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The importance of early detection of cognitive dysfunctions. Approach strategies in first episode of schizophrenia.


The concerns during the last decades to establish a clinical and evolutional pattern of the first psychotic episode and more specifically for the first episode of schizophrenia had the purpose to identify methods that would lead to maximal results concerning the social and familial reintegration of all people involved.

The pharmacological and clinical evaluations and the studies have revealed thought, perception and mood disturbances, an overwhelming importance being attributed to cognitive dysfunctions even from the prodromal stages. It seems that early diagnosis and intervention are crucial especially for the latter. Intervention strategies become thus essential for the protection of cognitive function, for keeping the patient away from the perception of degradation and for stimulating the patient to accept the treatment and to maintain a satisfactory social and professional status. (1)

Neurocognitive changes

Neurocognitive changes have a special importance due to the fact that they have imprinted multiple research directions as constant indicators before the onset of the disorder. It has been found that these changes are present even in non-medicated patients, cognitive impairment being less severe then in chronic patients, and more accentuated in those with persistent negative symptoms (2).

The more obvious cognitive areas involve impairment in attention, verbal and spatial memory, abstraction capacity and language. Another feature of cognitive deficit in the first psychotic episode is the deterioration of executive function, including the ability to elaborate and perform a strategy (3).

Saykin et al. (4) concluded that verbal memory impairment is the most important primary deficit that is present from early stages, but spatial cognition, fine motor coordination and visual memory are also affected.

Another study (5) that included the largest number of untreated patients with a first episode of schizophrenia showed that important impairment in a broad range of cognitive areas is a main characteristic of schizophrenia, cognitive dysfunction not being caused by treatment, chronic evolution or institutionalization.

Verbal memory impairments may trigger serious social dysfunction, and become progredient in time.

Neurocognitive changes have a predictive value for the evolution of the illness and for the efficiency of the treatment plan (6, 7, 8, 9); there are only a few studies that proved that the level of cognitive deficit is an important prognosis factor concerning the functional abilities (social, occupational, etc.). As a result of these evidences, there is a suggestion to establish the cognitive deficits among DSM-V diagnosis criteria for schizophrenia. Although they have a predictable value and they are present already during the prodromal stages, the introduction of cognitive deficits among diagnosis criteria does not refer to section "A" symptoms because they are not useful and specific indicators for differentiating from other psychosis. Specific cognitive enhancement treatment as add on focused on remediating cognitive impairment (10). It was considered that a treatment started as soon as possible has better long-term effects. More importantly, the delay of time period from the onset of the first symptoms until the beginning of the treatment is correlated with a worse evolution (11). It is also well known that disengagement from treatment is a major concern in Psychiatry (12).

Thus, appeared the concept of DUP (duration of untreated psychosis) that stands for the period of time in which the disorder is untreated, starting with the first symptoms of manifested psychosis until the first attempts to initiate treatment.

Most studies showed that a great number of patients who start taking antipsychotic s have a history of weeks, months or years of previous symptoms. The average duration of untreated psychosis is 52 weeks (13, 14). The risk of relapse reproduction within the first two years was higher for patients with a first episode of schizophrenia when compared to other psychosis. The delay in starting treatment coincided with a worse prognosis. Edwards found poorer social functioning, negative and depressive symptoms in patients with a high DUP (15).

Persistent primary negative symptoms were associated with male sex, poorer premorbid adjustment, prolonged DUP, lower level of insight and worse vocational functioning (2). De Haan et al. (16) also correlate prolonged DUP with accentuated negative symptoms.

Most of the above mentioned studies found a relationship between prolonged DUP and adverse clinical and evolutional profile, confirming in a certain way the hypothesis of manifested psychosis toxicity issues by Birchwood in 1998 (17).

There are also neurobiological and brain imaging studies which showed that objective changes increased within the first years of the illness evolution even more as the disorder was untreated. Modern research highlighted the fact that the first episode of schizophrenia represents a critical therapeutic opportunity, according to de Haan et al. (16).

Analyzing several clinical studies regarding the typical duration of untreated psychoses, it results that therapeutic delay confirms the model: prolonged neurotoxicity--irreversible brain changes cognitive deficits--pharmacological resistance.

Using neuroimaging techniques, Hoff et al. (18) studied the toxic brain processes which can lead to cognitive deficits, ventricular enlargement or decreased cortical density in patients with first schizophrenia episode.

Fannon et al. (19) assessed with the help MRI the aspect of the gray matter in patients minimally treated or untreated and they observed an important temporal deficit and ventricle enlargement, but they could not prove an evident correlation between the volume of cerebral substance and negative and positive symptoms. Negative symptoms may be correlated with a reduced functionality in frontal striatum or prefrontal cortex circuits.

Reduced gray matter and ventricular enlargement were correlated with cognitive symptoms. From the imagistic point of view, prolonged DUP was significantly correlated with cerebral sulci enlargement in patients with first schizophrenia episode and a second assessment of cerebral morphology after five years showed a progressive frontal and central atrophy. Dissymmetric cognitive theories, synaptic connectivity developmental reducing model, early and late neuro developmental models, late-early interactional model are still valid, allowing the elaboration of complex models.

DUP takes part of a larger concept, respectively DUI (Duration Untreated Illness) which also includes the prodromal stage, the stage were behavioural, emotional and patient's life condition changes were present.

Early intervention strategies

Usually, early intervention can be approached by three strategies:

a) Early intervention in the prodromal stage, which would coincide with the primary intervention, whose consequences would be a lower incidence of the disorder, an unusual intervention in Psychiatry, similar with mammography for breast cancer or prevention of general progressive paralysis by eradicating syphilis. Larsen et al. (20) published a study in 2001, whose objective was to review the most significant studies regarding rapid intervention in psychosis, critically revising the ones with the highest impact. The results of using antipsychotics in prodromal stage were interesting, but they need a replication of the study using a double blind placebo controlled study design in order to understand the significance of these results. This kind of pharmacological treatment is still subject of vivid debate about ethical issues. Early interventions after the onset of a psychosis, respectively treatment applied as soon as possible after the first signs of illness resulting in lower DUP and lower prevalence would be similar to the secondary prevention.

b) The ways of early intervention after the onset of psychosis are represented by:

Psychopharmacological treatment with the lowest doses of medication that would offer the best remission; current researches have led to the discovery of new medication classes whose benefits were sustained by several studies, the most important one targeting the population with first episode of schizophrenia being EUFEST study (European First Schizophrenia Trial) (21).

Psychotherapy, understood under a broader assumption (cognitive behavioural therapy--CBT) and social interventions (cognitive remediation therapy--CRT, psychological intervention for the families and close persons and supportive psychotherapy) (22).

c) Tertiary prevention--the effective period of time when the treatment is applied in order to prevent relapses. This type of intervention does not take part of the early intervention concept.


Over the years, a certain consensus was achieved regarding the approach of the patient and the acceptance of the concept of schizophrenia as a syndrome. The results of recent research imposed early psychosis as the start point for therapeutic initiative. Continuity of care is considered by patients and clinicians an essential feature of good quality care in long-term disorders yet there is a general agreement that it is a complex concept.

Most policies emphasize it and encourage systems to promote it (23).

The first episode of schizophrenia represents an opportunity due to the fact that the period of time between the onset of the illness and the beginning of treatment is an independent predictor of the evolution of the disorder.

Date of Submission: May, 24, 2013 / Acceptance: July, 18, 2013


The authors declare they have no potential conflicts of interest to disclose.


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(21.) Kahn, R. S., Fleischhacker, W. W., Boter, H., Davidson, M., Vergouwe, Y., Keet, I. P., Gheorghe, M. D., Rybakowski, J. K., Galderisi, S., Libiger, J., Hummer, M., Dollfus, S., L'Opez-Ibor, J. J., Hranov, L. G., Gaebel, W., Peuskens, J., Lindefors, N., Riecher-Rossler, A., Grobbee, D. E. EUFEST study group, 2008. Effectiveness of anti-psychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 1085-1097.

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(23.) Burns, T., Catty, J., White, S., Clement, S., Ellis, G., Jones, I. R., Lissouba, P., McLaren, S., Rose, D., Wykes, T. Continuity of care in mental health: understanding and measuring a complex phenomenon. Psychol Med. 2009; 39(2): 313-23.

Claudia Sultanica STEFANESCU--M. D., Drd., "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania; Psychiatrist, Psychiatric ward, Emergency County Hospital Bistrita-Nasaud, Bistrita, Romania

Rodica MACREA--M. D., Ph. D., Professor, Department of Neuroscience, Discipline of Psychiatry and Child Psychiatry, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania

Ioana Valentina MICLUTIA--M. D., Ph. D., Professor, Department of Neuroscience, Discipline of Psychiatry and Child Psychiatry, "Iuliu Hatieganu " University of Medicine and Pharmacy, Cluj-Napoca, Romania; Senior Psychiatrist, II Psychiatric Ward, Cluj County Emergency Hospital, Cluj-Napoca, Romania

Correspondence: Claudia Sultanica STEFANESCU

Address: Emergency County Hospital Bistrita-Nasaud, Bistrita, Romania

Psychiatric section, 43, General Grigore Batan Boulevard

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Author:Stefanescu, Claudia Sultanica; Macrea, Rodica S.; Miclutia, Ioana V.
Publication:Bulletin of Integrative Psychiatry
Article Type:Report
Date:Sep 1, 2013
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