Brain weight refers to the basic mass measurement of a post-mortem brain, either at time of autopsy (‘fresh’) or after formalin fixation (‘fixed’). Its ease of collection means it is a routine measurement at autopsy and has become a widely used tool for insight into brain integrity. If brain weight is altered, this provides a non-specific indication of neuropathology. It is often a presumed equivalent of the MRI findings of decreased brain volume.

What is the evidence for brain weight?

Moderate quality evidence suggests the brain of a person with schizophrenia is significantly lower in weight than a healthy brain. Moderate quality evidence suggests that male brain weight is significantly inversely correlated with age at disease onset, such that an earlier age at onset indicated a heavier brain weight.

October 2020

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CT imaging 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.

What is the evidence for CT brain structure?

Moderate quality evidence suggests reduced temporal lobe volume in people with schizophrenia. Moderate to low quality evidence is unclear as to the utility of structural imaging as a means of identifying individual structural abnormalities in patients following a first episode of psychosis.

October 2020

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Dermatoglyphics, also referred to as 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. Alterations in the patterns and counts of dermatoglyphics may be an indication of disruption to foetal development in the early- to mid-gestation period. A triradius occurs where three ridge systems meet at a point, and occurs four times on the palm, at the base of each of the four digits (a, b, c, and d). Dermatoglyphic indices include: fingertip patterns; finger ridge counts, which are the number of ridges between the center of the fingertip patterns and their corresponding triradius; palmar ridge counts, which are the number of ridges on the palm connecting two triradii; fluctuating asymmetries, which are the differences in ridge counts or pattern types between parallel structures on the left and right hands; and the ATD angle, which is the angle formed by lines drawn from the most remote triradius near the base of the palm, to triradii a and d, located close to the index and little fingers respectively.

What is the evidence for dermatoglyphics?

Moderate to high quality evidence found a medium-sized effect of reduced total ridge count and a-b palmar ridge count in people with schizophrenia compared to controls, with no differences in ATD angle, fingertip pattern asymmetry or ridge count asymmetry.

February 2022

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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.

What is the evidence for DTI brain structure?

Compared to controls, moderate quality evidence finds white matter reductions in people with schizophrenia in the anterior commissure, corpus callosum, fornix, internal capsule, bilateral arcuate fasciculus, bilateral cingulum, bilateral cortico-ponto-cerebellum tract, bilateral cortico-spinal tract, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, bilateral inferior cerebellar penduculus, bilateral optic radiation, bilateral anterior and posterior segment of the arcuate fasciculus, bilateral superior longitudinal fasciculus 1, 2 and 3, bilateral superior cerebellar penduculus, and bilateral uncinate fasciculus. There was reduced white matter in the left, but not the right, arcuate fasciculus in people with schizophrenia who are experiencing auditory hallucinations.

Moderate quality evidence finds similar decreases in white matter integrity in people with schizophrenia and people with bipolar disorder in the genu of the corpus callosum extending to anterior thalamic radiation/cingulum fibres/inferior fronto-occipital fasciculus, and in left posterior cingulum fibres.

Moderate to high quality evidence found decreased whole brain white matter was associated with a small decrease in positive and general symptoms, and a small increase in negative symptoms. Review authors state these relationships could be explained by older age, which was associated with decreased whole brain white matter. This is because older age has been associated with less severe positive symptoms and more prominent negative symptoms.

High quality evidence found similar reductions in white matter in the genu, but not splenium, of the corpus callosum of male and female patients compared to controls. Although not significant, the reductions were slightly larger in females than in males.

January 2020

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MRI is a used to visualise the structure of the brain and other regions of the body. It uses the magnetic properties inside cells (such as protons) to create a 3D image of the target region. Understanding structural brain alterations in people with schizophrenia may help understand changes in brain development associated with the illness onset or progression, and may help to inform future treatment strategies.

What is the evidence for MRI brain structure?

Moderate to high quality evidence found grey matter reductions in bilateral frontal lobe, anterior and posterior cingulate gyri, superior and medial temporal gyrus, inferior parietal gyrus, corpus callosum, cerebellum, thalamus (particularly mediodorsal, and an absent adhesio interthalamica), insula, amygdala, hippocampus, and parahippocampus in people with schizophrenia compared to controls. Volume increases were found in the caudate, putamen, right globus pallidus, cerebrospinal fluid, and ventricles (lateral, third, and fourth, and a large cavum septum pellucidum). There were white matter reductions in bilateral frontal lobe, anterior commissure, corpus callosum, fornix, internal capsule, left anterior segment of the arcuate fasciculus, left long segment of the arcuate fasciculus, bilateral arcuate fasciculus, bilateral cingulum, bilateral cortico-ponto-cerebellum tract, bilateral cortico spinal tract, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, bilateral inferior cerebellar penduculus, bilateral optic radiation, bilateral posterior segment of the arcuate fasciculus, bilateral superior longitudinal fasciculus 1, 2 and 3, bilateral superior cerebellar penduculus, and bilateral uncinate fasciculus. Moderate to low quality evidence found an absence of normal leftward asymmetry in the planum temporale and Sylvian fissure, and an excess rightward asymmetry in the superior temporal gyrus (particularly posterior). There was also a higher frequency of abnormal (reversed) asymmetry in the frontal and occipital lobes in people with schizophrenia than controls.

Moderate to high quality evidence found auditory hallucinations were associated with grey matter volume reductions in the left superior temporal gyrua, and lower quality evidence also found associations with reductions in insula grey matter volume. Patients with persistent negative symptoms showed reductions in bilateral medial frontal gyrus, left precentral gyrus, left middle frontal gyrus, left caudate nucleus (caudate head), bilateral parahippocampal gyri, left anterior cingulate, thalamus, and insula.

Moderate quality evidence found similar patterns of grey matter abnormalities in antipsychotic-naïve and treated first-episode patients (compared to controls) in the frontal (gyrus rectus), superior temporal, left hippocampal, and insula cortex. Grey matter in the left supramarginal gyrus and left middle temporal gyrus were increased in antipsychotic-naive patients, but decreased in treated patients, while left median cingulate/paracingulate gyri and right hippocampus grey matter were decreased in antipsychotic-naive patients, but increased in treated patients. There was also reduced grey matter volume in the cerebellar vermic lobule IV/V/VII, left cerebellar lobule IV/V, and left cerebellar Crus I in antipsychotic-naïve patients. Increased antipsychotic dose over time (>2 years) was associated with small decreases in parietal and occipital lobe volume, and small increases in basal ganglia volume.

Moderate quality evidence found regions of structural and functional overlap in drug-free patients compared to controls. There was decreased grey matter volume and decreased functional activity in the left medial posterior cingulate/paracingulate gyrus, right temporal pole/superior temporal gyrus, left fusiform gyrus, left inferior parietal gyrus, and left caudate nucleus. There was decreased grey matter volume and increased functional activity in the left superior temporal gyrus, right superior temporal gyrus, left fusiform gyrus, and right lingual gyrus. There was increased grey matter volume and decreased functional activity in the left cerebellum, right gyrus rectus, and right inferior parietal gyrus. There was increased grey matter volume and increased functional activity in the left insula and left cerebellum (lobule IX).

Compared to people with bipolar disorder, moderate to high quality evidence found small reductions in the amygdala, left insula, bilateral hippocampal regions in people with schizophrenia. There was a distinct region of the pregenual cingulate cortex (anterior Brodmann area 24) where grey matter reduction was detected in bipolar disorder and not schizophrenia. Compared to people with an autism spectrum disorder, moderate to low quality evidence found overlapping grey matter volume decreases in the right posterior cingulate cortex, right parahippocampus, and right putamen, and to a lesser extent the right insula and left thalamus.

Moderate quality evidence found people at high genetic risk for schizophrenia showed reduced hippocampus, anterior cingulate, left basal ganglia/claustrum, left thalamus/putamen, right superior frontal gyrus, left insula, left inferior temporal gyrus, and right inferior network, as well as increased left medial frontal gyrus and third ventricle volume compared to controls. People at high clinical risk for schizophrenia showed decreases in the parahippocampus, hippocampus, right anterior cingulate, insula, right middle/superior temporal gyrus, right inferior frontal gyrus, and right frontal gyrus compared to controls. People at high clinical risk showed decreases in the bilateral anterior cingulate compared to people at high genetic risk, and people at high genetic risk showed decreases in the left parahippocampus, insula, and right superior temporal gyrus compared to people at high clinical risk. Moderate to low quality evidence found high risk individuals who transitioned to psychosis had greater pituitary volumes compared to controls and reduced grey matter in the insula, cingulate cortex, superior temporal gyrus, prefrontal cortex, and cerebellum compared to high risk individuals who did not transition to psychosis.

October 2020

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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.

What is the evidence for minor physical anomalies in people with schizophrenia?

Moderate to high quality evidence found a large increase in overall MPA scores in people with schizophrenia compared to controls without schizophrenia. There were also increased MPA scores in people with schizophrenia compared to their relatives, with no differences between relatives and controls.

Moderate quality evidence suggests MPA frequency is increased in six regions: head, eyes, ears, mouth, hands and feet. Specific MPAs include tongue with irregular smooth-rough spots, single transverse palmar crease (one crease extending across the palm of the hand), syndactyly (wholly or partially united) 2nd and 3rd toes, malformed ears, low set ears, smaller head circumference, and curved fifth finger.

Moderate to high quality found no differences between people with schizophrenia and controls in second-to-fourth digit ratio, apart from the right hand of males with schizophrenia which showed increased second-to-fourth digit ratio than controls. Second-to-fourth digit ratio is constant throughout life and is the ratio of the length of the index finger (second digit) to the length of the ring finger (fourth digit) of the same hand. Higher 2D:4D ratio is suggested to be the result of lower levels of fetal testosterone.

February 2022

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Morphometrics is the measurement of the variation in the structure or form of organisms. In the mid-1900s, William Herbert Sheldon introduced the notion that there were three components that determine the morphology of a human individual: mesomorphy (musculoskeletal robustness relative to height); endomorphy (relative fatness); and ectomorphy (relative erectness or slenderness). 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.

What is the evidence for morphometrics?

High quality evidence shows people with schizophrenia are often slighter shorter in height than people without schizophrenia. Moderate to low quality evidence also finds people with schizophrenia are often be more erect and slender, and have a lower body mass compared to both people without schizophrenia and people with other mental disorders.

February 2022

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Most neurons have a cell body, an axon, and dendrites. Neurons communicate with other cells over synapses, or gaps between the neurons. Usually, axons send out signals and dendrites receive signals across the synapse, although synapses can also connect an axon to another axon or a dendrite to another dendrite. This process is partly electrical and partly chemical and can be excitatory or inhibitory. A group of connected neurons is called a neural circuit, involving sensory, motor, and interneurons.

Studies have shown grey matter reductions in people with schizophrenia, which may involve a loss of neurons and/or changes in synaptic density. This topic presents the results of studies assessing changes in neuronal structure.

What is the evidence for changes in neurons in people with schizophrenia?

Moderate to high quality evidence finds a small to medium-sized effect of decreased density of postsynaptic elements in people with schizophrenia, mainly in cortical regions and in dendritic spine density. There is also a small effect of reduced parvalbumin interneuron density in the pre-frontal cortex of people with schizophrenia.

October 2020

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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.

What is the evidence for OCT?

Moderate quality evidence finds a medium-sized effect of thinner overall peripapillary retinal nerve fibre layer thickness in people with schizophrenia compared to controls. There were small effects of thinner nasal and temporal peripapillary retinal nerve fibre layers as well as thinner ganglion cell + inner plexiform layers in patients. There were no significant differences in superior or inferior retinal nerve fibre layers or in choroidal or macula thickness and volume.

February 2021

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Telomeres are protective caps on the ends of chromosomes. They are linked to aging as they shorten with each cell division, and when they reach a critical length the cell stops dividing or dies. Chronic stress has been associated with reduced telomere length, resulting in the recognition of an association between adverse social and environmental influences and accelerated aging. Schizophrenia has also been associated with adverse environmental influences.

What is the evidence for telomere length in people with schizophrenia?

Moderate to high quality evidence finds a medium-sized reduction in telomere length in people with schizophrenia compared to controls.

October 2020

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