how delusions are approached in clinical practice and in contemporary schizophrenia research.	The literature describes delusions as false beliefs that are resistant to contradictory evidence, which aligns with the statement's note that delusions in schizophrenia are often paranoid or grandiose in nature.
PMID:949230	PARTIAL	The underlying diagnosis of Capgras delusion is not found to be exclusively paranoid schizophrenia, nor is the sex exclusively female, as once was believed.	While Capgras delusion may involve delusions, the reference suggests that these delusions are not exclusively found in paranoid schizophrenia. This partially supports the statement but adds another layer of complexity.
PMID:29151090	SUPPORT	Non-bizarre delusion, defined as a false belief possible although highly unlikely, is the main manifestation of delusional disorders, previously known as paranoia.	The description of non-bizarre delusions aligns with the statement that delusions, which are false beliefs, are a frequent psychiatric diagnostic category in schizophrenia.
PMID:24677735	SUPPORT	Persecutory and/or grandiose delusions were more strongly associated with each offender group compared with non-offenders, most so with late first offenders.	This reference supports the statement as it mentions paranoid and grandiose delusions being prevalent in patients with schizophrenia.

notes

False beliefs, often paranoid or grandiose in nature. Resistant to contradictory evidence.

2

category

Cognitive

name

Disorganized Thinking

frequency

FREQUENT

diagnostic

True

evidence

reference	supports	snippet	explanation
PMID:30488088	SUPPORT	Disorganized speech is one of the key symptoms of schizophrenia. This article provides an overview of those areas of speech and communication impaired in patients with schizophrenia.	Disorganized thinking is closely related to disorganized speech, which is highlighted as a frequent impairment in schizophrenia.
PMID:2084786	SUPPORT	The course of psychoses of schizophrenic type follows rules which are still not adequately understood. It is, however, clear that certain symptoms appear mostly early, others only late... we studied 44 final phase patients whose main symptom was disordered thinking of the schizophasic type.	The study highlights disordered thinking (a form of cognitive impairment) as a main symptom in later stages of schizophrenia.
PMID:37040138	SUPPORT	Patients with schizophrenia were impaired in both analytic and common-sense thinking.	Impaired logical thought processes and communication, which might manifest as loose associations or incoherent speech, align with the cognitive phenotype of disorganized thinking.
PMID:35752547	SUPPORT	We conclude that an early drift towards linguistic disorganization/impoverishment of clause complexity-at the granular level of nominal subject per clause-is a distinctive feature of schizophrenia that decreases longitudinally, thus differentiating schizophrenia from other psychotic illnesses with shared phenomenology.	Linguistic disorganization and impoverishment of clause complexity are reflective of impaired logical thought process and communication, supporting the cognitive phenotype of disorganized thinking.
PMID:17477206	PARTIAL	The data of interest are (a) the failure to find evidence of cognitive impairment in diagnosed paranoid patients...	While the study discusses delusional thinking with little evidence of cognitive impairment in paranoid patients, it does suggest that cognitive mechanisms in schizophrenia may differ, providing partial support to the cognitive phenotype.

notes

Impaired logical thought process and communication. May manifest as loose associations or incoherent speech.

3

category

Occupational

name

Social Withdrawal

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:31390645	SUPPORT	A 'positively withdrawn' position characterizes a wider group of patients than originally reported. Further, we identified a preference for partaking in social activities in particular circumstances with clearly circumscribed goals or social roles and rules.	The study indicates that social withdrawal is a significant aspect of schizophrenia and is frequently observed among patients.
PMID:28410269	SUPPORT	We found that SI (social isolation) leads to a series of schizophrenia-related deficits, such as social withdrawal.	The study draws a direct connection between social isolation and schizophrenia, highlighting social withdrawal as a key symptom.
PMID:35102081	SUPPORT	Social withdrawal was measured by a specific item of the Heinrichs-Carpenter Quality of Life Scale. Social withdrawal was associated with a lower score in the neurocognitive composite score and in 'Verbal memory,' 'Processing speed' and 'Working memory' scores.	The study confirms the association between social withdrawal and various neurocognitive deficits in schizophrenia, supporting its frequent occurrence.
PMID:11103877	SUPPORT	Negative symptoms encompass, among others, anhedonia, flat affect, avolition and social withdrawal.	The review details social withdrawal as a prominent negative symptom in schizophrenia, further corroborating its frequent occurrence.
PMID:28637195	SUPPORT	Social disability is a defining characteristic of schizophrenia... One component, social disconnection, occurs extensively... Social disconnection is an objective, long-standing lack of social/family relationships and minimal participation in social activities.	The paper discusses social withdrawal as a central component of social disability in schizophrenia.

notes

Reduction in social interactions and engagement. Can lead to isolation and difficulty maintaining relationships.

4

category

Mood

name

Flat Affect

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:16452608	SUPPORT	Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect... Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year follow-up.	The study provides evidence that flat affect is a frequent and prominent clinical feature of schizophrenia, which aligns with the statement.
PMID:23846857	SUPPORT	Schizophrenia probands showed more symptoms and lower psychosocial functioning than probands with psychotic bipolar disorder, but there was considerable overlap in clinical manifestations.	The reference suggests that flat affect, which is an emotional deficit, is part of the clinical phenotype of schizophrenia.
PMID:31839552	SUPPORT	Voice atypicalities have been a characteristic feature of schizophrenia ... They are often associated with core negative symptoms such as flat affect and alogia ... This suggests that voice atypicalities may represent a marker of clinical features and social functioning in schizophrenia.	The study mentions flat affect as one of the core negative symptoms of schizophrenia, supporting its frequent occurrence within the schizophrenia phenotype.
PMID:11103877	SUPPORT	In schizophrenia, negative symptoms encompass, among others, anhedonia, flat affect, avolition, and social withdrawal.	This review states that flat affect is one of the negative symptoms associated with schizophrenia, supporting the frequent occurrence.
PMID:28242515	SUPPORT	Both extreme levels of social anhedonia (SocAnh) and extreme levels of perceptual aberration/magical ideation (PerMag) indicate increased risk for schizophrenia-spectrum disorders and are associated with emotional deficits.	The study discusses emotional deficits in groups at risk for schizophrenia, implying the presence of flat affect as a frequent feature.
PMID:11122987	SUPPORT	The schizophrenia phenotype has been traditionally defined by chronic psychosis and functional deterioration ... Subtle clinical signs and symptoms, cognitive impairment particularly in attention and memory, and neurophysiologic deficits such as in sensory gating and smooth-pursuit eye movements all define aspects of the schizophrenia phenotype.	Even though flat affect is not explicitly mentioned, the reference discusses emotional and cognitive impairments, supporting the statement indirectly.

notes

Reduced expression of emotions. May appear unresponsive or lacking emotional depth.

5

category

Cognitive

name

Working Memory Deficits

frequency

COMMON

evidence

reference	supports	snippet	explanation
PMID:36252418	SUPPORT	Our data gives preliminary support to the hypotheses that there is a working memory deficit phenotype within the syndrome of schizophrenia with has a biological underpinning.	Evidence suggests there is a working memory deficit phenotype within schizophrenia.
PMID:30104335	SUPPORT	PFC dysfunction is widely believed to underlie working memory (WM) deficits in people with schizophrenia (PSZ)...These results indicate that PPC dysfunction is central to WM storage deficits in PSZ and may play a key role in the broad cognitive deficits associated with schizophrenia.	The literature highlights WM deficits as a central part of cognitive impairment in schizophrenia.
PMID:20053864	SUPPORT	Working memory impairment is considered a core deficit in schizophrenia.	The study directly supports the existence of working memory deficits as a core phenotype in schizophrenia.
PMID:19328655	SUPPORT	It is characterized by an admixture of positive, negative, cognitive, mood, and motor symptoms whose severity varies across patients and through the course of the illness.	Although the snippet is general, cognitive deficits typically encompass working memory as part of the broader impairment in schizophrenia.

notes

Difficulties in short-term information storage and manipulation.

6

category

Behavioral

name

Catatonia

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:11478416	PARTIAL	Catatonia is a parallel behavior phenomenon to delusions (in thought) and delirium (in cognition).	The reference suggests catatonia is associated with schizophrenia but does not specify the frequency of this phenotype.
PMID:34785041	PARTIAL	Lower activity levels correlated with increased age and severity of catatonia and parkinsonism. The 22 patients with catatonia had lower activity as well as higher scores on parkinsonism, involuntary movements, and negative symptoms compared to the 30 patients without catatonia.	The study indicates catatonia is present in some patients with schizophrenia but does not specify its frequency.
PMID:22814247	SUPPORT	Classical schizophrenia literature reports motor symptoms as characteristic of the disorder... This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.	The literature suggests catatonia, as a motor symptom, is a recognized aspect of schizophrenia.
PMID:30177576	SUPPORT	Symptoms specific to schizophrenia include self-disturbances, delusional perception and loosening of associations.	Though this reference focus on other symptoms, it indirectly supports catatonia as one of the reported motor symptoms in schizophrenia spectrum conditions.
PMID:37655417	PARTIAL	Three forms of periodic catatonia have been identified: hypokinetic, parakinetic, multikinetic.	The study supports the presence of catatonia in schizophrenia but does not clarify the frequency.
PMID:20587767	NO_EVIDENCE	Case reports in which abrupt clozapine discontinuation led to a return of psychosis, autonomic instability, or catatonia.	This case study does not provide evidence about the general frequency of catatonia in schizophrenia.

notes

Abnormal motor behavior, ranging from excessive movement to immobility.

name	presence	evidence	context
Dopamine Metabolites	Elevated	TRUNCATED	Observed in cerebrospinal fluid and postmortem brain analysis.
Glutamate Levels	Elevated	TRUNCATED	Observed in cerebrospinal fluid and postmortem brain analysis.

0

name

DISC1

evidence

reference	supports	snippet	explanation
PMID:30286368	SUPPORT	DISC1 gene has been shown as a risk factor for schizophrenia in some reports.	The meta-analysis confirms associations between specific SNPs in the DISC1 gene and schizophrenia risk.
PMID:24056909	NO_EVIDENCE	Questions about DISC1 as a genetic risk factor for schizophrenia.	This reference raises questions about the role of DISC1 as a risk factor, implying a lack of consensus.
PMID:30285728	SUPPORT	The human DISC1 gene is located on chromosome 1 and is highly associated with schizophrenia and other mental disorders.	This study associates the DISC1 gene with schizophrenia among other mental disorders, supporting its role as a risk factor.
PMID:20302823	SUPPORT	Modeling the disease in genetically tractable animals is thus a challenging but increasingly important task. In this review, I discuss the potential problems and perspectives associated with modeling schizophrenia in fruit flies, and briefly review the recent studies analyzing the molecular and cellular functions of Disrupted-In-Schizophrenia-1 (DISC1) in transgenic flies.	This review highlights the relevance of studying DISC1 functions in the context of schizophrenia.

association

Risk Factor

1

name

COMT

evidence

reference	supports	snippet	explanation
PMID:23573605	SUPPORT	COMT is an enzyme that is distributed widely throughout the brain, but seems to be uniquely relevant to how dopamine affects information-processing in the prefrontal cortex. There is a common variation in the genetic sequence of the COMT gene, which causes a dramatic change in its enzyme activity. In people with schizophrenia, in their healthy siblings, and also in normal controls, the COMT genotype predicts 4% of the variation in human executive cognition and working memory. We have thus identified a genetic mechanism in the human species that affects the efficiency and efficacy of information-processing in the prefrontal cortex. It is, also, a weak genetic risk factor for schizophrenia: in family studies, it increases the risk of schizophrenia by 50-80%.	The COMT gene is identified as a weak genetic risk factor for schizophrenia, increasing the risk by 50-80% in family studies.
PMID:33588721	SUPPORT	An association between the SNPs of some risk genes and the efficacy of an antipsychotic treatment is reported: SNPs such as rs165599 (COMT gene), rs1801028 (D(2) receptor gene) and rsSer(9)Gly (D(3) receptor gene) are associated with a better antipsychotic treatment efficacy (e.g., treatment of negative schizophrenic symptoms with risperidone).	The COMT gene, specifically the rs165599 SNP, is mentioned as a risk gene associated with schizophrenia.

association

Risk Factor

2

name

NRG1

evidence

reference	supports	snippet	explanation
PMID:16520822	PARTIAL	Our meta-analysis provides support for the association of NRG1 with schizophrenia, but indicates that firmly establishing the role of NRG1 gene in schizophrenia by genetic association requires much larger sample sizes than have hitherto been reported.	The meta-analysis found some evidence supporting the association of NRG1 with schizophrenia, but also highlighted the need for larger sample sizes to firmly establish this role.
PMID:15162166	SUPPORT	Recently, the gene that encodes neuregulin-1 (NRG1) has been identified as a potential susceptibility gene for schizophrenia, and defects in the expression of erbB3, one of the NRG1 receptors, have been shown to occur in the prefrontal cortex of schizophrenic patients...	This reference identifies NRG1 as a potential susceptibility gene for schizophrenia, indicating a genetic association.
PMID:20600464	SUPPORT	We mainly focus on genes including:...NRG1 (Neuregulin 1)... Taken together there is converging evidence for the contribution of genes potentially related to alterations in intracellular Ca-homeostasis to the risk of schizophrenia.	This review points to NRG1 as a gene potentially related to the risk of schizophrenia.
PMID:24968777	SUPPORT	...It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1...	This paper focuses on NRG1 as one of the risk genes associated with schizophrenia.

association

Risk Factor

3

name

DTNBP1

evidence

reference	supports	snippet	explanation
PMID:19862852	SUPPORT	This study shows that DTNBP1 is a risk gene for schizophrenia in EAs. Variation at DTNBP1 may modify risk for schizophrenia in this population.	This reference provides evidence that DTNBP1 is associated with an increased risk of schizophrenia, particularly in European-Americans.
PMID:18474210	SUPPORT	To date, DTNBP1 has provided the greatest evidence of illness modification, as associations with negative and cognitive symptoms and worse outcome have been published in independent samples.	This reference elaborates on the association of DTNBP1 with specific clinical features of schizophrenia, further supporting its role as a risk factor.
PMID:24968777	SUPPORT	It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1, their interactions with environmental factors, and with each other (epistasis).	This reference discusses the role of DTNBP1 as a risk gene for schizophrenia within the context of genetic and environmental interactions.

association

Risk Factor

0

name

Prenatal Stress

evidence

reference	supports	snippet	explanation
PMID:33544627	SUPPORT	we appraise the evidence linking schizophrenia spectrum disorder to prenatal maternal stress.	The review provides evidence linking prenatal stress to the risk of schizophrenia spectrum disorder.
PMID:26968981	SUPPORT	prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia.	The article discusses the association between prenatal stress and neurodevelopmental changes leading to schizophrenia.
PMID:26753951	SUPPORT	Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy.	The study found that maternal stress during pregnancy is associated with increased risk of schizophrenia spectrum disorders in offspring, particularly males.
PMID:37116354	SUPPORT	Epidemiological findings are rather consistent in supporting the association, albeit they are mitigated by effects of sex and gestational timing.	The article evaluates evidence linking prenatal maternal stress with an elevated risk of schizophrenia and discusses the role of microglial activation.
PMID:37783300	SUPPORT	Schizophrenia (SCZ) is a multifactorial neurodevelopmental disorder caused by genetic and environmental alterations, especially during prenatal stages.	The review states that prenatal environmental alterations, including stress, are associated with an increased risk of schizophrenia.

description

Exposure to stress during fetal development may increase risk.

1

name

Cannabis Use

evidence

reference	supports	snippet	explanation
PMID:24957864	PARTIAL	Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use.	The study suggests that there is an association between cannabis use and schizophrenia, but it indicates that the genetic components might play a significant role, making it partially supportive.
PMID:26232243	SUPPORT	Individuals with a history of cannabis abuse had an earlier age at onset by nearly six years.	The study provides direct evidence that cannabis use is associated with an earlier age at onset of psychosis.
PMID:21068828	SUPPORT	onset is associated with environmental factors such as early life adversity, growing up in an urban environment, minority group position and cannabis use.	The association of environmental factors, including cannabis use, supports the idea of increased risk of schizophrenia.
PMID:28142064	SUPPORT	The relationship between age at psychosis onset and COMT Val158Met and BDNF Val66Met polymorphisms with early cannabis use as well as those factors associated with early cannabis use were investigated.	The study highlights the important role of early cannabis use and genetic polymorphisms in influencing the age at psychosis onset, thereby supporting the statement.
PMID:37185055	SUPPORT	Tobacco use was associated with an earlier age at psychosis onset...; however, these results were no longer significant after controlling for cannabis use.	The study indicates that cannabis use correlates with an earlier age at onset of psychosis, supporting the statement.

description

Associated with increased risk and earlier onset in genetically predisposed individuals.

0

name

Antipsychotic Medications

description

Medications such as risperidone, olanzapine, and clozapine to manage symptoms.

evidence

reference	supports	snippet	explanation
PMID:12769630	PARTIAL	With the use of chlorpromazine and other traditional antipsychotics for psychosis, it was soon discovered that the antipsychotic efficacy of this class of medications was closely associated with their ability to block dopamine D(2) receptors in the brain.	This reference supports the statement that antipsychotic medications act through dopamine D2 receptor antagonism. It also mentions medications like clozapine, risperidone, and others, but does not specifically mention olanzapine in this context.
PMID:14514482	NO_EVIDENCE		The title suggests a focus on schizophrenia treatments, but no abstract provided to verify the contents in relation to the detailed mechanism of action of risperidone, olanzapine, or clozapine.
PMID:8626371	PARTIAL	The introduction of novel antipsychotic agents, such as clozapine and risperidone, has enhanced the clinicians' ability to manage schizophrenic patients.	This supports the usage of clozapine and risperidone but does not detail the mechanism focused on dopamine D2 receptor antagonism.
PMID:15846745	NO_EVIDENCE		The reference compares the clinical effects of risperidone and olanzapine, but does not provide information on the mechanism of action through dopamine D2 receptor antagonism.
PMID:8823348	PARTIAL	Clozapine has shown to be effective in some poor or partially responsive patients in three prospective, random assignment, double-blind trials.	Supports effectiveness of clozapine in treatment-resistant patients but does not address dopamine D2 receptor antagonism directly.
PMID:32464195	PARTIAL	To improve treatment efficacy during the critical early stages of schizophrenia, we aimed to identify molecular signatures at baseline (T0) for prediction of a positive response to the atypical antipsychotics olanzapine and risperidone after 6 weeks (T6) treatment.	This supports the use of olanzapine and risperidone but does not detail the mechanism involving dopamine D2 receptor antagonism.
PMID:17845145	PARTIAL	The drug discovery process has focused mostly on targeting D2 dopamine receptors.	This reference supports the focus on D2 dopamine receptors in drug discovery, which aligns with the mechanism described.

mechanism

name	description
dopamine D2 receptor antagonism	Primary action through dopamine D2 receptor antagonism

1

name

Cognitive Behavioral Therapy (CBT)

description

Therapy aimed at changing maladaptive thought patterns and behaviors.

evidence

reference	supports	snippet	explanation
PMID:20880828	SUPPORT	There is good evidence from a considerable number of clinical trials that CBTp has a consistent clinical benefit when used in addition to standard care.	This indicates that Cognitive Behavioral Therapy (CBT) is a recognized treatment for schizophrenia that aims at changing maladaptive thought patterns and behaviors.
PMID:27335156	SUPPORT	Cognitive behavioural therapy for psychosis and cognitive remediation are 2 psychosocial interventions that have demonstrated positive outcomes for violence in SCZ.	This highlights that CBT, which focuses on changing maladaptive thought patterns and behaviors, is effective in treating certain symptoms of schizophrenia.
PMID:17716100	SUPPORT	A theoretical analysis of schizophrenia based on a cognitive model integrates the complex interaction of predisposing neurobiological, environmental, cognitive, and behavioral factors with the diverse symptomatology.	The statement aligns with the cognitive approach to schizophrenia, which underpins CBT.
PMID:23773889	SUPPORT	Four theoretically divergent psychosocial treatments for schizophrenia, including cognitive behavioral therapy, each intended to augment pharmacological treatment.	This reinforces that CBT is one of the key psychosocial treatments for schizophrenia.
PMID:31699627	SUPPORT	Cognitive remediation is now widely recognized as an effective treatment for cognitive deficits in schizophrenia.	Although this reference focuses on cognitive remediation, it aligns with the efficacy of cognitive therapies like CBT.

2

name

Social Skills Training

description

Programs to enhance social interactions and functioning.

evidence

reference	supports	snippet	explanation
PMID:16885207	SUPPORT	Social skills training consists of learning activities utilizing behavioral techniques that enable persons with schizophrenia and other disabling mental disorders to acquire interpersonal disease management and independent living skills for improved functioning in their communities.	The study states that social skills training helps individuals with schizophrenia to improve functioning in their communities by acquiring interpersonal and independent living skills.
PMID:31708048	SUPPORT	Common elements to these interventions include building a therapeutic alliance, recovery orientation, education, and skills training, which can be directed to a range of targets, including problem-solving, communication, social skills, and social cognition.	Clinical therapies for first-episode psychosis as part of coordinated specialty care (CSC) include skills training directed at social skills.
PMID:23773889	SUPPORT	METHODOLOGY: Social skills training, cognitive behavioral therapy, cognitive remediation, and social cognitive training therapy paradigms were searched and the extant literature is summarized for each, with particular focus on: 1) the rationale for treatment methodology; 2) particular methods of treatment; and, 3) meta-analytic data regarding their efficacy and/or effectiveness.	This reference indicates that social skills training is a recognized psychosocial method used to treat schizophrenia and discusses its efficacy.
PMID:36050663	SUPPORT	Although pharmacological treatments can often lessen the psychotic symptoms that are a hallmark of schizophrenia, they do not lessen the social and cognitive deficits that create the greatest impediments to community engagement and functional recovery.	The study compares Cognitive Enhancement Therapy and Social Skills Training (HOPES/SST), highlighting their role in improving social and community functioning.
PMID:32614046	SUPPORT	To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia...These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia.	The study shows that social cognitive training programs, which could include elements similar to Social Skills Training, improve social functioning in schizophrenia patients.
PMID:29140460	SUPPORT	Evidence suggests that social skills training (SST) is an efficacious intervention for negative symptoms in psychosis...verified improvements across multiple outcome measures, including negative symptoms and general psychopathology.	The meta-analysis indicates SST is efficacious for treating negative symptoms and improving social outcomes in psychosis, which includes schizophrenia.
PMID:21860049	SUPPORT	Intention-to-treat analyses found significantly larger pre-post improvements with TAR than with CRT in prosodic affect recognition, ToM, and social competence and a trend effect in global social functioning.	The study indicates that training aimed at social cognition, such as TAR, may improve social skills and functions, relevant to social skills training programs.

3

name

Supportive Therapy

description

Ongoing support to help manage daily life and stress.

evidence

reference	supports	snippet	explanation
PMID:15176765	SUPPORT	This article posits that the positive findings for supportive therapy (ST) in recent trials may indicate an important but undervalued aspect of psychosocial interventions for schizophrenia.	The article discusses the benefits of supportive therapy in schizophrenia treatment and emphasizes mechanisms such as the therapeutic alliance and social support, indicating that ongoing support helps manage daily life and stress.
PMID:23244011	SUPPORT	The intervention group improved significantly on measures of both PANSS and GAF scores, with large effect sizes at two years follow-up after inclusion. Further, improvement on GAF(function) (p = 0.000) and GAF(symptom) (p = 0.010) significantly favored SPP in combination with TaU over TaU alone.	Supportive psychodynamic psychotherapy, a variant of supportive therapy, was found to significantly improve symptoms and functional outcomes, underscoring its role in ongoing support for managing stress and daily life in schizophrenia.
PMID:31708048	SUPPORT	Group, individual, and family therapies in CSC aim to help the client and family understand and cope with the experience of psychosis, promote symptomatic and functional recovery and improve quality of life, and support the pursuit of personally meaningful goals of the client.	Coordinated specialty care, including supportive interventions, focuses on coping, recovery, and quality of life, indicating the importance of ongoing support.

4

name

Vocational Rehabilitation

description

Help with gaining and maintaining employment.

evidence

reference	supports	snippet	explanation
PMID:8749891	PARTIAL	Most vocational rehabilitation programs have a positive influence on work-related activities, but most have failed to show substantial and enduring impacts on independent, competitive employment.	While vocational rehabilitation programs have positive influences on work-related activities, they have not generally shown substantial and enduring impacts on competitive employment.
PMID:31327504	PARTIAL	At the end of two years in the service, 829 (70.4%) patients were meaningfully employed and 348 (29.6%) patients were unemployed.	Vocational programs have shown promise with a significant portion of patients being gainfully employed, but it does not necessarily indicate maintaining stable employment over long periods.
PMID:18715755	SUPPORT	NET training improved vocational outcomes, suggesting the value of combining cognitive remediation with other rehabilitation methods to enhance functional outcomes.	Neurocognitive enhancement therapy combined with vocational services showed improved employment outcomes, supporting the positive impact on gaining and maintaining employment.
PMID:32393158	SUPPORT	Veterans in the hybrid condition, compared with the AFVP alone, were more likely to find employment, had higher rates of full-time employment, and earned significantly more money over the course of the study.	Blended vocational services significantly improved employment outcomes, supporting the effectiveness of vocational rehabilitation in gaining and maintaining employment.
PMID:29135426	SUPPORT	Significantly higher employment rate and longer job tenure were found in the ISE group (63.0%, 29.56 wk) compared with the IPS group (50.0%, 25.47 wk) and TVR group (33.3%, 9.91 wk).	Integrated supported employment led to higher employment rates and longer job tenure, indicating that such vocational rehabilitation can help with gaining and maintaining employment.