Review Prevalence of Neuroradiological Abnormalities in First-Episode Psychosis A Systematic Review and Meta-analysis 2023 Blackman et al

[Andy]

Key Points

Question How common are neuroradiological abnormalities in first-episode psychosis?

Findings In this systematic review and meta-analysis, we found approximately 6% of patients with first-episode psychosis had an abnormality that required a change in clinical management. The number of patients needed to scan to detect 1 clinically relevant abnormality was estimated to be 18.

Meaning These findings support the routine use of magnetic resonance imaging as part of the initial assessment in patients presenting with first-episode psychosis.


Abstract

Importance Individuals presenting with first-episode psychosis (FEP) may have a secondary (“organic”) etiology to their symptoms that can be identified using neuroimaging. Because failure to detect such cases at an early stage can have serious clinical consequences, it has been suggested that brain magnetic resonance imaging (MRI) should be mandatory for all patients presenting with FEP. However, this remains a controversial issue, partly because the prevalence of clinically relevant MRI abnormalities in this group is unclear.

Objective To derive a meta-analytic estimate of the prevalence of clinically relevant neuroradiological abnormalities in FEP.

Data Sources Electronic databases Ovid, MEDLINE, PubMed, Embase, PsychINFO, and Global Health were searched up to July 2021. References and citations of included articles and review articles were also searched.

Study Selection Magnetic resonance imaging studies of patients with FEP were included if they reported the frequency of intracranial radiological abnormalities.

Data Extraction and Synthesis Independent extraction was undertaken by 3 researchers and a random-effects meta-analysis of pooled proportions was calculated. Moderators were tested using subgroup and meta-regression analyses. Heterogeneity was evaluated using the I2 index. The robustness of results was evaluated using sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests.

Main Outcomes and Measures Proportion of patients with a clinically relevant radiological abnormality (defined as a change in clinical management or diagnosis); number of patients needed to scan to detect 1 such abnormality (number needed to assess [NNA]).

Results Twelve independent studies (13 samples) comprising 1613 patients with FEP were included. Of these patients, 26.4% (95% CI, 16.3%-37.9%; NNA of 4) had an intracranial radiological abnormality, and 5.9% (95% CI, 3.2%-9.0%) had a clinically relevant abnormality, yielding an NNA of 18. There were high degrees of heterogeneity among the studies for these outcomes, 95% to 73%, respectively. The most common type of clinically relevant finding was white matter abnormalities, with a prevalence of 0.9% (95% CI, 0%-2.8%), followed by cysts, with a prevalence of 0.5% (95% CI, 0%-1.4%).

Conclusions and Relevance This systematic review and meta-analysis found that 5.9% of patients presenting with a first episode of psychosis had a clinically relevant finding on MRI. Because the consequences of not detecting these abnormalities can be serious, these findings support the use of MRI as part of the initial clinical assessment of all patients with FEP.

Open access, https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2806887

 

[Andy]

Make brain scans routine for new psychosis patients, experts say

Study finds MRI scans led to different diagnosis or change in care in 6% of cases

https://www.theguardian.com/science...outine-for-new-psychosis-patients-experts-say

 

[Arnie Pye]

This idea that people with psychosis need brain scans for proper diagnosis is not exactly surprising to me. Some people with schizophrenia turn out to have had severe vitamin deficiencies, or their mothers did during pregnancy.

Title : Some People With Schizophrenia May Simply Have a Vitamin Deficiency

Link : https://scitechdaily.com/some-peopl...y-have-a-vitamin-deficiency/?expand_article=1

Low folate is well known to increase the risk of Neural Tube Defects. But how many pregnant women know that low levels of Vitamin B12 have the same risk?

https://gpnotebook.com/simplepage.cfm?ID=x2020062211455405391

Anyone going to a doctor and suggesting that they might be short of mineral X or vitamin Z is usually dismissed with the comment that the patient just needs to eat a healthy diet. And I think lots of people will never admit to themselves that their diet is unhealthy or who may not even know their diet is unhealthy? Even if the diet is healthy, low levels of iron are extremely common in menstruating women. Women who are restricted in their movements by their religion/culture or who rarely expose any skin will probably have very low levels of vitamin D. But doctors tend to see nutrients as totally unimportant. And what effect does that have on pregnant women while they are growing the next generation? Or people who are on PPIs? Or who have unsuspected Crohns, Coeliac Disease, or Ulcerative Colitis?

 

[SNT Gatchaman]

I think the problem here is that our neuroimaging technology is not yet up to the task required of it. I have no expertise in psychiatry but I've reported my fair share of CTs and MRIs for first episode of psychosis in young people. They're nearly always reported as "normal", with occasional incidental findings that we don't believe are clinically relevant, although in hindsight that may change as we learn more.

I don't know how many new-onset psychosis patients are not referred for scans. On the other hand, typically the rare floridly immune-mediated brain conditions (such as anti-NMDA receptor encephalitis) are already under the care of neurology, rather than psychiatry. Similarly overt focal neurological signs associated with eg a brain tumour usually have the patient under the care of neuro-oncology/neurosurgery already.

So I suspect that over time this has led to the thinking in psychiatry that there are a minority "organic" or secondary causes of psychosis, and that the rest are primary (which could be rudely characterised as "they've just gone mad for some reason, probably a chemical imbalance"). There are diagnostic clues suggesting "organic" eg visual hallucinations as opposed to auditory. In reality it may well be that basically all psychosis is organic/structural, but that we currently lack the techniques to evaluate and demonstrate this in clinical practice.

We're probably at an inflection point and I hope that in the near future all patients will get a high-quality (in terms of acquisition and interpretation) brain MRI. Newer research techniques will need to move into clinical practice, but it's possible that they will be complemented or superseded by more advanced blood tests.

 

[SNT Gatchaman]

Because several causes of secondary psychosis result in structural brain abnormalities, brain imaging is considered essential by many psychiatrists during the assessment phase. [...] Some guidelines recommend scanning all patients with FEP [First Episode of Psychosis], while others recommend that MRI be restricted to cases in which a secondary cause is suspected.

Most radiological abnormalities in patients with FEP are incidental and do not require any clinical action.

Among clinically relevant abnormalities, white matter abnormalities were the most common, with a prevalence of 0.9% (95% CI, 0% to 2.8%), followed by cysts

A barrier to resolving the debate about the routine use of MRI in the assessment of FEP has been uncertainty about the prevalence of clinically relevant abnormalities, with estimates ranging from 0% to more than 10%. Beyond guidelines for individual clinical management, there is also the issue of population health. In otherwise healthy individuals, white matter hyperintensities reliably predict later cognitive decline, greater cerebrovascular risk, and increased mortality in epidemiological studies

 

[SNT Gatchaman]

Twelve studies were eligible [...] published between 1991 and 2021 and reported a pooled sample of 1613 patients with FEP. Nine studies reported clinically relevant abnormalities, with a pooled sample of 1318 patients. Eight studies included a healthy control group, with a pooled sample of 3265 patients (FEP = 1399; control = 1866). [..] Ten studies excluded patients in whom a potential secondary cause of psychosis was suspected before neuroimaging, such as a positive finding on a neurological examination (not reported in 2 studies).

The supplementary data indicates 13 studies evaluated, but I might be missing something.

Scanner field strength was reported in 10 samples, with 1.5 T (n = 6) being the most common. MRI scans were interpreted by a neuroradiologist in 9 samples. In the other 3 samples, MRI scans were reported by a general radiologist (n = 1) or a psychiatrist (n = 1)

So a lot of this data relates to very outdated MRI scanner technology (1.5 T). 2 studies were not reported by a sub-specialist neuroradiologist, 9 were. That doesn't add up to 12 but I may have missed something about inclusion/exclusion.

1 study only reported the presence or absence of white matter abnormalities.

Patients with FEP had a significantly higher prevalence of radiological abnormalities overall, as well as clinically relevant abnormalities compared with healthy controls, after removal of an outlier. White matter abnormalities, predominantly small hyperintensities, were the most common finding overall and the most common clinically relevant finding. The NNA to detect 1 clinically relevant abnormality was 18.

White matter lesions are closely associated with neuroinflammatory processes in psychosis, as well as immune-mediated neurological disorders such as multiple sclerosis, supporting an etiological role of the immune system in psychosis.

 

[SNT Gatchaman]

Secondary causes of psychosis are associated with particular clinical variables, such as visual hallucinations and delusions of misidentification.

Interestingly, we found the prevalence of brain tumors in FEP was very low (with the estimated NNA to detect 1 tumor of around 1000) despite this being one of the main concerns of psychiatrists. However, because all the studies in this meta-analysis excluded patients with clinical evidence suggestive of a secondary medical (“organic”) cause, our results are likely to underestimate the true prevalence of tumors in patients with FEP more broadly, as such cases are more likely to present with neurologic features, such as apraxia, visual field deficits, and anomia [anosmia?].

Research MRI studies have identified widespread differences in gray and white matter density in FEP compared with controls. However, these studies typically use voxel-based morphometry and involve alterations that are too small to be detected by the naked eye. Although most radiological abnormalities in FEP do not necessitate a change in management, it is worth noting that these apparently benign findings may be associated with relatively poor outcomes across the life span and a marker of neurovascular health. This suggests that they could reflect the macroscopic sequelae of suboptimal brain development and as such may represent determinants of a poor outcome, even if they do not lead to a diagnosis of secondary psychosis.

So it's not clear to me what the clinically-relevant findings in FEP are currently. It sounds like white matter hyperintensities, which are typically viewed as "non-specific". They might indicate more widespread abnormalities of BBB (tag) and immune cell trafficking into the perivascular space (tag), with impairment of neurovascular coupling (tag). I don't know how that changes management strategies of psychosis in the short or long term though.

One point worth emphasising in the above quote though is the fact that abnormalities are too hard to pick up without machine analysis. This is similar to the structural findings now being described in functional neurological disorder.

 

[RedFox]

Individuals presenting with first-episode psychosis (FEP) may have a secondary (“organic”) etiology to their symptoms that can be identified using neuroimaging.

Their use of terminology is odd here. Presumably, all psychosis has biological origins, some understood, others not. But it's strange that only understood causes are called "organic." A better term would be identifiable cause?