The catchment site in India comprises of 4 adjoining taluks (administrative sub-districts) in the district of Kanchipuram of Tamil Nadu state in Southern India. The site lies about 50 km from the state capital of Chennai (formerly Madras) and extends for about 50 km end-to-end. The catchment area is comprised of 16 towns and 448 villages with a population of about 1 million individuals, with more than 60% of the population being between the ages of 18 and 64 years (the age group of interest for INTREPID II). 

Country
India

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INTREPID II is being conducted, nearly 30% of the population lives below the poverty line. Although English is the official language of the country, over 500 native languages are spoken in Nigeria, including Hausa, Yoruba, Igbo and Fula. â€‹ â€‹The catchment site in Nigeria comprises 3 Local Government Areas in and around the metropolitan city of Ibadan, the capital of Oyo State, South West Nigeria: Idaban North East, Ibadan South East, and Ona-Ara.The catchment areas have a population over a million individuals, with close to 52% of the population being between the ages of 18 and 64 years (the age group of interest for INTREPID II).

Country
Nigeria

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​The catchment area for this study is in Trinidad and consists of the municipalities of Diego Martin, Port of Spain, San Juan/Laventille, Tunapuna/Piarco, Arima, Chaguanas and Sangre Grande. The population at risk is 487,159. 

Country
Trinidad and Tobago

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The Early Career Award (formerly Travel Award) program is intended to sponsor individuals who have, through their research, teaching or clinical activities, demonstrated a professional and scientific interest in the field of schizophrenia research. Candidates must indicate their interest in schizophrenia research and, if possible, provide evidence of continuing and future involvement and activity in the field. Individuals must be graduate students, residents, fellows, or new/young faculty members who have completed their last training within 5 years. Candidates who are members of an ethnic minority group underrepresented in biomedical science areas are strongly encouraged to apply.

Awardees are required to submit a poster/oral presentation abstract. It is the belief of the Society that the opportunity to attend its scientific meeting will stimulate the interest of young scientists in schizophrenia research by affording them the opportunity to attend an outstanding scientific program in clinical and basic research. The program will also allow awardees the opportunity to become aware of the most recent, and often unpublished, advances in schizophrenia research, meet internationally distinguished researchers and clinicians, and interact with world authorities working on the frontier of this field.

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npj Schizophrenia is an open access, online-only journal that aims to publish high-quality original papers and review articles relevant to all aspects of schizophrenia and psychosis, from molecular and basic research through environmental or social research, to translational and treatment-related topics. npj Schizophrenia publishes papers on the broad psychosis spectrum including affective psychosis, bipolar disorder, the at-risk mental state, psychotic symptoms, and overlap between psychotic and other disorders.

npj Schizophrenia is published in partnership between The Schizophrenia International Research Society and Nature Publishing Group. Authors whose papers are accepted for publication within npj Schizophrenia are required to pay an article processing charge (APC). All SIRS members are entitled to a discounted APC (50% reduction on the full rate) if an article for which they are the corresponding author is accepted for publication within the journal.

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The Research Harmonisation Group (RHG) consist of from five to twenty senior researchers who have a research track record in the topic covered by the Group (the 2020 the research topic is epidemiology). At least half the members should be early career researchers (post docs, first time lecturers) who are nurtured by senior members of the group. The Society recognizes early career researchers as individuals who are less than 40 years of age or within five years post-doc of their terminal degree taking into account career breaks.  The senior researchers and early career researchers must be SIRS members.

The RHG must demonstrate that they have input from consumers who have shown an interest in research in the topic covered by the group but are not necessarily members. The purpose of Research Harmonisation Groups (RHG) is to produce methods for sharing and/or comparing data across countries to increase the creative drive of schizophrenia research internationally.

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Schizophrenia Bulletin seeks to review recent developments and empirically based hypotheses regarding the etiology and treatment of schizophrenia. We view the field as broad and deep, and will publish new knowledge ranging from the molecular basis to social and cultural factors. We will give new emphasis to translational reports which simultaneously highlight basic neurobiological mechanisms and clinical manifestations. Much of the Bulletin content will be invited reviews and manuscripts organized as a theme by special guest editors. Also, the Bulletin will carry unsolicited manuscripts of high quality that report original data related to theme issues or where the Bulletin can provide a special venue for a major study.

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Schizophrenia Research is an international, multidisciplinary journal that promotes rapid publication of new international research that contributes to the understanding of schizophrenic disorders. It is hoped that this journal will aid in bringing together previously separated biological, clinical and psychological research on this disorder, and stimulate the synthesis of these data into cohesive hypotheses.

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Schizophrenia International Research Society aims for action and not just words. The SIRS community must be representative of the communities we seek to help. We have made some progress, but still not enough, on gender discrimination. We now need to commit to actions that will reduce other sources of discrimination, including race. SIRS affirms a commitment to diversity within our research endeavors so we can understand the effects of structural discrimination and how it affects the onset, maintenance and exacerbation of problems for people with a diagnosis of schizophrenia. This requires us to monitor and report on diversity among our research participants and investigate its effects on our scientific understanding.

As a global community of researchers, clinicians, educators, students and people with lived experiences, we have a shared and individual responsibility towards eradicating inequality, discrimination and injustice. We do this not only through our research, but in our everyday life. This can only be done through joint and individual education. Our task is to understand white privilege and eschew white exceptionalism, so we can use this knowledge to improve our research and the ambitions of the community as a whole. We have already taken some concrete and meaningful steps, including a commitment to anti-racism. But words are not enough. We need to act. So, in developing our next 5-year strategy, the building of an inclusive, diverse and equitable society focused on improving the lives of people with a diagnosis of schizophrenia will be a central theme. The society commits to ensuring that every committee will have representation of women and ethnic minorities, every conference will have plenary speakers from under-represented groups and that all our awards will ensure that diversity is a key consideration, including our new Research Harmonization Award.

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Special Interests Groups at the Schizophrenia International Research Society Include:

• Accelerated Aging and Stress in Severe Mental Disorders: monica.aas@medisin.uio.no  
• Developmental Trauma and Psychosis Network (DTPN): m.bloomfield@ucl.ac.uk
• Global Initiative for Integrated Research on Psychosis: ncrossley@uc.cl or craig.morgan@kcl.ac.uk
• Treatment Response and Resistance in Psychosis: oliver.howes@lms.mrc.ac.uk
• Lifestyle Interventions in Schizophrenia: Improving the Outcome: peter.falkai@med.uni-muenchen.de
• Trials in Schizophrenia: thomas.raedler@albertahealthservices.ca
• Multicenter, multimodal study of first episode psychosis: molecules, circuits, and clinical manifestations: asawa1@jhmi.edu
• Physical Health Comorbidity Among People with Schizophrenia: d.siskind@uq.edu.au
• Social Cognition Across the Autism-Psychosis Spectrum: Working towards an International Consensus Battery: t.b.ziermans@uva.nl

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Schizophrenia is a mental illness that occurs in about 1% of the population and usually begins to show signs in late adolescence or early adulthood. It appears slowly with a decline in ability to concentrate and focus on schoolwork or other activities, withdrawal from friends and social groups, and an increase in what appears as day dreaming and “escape from reality”. Often this happens without those closest to the person realizing what is happening until a crisis appears. For information about schizophrenia, please view the various videos below.

The society depends on contributions from individuals and corporations with an interest in combating mental illness. There are not enough funding opportunities for research on schizophrenia provided by public and private funds. Thus, the society hopes to bridge this gap in order to facilitate more rapid progress toward eradicating schizophrenia. Please consider donating by clicking here.

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First generation ‘typical’ antipsychotics are an older class of antipsychotic than second generation ‘atypical’ antipsychotics. They are used primarily to treat positive symptoms including the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). These include:

• Benperidol

• Bromperidol

• Chlorpromazine

• Droperidol

• Flupentixol

• Fluphenazine

• Fluspirilene

• Haloperidol

• Levomepromazine

• Loxapine

• Metiapine

• Molindone

• Penfluridol

• Perazine

• Perphenazine

• Perazine

• Perphenazine

• Pimozide

• Piperacetazine

• Pipotiazine

• Sulpiride

• Thioridazine

• Trifluoperazine

• Zuclopenthixol

• Side effects

• All antipsychotics versus placebo

• First versus second generation

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions).

• Amisulpride

• Aripiprazole

• Asenapine

• Blonanserin

• Brexpiprazole

• Cariprazine

• Carpipramine

• Clocapramine

• Clotiapine

• Clozapine

• Iloperidone

• Lurasidone

• Mosapramine

• Olanzapine

• Paliperidone

• Perospirone

• Quetiapine

• Remoxipride

• Risperidone

• Sertindole

• Ziprasidone

• Zotepine

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There are a number of supplementary (or adjunctive) treatment that are administered in conjunction with a patient’s ongoing antipsychotic therapy. These include:

• Adenosine modulates (particularly dipyridamole and propentofylline) may improve symptoms, particularly positive symptoms, in people with schizophrenia.
• Amphetamines: single-dose dexamfetamine or methylphenidate increases severity or frequency of positive symptoms, particularly in patients who are not in remission.
• Analeptics (such as modafinil) have been suggested as potential adjunctive treatments for schizophrenia. Modafinal is a wake-promoting drug (mechanisms of action unknown) which is thought to help with the sedation side-effects of antipsychotics. 

• Anti-inflammatory: growing evidence suggests that inflammatory processes may contribute to the development of schizophrenia. This suggests a potential role for anti-inflammatory medications, such as non-steroidal agents (e.g., aspirin) which may be potentially useful therapeutic strategies, particularly in combination with ongoing antipsychotic medication.

• Anticholinergics block the action of the neurotransmitter acetylcholine. Anticholinergic medications may have some utility for the treatment of side effects of antipsychotic medications, including movement disorders like akathisia (a type of restlessness, a common side effect of many neuroleptics), as well as excessive salivation. 

• Anticonvulsant medications influence the actions of neurotransmitters including glutamate and GABA, leading to a decrease in brain cell (neuron) excitability. They may be prescribed as an immediate adjunct to antipsychotic medication in order to treat acute symptoms of psychosis, such as aggressive behaviour. They may also be used as part of an ongoing treatment regime in order to supplement antipsychotic effects or combat side effects like movement disorders. Anticonvulsant medications assessed in this topic primarily include valproate, carbamazepine, and lamotrigine.

• Anticraving medications (such as naltrexone) that aim to reduce craving for and use of substances may improve substance dependence in people with schizophrenia.

• Antidepressants: have been proposed as an additional therapy to standard antipsychotic treatments, in an attempt to improve functional outcomes and treat symptoms that are not addressed by the antipsychotic medication alone. Antidepressant medications have been studied as treatments for the symptoms of schizophrenia, particularly negative symptoms, as well as for treating people with co-occurring schizophrenia and depression.

• Benzodiazepines may be implemented as an adjunct to antipsychotic medication in order to treat acute symptoms of psychosis such as agitation, aggression, irritability, or anxiety. They may also be used to treat side effects of antipsychotic medications such as movement disorders including tardive dyskinesia, however they are associated with their own side effects and are associated with well-established patterns of tolerance and dependence, so they are prescribed with caution.

• Beta blockers can be prescribed in addition to standard antipsychotic regimes in order to target some side effects of these medications, including extrapyramidal symptoms such as akathisia (a type of restlessness, a common and early-onset side effect of many neuroleptics). Beta blockers have also been used to reduce the physical symptoms of anxiety in people with schizophrenia (for example, pounding heart, clammy hands, sweating), and have also been suggested to reduce aggression.

• Calcium channel blockers are prescribed with extreme caution due to their potential for extreme side effects, and the dopamine-blocking actions that may interfere or interact with neuroleptic medications.

• Cannabinoids

• Catecholamines: L-DOPA improve overall symptom severity and may benefit tardive dyskinesia.

• Cholinergic medications have been prescribed for tardive dyskinesia, which is a common side effect of antipsychotics, involving repetitive, involuntary movements most commonly occurring around the mouth and face. 

• Cholinesterase inhibitors (ChEI) (or anticholinesterase) have been proposed as an additional therapy to standard antipsychotic treatments in an attempt to improve functional outcomes and treat symptoms that are not addressed by the antipsychotic medication alone. 

• Erythropoietin

• Essential fatty acids: people with schizophrenia have shown to have lower levels of these essential compounds and their products,including omega-3 products docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), its esther, ethyl-eicosapentaenoic acid (E-EPA), omega-6 product arachidonic acid (AA), and their metabolites including prostaglandins (PGE).

• GABA (gamma-aminobutyric acid) is a common neurotransmitter in the brain, and GABA-ergic neurons are thought to interact with antipsychotic medications, contributing to side effects such as tardive dyskinesia. GABA-acting medications (such as baclofen, progabide, or sodium valproate) may contribute to increasing the activity of GABA neurons, potentially leading to reduced medication side effects. 

• GHB

• Glutamate receptor modulators: have been suggested as an adjunctive therapy to standard antipsychotic treatments, when individuals have sub-optimal responses to treatment. The glutamate receptor modulators that have been trialed in schizophrenia are predominantly amino acids, and act on several different aspects of the glutamatergic neurotransmission system. Agents include glycine, D-serine, D-cycloserine, D-alanine, CX516, sarcosine, N-acetyl cysteine, and memantine. These agents have been studied for efficacy in improving symptom severity and cognitive function.

• Mood stabilisers have been proposed as an adjunctive therapy to standard antipsychotic treatments when individuals have sub-optimal responses to treatment. Mood stabilisers may be implemented as an immediate therapy for acute symptoms of psychosis, but they may also be used as part of an ongoing treatment regime. Mood stabiliser medications assessed in this topic include lithium as well as anticonvulsant medications (valproate, carbamazepine, and lamotrigine).

• Nicotine

• Oestrogen is a hormone that has been proposed to confer a protective effect for schizophrenia.  This protective effect may mean that pre-menopausal women who develop schizophrenia may experience a less severe illness than males. Oestrogens are not used routinely for people with schizophrenia; however some studies have trialed the use of oestrogen as an additional, adjunctive treatment to standard antipsychotic treatment.

• Oxytocin is a neuromodulatory neuropeptide that is important for the correct processing of emotional stimuli in a social context. It has been proposed that difficulties in social cognition in schiozphrenia and other disorders such as autism, are underpinned by disruption in the dopaminergic/oxytonergic circuitry linked to socio-emotional processing. Oxytocin has been linked to prosocial behaviours in some studies, but not in others. So, oxytocin effects may be moderated by features of the social environment or individual differences.

• Promethazine medications are a type of sedative, in the class of antihistamine drugs. One widely known commercial promethazine is Phenergan. They work on the central nervous system, resulting in a decrease in brain cell activity. Promethazine has been used in combination with antipsychotics in situations where benzodiazepines may not be used in order to evoke sedative effects.

• Serotonin Modulators: atypical antipsychotics are thought to have some affinity for serotonin 5-HT receptors (e.g. clozapine, quetiapine and olanzapine among others) suggesting a potential for the use of serotonin-specific medications in the treatment of schizophrenia.

• Sodium nitroprusside

• Statins are effective cholesterol lowering agents and are used to prevent cardiovascular disease improving symptoms of schizophrenia when given in conjunction with antipsychotics.

• Testosterone is a hormone that has shown to be reduced in people with schizophrenia. Although not used routinely as a therapy for schizophrenia, some studies have trialed the use of testosterone as an additional, adjunctive treatment to standard antipsychotic treatments.

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Antecedents are physical and cognitive alterations observed in people prior to the onset of schizophrenia, usually in childhood and adolescence, and may be early indicators of illness progression. They are still being investigated, but may include motor and cognitive dysfunction, speech and language impediments, behavioural problems and psychopathology such as anxiety, delusions and hallucinations.

• Attention dysfunction

• Autonomic nervous system anomalies

• Behavioural disturbances and psychopathology

• Dermatoglyphic anomalies

• Eye tracking anomalies

• Face emotion processing anomalies

• Height and body mass index

• IQ and academic performance

• Mild physical anomalies

• Motor dysfunction

• Olfactory identification deficits

• Sleep disturbance

• Speech and hearing deficits

• Stress responsivity anomalies

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A diagnosis of schizophrenia is not a simple one, with symptoms varying across individuals. This category contains information about diagnostic tools for schizophrenia and related disorders, and early detection tools for identifying those at risk of a first episode of psychosis.

• Outcome Assessment Tools

• Early Detection

• First-Episode Psychosis

• High-Risk Groups

• Treatments for High-Risk Groups

• Duration of Untreated Psychosis and Outcomes

• Duration of Untreated Psychosis

• Cognition in High-Risk Groups

• Treatments for Cognitive Symptoms

• Schizoaffective Disorder

• Schizophrenia

• Schizophreniform Disorder

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• Treatments for constipation: adjunct medications prescribed to treat side effects such as constipation may contribute to increasing adherence to antipsychotics which can reduce the risk of psychotic relapse.

• Treatments for hyperprolactinaemia: one potential side effect of antipsychotic use is hyperprolactinaemia, which can disrupt sex hormones and the production and flow of breast milk, and can cause infertility and erectile dysfunction in men. Hyperprolactinaemia is caused by blocking of the D2 dopamine receptor at the anterior lobe of the pituitary gland, resulting in high prolactin levels. As different antipsychotics have different actions, they also differ in the degree to which they affect prolactin levels.

• Treatments for hypersalivation: antipsychotic medications (such as clozapine and olanzapine among others) may induce excessive (hyper) salivation, which can be uncomfortable and embarrassing as well as increasing the risk of aspiration pneumonia. Various pharmacological approaches have been used to try and alleviate this problem. Adjunctive medications prescribed to treat such side effects may contribute to increasing adherence to antipsychotic medications, which reduces the risk of psychotic relapse.

• Treatments for movement disorders: the antipsychotic promethazine and pyridoxal 5 phosphate (vitamin B6), the anxiolytic buspirone, the cognitive enhancer/stimulant pemoline, and the alkaloids dihydrogenated ergot alkaloid and L-Stepholidine, GABA-acting medications, branched-chain amino acids, enzyme VMAT2 inhibitors, ginkgo biloba, and the antiepileptic levetiracetam, the antidepressant isocarboxazid over the anticholinergic procyclidine all help reduce tardive dyskinesia. There were no significant benefits for tardive dyskinesia of ceruletide, vitamin E, cholinergic medications, noradrenergic or dopaminergic medications, benzodiazepines, evening primrose oil, lithium, oestrogen, the antidepressants selegiline and ritanserin, melatonin, the antihistamine cyproheptadine, the alkaloid papaverine, the cognitive enhancer piracetam, eicosapentaenoic acid derivative, and the antiepileptic levetiracetam. 

• Treatments for sexual dysfunction: sildenafil may improve sexual functioning in males with schizophrenia.

• Treatments for sleep disturbance

• Treatments for smoking cessation: heavy cigarette use may contribute to the increased mortality and reduced life expectancy reported within the schizophrenia population.

• Treatments for weight gain

• Herbal medicines

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Biochemical changes include the research into changes in biochemical levels in people with schizophrenia, which indicate markers for the disorder and can provide insights into improved drug treatments.

• Brain pH and lactate

• cAMP

• Cholesterol

• Dopamine is a neurotransmitter that is important for emotional and cognitive processing in the brain, particularly rewarding and pleasurable stimuli or experiences. Alterations of the dopamine system have been suggested in schizophrenia. This may be assessed as changes in levels of dopamine or its metabolites, or as changes in levels or activity of the mechanical components of the dopamine system, such as the receptors that receive dopamine, or the transporters that remove it.

• GABA (gamma-aminobutyric acid) is the most important inhibitor of neurotransmitters in the central nervous system and is often dysfunctional in people with mood disorders that has also been investigated in people with schizophrenia. GABA can be measured via peripheral levels in plasma, via central levels in cerebrospinal fluid, and in brain regions using magnetic resonance spectroscopy (MRS). Possible GABA dysfunction has led to interest in GABA-acting medications as possible adjunctive treatments for schizophrenia (such as baclofen, progabide, and sodium valproate).

• Homocysteine

• Hormonal Changes

• Hypothalamic-pituitary-adrenal axis (HPA)

• Infectious Agents

• Lipids

• Inflammatory and immunological change

• Melatonin

• Neurometabolites

• Neuropeptides

• Nitric Oxide (NO): disturbances in NO formation or release could interfere with the known functions of NO activity (including neural maturation and synapse formation) could have relevance for possible neurodevelopmental aetiology of schizophrenia.

• NMDA receptor function: there may be changes in levels of glutamate and its metabolites and changes in levels or activity of mechanical components of the NMDA receptor system (such as the receptors that ‘receive’ glutamate or the transporters that ‘remove’ it) in schizophrenia.

• Oxidative stress: there is decreases in catalase and superoxide dismutase in red blood cells, and decreases in nitrate and uric acid in plasma in people with first-episode psychosis.

• S100 proteins: there is a potential susceptibility of S100 gene in schizophrenia.

• Serotonin is a neurotransmitter whose dysregulation may underlie the negative symptoms and high rates of depression seen in people with schizophrenia. Selective serotonin reuptake inhibitors have been found to be effective in treating the negative symptoms of the disorder with acute tryptophan depletion (a dietary manipulation that lowers brain serotonin (5-HT) synthesis) being shown to worsen negative symptoms.

• Synaptic Proteins

• Translocator protein

• Vitamin B

• Vitamin D

• Zinc: reduced zinc levels in people with schizophrenia compared to people without schizophrenia, particularly in patients who were newly diagnosed and drug-naive.

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There are numerous changes of brain structure in people with schizophrenia, particular in the various regiuons of the brain

• Brain weight

• Amygdala 

• The arcuate fasciculus 

• The basal ganglia

• Cerebellum

• Cingulate cortex

• Claustrum

• Corpus callosum

• Default mode network

• Frontal Lobe

• Hippocampus

• Insular Cortex

• Occipital Lope

• Pareital Lobe

• Temporal Lobe

• Thalamus

• Ventricular System

• Wholve Brain Volume

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Cognition signs and symptoms include a lack of function mental actions or processes such as attention, memory, planning, problem solving, and social cognition. Research into cognition in people with schizophrenia has found anomalies across a range of thought processes, which interfere with the individual’s ability to function. 

• Attention

• Cognition in high-risk groups

• Cognition in schizophrenia and bipolar disorder

• Cognitive functioning related to symptoms

• Decision Making

• Defeatist performance beliefs are over-generalised negative thoughts about one’s ability to successfully perform goal-directed behaviour. This prevents the initiation of and engagement in social and employment opportunities and therefore is considered a possible contributing factor to negative symptoms and poor functional outcomes.

• Episodic future thinking refers to thought processes that contribute to the mental construction, imagination or simulation of possible future events. Episodic future thinking plays a role in planning, problem-solving, coping, regulating emotional states and goal-motivated behaviour.

• Executive functions are a group of cognitive processes involving control, mental flexibility, planning, inhibition, decision-making, initiation, abstraction, self-monitoring and pursuit of goals. Any impairment in executive functioning can also reflect impairments in other cognitive functions such as processing speed, attention, and memory. 

• Impulsivity is a predisposition towards unplanned reactions to internal or external stimuli, without regard to the consequences, which is a major feature in a variety of psychiatric disorders.

• Information processing involves a number of cognitive functions (including perception, attention, memory, decision making and the speed at which these cognitive functions are executed with impairments in information processing reflecting impairments in these other cognitive domains.

• Insight is defined as the awareness of having a mental disorder including an understanding of the social consequences associated with the disorder; the need for treatment; the effects of medication; an awareness of the implications; and awareness of the signs and symptoms of the disorder. Insight is clinically important as it is linked to non-adherence of treatment, as patients who lack insight may not believe they have a psychotic illness and therefore do not believe they need medication.

• IQ: moderate to high quality evidence finds a large effect of lower IQ in people with schizophrenia, including people with first-episode, youth-onset, or late-onset schizophrenia, with late-onset samples showing the greatest impairment.

• Language may be altered in people with schizophrenia and may present in the form of disorganised speech. 

• Learning: people with schizophrenia have poorer verbal learning, verbal memory, verbal paired associate learning and verbal recognition. Learning is the ability to acquire, or change, existing knowledge, behaviours or skills.

• Memory: people with schizophrrenia have poorer short-term, long-term, working, episodic, prospective, and memory binding in people with schizophrenia. Memory involves encoding, storage and retrieval of information.

• Metacognition refers to ‘thinking about thinking’ and involves active control over the cognitive processes engaged in thinking and acquiring knowledge or learning. Negative beliefs about thoughts (e.g. uncontrollability and dangerousness) and more cognitive confidence (confidence in one’s memory and attentional capabilities) have been absorbed in people with psychotic disorders.

• Psychomotor ability refers to a wide range of actions involving physical movement with poor psychomotor ability in people with schizophrenia, including people with first-episode schizophrenia, or early onset schizophrenia.

• Reasoning Ability refers to the ability to logically gather information to form conclusions and solve problems. People with schizophrenia may show impaired reasoning, with bias in the way they gather information, interpret events and develop beliefs. 

• Rigidity is an inability to change mental or behavioural sets when required (i.e. behavioural, cognitive or attitudinal) and plays a large affect in people with disabilities. 

• Social Cognition: people with schizophrenia often have impaired social perception, emotion perception, emotion processing, impaired social knowledge, biological motion processing, and empathetic abilities.

• Time perception involves the capacity to accurately process temporal information that is embedded in relevant events with the ability to perceive, remember, and organise behaviour in periods ranging from seconds to minutes mediates functions, from basic motor coordination to decision making in people with schizophrenia.

• Tone Perception: low-level sensory functioning may be impaired in people with schizophrenia and may contribute to higher-order cognitive and social impairments. Tone perception involves pitch discrimination, 

• Visuospatial ability refers to a person’s capacity to identify visual and spatial relationships among objects with poor global visuospatial ability often appearing in people with schizophrenia

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• Anxiety

• ADHD

• Autism

• Depression

• Dissociative Disorders

• Intellectual Disability

• Personality Disorders

• Polydipsia

• PTSD

• Substance Use

• Drug & Alcohol Use

• Smoking

• Auditory system dysfunction: people with schizophrenia may show increased rates of unrelated co-occurring dysfunction of the auditory system or structural abnormalities of the ear canal.

• Autoimmune diseases: people with schizophrenia may show increased rates of autoimmune diseases are caused by an overactive immune system.

• Blood disorders: people with schizophrenia may show increased rates of co-occurring conditions disorders of the blood such as leukocytosis (excess leukocytes), hypokalemia (reduced potassium), and neutropenia (low neutrophil levels).

• Cancer

• Cerebrovascular Disorder

• Dementia

• Diabetes

• Digestive Disorders: people with schizophrenia may show increased rates of co-occurring conditions, including appendicitis, gastric ulcers, irritable bowel syndrome, or celiac disease.

• Epilepsy

• Infectious Disabilities

• Metabolic Syndromes

• Musculoskeletal and connective tissues

• Obesity: people with a severe mental illness are at increased risk of obesity, which may be due to genetic and/or socio-economic factors, lifestyle choices, or metabolic effects of psychotropic medications. 

• Peripheral vascular disease

• Polycistic ovary syndrome

• Postoperative complications

• Reproductive and urological disorders

• Respiratory system dysfunction

• Skin Disorders

• Sleep Apnoea

• Thyroid Disorders

• Underweight

• Visual Impairment

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• Electroencephalography (EEG) uses electrodes on the scalp to measure electrical activity from the brain. Quantitative spectral EEG investigates several waveforms, and so the activity can be measured, but EEG also gives rise to event related potentials (ERP), which measure the EEG activity directly evoked by a stimulus, often using cognitive or perceptual stimuli.
• Functional magnetic resonance imaging (fMRI) is used to determine functional activation of brain regions when an individual performs tasks (or rests) inside an MRI scanner. Most commonly fMRI studies use visual, auditory, motor or sensory stimuli to evoke neural responses in the brain. Recent fMRI studies also examine activity of the brain at rest. Changes in blood flow are interpreted to represent brain activation (or deactivation) associated with a particular brain state (i.e, while performing a particular activity, or while the brain is at rest). Functional activity has been investigated in people with schizophrenia compared to people without schizophrenia to identify regions of increased or decreased brain function on the basis of blood flow.

• Magnetoencephalography (MEG) uses a helmet-shaped device containing MEG sensors (gradiometers) to noninvasively measure the magnetic fields produced by neural activity of the brain. MEG is able to localise the source of neural activity to particular brain regions, represented as positive and negative charges (dipoles), with greater accuracy than EEG, which is a measure of the electrical fields produced by neural activity. MEG can be used to measure continuous resting-state brain activity (spontaneous MEG), but also to assess event-related changes in brain activity. 

• Transcranial magnetic stimulation (TMS) is a non-invasive method that assesses inhibitory and excitatory mechanisms in the brain. Inhibitory processes include the cortical silent period, which is measured from the motor evoked potential onset to the return of electromyography.

• Computed tomography (CT): is a method for visualising the structural organisation of the brain using the attenuation of X-rays to generate image contrast. Tissues in regions of interest are highlighted based on their X-ray absorption properties, as dense tissues attenuate X-rays more than soft tissues, and air attenuates the least. Three-dimensional images are generated from a series of two-dimension X-ray images taken around a single axis of rotation.

• Optical coherence tomography (OCT):  is an imaging technology that assesses the thickness of the peripapillary retinal nerve fibre layer, macular thickness, and volume. It has been used to assess neurologic diseases such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, and more recently, schizophrenia.

• Diffusion tensor imaging (DTI): DTI is a specialised imaging technique that uses MRI technology to investigate the movement of water within tissues of interest. By applying a magnetic field, the movement (“diffusivity”) of water molecules can be visualised in vivo. The diffusion of water is influenced by the cellular structure of the surrounding tissues, and measures such as fractional anisotropy (FA) were derived as an approximate measurement for the freedom of movement. In areas of high structural coherence such as white matter, FA is highest, indicating that water is moving in relatively fixed directions. It is lower in grey matter, and close to zero in cerebrospinal fluid, indicating that water is moving freely. Consequently, changes in FA values are interpreted to be representing alterations in the structural integrity of the regional white matter.

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Early detection refers to the correct identification of individuals who are at high risk of developing schizophrenia, with an emphasis on the development of frank psychosis. Several assessment tools have been constructed to effectively identify such individuals. Sensitivity of an assessment tool refers to the proportion of people who develop psychosis that were previously identified by the assessment tool as being at high risk. Specificity is the proportion of people who do not develop psychosis that were previously identified as not being at high risk. Assessment tools therefore aim to have both high sensitivity and high specificity. Generally, there are two approaches that dictate the characteristics used as markers for detection.

• The ultra-high risk approach focuses on a triad of at-risk mental states defined as:

1. Having a family history of psychosis plus non-specific symptoms and a recent decline in functioning
2. Showing recent onset of attenuated psychotic symptoms with a decline in functioning
3. Symptoms must be brief, intermittent and limited

• Huber’s Basic Symptoms: focus in a detailed way of describing subjective disturbances, and may be an earlier indicator of risk than the first approach.

the mean rate of transition to psychosis in those assessed as being at clinical high risk for psychosis is around 16% by 2 years and 29% by 3 years. In people assessed as being at clinical high risk of obsessive-compulsive disorder are at higher risk of psychosis than people assessed as being at clinical high risk of bipolar disorder, which in turn has higher risk of psychosis than people assessed as being at high risk of depression. However, the rate of transition to psychosis are only one third the rate of transition to non-psychotic disorders in people at assessed as being at clinical high risk for non-psychotic disorders.

In children and adolescents assessed as being at clinical high risk of psychosis, transition rates were between 17% and 20% by 1 year follow-up and between 7% and 21% by 2 year follow-up. 36% of children and adolescents recovered from their clinical high risk status by 6-year follow-up, and 40% continued to meet clinical high risk criteria without transition to psychosis.

Studies with older samples reported higher transition rates than studies with younger samples, and more recent publications reported lower transition rates than older publications. Studies using the basic symptoms approach reported higher transition rates than studies using the ultra-high risk approach. Studies of people receiving psychosocial treatments (e.g. cognitive behavioral therapy) reported lower transition rates than studies of people receiving standard care (e.g. case management). Studies of people on antipsychotics also reported lower transition rates than studies of people not on antipsychotics. Evidence suggests:

• Instruments based on ultra-high risk criteria have good sensitivity and moderate specificity. Moderate to low quality evidence also suggests the BSABS scale as good sensitivity and moderate specificity. This indicates validated instuments are generally good at correctly identifying individuals who do develop psychosis, but not as good at identifying individuals who do not develop psychosis.
• The model with the best predictive value (86%) for transition to psychosis was a clinical model including:

1. Odd beliefs
2. Marked impairment in role functioning
3. Blunted affect
4. Auditory hallucinations and
5. Anhedonia/asociality.

• A biological model using grey matter volume, and a neurocognitive model using IQ, verbal memory, executive functioning, attention, processing speed, and speech perception, both had positive predictive values of 83%.
• An environmental model with a positive predictive value of 63% involved urbanicity, social-sexual aspects, and social-personal adjustment.
• The best combination model had a positive predictive value of 82% and involved: 

1. Disorganised communication
2. Suspiciousness
3. Verbal memory deficit and
4. Decline in social functioning.

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A population perspective provides epidemiological estimations of the prevalence and incidence of schizophrenia in different populations and regions worldwide. This topic considers the history and burden of schizophrenia, and the implications of mental health laws and policies on the treatment and management of the disorder.

• Burden of Schizophrenia
• History of Schizophrenia
• Schizophrenia Policy & Law
• Overall Incidence of Schizophrenia: the worldwide incidence of schizophrenia and how it varies according to place.
• Spatial Incidence Variation of Schizophrenia
• Worldwide Incidence of Schizophrenia
• Prevalence of Schizophrenia
• Spatial Prevalence of Schizophrenia
• Worldwide Prevalence of Schizophrenia

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Schizophrenia has a large genetic component and as such, families of people with schizophrenia may also be affected by the disorder. Schizophrenia has an impact on the family unit, and also cognitive and physiological alterations in relatives.

• Cognition in families related to schizophrenia: cognitive deficits have been reported in people with schizophrenia including deficits in memory, attention and executive functioning are most commonly reported, with lesser degree of dysfunction in perceptual and language processes. Cognitive deficits are present early in the course of the disorder and are stable over time, and may be heritable. First-degree relatives of people with schizophrenia may show attenuated signs of cognitive deficits.

• The collection of information relating to a person’s family history of mental illness can be a valuable tool for diagnosing and understanding their current mental state, in both clinical and research settings, where it may not be feasible to interview the family members themselves. A patient can usually correctly identify a particular family member with schizophrenia, if one exists.

• Familial coaggregation is the rate of related disorders found in a family. Many studies have suggested a fundamental association between schizophrenia and bipolar disorder. 

• Family relationships: several familial traits have been associated with increased risk for schizophrenia including familial high expressed emotion (hostility, emotional over-involvement, and critical comments); negative parental affective style (guilt induction, over-intrusiveness, and personal criticism); and communication deviance (lack of clarity in communication). People with schizophrenia may have had poor relationships with parents during childhood, with increased family instability, high communication deviance, negative emotions, and poor self-concept.

• Impact on families: a diagnosis of schizophrenia can have a large impact not only on the affected individuals, but also on the people closest to them. This topic considers the impact of schizophrenia on family members, and on the family as a unit. Sometimes the family of a person with schizophrenia may experience different types of burden, particularly during acute phases of the illness. 

• Physical anomalies in first-degree relatives: relatives of people with schizophrenia may show attenuated signs of the illness (such as physical features that are commonly identified with the disorder). Identifying these signs can help determine how genetics may contribute to the risk of schizophrenia.

• Psychopathology in first-degree relatives

• Sibship is a medical term meaning a group of individuals born of the same parents. Factors associated with sibship include birth order, number of siblings or number of births in the family, and inter-birth interval periods. It is not known how these factors may be associated with risk for schizophrenia. There is increased risk of schizophrenia in people who had one, four or five births in their family, or in children born less than 18 months before or after their closest sibling. First birth order may be associated with a reduced risk for schizophrenia.

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• What is schizophrenia and how is it diagnosed?

• Which risk factors are associated with schizophrenia?

• Which treatments are most effective?

• Will family members be affected?

• Would my treatment change if I also have another disorder?

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Brain functional alterations are investigated by using imaging technologies such as functional magnetic resonance imaging and electroencephalogram, and by assessing physical anomalies such as changes in chemical levels and bodily functions.

• Body functioning: changes in body functioning in people with schizophrenia, including movement and sleep disturbances.
• Biochemical changes: changes in biochemical levels in people with schizophrenia that may indicate markers for the disorder and can provide insights into improved drug treatments.
• Cerebral blood flow and metabolism: functional changes in the way the brains of people with schizophrenia are supplied with blood, and how nutrients are provided to cells.
• Electrophysiology: voltage changes or electric current in brain cells and tissue of people with schizophrenia.
• Brain structure: alterations in the brain structure of people with schizophrenia
• Bodily features: structural anomalies in bodily features in people with schizophrenia.
• Brain Regions: changes according to specific regions of the brain.

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Non-pharmaceutical physical treatments for schizophrenia include:

• Acupuncture
• Biofeedback is a technique in which information about the person’s body is fed back to the person so that they may be trained to alter the body’s conditions.

• Electroconvulsive therapy (ECT) is a seizure is electrically induced after the patient has been given a short-acting anaesthetic and is asleep.

• Exercise Therapy

• Transcranial Direct Current Stimulation (tDCS) is a non-invasive form of brain stimulation similar to transcranial magnetic stimulation, but instead of using magnets, it uses a low-intensity, constant current applied through scalp electrodes.

• Transcranial Magnetic Stimulation (TMS) uses an electromagnetic coil placed over the scalp to stimulate the nerve cells beneath it. In general, low frequency stimulation reduces nerve cell activity and high frequency stimulation increases nerve cell activity. Repetitive TMS (rTMS) has been tested as a possible treatment for schizophrenia.

• Vagus Nerve Stimulation (VNS) provides indirect modulation of brain network activity through the stimulation of cranial nerves. Invasive VNS involves surgical implantation of a small pulse generator under the skin which is programmed to deliver long-lasting, intermittent electrical stimulation of the vagus nerve. Non-invasive stimulation involves attaching a stimulator to the outer ear close to the ear canal, which delivers electrical impulses through the skin to the vagus nerve.

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People with schizophrenia usually have physical alterations to their central nervous system including functional and structural changes.

• Cortical release signs

• Movement Disorders

• Neurological Soft Signs

• Olfactory Functioning

• Pain Sensitivity

• Sleep Disturbance

• Temperature Regulation

• Biochemical Changes

• Cerebral blood flow and metabolism

• Eye Movement Dysfunction

• Dermatoglyphics

• Minor Physical Anomolies

• Morphometrics

• Telomere length

• Mismatch negativity (MMN) is an auditory event-related potential that is generated when a stimulus feature deviates from the regularity of previous auditory stimuli. This deviance can be a simple physical characteristic, such as tone duration, intensity, frequency or location; or more abstract presentation characteristics, such as a lower tone in a series of ascending tones. In this way, MMN generation relies on the creation of an auditory (echoic) memory trace for the preceding tones, in order to identify the subsequent deviance. MMN is thought to be an automatic, pre-attentional process and functions as an index of auditory discrimination and echoic memory integrity. MMN is observed as the difference in ERP wave response to the standard stimuli and the deviant stimulus. Larger differences between standard and deviant stimuli and lower probability of deviant occurrence are both associated with larger MMN amplitude.

• N100

• N170

• N250

• N400

• P100

• P200

• P300

• P50

• Prepulse inhibition

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Schizophrenia is a complex disorder and has been associated with many causative factors. With a heritability estimate around 80%, schizophrenia has a strong genetic component and this is reflected in the large number of genes that have been associated with the disorder. At present, the library does not include information on specific genes, but does provide general genetic information, information on family heritability, and the environmental risk factors that have been associated with the disorder. We also include information on the antecedents of schizophrenia, which are potentially very early signs of the disorder. Non-genetic risk factors include various prenatal and perinatal stressors, infectious agents, childhood and adulthood trauma and substance use. The strength of association between non-genetic factors and the subsequent development of schizophrenia is still largely unknown and the interaction effects between genetic and non-genetic factors vary from person to person.

• Genetic Risk Factors
• Genetic & Non-Genetic Risk
• Genetics
• Adult Life Events
• Childhood Adversity
• Congenital rubella syndrome
• Environmental Toxins
• Ethnicity
• Family Relationships
• Famine
• Infectious Agents
• Latitude, climate and winter birth
• Marital status
• Maternal diet and body mass index
• Maternal illness during pregnancy
• Migration
• Obstetric complications
• Parental age at birth
• Parental education
• Parental psychological factors
• Sex differences
• Sibship
• Social capital
• Socioeconomic Status
• Substance Use
• Traumatic Brain Injury
• Urban Environment

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• Age of Onset
• Childhood and early-onset schizophrenia
• Duration of untreated psychosis
• First-episode psychosis
• Late Onset Schizophrenia
• Mortality
• Remission & Recovery
• Psychotic Relapse

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The course and outcomes of disorders vary widely between individuals including chronic schizophrenia, early and late-onset schizophrenia, and first-episode psychosis. Outcomes affecting day to day life include quality of life, relationships, culture, employment, homelessness, violence and self-harm, and recovery and relapse.

• Absconding
• Creativity
• Criminal offending, aggression and violence
• Criminal victimisation
• Cultural differences
• Diet
• Drug & Alcohol Use
• Electronic device use
• Employment
• Functional Outcomes
• Homelessness
• Hope
• Loneliness
• Mortality
• Relationships
• Parenthood
• Pathways to Care
• Physical Activity
• Physical health monitoring
• Quality of Life
• Religosity
• Sex Differences
• Smoking
• Stigma and attitudes towards mental health
• Suicide and self-harm
• Treatment Adherence

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• Positive symptoms are a well-documented feature of schizophrenia and are arguably the most recognisable and conspicuous symptoms. Positive symptoms include hallucinations and delusions. The severity of positive symptoms can significantly affect a person’s day-to-day function, quality of life, and may also be associated with impaired cognitive ability. Positive symptoms have been shown to be more responsive to antipsychotic treatment than other symptom dimensions.

1. Hallucinations are defined as a perceptual experience that occurs in the absence of any external sensory input, and are most commonly auditory, but can occur in any modality.
2. Delusions are distortions or exaggerations of inferential thinking, which lack any logical consistency, are not explained by cultural beliefs, and persist regardless of contradictory evidence. Persecutory delusions involve the belief that people are “out to get” the individual, resulting in a lack of trust in others. Delusion of reference refers to the belief that neutral events are directed specifically towards the individual. Somatic delusions involve the belief that the individual has a physical ailment contrary to medical advice. Delusions of grandeur are characterised by an exaggerated belief that the individual has power, ability, or fame. Positive symptoms can cause extreme distress for the person.

• The ‘negative symptoms’ of schizophrenia refer to an absence of normal functions including a scarcity of facial expressions of emotion, reduced frequency and range of gestures and voice modulation, restricted eye contact, poverty of speech, reduced social interaction, reduced motivation, poor hygiene, and reduced experience of pleasure often manifesting as scarcity of recreation, inability to experience closeness, and reduced interest in any sexual activity. Deficit syndrome is a subtype of schizophrenia with persisting negative symptoms that is described by specifically defined assessments used primarily for research.

• Disorganisation symptoms (Positive Formal Thought Disorder) include disorganised speech and behaviour, as well as inappropriate affect. Severely disorganised speech is difficult to follow, being incoherent, irrelevant and/or illogical. Disorganised speech may also be deprived of content, which is sometimes referred to as negative formal thought disorder symptoms. Disorganised behaviour includes bizarre or inappropriate behaviour, actions or gestures. Inappropriate (incongruous) affect involves exhibiting incorrect emotional responses for a given context. Symptoms of disorganisation have been identified as risk factors for poor illness outcome, and have a significant negative effect on a person’s day-to-day functioning and quality of life. There is evidence to suggest that disorganisation symptoms may be associated with impaired cognitive performance.

• Movement disorders have been reported in people with schizophrenia, with tardive dyskinesia among the most commonly reported. This disorder is a ‘hyper-kinetic’ (excessive movement) disorder, characterised by jerky, involuntary movements, usually of the face and/or limbs. Parkinsonism is another movement disorder associated with schizophrenia, and is a ‘hypo-kinetic’ (reduced movement) disorder, characterised by slowness of movement and rigidity. Movement disorders are primarily associated with the use of antipsychotic medications, however they have also been reported in people who are antipsychotic-naïve.

• Dermatoglyphics (epidermal ridges) are the distinct patterns and lines on the hands and fingers. These ridges appear on the hands between weeks 6 and 15 during foetal development, and remain largely unchanged after this period. 

• Dissociation is described as disruption or discontinuity in the normal integration of consciousness, memory, identity, emotion, perception, body representation, motor control, or behaviour. Common dissociative experiences include mild forms of absorption, such as daydreaming. Less common and more severe dissociative experiences include amnesia, derealisation, depersonalisation, and fragmentation of identity.

• Functional laterality refers to a natural asymmetry in left or right-side dominance, for example in terms of handedness, or brain function. 

• Minor physical anomalies (MPAs) are subtle anatomical deviations that have little functional or aesthetic impact. They may be traced to events occurring prenatally and may represent risk markers for underlying illness susceptibility. MPAs may be important risk indicators when an individual is already at high risk of developing psychosis, for example, having a first-degree relative with psychosis, and when multiple MPAs occur together in one individual.

• Morphometrics is the measurement of the variation in the structure or form of organisms. The study of body shapes and their prevalence in both physical and mental disorders may provide insight into the biology of and risk for schizophrenia.

• Neurological soft signs (NSS) are neurological abnormalities that can be identified by clinical examination using valid and reliable testing measures (integrative sensory functioning, motor coordination, and complex motor sequencing).

• Olfactory functioning: impaired odour detection, identification, and discrimination in people with schizophrenia compared to people without schizophrenia. 

• Pain Sensitivity

• Personality & Temperament

• Sleep Disturbance: people with schizophrenia show large effects of shorter total sleep time, more awake time, longer sleep onset latency, and lower sleep efficiency. 

• Temperature Regulation

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• Children

• Children of people with schizophrenia

• Elderly

• Ethnic Groups

• Forensic Settings

• Homeless People

• Indigenous Populations

• Migrants

• Refugees

• Sex Differences

• Siblings

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• Treatments during pregnancy and breastfeeding

• Treatments for aggression and agitation

• Treatments for childhood and early-onset schizophrenia

• Treatments for cognitive symptoms

• Treatment for Dual Diagnosis

• Treatments for elderly people and people with late-onset schizophrenia

• Treatments for first-episode psychosis

• Treatments for high-risk groups

• Treatments for medication non-adherence

• Treatments for medication-resistant schizophrenia

• Treatments for negative symptoms

• Treatments for relapse prevention

• Treatments for schizoaffective disorder

• Antipsychotic combination treatment (antipsychotic polypharmacy) has been utilised in clinical practice for patients who are unresponsive or partially responsive to antipsychotic monotherapies.

• Costs of Schizophrenia Treatment

• Dosage of Schizophrenia Treatment

• Mode of Administration

• Placebo Response

• Switching Medication

• Alternative Treatments: possible replacement for antipsychotic medications, which can be associated with severe side effects. Alternative therapies may have less debilitating side effects, and so assessing their efficacy is important.

• Anticonvulsants

• Cannabidiol

• Essential fatty acids

• Glutamate receptor modulators

• Herbal Medicines

• Nicotine

• Serotonin Modulators

• Benzodiazepines

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