Neurometabolites

What are neurometabolites?
Products of normal chemical metabolism may be altered in schizophrenia. Changes in metabolite levels may be indicative of altered biochemical activity. Magnetic resonance spectroscopy (MRS) has been used to measure levels of neurometabolites, such as N-acetylaspartate (NAA), creatine (Cr), and glutamine (Gln). These derivatives are indirect indicators of biochemical activity. Alteration in levels of NAA/Cr is associated with the protective myelin sheath surrounding neurons, which is used as a marker of neural cell viability. Decreased levels of NAA are associated with neuron death, or injury to the part of the neuron that connects to other cells, the axon. Gln is a metabolite of the neurotransmitter, glutamate (Glu).
What is the evidence on neurometabolites?
High quality evidence found a small decrease in myo-inositol levels in the medial prefrontal region in people with schizophrenia compared to controls. Moderate to high quality evidence found N-acetylaspartate levels were reduced in the frontal lobe, temporal lobe, thalamus, hippocampus, cerebellum, and cingulate cortex. Lower quality evidence also found reduced N-acetylaspartate in the parietal lobe, basal ganglia, and occipital lobe (white matter only). N-acetylaspartate may be increased in the striatum and the lenticular nucleus. There were small to medium-sized reductions in glutamate, and increases in glutamine, in the frontal cortex of people with schizophrenia, which may progress with age.
In unmedicated people with schizophrenia (drug naive or drug free), there were reductions in N-acetylaspartate in the thalamus and in frontal white matter (using <3T MRI scanners only), and medium-sized increases in glutamate+glutamine in the medial prefrontal cortex, and increases in choline in the basal ganglia. There were no changes in glutamate, creatine or myo-inositol in unmedicated patients.
In first-degree relatives of people with schizophrenia, there were N-acetylaspartate reductions in the anterior cingulate and in the hippocampus. In people at either clinical or genetic high-risk of schizophrenia, there were N-acetylaspartate reductions in the thalamus and in the N-acetylaspartate/creatine ratio in the prefrontal cortex.
October 2020
Fact Sheet Technical Commentary
NeuRA Libraries
-
Bipolar Disorders Library
- Assessment and diagnosis
-
Signs and symptoms
- General signs and symptoms
-
Cognition
- Attention
- Cognition and bipolar type
- Cognition and functioning
- Cognition and symptoms
- Cognition in bipolar versus depression
- Cognition in bipolar versus schizophrenia
- Cognition in children with bipolar disorder
- Cognition in first-episode bipolar disorder
- Cognition in late-life bipolar disorder
- Cognition in relatives
- Decision making
- Episodic future thinking
- Executive functioning
- Impulsivity
- Insight
- IQ and general cognition
- Language
- Learning
- Memory
- Metacognition
- Processing speed
- Reasoning
- Social cognition
- Visuospatial ability
-
Treatments
-
Physical
- Non-pharmaceutical
-
Pharmaceutical
- Mood stabilisers
- Antidepressants
- Antipsychotics
- Adjunctive and alternative treatments
-
Treatments for specific symptoms and populations
- Treatments during pregnancy and breastfeeding
- Treatments for aggression and agitation
- Treatments for bipolar II disorder
- Treatments for bipolar versus unipolar depression
- Treatments for children
- Treatments for cognitive symptoms
- Treatments for dual diagnosis
- Treatments for elderly patients
- Treatments for first-episode bipolar disorder
- Treatments for high-risk groups
- Treatments for medication resistance
- Treatments for mixed states
- Treatments for rapid cycling
- Treatments for relapse prevention
- Treatments for suicide and self-harm
- Other
- Psychosocial
-
Physical
-
Risk factors and antecedents
- Antecedents
-
Non-genetic risk factors
- Adult life events
- Childbirth
- Childhood adversity
- Environmental toxins
- Ethnicity
- Familial factors
- Infectious agents
- Maternal diet during pregnancy
- Maternal illness during pregnancy
- Migration
- Obstetric complications
- Parental age
- Parental education
- Parental psychological factors
- Rheumatoid arthritis
- Sibship
- Socioeconomic status
- Substance use
- Traumatic brain injury
- Urbanicity
- Winter birth
-
Illness course and outcomes
- Absconding
- Age at onset
- Attitudes to medication
- Creativity
- Criminal offending, aggression and violence
- Criminal victimisation
- Cultural differences
- Dietary intake
- Drug and alcohol use
- Employment
- First-episode bipolar disorder
- Functional outcomes
- Homelessness
- Hope
- Menopause
- Mortality
- Parenthood
- Pathways to care
- Pediatric bipolar disorder
- Physical activity
- Physical health monitoring
- Quality of care
- Quality of life
- Recovery
- Relapse
- Relationships
- Religiosity
- Smoking
- Stigma
- Suicide and self-harm
- Treatment non-adherence
- Treatment resistance
- Insights for families
-
Physical features
-
Functional changes
- Body functioning
-
Biochemical changes
- Brain pH and lactate
- Calcium
- Complex I and IV
- Dopamine
- GABA
- Gut microbiota
- Homocysteine
- Hypothalamic-pituitary-adrenal axis
- Infectious agents
- Inflammation and immune system dysfunction
- Insulin-like growth factor
- Lipids
- Neurometabolites
- Neuropeptides
- Neurotrophins
- NMDA receptor function
- Oxidative stress
- S100 proteins
- Serotonin
- Uric acid
- Vitamin B
- Cerebral blood flow and metabolism
- Electrophysiology
- Structural changes
-
Functional changes
-
Co-occurring conditions
- Mental disorders
-
Physical disorders
- Asthma
- Blood disorders
- Cancer
- Cerebrovascular disease
- Dementia
- Diabetes
- Digestive disorders
- Epilepsy
- Fibromyalgia
- Heart disease
- Infectious diseases
- Metabolic syndrome
- Multiple sclerosis
- Musculoskeletal and connective tissues
- Obesity
- Optical alterations
- Osteoporosis
- Pain and migraine
- Parkinson’s disease
- Peripheral vascular disease
- Premenstrual syndrome
- Respiratory disease
- Sleep apnea
- Thyroid disorders
- Visual impairment
- Wilson’s disease
- Substance use
- Epidemiology
- General information
-
Post-Traumatic Stress Disorder Library
-
Schizophrenia Library
- Assessment and diagnosis
-
Signs and symptoms
-
General signs and symptoms
- Dermatoglyphics
- Disorganised symptoms
- Dissociation
- Early detection
- Functional laterality
- Minor physical anomalies
- Morphometrics
- Movement disorders
- Negative symptoms
- Neurological soft signs
- Olfactory functioning
- Pain sensitivity
- Personality and temperament
- Positive symptoms
- Psychotic relapse
- Sleep disturbance
- Temperature regulation
- Voice patterns
-
Cognition
- Attention
- Cognition in high-risk groups
- Cognition in schizophrenia and bipolar disorder
- Cognitive functioning related to symptoms
- Decision making
- Defeatist performance beliefs
- Episodic future thinking
- Executive functioning
- Impulsivity
- Information processing
- Insight
- IQ
- Language
- Learning
- Memory
- Metacognition
- Psychomotor ability
- Reasoning ability
- Rigidity
- Social cognition
- Time perception
- Tone perception
- Visuospatial ability
-
General signs and symptoms
-
Treatments
-
Physical
-
Pharmaceutical
-
First-generation antipsychotics
- All antipsychotics versus placebo
- Benperidol
- Bromperidol
- Chlorpromazine
- Droperidol
- First versus second generation
- Flupentixol
- Fluphenazine
- Fluspirilene
- Haloperidol
- Levomepromazine
- Loxapine
- Metiapine
- Molindone
- Penfluridol
- Perazine
- Perphenazine
- Pimozide
- Piperacetazine
- Pipotiazine
- Sulpiride
- Thioridazine
- Trifluoperazine
- Zuclopenthixol
-
Side effects
- Blood disorders
- Bone density
- Cancer
- Cardiometabolic changes and weight gain
- Catatonia
- Constipation
- Dysphagia
- Extrapyramidal
- Hyperprolactinaemia
- Hypersalivation
- Hyponatraemia
- Mortality
- Neuroleptic malignant syndrome
- Neutropenia
- Oculogyric crisis
- Pancreatitis
- Polycystic ovarian syndrome
- Sedation
- Seizures
- Sexual dysfunction
- Thyroid dysfunction
-
Second-generation antipsychotics
- All antipsychotics versus placebo
- Amisulpride
- Aripiprazole
- Asenapine
- Blonanserin
- Brexpiprazole
- Cariprazine
- Carpipramine
- Clocapramine
- Clotiapine
- Clozapine
- First versus second generation
- Iloperidone
- Lurasidone
- Mosapramine
- Olanzapine
- Paliperidone
- Perospirone
- Quetiapine
- Remoxipride
- Risperidone
- Second versus second generation
- Sertindole
- Ziprasidone
- Zotepine
-
Side effects
- Blood disorders
- Bone density
- Cancer
- Cardiometabolic changes and weight gain
- Catatonia
- Constipation
- Dysphagia
- Extrapyramidal
- Hyperprolactinaemia
- Hypersalivation
- Hypomania
- Hyponatraemia
- Mortality
- Neuroleptic malignant syndrome
- Neutropenia
- Oculogyric crisis
- Pancreatitis
- Polycystic ovarian syndrome
- Sedation
- Seizures
- Sexual dysfunction
- Thyroid dysfunction
-
Adjunctive treatments
- Adenosine modulators
- Amphetamines
- Analeptics
- Anti-inflammatory
- Anticholinergic
- Anticonvulsants
- Anticraving agents
- Antidepressants
- Benzodiazepines
- Beta blockers
- Calcium channel blockers
- Cannabinoids
- Catecholamines
- Cholinergic medications
- Cholinesterase inhibitors
- Erythropoietin
- Essential fatty acids
- Estrogen
- GABA agonists
- GHB
- Glutamate receptor modulators
- Herbal medicines
- Mood stabilisers
- Oxytocin
- Promethazine
- Serotonin modulators
- Sodium nitroprusside
- Statins
- Testosterone
- Alternative treatments
-
Treatments for specific symptoms and populations
- Treatments during pregnancy and breastfeeding
- Treatments for aggression and agitation
- Treatments for childhood and early-onset schizophrenia
- Treatments for cognitive symptoms
- Treatments for constipation
- Treatments for depressive symptoms
- Treatments 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 hyperprolactinaemia
- Treatments for hypersalivation
- Treatments for medication non-adherence
- Treatments for medication-resistant schizophrenia
- Treatments for movement disorders
- Treatments for negative symptoms
- Treatments for relapse prevention
- Treatments for schizoaffective disorder
- Treatments for sexual dysfunction
- Treatments for sleep disturbance
- Treatments for smoking cessation
- Treatments for social functioning
- Treatments for weight gain
- Other pharmaceutical topics
-
First-generation antipsychotics
- Non-pharmaceutical
-
Pharmaceutical
-
Psychosocial
-
Therapies
- Acceptance and commitment therapy
- Animal-assisted therapy
- Art and drama therapies
- Avatar therapy
- Case management
- Cognitive behavioural therapy
- Community care
- Cost
- Crisis intervention
- Crisis planning
- Dance therapy
- Day centres and day hospitals
- Dialectical behavioural therapy
- Distraction techniques
- Educational therapies
- Enriched intervention
- Family intervention
- Genetics counselling
- Group therapy
- Home-based care
- Hypnosis
- Inpatient and outpatient care
- Integrated care
- Life skills programs
- Metacognitive training
- Mindfulness
- Monetary incentives
- Morita therapy
- Music therapy
- Nidotherapy
- Open dialogue approach
- Peer support
- Physical restraint
- Prevention programs
- Problem solving skills training
- Psychodynamic psychotherapy
- Shared decision making
- Strengths-based delivery
- Supported housing
- Supportive therapy
- Telemental health
- Therapeutic relationship
- Token economies
- Trauma-focused therapies
- User-held records
- Virtual reality
-
Therapies for specific symptoms and populations
- Therapies for childhood onset and early onset schizophrenia
- Therapies for cognition
- Therapies for dual diagnosis
- Therapies for fathers with schizophrenia
- Therapies for first-episode psychosis
- Therapies for insight
- Therapies for internalised stigma
- Therapies for mothers with schizophrenia
- Therapies for negative symptoms
- Therapies for positive symptoms
- Therapies for PTSD symptoms
- Therapies for quality of life
- Therapies for smoking
- Therapies for social functioning
- Therapies for treatment non-adherence
- Therapies for treatment resistance
- Therapies for unemployment
- Therapies for weight gain
- Treatments for high-risk groups
-
Therapies
-
Physical
-
Risk factors and antecedents
-
Antecedents
- 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
-
Non-genetic risk factors
- Adult life events
- Childhood adversity
- Congenital rubella syndrome
- Environmental toxins
- Ethnicity
- Family relationships
- Famine
- Genetic and non-genetic risk
- 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
- Genetic risk factors
-
Antecedents
-
Illness course and outcomes
- Absconding
- Age at onset
- Childhood and early-onset schizophrenia
- Creativity
- Criminal offending, aggression and violence
- Criminal victimisation
- Cultural differences
- Diet
- Drug and alcohol use
- Duration of untreated psychosis
- Duration of untreated psychosis and outcomes
- Electronic device use
- Employment
- First-episode psychosis
- Functional outcomes
- Homelessness
- Hope
- Late-onset schizophrenia
- Loneliness
- Mortality
- Parenthood
- Pathways to care
- Physical activity
- Physical health monitoring
- Psychotic relapse
- Quality of care
- Quality of life
- Relationships
- Religiosity
- Remission and recovery
- Sex differences
- Smoking
- Stigma and attitudes towards mental health
- Suicide and self-harm
- Treatment adherence
- Treatment-resistance
- Insights for families
-
Physical features
-
Functional changes
- Body functioning
-
Biochemical changes
- Brain pH and lactate
- cAMP
- Cholesterol
- Dopamine
- Endocannabinoids
- GABA
- Hormonal changes
- Hypothalamic-pituitary-adrenal axis
- Infectious agents
- Inflammation and the immune system
- Lipids
- Melatonin
- Melatonin
- Neurometabolites
- Neuropeptides
- Neurotrophins
- Nitric oxide
- NMDA receptor function
- Oxidative stress
- S100 Proteins
- Serotonin
- Synaptic proteins
- Trace elements
- Vascular endothelial growth factor
- Vitamin B
- Vitamin D
- Cerebral blood flow and metabolism
- Electrophysiology
- Structural changes
- Brain regions
-
Functional changes
-
Co-occurring conditions
- Mental disorders
-
Physical disorders
- Auditory system dysfunction
- Autoimmune diseases
- Blood disorders
- Cancer
- Cerebrovascular disease
- Dementia
- Dental disease
- Diabetes
- Digestive disorders
- Epilepsy
- Heart disease
- Infectious diseases
- Metabolic syndrome
- Musculoskeletal and connective tissues
- Obesity
- Optical alterations
- Peripheral vascular disease
- Polycistic ovary syndrome
- Postoperative complications
- Reproductive and urological disorders
- Respiratory system dysfunction
- Sexual dysfunction
- Skin disorders
- Sleep apnea
- Thyroid disorders
- Underweight
- Substance use
- Epidemiology
- General information
-
Podcast Library
Green - Topic summary is available.
Orange - Topic summary is being compiled.
Red - Topic summary has no current systematic review available.