Case Report
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Jun 22, 2017; 7(2): 128-132
Published online Jun 22, 2017. doi: 10.5498/wjp.v7.i2.128
Cognitive correlates of neuroimaging abnormalities in the onset of schizophrenia: A case report
Silvia Grassi, Giulia Orsenigo, Marta Serati, Elisabetta Caletti, Alfredo Carlo Altamura, Massimiliano Buoli
Silvia Grassi, Giulia Orsenigo, Marta Serati, Elisabetta Caletti, Alfredo Carlo Altamura, Massimiliano Buoli, Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy
Author contributions: Grassi S and Orsenigo G collected data; Serati M revised report; Caletti E performed neuropsychological tests; Altamura AC designed the report; Buoli M wrote the paper.
Institutional review board statement: This case report was exempted from IRB standards of University of Milan.
Informed consent statement: Patient gave his written informed consent and permission for disclosure of his protected health information.
Conflict-of-interest statement: Professor Altamura has served as a consultant or on Advisory Boards for Roche, Merck, Astra Zeneca, Bristol Myers Squibb, Janssen/Cilag and Lundbeck. Drs Grassi, Orsenigo, Serati, Caletti and Buoli do not have any affiliation with or financial interest in any organization that might pose a conflict of interest with the present article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Silvia Grassi, MD, Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via F. Sforza 35, 20122 Milan, Italy. silvia.grassi1@unimi.it
Telephone: +39-02-55035983 Fax: +39-02-55033190
Received: December 17, 2016
Peer-review started: December 19, 2016
First decision: April 18, 2017
Revised: April 27, 2017
Accepted: May 12, 2017
Article in press: May 15, 2017
Published online: June 22, 2017

Abstract

Increasing evidence shows that cognitive impairment and brain abnormalities can appear early in the first episodes of schizophrenia, but it is currently debated how brain changes can correlate with clinical presentation of schizophrenic patients. Of note, this report describes the case of a young schizophrenic male presenting parietal magnetic resonance/positron emission tomography abnormalities and cognitive impairment, documented by specific neuropsychological tests. In our knowledge only few studies have investigated if neuropsychological abnormalities could be concomitant with both structural and functional neuroimaging. This case shows that impairment in specific cognitive domains is associated with structural/functional brain abnormalities in the corresponding brain areas (frontal and parietal lobes), supporting the hypothesis of disconnectivity, involving a failure to integrate anatomical and functional pathways. Future research would define the role of cognitive impairment and neurodegeneration in psychiatric nosography and, in particular, their role in the early phases of illness and long-term outcome of schizophrenic patients.

Key Words: Positron emission tomography, Magnetic resonance, Schizophrenia, Neuropsychology

Core tip: Schizophrenia is associated with impairment in executive function, verbal memory, verbal fluency and attention. Neuropsychological tests are associated with structural and functional brain alterations. This case report is an example of the potential correlation between clinical symptoms (e.g., cognitive impairment) and brain changes. These data may help in the prediction of possible outcome of schizophrenia patients.



INTRODUCTION

A number of data would indicate schizophrenia as a progressive neurodegenerative disorder[1] whose outcome is influenced by many biological and clinical factors[2]. Of note, recent literature shows that neuropsychological deficits at onset may predict the clinical course of illness[3] being often associated with frontal and parietal lobe dysfunctions[4-6]. Moreover, a recent trial found that brain abnormalities of schizophrenic patients change according to age at onset. In particular, early onset patients show parietal abnormalities, while adult onset patients exhibit frontal and temporal ones[7].

To our knowledge there are few studies[8-10] associating cognitive frontal and parietal deficits with structural [magnetic resonance (MR)] and functional neuroimaging [positron emission tomography (PET)] and the anatomical and functional relationships underlying this deficit remain to be elucidated. Dysconnectivity, a failure in functional integration, is considered a key mechanism in the pathophysiology of cognitive impairments (in particular working memory performance) in individuals with schizophrenia[11].

The present paper deals with a recent diagnosed schizophrenic patient showing frontal and parietal lobe MR/PET abnormalities clinically associated with deficits in the corresponding cognitive domains.

CASE REPORT

The patient was a 19-year-old man admitted in our department. The patient showed nor psychiatric comorbidity with an Axis I disorder neither personality disorders. A neurological exam, performed by a neurologist, was negative. Diagnosis of undifferentiated schizophrenia and exclusion of comorbid conditions were assessed through the administration of semi-structured interviews based on DSM-IV criteria (SCID I and II). Patient had family history for psychiatric disorders: The father was an alcohol abuser, one schizophrenic uncle (father’s brother) committed suicide and the grandmother in mother line was affected by bipolar disorder. At the admission in our ward the patient was drug-naïve and showed persecutory delusion, auditory hallucinations, thought/behavioural disorganization and a duration of untreated psychosis of 9 mo[12]. Baseline score at Positive and Negative Syndrome Scale[13] was 84, while baseline score at Brief Psychiatric Rating Scale was 55[14]. In the first days of admission patient underwent to neuropsychological tests, cerebral MR and cerebral PET.

A neuropsychological battery was designed to encompass the areas believed to be affected by Schizophrenia[15]. Results and standard scores are summarized in Table 1. Patient’s neurocognitive performances provided evidence for impairment in the following domains: Executive function (Cognitive Estimation, Verbal fluency, Trail Making Test), verbal memory, verbal ability (Boston Naming Test, phonemic Verbal Fluency) and attention (Visual Search, Trail Making Test). In addition, the patient failed in two Wechsler Adult Intelligence Scale[16] subscales: Verbal Comprehension Index and Perceptual Organization Index.

Table 1 Neuropsychological results.
TestPatient scoreNormal valueResultZ-score
Mini-mental state examination27.1924-29.19Normal0.45
Executive functions: Tower of London2520-36Normal-0.75
Frontal assessment battery15.9813.5-17.3Normal-0.95
Cognitive estimation task19.970-18Failed2.43
Bizarreness60-4Failed4
Problem solving: Raven’s progressive matrices29.0518.6-33.05Normal0.89
Assessment of cognitive impairment in memory
Verbal memory and learning
Digit Span5.753.75-8.75Normal-0.4
Verbal Learning10.506.50-21.50Normal-0.93
Recall of prose: Immediate and after 10 min3.508.00-27.50Failed-2.92
Spatial short-term memory (Corsi test)4.503.50-8.50Normal-1.20
Attention and speed information processing
Trail making test
Part A33< 93 sNormal
Part B, dual task161< 282 sNormal
Part B-A128< 186 sBorderline score-1.36
Visual search34.2531-51.25Borderline score
Verbal fluency
Phonemic2317-59Borderline score-1.43
Categories3225-58Normal-1.15
Language
Boston naming test3143-60Failed-4.82
Token test3229-36Normal-0.29
Wechsler adult intelligence scale-revisedGeneral IQ = 75 (verbal IQ = 81; performance IQ = 74)80-120Borderline score-2.50
VCI = 5.5; POI = 6.25

MR was performed using a circular polarized head coil and included Turbo Spin-Echo T1-weighted sequences, T2-weighted sequences and FLAIR. Imaging in three planes was performed using 5-mm slice thickness. MR revealed normal-sized ventricles, normal-sized subarachnoidal spaces, no abnormalities in gray matter, but bilaterally soft hyper-intensities in superior parietal lobe[4] periventricular white matter.

Fluorodeoxyglucose (FDG) was injected in condition of rest and fasting and after 30 min three-dimensional scan was performed. The images were compared to a cohort of normal ones. Fluoro-D-Glucose PET (Figures 1 and 2) showed glucose frontal and parietal lobes hypo-metabolism bilaterally. No further abnormalities in FDG distribution were observed.

Figure 1
Figure 1 D-glucose (fluorodeoxyglucose) positron emission tomography, transversal sections. Pointer 1 displays the frontal lobe hypo-metabolism; pointer 2 displays the parietal lobe hypo-metabolism.
Figure 2
Figure 2 Fluoro-D-glucose (fluorodeoxyglucose) positron emission tomography, coronal sections. Pointer 1 displays the frontal lobe hypo-metabolism; Pointer 2 displays the parietal lobe hypo-metabolism.

MR and PET were performed by neuroradiologists collaborating within our department.

Of note, neuropsychological results are consistent with outlined MR abnormalities and PET images (fronto-parietal abnormalities)[17].

DISCUSSION

The present case report confirms data from literature of early cognitive deficits in the course of schizophrenia[18,19] and neuroimaging parietal abnormalities in early onset schizophrenic patients[7,20,21]. In addition, the correspondence between cognitive deficits and morphological/functional brain alterations[22] contributes to clarify the influence of brain changes in schizophrenia clinical presentation as well as to support the hypothesis of schizophrenia as a neurodegenerative disorder[23,24]. Recent trials found that brain abnormalities are more severe in patients with a longer duration of illness[25-27], novel antipsychotics are promising molecules for their efficacy in stopping the neurodegenerative process[28,29]. In this context cognitive and neuroimaging follow-up of our case can be useful to discriminate if neurodegenerative process of schizophrenia progresses in the course of illness or it is specific of early stages[24,30,31]. Finally, it would be important in the future to define the role of neuroimaging abnormalities in influencing outcome. MR and PET could be useful tools to make diagnosis and to predict long-term course of schizophrenic illness.

COMMENTS
Case characteristics

A 19-year-old male patient with severe schizophrenia presentation.

Clinical diagnosis

Patient was hospitalized because of prominent persecutory delusion, auditory hallucinations, aggressiveness and thought/behavioural disorganization.

Differential diagnosis

Bipolar disorder, substance use disorder.

Laboratory diagnosis

Routine blood tests were resulted within normal limits.

Imaging diagnosis

At magnetic resonance imaging bilaterally soft hyper-intensities in superior parietal lobe periventricular white matter were detected, while positron emission tomography showed glucose parietal lobes hypo-metabolism bilaterally.

Pathological diagnosis

Schizophrenia, acute episode.

Treatment

Ziprasidone 80 mg × 2 and Gabapentin 300 mg × 3.

Related reports

Severe cognitive impairment as showed by neuropsychological tests.

Term explanation

Dysconnectivity means abnormal functional integration among brain regions resulting in impaired modulation of neurotransmitters.

Experiences and lessons

It is important to perform imaging evaluation and neuropsychological tests to better define long-term outcome of schizophrenia patients.

Peer-review

This case report is novel and well designed.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Psychiatry

Country of origin: Italy

Peer-review report classification

Grade A (Excellent): A

Grade B (Very good): B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Belli H, Kravos M S- Editor: Ji FF L- Editor: A E- Editor: Li D

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