**2.1. Cognitive domains affected**

It is important to point out that there are similar cognitive impairments, in much lower intensity, in close relatives, and these deficits can be considered as potential cognitive endophenotype markers of the disorder [8–13]. From this data, it can be accepted that, in many cases, the effect of these alterations, potentially, may be affecting the functioning of any family nucleus

These data show the existence of a biological basis, despite the undeniable influence of environmental factors on the development and course of both pathologies. In this sense, the DSMIV-TR [14] notes that: *"Although numerous data suggest the importance of genetic factors in the etiology of schizophrenia, the existence of a substantial discrepancy in the frequency of monozygotic* 

As expected, this cognitive dysfunction has influence in the main aspects of daily life [15]. Respecting the family point of view, there is also a great ignorance of the existence and influence of these cognitive symptoms present in the affected relatives. In general, it is suggested that the psychoeducational programs made for this subject directed to family members provide them with an important first step. These programs provides means in order to understand these factors, which make an important stain in their overall functioning, and therefore, in the daily life of these patients [16–19]. On the other hand, it is important to point out that the same patients do not usually present insight of their deficits, and when they do, although they are usually associated with higher levels of adherence to treatment, they also tend to do so with a loss of self-confidence [20]. This fact indicates that family interventions in the education of cognitive aspects should not only stay there and should also involve a research for solutions of family support in other ways. At this point, it cannot be ignored the effect on the family dynamics of the probable presence (even being slight) of these deficits in any of the relatives of the affected subjects. Their awareness and identification are important in order to

One of the main recently advances of the concept of schizophrenia has been the confirmation that this disorder is primarily associated to cognitive deficits, do not being a consequence to symptoms or drugs [21]. Nevertheless, the idea that cognitive domains played a fundamental role in this disorder was not so recent. Since the first descriptions of schizophrenia, which was known under the Dementia praecox label, the aspects related to what it is now understood as cognitive deficit were considered as central symptoms of the picture. Besides the essential idea of Bleuler was that the core of schizophrenia, its fundamental symptoms, was the fragmentation of the thought process and delusions and hallucinations were accessory symptoms, a consequence of the main process [22, 23]. It has also been shown that this cognitive deficit has not only been described in long-standing schizophrenic patients [24], but is also present in patients with a first psychotic episode [25–27], in remission [28], in patients without antipsychotic medication [21, 29] and even in studies in high-risk subjects [30] and in

It is estimated that among 61–78% of patients with schizophrenia manifest a significant level of cognitive deficit [1] reaching between 1 and 2 standard deviations below the control

and not only the patient or relative at risk of developing disease.

*twins also indicates the importance of environmental factors".*

44 Psychosis - Biopsychosocial and Relational Perspectives

carry out a family intervention.

**2. Cognitive deficit in schizophrenia**

close relatives and healthy patients with schizophrenia [12].

Patients with schizophrenia have, comparing with healthy subjects, problems in performing almost all conventional neuropsychological tests. The most widely affected functions are executive tasks. Memory and attention, in their different modalities, are not the only ones affected, but it is these domains that stand out especially about a generalized cognitive dysfunction. The functions relatively preserved in schizophrenia are usually verbal knowledge and linguistic comprehension and naming. Cognitive functioning in schizophrenia is considered a primary or essential characteristic of the disorder [15, 63], so that schizophrenia is now considered to be a complex disorder whose base is fundamentally neurocognitive [64, 65]. For a review of the characteristics of these disturbances see **Table 1**.

Balanzá-Martínez and Tabarés-Seisdedos [66] highlight the following aspects:

• On a generalized cognitive impairment, the most intense deficits are linked to memory, attention and executive

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• They are not secondary to psychotropic drugs, institutionalization or symptoms, although they may be related

• There is evidence of a broad cognitive deterioration in schizophrenia, which can be considered moderate to

• The cognitive deterioration does not keep too much relation with the majority of the measures of symptomatology, something in contrast with the studies that highlight moderate but statistically reliable associations

• Interestingly, they found no significant relationship between the duration of the disorder and cognitive decline. Crespo, Rodriguez-Sanchez, Barbas-Calvo, Duarte-Armolea and González-Blanch [70] clarify that the existence of these deficits (to a much lesser degree) is not exclusive to patients and is often found within first-degree family members. Considering the affected domains and controlling medication variables, it can be considered: • Attention: Difficulty to inhibit irrelevant information. Presence of these deficits in both patients and their

• Executive functions: Difficulties in the use of problem solving strategies, self-control and supervision of own behavior. In first-degree patient's relatives, there have been problems in verbal fluency, inhibition of an arrogant

• Working memory: Deficit in the storage capacity of information (verbal and spatial) and also emphasize the role of working memory as an essential element for the processing of information, which malfunction compromises the execution of other cognitive systems. It is interesting to complete it with the study of Guimon, Padani, Lutz, Eack, Thermenos and Keshavan [71] about how emotional distracters impacted more on their performance in working memory tasks than in control subjects. Also note that Botero *et al.* [72] tested performance on tasks involving verbal work memory and the results were lower in subjects with schizophrenia and their relatives that

• Memory: Deficits to remember are present, to a lesser degree, in healthy relatives of patients. These memory

• Psychomotor functioning: Significant psychomotor slowdown even in first episode patients and, to a lesser

• Studies of diverse world regions in which a study of cognition is carried out present very few differences to each

• The cognitive deficits are somewhat greater in the domains of processing speed and episodic memory.

• They affect significantly the majority of patients.

• They are indicators of functional prognosis. • Nowadays, they constitute a therapeutic objective. The meta-analysis conducted by Shaefer *et al.* [69] concluded:

• They are very stable during the evolution of the disorder.

• They are present since the first episode, even in the premorbid stages.

• They are also present in healthy patients relatives (cognitive endophenotypes) [67, 68].

severe compared to control subjects in all the neurocognitive measures studied.

children (higher than controls and young subjects at high risk for affective disorders).

deficits are aggravated by attention problems, working memory and coding difficulties.

• Speed of processing: Indicate a slowdown that affects other cognitive domains.

**Table 1.** Presence of cognitive disturbance in schizophrenia and first grade relatives.

• The studies showed higher percentages of involvement in male patients.

between cognition and negative or disorganized symptoms [32].

response pattern or tasks with a change in cognitive function.

in the controls of the community.

degree, in parents of patients.

functions.

other.

to negative symptoms.

#### **2.2. Description of the disturbance in the affected domains**

In general, it can concluded that the meta-analysis by Schaefer *et al* [69] would indicate that patients with schizophrenia would present important alterations in: Attention, especially in sustained attention and interference control; significant deficits in the operational memory (maintenance of information and manipulation) and important alterations in long-term memory. However, the implicit memory, specifically the so-called procedural memory, related to the ability to learn psychomotor skills, would be relatively preserved [73] and the recognition of verbal material was not as altered as the delayed memory. They presented important alterations in the different components of the executive functions such as cognitive flexibility and planning and serious alterations in the speed of processing.

Going in dept. the studies of executive functions in schizophrenic patients, these tend to describe a greater presence of persistent responses. The Wisconsin card sorting test [74] indicates that these patients tend to have a low number of categories achieved and many persistent responses, which can be seen as a deficit of cognitive flexibility [75]. This inability to select the relevant information and reject the irrelevant has also been documented using tasks such as the Stroop test [76–78] or the Tower of Hanoi [79].

This inability to inhibit response (which would affect to planning and organizing actions, persist in an activity and find novel solutions) is present, to a greater or lesser degree, in these patients, even in the case of not showing up serious dysfunctions in attention capacity and operative memory (necessary for an adequate executive functioning) [52, 70].

Regarding to memory in schizophrenia, it is common to see studies showing general alterations in all memory processes. It shows that there is poor performance in declarative (explicit) memory, short-term and long-term memory, intentional learning, operational memory, semantic memory and priming. However, non-declarative memory (implicit) seems be less affected and procedural memory seems to be preserved [80, 81].

Some authors have considered that the alteration of autobiographical memory [82] as well as in prospective memory (the ability to remember the performance of planned actions in the future) [83] and the memory of the source (of the contextual aspects of the information: Where, when, etc.) [84] are the product of a general deficit, especially related to a reduced executive function [70].

The studies of working memory in schizophrenia reflect the existence of deficits in the capacity of storage/apprehension [85], although it is considered if such storage difficulties could be linked to alterations in the process of coding the information (more related to the executive function), Balanzá-Martínez and Tabarés-Seisdedos [66] highlight the following aspects:

• They affect significantly the majority of patients.

dysfunction. The functions relatively preserved in schizophrenia are usually verbal knowledge and linguistic comprehension and naming. Cognitive functioning in schizophrenia is considered a primary or essential characteristic of the disorder [15, 63], so that schizophrenia is now considered to be a complex disorder whose base is fundamentally neurocognitive

In general, it can concluded that the meta-analysis by Schaefer *et al* [69] would indicate that patients with schizophrenia would present important alterations in: Attention, especially in sustained attention and interference control; significant deficits in the operational memory (maintenance of information and manipulation) and important alterations in long-term memory. However, the implicit memory, specifically the so-called procedural memory, related to the ability to learn psychomotor skills, would be relatively preserved [73] and the recognition of verbal material was not as altered as the delayed memory. They presented important alterations in the different components of the executive functions such as cognitive flexibility

Going in dept. the studies of executive functions in schizophrenic patients, these tend to describe a greater presence of persistent responses. The Wisconsin card sorting test [74] indicates that these patients tend to have a low number of categories achieved and many persistent responses, which can be seen as a deficit of cognitive flexibility [75]. This inability to select the relevant information and reject the irrelevant has also been documented using tasks such

This inability to inhibit response (which would affect to planning and organizing actions, persist in an activity and find novel solutions) is present, to a greater or lesser degree, in these patients, even in the case of not showing up serious dysfunctions in attention capacity and

Regarding to memory in schizophrenia, it is common to see studies showing general alterations in all memory processes. It shows that there is poor performance in declarative (explicit) memory, short-term and long-term memory, intentional learning, operational memory, semantic memory and priming. However, non-declarative memory (implicit) seems be less

Some authors have considered that the alteration of autobiographical memory [82] as well as in prospective memory (the ability to remember the performance of planned actions in the future) [83] and the memory of the source (of the contextual aspects of the information: Where, when, etc.) [84] are the product of a general deficit, especially related to a reduced

The studies of working memory in schizophrenia reflect the existence of deficits in the capacity of storage/apprehension [85], although it is considered if such storage difficulties could be linked to alterations in the process of coding the information (more related to the executive function),

operative memory (necessary for an adequate executive functioning) [52, 70].

affected and procedural memory seems to be preserved [80, 81].

executive function [70].

[64, 65]. For a review of the characteristics of these disturbances see **Table 1**.

**2.2. Description of the disturbance in the affected domains**

46 Psychosis - Biopsychosocial and Relational Perspectives

and planning and serious alterations in the speed of processing.

as the Stroop test [76–78] or the Tower of Hanoi [79].


The meta-analysis conducted by Shaefer *et al.* [69] concluded:


Crespo, Rodriguez-Sanchez, Barbas-Calvo, Duarte-Armolea and González-Blanch [70] clarify that the existence of these deficits (to a much lesser degree) is not exclusive to patients and is often found within first-degree family members. Considering the affected domains and controlling medication variables, it can be considered:


**Table 1.** Presence of cognitive disturbance in schizophrenia and first grade relatives.

rather than in processes related to the actual maintenance of the information. Authors such as Sharma and Antonova [86] and Brebion *et al*. [87] consider that schizophrenic patients did not use the properties/facilities of the material to be memorized in learning (for example, grouping it by categories or sequences) because they presented problems when are making complex coding strategies (based on the characteristics of the information). Although, these alterations in coding could be secondary related to the generalized slowdown in processing speed [88]. It is also point out that deficits in working memory could be due to errors in the search, maintenance and manipulation of information.

is found in early stages of the disorder [101]. They also found that people with schizophrenia have major alterations in the theory of mind. In general, they also found alterations, although to a lesser extent to the previous ones, in social perception (ability to identify roles, social norms and social context as well as social knowledge that refers to the conscience of roles, norms and objectives that characterize social situations and direct interactions) [102]. However, Savla *et al*. [100] did not find significant differences in attribution biases between

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Regarding the presence of alterations in social cognition in relatives of patients, it is usually noted that patients score significantly worse in all domains of social cognition evaluated compared to controls and in the attribution style domain compared to family members [103].

In the Mondragón-Maya *et al*. review [104] point out that consistent discoveries on deficits in the theory of mind have been reported in family members of patients with schizophrenia compared to control subjects. In this sense, two meta-analyzes have reported effects (from modest to moderate) on alterations of the theory of the mind in unaffected relatives [105, 106]. Moreover, Mondragón-Maya *et al*. [104] consider that studies of the other fields of social cognition in family members offer more scarce and inconsistent results, requiring further investigation. Cella *et al.* [107] and the meta-analysis of Lavoie *et al*. [106] reported moderate déficits in social perception in relatives of schizophrenia versus controls. However, later, Lavoie *et al*. [108] did not find that parents of patients with schizophrenia showed worse performance than controls in social perception tasks. Regarding attribution style, Rodríguez *et al*. [103] reported that there were no deficits in the unaffected relatives of patients with schizophrenia. Studies on emotional processing in unaffected family members of patients with schizophrenia are also scarce. Despite this, some studies have reported worse performance of their relatives to identify emotions compared to controls [109]. The meta-analysis of Lavoie *et al*. [106] found a moderate deficit in emotional processing of unaffected family members, especially in tasks of emotional identification. However, this result is not completely generalize and needs further investigation, since it focuses on emotional identification skills, more than other components

It is important to emphasize that these deficits are not a direct consequence of pharmacological treatment, nor of the institutionalization situation or other factors such as lack of motivation or distractibility due to psychotic symptoms [3]. Cognitive deficits in schizophrenia affect the majority of cognitive functions [6], but they are especially marked in executive functions and memory [3, 4]. This cognitive deficit is presented with autonomy of positive and negative

The systematic review of Dominguez *et al*. [32] (58 studies, 5009 individuals) shows a relation between the psychopathological dimensions of psychosis (negative, positive, disorganized and depressive) and measures of neurocognitive impairment in subjects with non-bipolar psychosis. The results showed that negative and disorganized symptoms are significantly but modestly associated with cognitive deficits. The positive and depressive dimensions

symptoms, even when there is a greater association with this latter ones [63, 110].

people with schizophrenia and non-diagnosed controls.

of emotional processing, such as emotional regulation [104].

**2.5. Clinical status and cognition**
