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Cognition in Schizophrenia Essay.

Cognition in Schizophrenia Essay.

 

Attention deficits are considered to be fundamental in patients with schizophrenia. During attention tasks, patients with schizophrenia have been shown to display increased brain activity in some neuroimaging studies but reduced brain activity in others. These conflicting findings may be due to some study designs primarily eliciting transient engagement of attention and other study designs primarily eliciting sustained engagement of attention.Cognition in Schizophrenia Essay.

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In the present study, ten males with schizophrenia and fourteen age-matched, male controls performed a visual selective attention task. A mixed block/event-related fMRI design was used, allowing for separate analysis of transient and sustained phases of attention.Cognition in Schizophrenia Essay.

Results revealed that the schizophrenia group made significantly fewer correct responses and displayed a significantly slower mean response time than the control group. Voxel-wise random effects analyses revealed that both groups displayed activation in regions considered to constitute a core attentional network including the anterior cingulate gyrus, dorsolateral prefrontal cortex, insula and inferior parietal sulcus. Region of Interest (ROI) analyses revealed that across the entire sequence of task and non-task blocks, the schizophrenia group displayed a greater percentage of active voxels than controls in many ROIs. However, during transient periods most pertinent to task performance, the schizophrenia group displayed a lower percentage of active voxels than controls.Cognition in Schizophrenia Essay.

These results help to explain contrasting findings across previous studies and suggest that attention deficits displayed by patients with schizophrenia are more likely to reflect deficits in modulating brain activity in response to variations in transient, attention demanding stimuli, rather than deficits in sustained attention.Cognition in Schizophrenia Essay.

Keywords: Schizophrenia, Attention, Transient, Sustained, Maintenance of Task Set, Functional Magnetic Resonance Imaging (fMRI), Mixed design
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1. Introduction
Impaired attention is considered to be a fundamental cognitive deficit in patients with schizophrenia (Fioravanti, et al. 2005, Neuchterlein, et al. 1991). Brain imaging studies have consistently revealed that, during performance of attention tasks, the brain activity of patients with schizophrenia differs from that of controls, particularly in regions considered to constitute an attentional network including the dorsolateral prefrontal cortex (DLPFC), the insula, the anterior cingulate gyrus (ACG), the amygdala, hippocampus, ventral striatum, thalamus and cerebellum (Liddle, et al. 2006). While many of these neuroimaging studies have provided evidence that patients with schizophrenia display reduced brain activity as compared to controls (Barch, et al. 2001, Carter, et al. 1998, Karch, et al. 2009, Kerns, et al. 2005, Liddle, et al. 2006, Polli, et al. 2008, Quintana, et al. 2004, Schneider, et al. 2007, Weiss, et al. 2007), several studies have provided evidence of increased activity in patients with schizophrenia (Callicott, et al. 2000, Karch, et al. 2009, Manoach, et al. 2000, Manoach, et al. 1999, Weiss, et al. 2003).Cognition in Schizophrenia Essay.

There are a number of possible reasons for the contrasting findings across studies including: differences in the types of activation tasks used; differences in analysis techniques; differences in the degree to which task performance has become automated and task difficulty (Karch, et al. 2009, Manoach 2003). Regarding task difficulty, patients with schizophrenia have been shown to display greater cortical activity than controls on less demanding tasks of attention but less cortical activity than controls on more demanding tasks of attention (Karch, et al. 2009).Cognition in Schizophrenia Essay.

Such contrasting findings across studies are not surprising given that attention is a multi-faceted construct and given that different types of activation tasks are likely to engage to a different degree, the various aspects of attention (Dosenbach, et al. 2006, Huettel, et al. 2004). For instance, most activation tasks are likely to require some aspect of sustained attention that is maintained throughout performance of a task (i.e. maintenance of task set) as well as requiring more transient aspects of attention that are engaged during the most important moments of a task (Dosenbach, et al. 2006, Huettel, et al. 2004). Subsequently, study design is as important as the activation task used because study designs that utilize only a block design do not allow for the separate analysis of transient aspects of attention from the sustained aspects of maintenance of task set (Dosenbach, et al. 2006, Huettel, et al. 2004). Without making such a separation, it is not possible to determine whether activity in a given brain region is due to sustained attention that is continuously maintained throughout the task or whether it is due to more transient aspects of attention (Dosenbach, et al. 2006, Huettel, et al. 2004).Cognition in Schizophrenia Essay.

A mixed block/event-related design can be used across a wide range of conditions to extract and separately analyze transient signals that are related to the onset of a task-relevant block; transient signals that are related to the onset of a target; and sustained signals that endure across the entire task (Dosenbach, et al. 2006, Huettel, et al. 2004). Such different signals do appear to have overlapping but separate anatomical distributions that imply diverse functional roles (Dosenbach, et al. 2006).Cognition in Schizophrenia Essay.

The studies performed by Dosenbach et al. (2006) and Huettel et al. (2004) on normal participants and across numerous tasks have provided evidence of a core attentional network that is involved in the maintenance of task set (Dosenbach, et al. 2006, Huettel, et al. 2004).Cognition in Schizophrenia Essay.

A previous study from our lab utilized event related potentials (ERP) to explore the temporal dynamics of early sustained attention orienting and later “phasic” or transient aspects of attention deployment during a simple target detection in individuals with schizophrenia and “prodromal” individuals at imminent risk for schizophrenia (van der Stelt, 2006). This study found that the frontal selection positivity (SP) component of the ERP signal, which is thought to reflect “early” attention-related modulations of visual processing, is reliably elicited in healthy participants, but is significantly reduced, if not absent, in participants with schizophrenia as well as in prodromal individuals. This suggests that individuals both at risk for and suffering from schizophrenia show alterations in early attention orienting mechanisms, resulting in a failure of cortical feedback mechanisms to impart attentional influences on extrastriate visual cortices (van der Stelt, 2006). The neuroanatomical basis for this failure to deploy early attention to simple task-relevant color dimensions remains unclear. Furthermore, schizophrenia patients in this early ERP study, but not prodromal individuals, showed significant deficits in target-related P3 components.Cognition in Schizophrenia Essay. Taken together these findings raised the possibility that while certain neural pathways implicated in early attention deployment mechanisms may be altered in both patients and high-risk individuals, deficits in other cortical regions may not emerge until later in the disorder. Hence, the goal of the present study was twofold, (a) to investigate the neuroanatomical basis of the ERP findings by employing a mixed design fMRI task to dissociate activation during the two phases of attention deployment, and (b) to examine whether cortical activity in patients with schizophrenia differed during the “sustained” or “tonic” and “transient” or “phasic” phases of a selective attention task. To accomplish these aims, we designed a variant of the van der Stelt task implemented using a mixed-design fMRI paradigm, whereby an infrequent target event was embedded within blocks of task-relevant stimuli. Task-relevant stimuli were all colored blue whereas non-task stimuli were red. Targets were colored blue and were only embedded in a block of task-relevant stimuli (blue distractors) so that task-relevant blocks would heighten demand on attention processes whereas non-task blocks would place minimal demand on attention processes. Accordingly, the sustained phase of attention was defined as activation across the entire task, i.e. blue task-relevant blocks and the red non-task blocks. The transient phases of attention were defined as the onset of a task-relevant block and the onset of a target.Cognition in Schizophrenia Essay.

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2. Materials and methods
2.1 Participants
Fourteen male neurotypical participants and ten male patients with schizophrenia participated in this study. Data from two control subjects was discarded due to equipment failure and excessive motion. Data from one patient was excluded due to failure to follow task instructions. Data from twelve control subjects and nine patients with schizophrenia were included in the data analysis. Summary demographic information is included below in Table 1. All participants were matched for age and handedness.Cognition in Schizophrenia Essay.

Table 1
Demographic Characteristics

Scz (n=9) mean (SD) Ctr (n=12) mean (SD) t (17)
Age 29.8±12.0 (20–59) 25.5± 4.6 (20–34) 0.299
Full Scale IQ 111.68±6.4 (98–121) 113.63±6.01 (102–124) 0.487
Performance IQ 110.7±3.4 (103–116) 111.78±3.24 (106–117) 0.487
Verbal IQ 110.3±7.3 (95–121) 112.5 ±6.86 (99–124) 0.487
SANS Global Ratings
Affective Flattening or Blunting 2.89 (1.45)
Alogia 1.89 (1.54)
Avolition-Apathy 3.00 (1.41)
Anhedonia-Asociality 2.22 (1.92)
Attention 1.33 (1.73)
SAPS Global Ratings
Hallucinations 1.88 (1.9)
Delusions 1.78 (1.72)
Bizarre Behavior 0.33 (1.00)
Positive Formal Thought Disorder 0.22 (0.67)
*p < 0.0001 Scz: Schizophrenia; Ctr: Control; SANS: Schedule for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; IQ scores are estimated from the National Adult Reading Test (NART) (Nelson 1982).Cognition in Schizophrenia Essay. Patients and controls were originally recruited from the University of North Carolina at Chapel Hill's School of Medicine, with additional control subjects recruited through Duke University's Brain Imaging and Analysis Center healthy subject registry. Each subject was paid $20 an hour for two hours of participation in this study.Cognition in Schizophrenia Essay. The control group did not meet criteria for any current or past Axis I disorder as assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) (Spitzer, et al. 1992). All subjects had normal or corrected-to-normal vision and were screened for neurological illness, substance dependence, and substance abuse within the past month. Both groups also had no current or past history of migraines or major medical illness, including multiple sclerosis, stroke, insulin-dependent diabetes, significant head injury, and epilepsy within three years, had no history of treatment with ECT/rTMS within three months, were not pregnant at the time of scanning, and did not have a family history of neurologic or neurodegenerative disorder (e.g., Parkinson's, Huntington's chorea, Multiple Sclerosis). All procedures were approved by the institutional review boards at the University of North Carolina at Chapel Hill and at Duke University Medical Center, Durham, NC. After complete description of the study to the subjects, consent forms from both the University of North Carolina at Chapel Hill and at Duke University Medical Center were used to obtain informed consent. Negative results of urine toxicology were confirmed before study inclusion.Cognition in Schizophrenia Essay. 2.2 fMRI Task Participants performed a visual selective attention task that consisted of a mixed block and event-related design, as displayed in Figure 1. Alternating blocks of task-relevant stimuli and non-task stimuli were presented, with rare target events only presented during the task-relevant blocks. There were 2 categories of stimuli: Targets, which were identified as blue closed circles and non-target stimuli, which were incomplete blue, incomplete red, or complete red circles. The stimuli were presented in alternating blocks of red and blue stimuli with targets only presented in the blue blocks. This created task-relevant blocks (with all blue events, including the targets) and task-irrelevant blocks (with all red events). Participants were required to identify the rare target events (complete blue circles) and were informed that targets would not be presented during the blocks of red colored shapes. In both the task-relevant blocks and the non-task blocks, participants were required to press a particular button to non-targets and a unique button to targets. Cognition in Schizophrenia Essay.Targets appeared on 5% of task-relevant trials and 110 targets were presented in total. Stimuli were presented for 500ms with an ISI of 1000ms and a fixation cross was presented during the interval between trials. Each run contained 196 stimuli presented centrally against a white background. Participants performed 10 runs of the task, each of 4 min and 54 sec duration. Participants were trained on the task immediately prior to the scanning session. All stimuli were presented using CIGAL presentation software on a Windows-compatible computer and displayed to participants in the scanner through magnet-compatible goggles (Magnetic Resonance, Inc).Cognition in Schizophrenia Essay. An external file that holds a picture, illustration, etc. Object name is nihms192871f1.jpg Figure 1 Visual Selective Attention Task that served as the fMRI Activation Task and the associated analysis conditions.Cognition in Schizophrenia Essay. 2.3 Imaging Scanning was performed on a General Electric 4T LX NVi MRI scanner system equipped with 41 mT/m gradients (General Electric, Waukesha, Wisconsin, USA). A quadrature birdcage radio frequency (RF) head coil was used for transmit and receive. A high resolution T1-weighted image with 68 slices was acquired using a 3D fast SPGR pulse sequence (TR = 500 ms; TE = 20 ms; FOV = 24 cm; image matrix = 256 × 256; voxel size = 0.9375 × 0.9375 × 1.9 mm) and used for coregistration with the functional data. This structural image was aligned in a near axial plane defined by the anterior and posterior commissures. Whole brain functional images were acquired using a gradient-recalled inward spiral pulse sequence (Glover and Law 2001, Guo and Song 2003) sensitive to blood oxygenation level dependent (BOLD) contrast (TR, 1500 ms; TE, 31 ms; FOV, 24 cm; image matrix, 64 × 64; α = 62°; voxel size, 3.75 × 3.75 × 3.8 mm; 34 axial slices). The functional images were aligned similarly to the T1-weighted structural image. A semi-automated high-order shimming program ensured global field homogeneity.Cognition in Schizophrenia Essay. 2.4 Imaging Data Analysis Prior to statistical analysis, head motion was analyzed by center of mass measurements in three orthogonal planes. No participant had greater than a 3-mm deviation in the center of mass in any dimension. In addition, imaging epochs with mean intensities greater than three standard deviations of the average intensity in a run were excluded from analyses.Cognition in Schizophrenia Essay. Image preprocessing was performed with custom programs and SPM modules (Wellcome Department of Cognitive Neurology, UK). Images were time-adjusted to compensate for the interleaved slice acquisition and then motion-corrected to compensate for small head movements. The realigned and motion-corrected images were then normalized to the Montréal Neurological Institute (MNI) template found in SPM. These normalized functional data were then high-pass filtered and spatially smoothed with an 8 mm isotropic Gaussian kernel prior to statistical analysis. These normalized and smoothed data were used in the remaining analyses described below.Cognition in Schizophrenia Essay. To identify voxels activated by events of interest, each subject's data was analyzed using a random effects assessment of statistical maps generated from a voxel-based analysis. The first part of the analysis involved excising epochs of image volumes from the continuous time-series of volumes. For the target events, the epoch consisted of two images before (−3.0 s) and nine images after (13.5 s) the event onset. The onset of task blocks epoch was two images before (−3.0 s) and five images after (7.5 s) the onset of the task block, while the sustained activation epoch was longer, consisting of ten images before (−15 s) and forty-seven images after (70.5 s) of that same onset of the task block (Figure 1). The average intensity of all epochs of the three conditions (target events, task block onset and sustained activation) was computed over all trials. A t-statistic was calculated for each condition by calculating the correlation of the averaged epoch with a canonical hemodynamic response (HDR) reference template at each voxel. The theoretical HDR template for the target events was adapted from a typical event-related BOLD waveform (Huettel and McCarthy 2000). For the onset of task blocks condition and the sustained activation condition, a modified box-car waveform was used for the HDR template. The t-statistics were calculated separately for each subject. Finally, the individual t-maps from each subject were run through a random effects analysis that assessed the significance of differences across participants for each condition.Cognition in Schizophrenia Essay. To reduce the number of statistical comparisons and limit the possibility of Type I error, the results of the random effects analyses above were limited to just those voxels that had a significant HDR evoked by that particular condition. For this analysis, we thresholded our activation at a false discovery rate (FDR) of 0.05 (Genovese, et al. 2002). We used the t-maps across all participants to produce an average t-map for each condition, and then calculated the FDR threshold for each averaged t-map. The random- effects analysis for each event type was then masked by the corresponding averaged t-map thresholded at the FDR threshold calculated above.Cognition in Schizophrenia Essay. Region of interest (ROI) analyses were also performed to assess between-group differences. First, structural ROIs were manually drawn on the same MNI T1-weighted template brain used for the spatial normalization in specified regions using ROI tracing software ITK-SNAP (Yushkevich, et al. 2006). These regions included the anterior cingulate gyrus (ACG), the inferior frontal gyrus (IFG), the middle frontal gyrus (MFG), the intra-parietal sulcus (IPS), the basal ganglia (BG), the caudate nucleus (CN) and the thalamus (TH). Finally, for each trial type and ROI combination, the extent of activation for all participants was calculated as the number of voxels in that ROI that reached or exceeded a specific threshold in the spatially normalized T-map compared to the total number of voxels in that region. Group comparisons were made by calculating the average extent of activation for all neurotypical participants and for all schizophrenic participants for each region and condition.Cognition in Schizophrenia Essay. Go to: 3. Results 3.1 Behavioral Performance As indicated in Table 2, the schizophrenia group made significantly fewer correct responses to targets than did the control group (F(1,17)=6.2, p<0.05) and displayed a significantly slower mean response time to targets than controls (F(1,17)=7.78, p<0.05).Cognition in Schizophrenia Essay. Table 2 Performance of control and schizophrenia groups on selective attention task Control Schizophrenia F(17) * Correct Responses To Targets (Maximum of 110) M=77.44; SD=16.54 M=54.0; SD=23.0 6.2 * Mean Response Time (Milliseconds) M=441ms; SD=109ms M=570ms; SD=85ms 7.78 *p < 0.05 3.2 Imaging Data Brain imaging data are displayed in figure 2 for the control group and figure 3 for the schizophrenia group. Each figure shows activation during three aspects of the mixed design task: activation that was sustained across the entire sequence of task-relevant and non-task blocks; activation that occurred in response to the onset of task-relevant blocks; and activation that occurred in response to the target events.Cognition in Schizophrenia Essay. An external file that holds a picture, illustration, etc. Object name is nihms192871f2.jpg Figure 2 Brain Activation Maps for the Control Group as displayed during three conditions of interest: sustained throughout task performance, onset of a task block and onset of a target. An external file that holds a picture, illustration, etc. Object name is nihms192871f3.jpg Figure 3 Brain Activation Maps for the Schizophrenia Group as displayed during three conditions of interest: sustained throughout task performance, onset of a task block and onset of a target.Cognition in Schizophrenia Essay. For the control group, the random effects differences displayed in figure 2 revealed that across the entire sequence of task-relevant and non-task blocks, sustained activation was apparent in the anterior cingulate gyrus (ACG), bilateral inferior frontal gyrus, bilateral insula, left inferior parietal sulcus and cerebellar regions. At the onset of task-relevant blocks, activation was apparent in all of these regions with additional activations apparent in the medial frontal gyrus, right inferior parietal sulcus, caudate and thalamus. A similar pattern of activation was displayed at the onset of target events, with thalamic and cerebellar activation being particularly apparent.Cognition in Schizophrenia Essay. The pattern of random effects differences displayed by the schizophrenia group, as shown in figure 3, appeared to differ from the pattern displayed by the control group. In the sustained attention condition, the schizophrenia group displayed activation in the ACG, post-central gyrus, inferior parietal sulcus and cerebellar regions. At the onset of task-relevant blocks, the schizophrenia group predominantly displayed activation in the post-central gyrus and the inferior parietal sulcus but displayed little activation in the ACG. At the onset of target events the schizophrenia group displayed activation in the ACG, insula, post-central gyrus and inferior parietal sulcus.Cognition in Schizophrenia Essay. Region of interest (ROI) analyses for both the control group and the schizophrenia group are displayed in Figure 4. Activation associated with the sustained attention condition is displayed in Figure 4a; activation associated by the onset of a task block is displayed in Figure 4b and activation associated with the onset of a target is displayed in Figure 4c. For the control group, the ROI analyses revealed that numerous regions were activated to a greater extent at the onset of task blocks and to an even greater extent in response to target events than were activated during the sustained attention period. For instance, in the ACG only 16% of voxels were active during the sustained attention period, whereas 34% of voxels were active in response to the onset of task blocks and 60% of voxels were active in response to target events. In the thalamus, 9% of voxels were active during the sustained attention period, whereas approximately 40% of voxels were active at the onset of the task-relevant blocks and approximately 75% of voxels were active in response to the target events.Cognition in Schizophrenia Essay. An external file that holds a picture, illustration, etc. Object name is nihms192871f4.jpg Open in a separate window Figure 4 Region of Interest (ROI) Percentage of Active Voxels for the Control Group and the Schizophrenia Group. Figure 4a displays the percentage of active voxels sustained across the task; Figure 4b displays the percentage of active voxels at the onset of a task block; and Figure 4c displays the percentage of active voxels at the onset of a target.Cognition in Schizophrenia Essay. Comparing the control group to the schizophrenia group, the ROI analysis indicated that in the sustained attention phase of the task, the schizophrenia group displayed a greater percentage of active voxels than the control group in many of the ROIs including the ACG, inferior frontal gyrus, medial frontal gyrus and thalamus, though the differences were not significant. However, during the transient phase of attention, as measured at the onset of task-relevant blocks and at the onset of target events, the schizophrenia group displayed a lower percentage of active voxels in all ROIs, than did the control group. These between group differences at the onset of task-relevant blocks were significant in the caudate nucleus (F(1,19)=8.85, p<0.01); the inferior parietal sulcus (F(1,19)=5.07, p<0.05); the medial frontal gyrus (F(1,19)=4.37, p<0.05) and the thalamus (F(1,19)=5.28, p<0.05). At the onset of target events, the between group difference was significant in the thalamus (F(1,19)=10.39, p<0.01). Interestingly, the thalamus of individuals with schizophrenia also displays a significant decrease in percent signal change in response to target events (F(1,19)=6.538, p<0.05). Given that the two groups showed significantly different accuracy and response time on the task, we decided to explore the nature of the association between task performance and extent of activation (percent voxels in range) to sustained attention and to target events. To achieve this, we computed Pearson's r correlations between the extent of activation for each ROI in all three conditions (i.e. sustained attention, transient attention, and target events). We then performed a Fisher's r to z transformation to identify regions where the correlation between brain activation and the behavioral performance measures significantly differed between groups. This analysis revealed a significant positive correlation between accuracy to target events and extent of activation to the sustained attention condition in the caudate nucleus in the healthy controls (r = 0.700; p < 0.05), and this correlation was significantly different from that of the patient group (control r = 0.700; patient r = −0.339; z = 2.26; p <0.05). Response time was not associated with activation to the sustained attention condition in any of the regions of interest. Additionally, a significant negative correlation was found between response time to target events and extent of activation to the target events in the basal ganglia in the participants with schizophrenia (r = −0.712; p < 0.05) and this was significantly different from that of the healthy group (control r = 0.231; patient r = −0.712; z = 2.09; p<0.05). No other significant correlations were found between behavioral measures and activation to target events.Cognition in Schizophrenia Essay. Go to: 4. Discussion The behavioral findings of the current study indicate that the schizophrenia group displayed reduced accuracy on a selective attention task compared to the control group, consistent with the well-established findings that attention deficits are fundamental cognitive deficits in schizophrenia (Fioravanti, et al. 2005, Neuchterlein, et al. 1991).Cognition in Schizophrenia Essay. The brain imaging data for the control group was consistent with the previous findings of Dosenbach et al (2006) and Liddle et al. (2006), revealing that sustained activation was apparent in a core attentional network that included the ACG, inferior frontal gyrus, insula, inferior parietal sulcus and cerebellar regions (Dosenbach, et al. 2006, Liddle, et al. 2006). Such a finding has been expanded upon in the present study by using a mixed block/event-related design to differentiate brain activity during sustained and transient phases of attention. Cognition in Schizophrenia Essay.While the relatively small sample size of our study requires a cautious interpretation of our preliminary findings, the observation that activation in these same regions was apparent during the transient phases of task-block onset and target onset suggests that these regions are commonly activated during both transient and sustained phases of attention. Activation that appeared to be more specific to the transient aspects of target selection occurred in the medial frontal gyrus, caudate, thalamus and inferior parietal sulcus. ROI analysis of the control group data revealed that in many regions in which activation was apparent during the sustained attention phase of the task, a greater percentage of voxels was activated at the onset of task-relevant blocks and an even greater percentage of voxels was activated at the onset of target events. This was apparent in the ACG, inferior frontal and thalamic regions and may suggest that, for the control group, activation within these regions of the attentional network is modulated according to the demands of the task and is further enhanced during the selection of task-relevant responses associated with target events.Cognition in Schizophrenia Essay. ROI analysis also revealed that during the sustained phase of the task, the schizophrenia group displayed a greater percentage of active voxels than the control group, in many regions of the attentional network including the ACG, inferior frontal gyrus, medial frontal gyrus and thalamus. However, during transient phases that were most pertinent to task performance – i.e. the onset of task-relevant blocks and the onset of target events – the schizophrenia group displayed a lower percentage of active voxels in all ROIs, relative to the control group.Cognition in Schizophrenia Essay. While still preliminary, this suggests that the schizophrenia group may have been less effective at modulating brain activity and attention processes in response to the varying demands of the target selection task. For the control group, attention processes appeared to be heightened at the most task-relevant moments and reduced during task-irrelevant periods. By contrast, the schizophrenia group may not modulate cortical activity as effectively in response to the changing demands of the task. This suggestion is consistent with those made in several previous studies. Barbalat et al. (2009) suggested that patients with schizophrenia display evidence of inefficient use of temporal episodic information (Barbalat, et al. 2009). Polli et al. (2008) concluded that reduced anterior cingulate activation in response to errors by patients with schizophrenia may reflect deficient modification of prepotent stimulus-response mappings in response to errors (Polli, et al. 2008). Finally, Liddle et al. (2006) suggested that patients with schizophrenia display a deficit in cerebral activation in the brain regions that are typically activated by attention captivating stimuli (Liddle, et al. 2006).Cognition in Schizophrenia Essay. Exploratory analysis of correlations between behavioral results and fMRI activations revealed that while the response accuracy to target events were significantly associated with the extent of activation to the sustained attention condition in the caudate nucleus in the healthy controls, such an association was absent in the patients. This pattern may reflect an underlying abnormal fronto-striatal projection deficit in schizophrenia patients, which may contribute to their poor behavioral regulation and task-appropriate response generation. The association between the viability of fronto-striate projections and task-appropriate response generation in schizophrenia will need to be further explored with multimodal imaging, namely the integration of white matter tractography and functional activation measures with behavioral performance speed and accuracy during selective attention tasks.Cognition in Schizophrenia Essay. In discussing the results of the present study, it is important to consider the value of the mixed block/event-related design and to consider what the results may have revealed had only a block design been used. The mixed design allows for the differentiation of brain activity that occurs during the sustained and transient phases of attention (Dosenbach, et al. 2006, Huettel, et al. 2004). Had only a block design been employed in the present study, the potentially misleading conclusion may have been drawn that the schizophrenia group displayed greater brain activity than the control group during performance of a selective attention task. Instead, the mixed design has revealed a richer picture – that the schizophrenia group displayed greater activity than controls during non-task periods, but displayed less activity than controls during task-relevant periods.Cognition in Schizophrenia Essay. One limitation of the current study is the slightly elevated IQ of our schizophrenia sample relative to IQ measures reported in recent metaanalysis studies (Woodberry et al, 2008). While there was no effect of IQ on the results of this study, the current sample of individuals with schizophrenia may not be representative of the schizophrenic population as a whole. We propose, however, that individuals with schizophrenia with lower IQs than those from the current sample would exhibit greater behavioral deficits on the current task and this would be associated with greater differences in brain activity modulation in response to variations in attentional modulation. Future studies will be needed to address the validity of this hypothesis.Cognition in Schizophrenia Essay. In conclusion, the findings of the present study help to explain contrasting findings across previous studies and suggest that attention deficits displayed by patients with schizophrenia may reflect deficits in modulating brain activity in response to variations in transient, attention demanding stimuli, rather than deficits in sustained attention. Go to: Acknowledgments This research was supported by grants from NIMH (MH58251), The UNC-Schizophrenia Research Center – an NIMH Silvio O. Conte Center for the Neuroscience of Mental Disorders (MH64065), UL1RR025747 from the NIH Clinical and Translational Science Award Program of the Division of Research Resources, and The Foundation of Hope of Raleigh, N.C. Assistance for this study was provided by the Neuroimaging Core of the UNC Neurodevelopmental Disorders Research Center Gabriel Dichter was supported by Postdoctoral Research in Neurodevelopmental Disorders, NICHD T32-HD40127, and a career development award from UNC-Chapel Hill, NIH/NCRR K12 RR023248.Cognition in Schizophrenia Essay. Assistance for this study was provided by the Neuroimaging Core of the UNC Neurodevelopmental Disorders Research Center. We thank Susan Music, Garett Rosania, and Justin Woodlief for technical assistance. Role of Funding Source This research was supported by grants from NIMH (MH58251), The UNC-Schizophrenia Research Center – an NIMH Silvio O. Conte Center for the Neuroscience of Mental Disorders (MH64065), UL1RR025747 from the NIH Clinical and Translational Science Award Program of the Division of Research Resources, and The Foundation of Hope of Raleigh, N.C. Gabriel Dichter was supported by Postdoctoral Research in Neurodevelopmental Disorders, NICHD T32-HD40127, and a career development award from UNC-Chapel Hill, NIH/NCRR K12 RR023248. The NIMH, the NIH, The Foundation of Hope, and the NICHD had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.Cognition in Schizophrenia Essay. Go to: Footnotes Conflict of Interest All authors declare that they do not have any conflicts of interest. Role of Contributors Aysenil Belger and James Carter conceptualized and designed the study and wrote the protocol. James Carter, Carolyn Bellion, and Kimberly Carpenter managed the literature searches and analyses of clinical data. Dr. Gabriel Dichter assisted in the acquisition of the imaging and clinical demographics data. Dr. James Carter, Mr. Joshua Bizzell, and Mr. Cy Kim undertook the image processing and statistical analysis. Dr. James Carter wrote the first draft of the manuscript. All authors participated in the interpretation and discussion of the results, and subsequent drafts and review of the manuscript.Cognition in Schizophrenia Essay. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Cognition in Schizophrenia Essay. Schizophrenia Research: Cognition will serve an important function – a place where interests converge and investigators can learn about the recent developments in this area. This new journal will provide rapid dissemination of information to people who will make good use of it. In this initial article, we comment globally on the study of cognition in schizophrenia: how we got here, where we are, and where we are going.Cognition in Schizophrenia Essay. The goal of this first article is to place the study of cognition in schizophrenia within a historical and scientific context. In a field as richly textured as ours it is impossible to hit all the important areas, and we hope the reader will forgive our omissions. Phrased in cognitive terms, our limited presentation of the past is a matter of selective memory, the present is a matter of selective attention, and the future is a matter of selective prospection. This broad introduction emphasizes that cognition in schizophrenia provides clues to pathophysiology, treatment, and outcome. In fact, the study of cognitive impairment in schizophrenia has become wholly intertwined with the study of schizophrenia itself.Cognition in Schizophrenia Essay. Keywords: Cognition, Schizophrenia, History Here at last – a journal dedicated to the topic of cognition in schizophrenia: Schizophrenia Research: Cognition. The launch of this journal raises several questions. First: What took so long? Cognition in schizophrenia has been a major focus for a very long time. Exactly how long is somewhat arguable – as seen in the next section, 20, 50, or 100 years are all acceptable answers. From this long-term historical context, it is surprising that it took until 2014 for a publisher to launch a journal focused on cognition in schizophrenia. On the other hand, one could ask provocatively: why do we even need a journal dedicated to this topic? While everyone now agrees that cognition in schizophrenia is an important topic, it is so important that it pervades a wide range of topics. A perusal of schizophrenia-focused journals such as Schizophrenia Bulletin and Schizophrenia Research shows that cognition is a feature of many articles, even those that are not specifically about cognition, including clinical trials, genetics, outcome, and neuroscience.Cognition in Schizophrenia Essay. Schizophrenia Research: Cognition is expected to serve an important function as an international niche journal – a place where interests converge and investigators gather well-packaged information. It is also intended to take scientific risks. Considering that the journal is open access and will have a fast turn-around, this journal will be a place for rapid dissemination of information to people who will make the most of it. Appropriately for this inaugural issue, the two authors of this paper have been asked to comment on how we got here, where we are, and where are we going. That is, the goal of this first article is to place the study of cognition in schizophrenia within a historical and scientific context. Of course, when the questions are this broad, the answers are not straight forward. Where we came from is a matter of perspective, and we really do not know where we are going with any degree of confidence. But we can make some good guesses.Cognition in Schizophrenia Essay. We begin with a discussion of the past, fully realizing that some readers (especially younger ones) will be tempted to skip over any section that looks overly retro or sentimental. However, the history of cognition research in schizophrenia is not separable from the history of schizophrenia itself.Cognition in Schizophrenia Essay. Go to: 1. Where we came from The history of cognition research in schizophrenia can be roughly carved up into 3 eras: the early clinical observations that occurred in the beginning of the 1900s, the assessment-based approaches that emerged after World War II, and the more recent era (roughly the last 20 years) in which cognition research merged into other disciplines. In many ways the three eras are quite distinct in their emphases and their methods, and all reflect their contemporaneous scientific contexts.Cognition in Schizophrenia Essay. 1.1. Clinical observations and formulations in the early 20th century Until recently, most psychology majors in college were required to take a course on the history of psychology (usually called "History and Systems"). In such a course, students learned historical facts about psychology, one which is that William Wundt is credited with founding the world's first psychology laboratory in Leipzig, Germany in 1879. Wundt had a long career and trained many students who served as emissaries and conveyed the principles of experimental psychology far and wide. One of his disciples was Emil Kraepelin, who maintained a lifelong interest in psychological phenomena and its applications to psychiatric disorders.Cognition in Schizophrenia Essay. It is Kraepelin's distinction between schizophrenia (dementia praecox) and bipolar disorder that continues to be reflected in the key diagnostic systems (Diagnosis and Statistical Manual, DSM; International Classification of Diseases, ICD) up to the present time. His tendency to label, separate, and divide was not limited to psychiatric disorders; he also noted attentional processing abnormalities in schizophrenia and divided them into two types (Kraepelin, 1971; Nuechterlein and Dawson, 1984). One was a disorder in active attention (aufmerksamkeit) in which patients "lose both inclination and ability on their own initiative to keep their attention fixed for any length of time" (pp. 5–6). The second was an abnormality in passive attention (auffassung) in which there was an "irresistible attraction to casual external impression" (pp. 6–7). In modern parlance, we might call active attention vigilance, and passive attention distractibility. The key point is that his efforts to classify did not stop at diagnoses, but also included efforts to parse cognition.Cognition in Schizophrenia Essay. If Kraepelin was astute and systematic, Eugen Bleuler was downright prescient. Aside from giving schizophrenia its mysterious (and frequently confusing) name, Bleuler understood at an intuitive level that cognitive impairment was a core part of the illness (Bleuler, 1950). He started by making an important distinction between two types of symptoms: fundamental and accessory. Fundamental symptoms are essentially cognitive in nature. They were separated into simple fundamental symptoms, including problems in association, affectivity, and ambivalence. These simple fundamental symptoms combined to form compound fundamental symptoms, including disturbances in attention. Attention for Bleuler was rather allencompassing. It included some features that we would call vigilance, but also expanded into areas that we might call social withdrawal: "it is evident that the uninterested or autistically encapsulated patients pay very little attention to the outer world" (p. 68). In contrast to fundamental symptoms, accessory symptoms were derived from fundamental symptoms and they constitute what we would now call the positive symptoms of schizophrenia: hallucinations, delusions, and behavioral and speech abnormalities. He went on to say that the fundamental symptoms do not necessarily lead to being hospitalized. Instead "it is primarily the accessory phenomena which make his retention at home impossible, or it is they which make the psychosis manifest and give occasion to require psychiatric help" (p. 94).Cognition in Schizophrenia Essay. Bleuler made many conceptual contributions, but perhaps most relevant to this discussion is his view that psychotic symptoms were secondary to fundamental symptoms, including attentional problems. His hierarchy of symptoms is counter-intuitive, and unfortunately would soon be forgotten. He specifically proposed that the features of illness that were most dramatic, and that necessitated treatment, were somewhat removed from the disease process. He even went on to say that their manifestation was arbitrary: "almost the totality of the heretofore described symptomatology of dementia praecox is a secondary, in a certain sense, an accidental one" (p. 349). Along these lines he proposed that the fundamental symptoms were stable over time, whereas the accessory symptoms waxed and waned.Cognition in Schizophrenia Essay. In the brilliant, ground-breaking, works of Kraepelin and Bleuler we see the conceptual building blocks of modern studies of cognition. If scientific history was linear and progressive, the field would have moved right along to examine the implications of these insights into the cognition of schizophrenia – but that did not happen. A few notable thinkers (e.g., K. Goldstein, N. Cameron) continued to focus on psychological/cognitive phenomenon in schizophrenia with difficult-to-define concepts such as "abstraction" and "over-inclusive thinking" but it was a niche interest (Bolles and Goldstein, 1938; Cameron, 1939). Instead, much of the focus shifted to the more noticeable and more dramatic "accessory" psychotic symptoms and the importance of cognition was largely forgotten, temporarily.Cognition in Schizophrenia Essay. 1.2. Competing approaches to cognition 1950 – 1980 The post-World War II era was characterized by two distinct, highly empirical, views of the cognitive problems in schizophrenia. One view was shaped by experimental psychology and it tried to characterize and understand schizophrenia in terms of basic psychological phenomenon (shades of Wundt). This approach is probably best represented by the famous Biometrics Research Unit at the New York State Psychiatric Institute at Columbia University, which was founded by Joseph Zubin in 1954 (Zubin, 1950; Zubin and Spring, 1977). (No less than 3 organizations bestow awards named after Joseph Zubin.) The scientific approach that Zubin and others from the Biometrics program defined was experimental psychopathology and it sought a theoretical understanding of the etiology of schizophrenia. Their approach to schizophrenia emphasized objective measurement and strong experimental methodology. It also relied on the assumption that the most fruitful way to study the etiology of psychiatric disorders lies in integrative frameworks that use multiple levels of analysis simultaneously (i.e., genetic, biological and psychosocial). This integrative approach is taken for granted now, but was remarkable in the 1960s when it was proposed. As an example of this integrative approach, Zubin, Samuel Sutton, and others examined event related potentials (ERPs) in combination with cognitive tasks (Sutton et al., 1965). This led to a long-standing productive examination of ERP abnormalities in schizophrenia, including the P300, a waveform that is used to reflect allocation of attentional processes.Cognition in Schizophrenia Essay. To better decompose psychological processes, a substantial amount of effort during this era was devoted to understanding very simple performance-based tasks, such as reaction time (Nuechterlein and Dawson, 1984). Indeed, reaction time was described as the "closest thing to a north star of schizophrenia research" (Cancro et al., 1971). Many studies examined cued reaction time tests in which subjects received trials with regular and irregular intervals between a warning signal (instructing the subject to get ready) and the imperative stimulus (instructing the subject to respond). David Shakow and colleagues noticed that, unlike controls, patients were unable to benefit from temporal regularity of the intervals (called a set index) once they exceeded a few seconds (Rodnick and Shakow, 1940; Shakow, 1962). Surprisingly, at the longer intervals, the patients were faster for the irregular versus regular trials, a pattern called the cross-over effect. This pattern of performance was perplexing and it never received a clear explanation (aside from largely descriptive explanations of failure to maintain set), but it occupied a prominent role in experimental research, partly because it was unexpected and wonderfully measurable.Cognition in Schizophrenia Essay. This line of highly empirical research set the stage for clinical psy-chopathology researchers who unabashedly borrowed from experimental psychology, a practice that is commonplace now. This type of translational research took many forms, including borrowing from models of attention, perception, sensory gating, or emotional reactions (Braff, 1993; Green et al., 2011a; Kring and Neale, 1996; Nuechterlein and Dawson, 1984; Nuechterlein et al., 1994). The goal was to closely measure deficits in schizophrenia in precise experimental paradigms, and then infer what the results mean about underlying deficits in the disorder based on existing experimental models. By using normal cognition models as the framework, the results in patients may implicate one visual process or one type of attentional abnormality more than another. A distinctly different slant on cognition in schizophrenia was taking hold at the same time as the experimental psychology/psychopathology approach. Although similarly measurement focused, this other approach had its roots in clinical neuropsychology. Human clinical neuropsychology emerged in the post war era, fortified by numerous illustrative case studies of focal lesions from combat injuries (Luria, 1980). In this context, it is not surprising that a cottage industry of studies emerged that compared schizophrenia to neurological patients on standardized clinical neuropsychological assessments. These types of comparisons were in keeping with the common referral questions for psychiatric patients, which were for the purpose of differential diagnosis. Typically the neuropsychologist was asked to determine whether cognitive impairments in a patient were "organic" meaning neurological versus "functional" meaning not neurological. This type of question sounds jarring from a modern viewpoint – it assumes that cognitive deficits are not a core part of schizophrenia, that cognitive deficits for psychiatric patients are not brain-based, and that this distinction between organic and functional is both meaningful and informative. The demise of the word "organic" in the research literature reflects a fundamental shift in assumptions.Cognition in Schizophrenia Essay. Beyond the conceptual problems, the endeavor to distinguish two types of cognitive impairment was largely futile. After a very large number of studies, the inescapable conclusion was neuropsychological tests could not distinguish cognitive impairments that accompany schizophrenia from those that accompany head injury (Goldstein, 1986; Heaton et al., 1978). In retrospect, it is an unsurprising conclusion and the efforts to discriminate schizophrenia from head injury reflect a time-limited zeitgeist. Although problems in differential diagnosis could be attributed to the tests themselves, the problem in this line of research was the conceptual framing and the stated goals, not the assessment methods. The measures for the most part were reliable and would have been informative for different types of research questions, such as those considered in the next section.Cognition in Schizophrenia Essay. Neither of these approaches paid much attention to clinical symptoms. We can speculate about the reasons for the omission. First is that the people conducting the studies were mainly clinical and experimental psychologists and not directly involved in treating schizophrenia. Second is that the overlap between cognition and psychotic symptoms tend to be rather modest (Gold, 2004; O'Leary et al., 2000). Third is that, at least for the experimental psychology approach, the emphasis was on cognitive vulnerability factors that would be relatively impervious to changes in clinical state (reminiscent of Bleuler). Fourth is that there was not much effort to parse different types of clinical symptoms until the re-focusing on negative and disorganized symptoms in the 1980s (Andreasen and Olsen, 1982; Crow, 1980). Although cognition and clinical symptoms can safely be considered different domains of schizophrenia, we learned later that there is value in considering areas of shared variance, such as negative and disorganized symptoms.Cognition in Schizophrenia Essay. 1.3. Ramping up to the present: 1980s and 1990s It is impossible to adequately summarize the ferment and the excitement that characterized the research in cognition in schizophrenia during the latter part of the 20th century. In a selective review such as this one, many key findings and research directions unfortunately will be omitted. For the purposes of illustration, we have selected 3 themes that took root in this period and will also be discussed in terms of current research. 1.3.1. Cognition and neuroscience Nothing makes a point quite like a picture of the brain. And what made a very big impression were the initial pictures of the brains of people with schizophrenia (Johnstone et al., 1976; Weinberger et al., 1979). Their brains simply looked different – for example the ventricles appeared to be larger in schizophrenia (Raz and Raz, 1990; Weinberger et al., 1979). The larger ventricles reflected the relative reduction of brain tissue to cerebral spinal fluid. Further, the brain changes were often associated with cognitive impairment, thereby giving cognitive deficits firm neural footing. Consider how the world view for cognition in schizophrenia changed with these neuroimaging applications.Cognition in Schizophrenia Essay. Only a few years previously, investigators were administering tests to separate the organic from functional origins of impairment. Suddenly it was obvious that many schizophrenia patients have brains that are not entirely normal and these give rise to cognitive problems. Nonetheless, the inferences were limited from these early studies: for one, the ratio of ventricle to brain is entirely non-specific regarding the affected brain regions, as well as diagnosis. Also the spatial resolution of these imaging techniques (computerized tomography) was very limited compared with later methods.Cognition in Schizophrenia Essay. The early structural findings were soon followed by functional neuroimaging studies. Initially these were studies of positron emission tomography (PET) in schizophrenia (Berman et al., 1986; Weinberger et al., 1986). Similar to the effects of the early structural imaging, the functional neuroimaging studies forced a reconsideration of brains in schizophrenia. Not only did the brains look different from healthy brains, they functioned differently as well. A common observation was that schizophrenia patients did not activate their frontal lobes as much, and as reliably, as control samples (i.e. hypofrontality) (Andreasen et al., 1992; Buchsbaum et al., 1992; Gur and Pearlson, 1993). Much like the findings of enlarged ventricles, hypofrontality was wholly non-specific for diagnosis (other disorders also showed it), and for mechanisms (there are too many different ways to have reduced frontal activity). Also, functional magnetic resonance imaging (fMRI) would soon replace PET for cognitive activation studies in schizophrenia, although PET is still the method of choice for other types of studies, such as those assessing drug receptor occupancy. The variety of neuroscientific methods used currently to study schizophrenia is huge, and ranges from molecular neurobiology to genomics, to a focus on systems and networks. But this research direction was launched with the early neuroimaging studies and the striking realization that the brain in schizophrenia (as well as its cognitive processes) is available for rigorous study – just as it is in any other brain-based disorder.Cognition in Schizophrenia Essay. 1.3.2. Cognition and outcome in schizophrenia The introduction of antipsychotic medications in the 1950s carried great promise and high expectations. Some of that promise was realized: the antipsychotic medications did indeed reduce psychotic symptoms in the majority of patients with schizophrenia (Braslow, 1997). It was natural to expect that psychotic symptom reduction would be accompanied by functional improvements and community integration. But that did not happen – in fact, the introduction of these powerful medications made rather little difference for community integration (Hegarty et al., 1994; Jaaskelainen et al., 2013). The reasons were elusive: if the clinical psychotic symptoms were not holding patients back from community reentry, then what was? This puzzle highlighted the difference between remission, meaning the reduction of symptoms, versus recovery, meaning full community participation.Cognition in Schizophrenia Essay. We know from numerous studies that cognitive impairment is an important correlate and determinant of functioning in schizophrenia (Green, 1996; Green et al., 2000, 2004). Though perhaps not intuitive, cognition is a much better correlate of outcome than psychotic symptoms. We also know that antipsychotic medications have minimal effects on cognition (Keefe et al., 2007a,b). Herein lies the explanation for the discrepancy – antipsychotic medications treat psychotic symptoms, but not cognition. Cognition is related to outcome, but psychotic symptoms are not consistently related. That is why the introduction of antipsychotic medications changed the level of symptomatology for inpatient units, but did little for overall recovery rates.Cognition in Schizophrenia Essay. This association between cognition and outcome is robust – it was replicated and extended in many in countries, using many different types of assessments, in different patient groups across phase of illness, including prodromal (Carrion et al., 2011; Horan et al., 2012). The findings from the last couple of decades established the link between cognition and functioning. As will be seen in the next section on current studies, the questions have shifted from whether cognition is related to outcome to how cognition is related to outcome. Further, not all types of cognition are equally important when it comes to navigating the real world.Cognition in Schizophrenia Essay. 1.3.3. Cognition and interventions Once it was established that cognition is a core feature of schizophrenia and that it is related to functional recovery, it followed naturally to ask whether treatments can enhance cognition. After all, if cognition was holding people with schizophrenia back from full participation in their daily lives, then cognition enhancement should eliminate this barrier. Intervention studies for cognition in schizophrenia can be grouped into two general categories that we will consider separately: cognitive remediation and psychopharmacology.Cognition in Schizophrenia Essay. The studies on cognitive remediation from the 1980s and 1990s included highly focused experimental manipulations on a particular task, as well as broad rehabilitation programs that borrowed heavily from cognitive rehabilitation with brain-injured patients (Ben-Yishay et al., 1985; Green, 1993, 1998). For experimental manipulations, investigators explored the modifiability of performance on cognitive tasks (e.g., reaction time, problem solving, vigilance, verbal memory) using a range of approaches (such as coaching, monetary reinforcement, or instructions on performance strategies). For example, the Wisconsin Card Sorting Test was the testing ground for a variety of manipulations – results usually showed that patients' performance can be improved (Goldberg et al., 1987; Green et al., 1992). These studies demonstrated that the performance deficits were not fixed, and also that the improvements sometimes persisted over time.Cognition in Schizophrenia Essay. In contrast to the focused efforts to demonstrate modifiability on a task, more comprehensive and longer-lasting cognitive programs were also applied to schizophrenia patients (Brenner et al., 1990; Hogarty et al., 2004; van der Gaag et al., 2002). These programs were usually applied to small groups of patients and were extensions of the psychiatric rehabilitation programs. Beyond the typical procedures and structure of psychiatric rehabilitation, they included cognitive exercises that could be done in the group format.Cognition in Schizophrenia Essay. These early approaches might appear overly focused (for the task manipulations) and less than novel (for the rehabilitation programs), but they established the ground work for later studies by demonstrating: 1) that task performance for schizophrenia patients can be modified, even on tasks that reflected core and relatively enduring impairments, and 2) the training exercises were well tolerated by patients, similar to other ongoing psychosocial interventions.Cognition in Schizophrenia Essay. Regarding psychopharmacological approaches to cognition enhancement in schizophrenia – it started with a mirage. With the introduction of second-generation antipsychotic medications, many people (including the authors of this article) thought they had cognitive benefits when compared to first-generation medications. Initial suggestions of this effect came from examining patients who were placed on clozapine, and who showed cognitive benefits in some cognitive domains and not others (Goldberg et al., 1993; Hagger et al., 1993). Evaluations of the cognitive effects of risperidone and olanzapine followed as they were introduced to market (Green et al., 2002; Purdon et al., 2000). Comparisons of second- to first-generation medications (some controlled and some not) added support to the idea that the more recent medications had cognitive benefits (Harvey and Keefe, 2001; Woodward et al., 2005). However, there were also some warning signs. First, the interpretation of the results was limited by relatively small sample sizes, and many of the earlier studies were uncontrolled. Second, concerns persisted that the doses of the medications were not well-matched (with relatively higher, and perhaps more sedating, dosing for the first-generation medication). These problems were addressed more directly in recent studies that are covered in the next section.Cognition in Schizophrenia Essay. Almost all of the focus on psychopharmacology was on second-generation medications, as opposed to novel drugs with distinctly different mechanisms of action. In retrospect, this tunnel vision was unfortunate. However, there are several possible reasons for it: First, the introduction of second-generation medications generated genuine optimism about previously unmet treatment needs, including cognition and negative symptoms. There was a hope (or even an expectation) that the clinicians could get all the treatment needs for schizophrenia met in a single pill. Second, because these drugs were on the market (or close to coming on the market), pharmaceutical companies had an interest in funding investigator-initiated grants to demonstrate the full range of effects. Finally, there was a scientific basis to expect cognition enhancement. For example, animal studies indicated that second-generation medications could reverse induced cognitive deficits in a way that first-generation medications could not (Young et al., 2009). So, it was not entirely a mirage; but it turned out to be overly optimistic.Cognition in Schizophrenia Essay. Go to: 2. Cognition in schizophrenia: present Current research on cognition in schizophrenia naturally has grown out of its past. There are many areas of investigation at the present that clearly define the field. These include the definition and assessment of social cognition, cognitive and affective neuroscience, treatment of cognitive and social cognitive deficits, and the influences of genomic factors on cognition and its end-product in schizophrenia, everyday disability, and phase of illness. We will discuss each of these domains briefly.Cognition in Schizophrenia Essay. 2.1. Social cognition Social cognition refers broadly to the domains of cognitive functions that are employed in socially relevant situations (Harvey and Penn, 2010). These include emotion processing, social perception, theory of mind/mental state attribution, and attributional style/bias, as well as more complex and developing concepts such as social metacognition (Pinkham et al., in press). It is clear that social cognition is of considerable importance for understanding social outcomes (Couture et al., 2006), with the correlation between impairments in social cognitive processes and functional outcomes more substantial than the correlations between neurocognitive deficits and these same outcomes (Fett et al., 2011). The study of social cognition is quite robust, in that more articles on social cognition are submitted to journals such as this one than articles focused only on neurocognition.Cognition in Schizophrenia Essay. At the same time, the study of social cognition is in some ways less developed than that of neurocognition. A National Institute of Mental Health (NIMH) task force concluded that the domains of social cognition were less well defined than in neurocognition and that, as outcomes measures, many social cognitive tasks have some major deficiencies (Green et al., 2008). These include poor psychometric properties, and apparently similar outcome measures with minor variations, but few comparisons among them. In fact, an expert survey of social cognition produced 168 different domains and 108 different outcomes measures, with many of these domains and measures being very closely related to each other (Pinkham et al., in press). The similarity of many of these measures to each other has led to challenges in direct comparisons of their usefulness, as many of these assessments have overlapping content. Several efforts are underway to identify optimal social cognition measures and these studies will add clarity to the field.Cognition in Schizophrenia Essay. 2.2. Cognitive, social, and affective neuroscience Considerable progress has been made regarding the functional and structural neuroimaging of cognition in healthy samples. The increased understanding of normal regional brain activity and functionally connected neural networks has been applied to developments in schizophrenia research. For example, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) Initiative attempted to validate selective cognitive tests that are tied to specific neural networks and subprocesses (Carter and Barch, 2007). A data-collection extension of this initiative developed 4 performance-based tasks and examined their correlation with measures of both everyday functioning and performance-based measures of functional capacity (Gold et al., 2012). Although the correlations among indices of disability and performance on these measures were modest, the fact that this initiative could identify highly selective cognitive measures that were linked to specific neural systems reflects the substantial progress in this area.Cognition in Schizophrenia Essay. Aside from cognitive neuroscience, the rapid emergence of social and affective neuroscience is now influencing schizophrenia research (Ochsner, 2008). These domains of inquiry focus on the neural substrates of social and emotional processes in healthy and impaired populations. For example, considerable work has gone into the patterns of neural activation during identification of facial emotion in schizophrenia (Anticevic et al., 2012; Taylor et al., 2012). Given the prominence of social processing and affective impairments in schizophrenia, this research direction can help to identify underlying neural abnormalities that give rise to social and emotional functioning. Cognition in Schizophrenia Essay.There are also rich possibilities to examine the intersection of cognition and emotion, including whether emotion dysregulation is associated with difficulties regulating cognitive efforts, the cognitive impact of negative or traumatic emotional experiences, and the impact of differences in emotional reactivity on the ability to perform cognitive operations. In addition, examination of underlying commonalities and differences in brain activation during emotional and cognitive tasks could inform treatments jointly aimed at emotional factors and cognitive deficits. Overall, social and affective neuroscience are expanding rapidly in basic behavioral science, and they are well positioned to shed light on the neural basis of both social and motivational problems associated with schizophrenia (Green et al., 2013).Cognition in Schizophrenia Essay. 2.3. Treatment of cognitive and functional deficits Interventions targeting the disability of schizophrenia have been attempted for decades as described above. However, many interventions were aimed at social, vocational, and residential skills deficits in the absence of any interventions aimed at cognition. As cognitive impairments are primary correlates of functional deficits, it stands to reason that cognitive deficits might well underlie the skills deficits that lead to disability and might be "rate limiters" of treatment improvements. Meta-analyses of interventions aimed at disability reduction have suggested that, in general, treatment of cognitive and skills deficits should proceed in parallel to yield functional benefits (Wykes et al., 2011).Cognition in Schizophrenia Essay. Cognitive remediation therapies have made substantial gains in the past two decades. Advancing past repetitive drill and practice interventions, the current cognitive remediation interventions share several critical features. They include dynamic difficulty titration, elimination of focus on "training the test", feedback and encouragement, and a user-friendly interface with visually appealing graphics. These features combine to promote engagement and levels of adherence with treatment that are greater than before.Cognition in Schizophrenia Essay. Training on specific cognitive skills is consistently found to be effective for improving cognition, but not necessarily for improving functioning. Studies of both comprehensive rehabilitation interventions and targeted skills training programs show that short term treatments generally show functional gains only when additional skills training is included (e.g., Bell et al., 2008; McGurk et al., 2007). This situation may be offset by findings that substantial doses of cognitive remediation (50 hours or more) are associated with both substantial cognitive changes (cognition change of up to d N 0.80) and improvements in functional skills (Fisher et al., 2009). Clearly an important issue to be resolved is whether a substantial dose of cognitive remediation can by itself improve daily life. In other words, does an improvement of 10 IQ points yield functional gains if the time frame for detecting these gains is long enough? It will be important for regulatory approval (and payer participation) to know whether concomitant skills training programs are necessary to realize the full benefits of cognitive remediation.Cognition in Schizophrenia Essay. An important related issue concerns approval by regulatory agencies for treatments for cognition in schizophrenia. The overall goal of the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Initiative was to construct a regulatory pathway for cognitive enhancement (Marder and Fenton, 2004). Although MATRICS was aimed at pharmacological treatments, there does not appear to be a substantial distinction in the approval process for pharmacological and remediation-oriented interventions. At present both pharmacological and remediation-oriented strategies are under consideration for approval, though none have been approved so far. Pharmacological interventions would be considered as therapies added to a foundation of antipsychotic treatment for symptom management. Cognitive remediation interventions delivered with a computer, in person, or remotely would be considered to be medical devices and would be approved accordingly. As treatments are approved for cognition, one of the critical issues is the extent to which payers or regulators will expect to see functional gains to maintain approval for treatments with pharmacological or remediation-focused cognitive enhancing treatments.Cognition in Schizophrenia Essay. 2.4. Genomic influences on cognition Studies of the genomic influences on schizophrenia represent a large share of the research allocation on the condition, with samples of patients in the tens of thousands. Cognitive deficits are clearly central to the illness and meet several critical criteria for being considered as important "endophenotypes" (Braff et al., 2007). They are stable, present in attenuated form in relatives, presumed to be genetically simpler than the illness phenotype, and measured with high reliability. In addition, they are among the most heritable of all illness-related traits, at least in families affected by severe mental illness.Cognition in Schizophrenia Essay. The heritability of a variety of cognitive functions in families of people with schizophrenia been demonstrated in a multiple studies (Gur et al., 2007). Memory, attention, and executive functions seem to have a strong familial component that is substantially heritable. In addition, while disability is a complex phenotype, the skills underlying disability may be less complex. The components of disability, including everyday living skills and employment appear to be quite heritable behavioral traits (McGrath et al., 2009). The skills that underlie disability include cognition, as well as the ability to perform cognitively demanding everyday living skills.Cognition in Schizophrenia Essay. Previous studies have identified genomic variation associated with cognitive endophenotypes (Greenwood et al., 2011). These include verbal memory, working memory, indices of attention / vigilance, and social cognitive processes. Further, sensory gating endophenotypes, such as P50 suppression and startle blink responses, also have strong genomic linkages. The full value of these findings will depend on their replication, and several related studies are in process.Cognition in Schizophrenia Essay. 2.5. Functional capacity The study of functional capacity has increased substantially in the last decade. This concept refers to the ability to perform functionally relevant skills, including those relevant to social, vocational, and residential functions (Harvey et al., 2009; McKibbin et al., 2004). Multiple sophisticated performance-based assessments have been developed (Green et al., 2011b), including computerized assessments described for the first time in this issue. Several studies have suggested that these skills may be more proximal to real-world disability than cognitive deficits and they share features with cognitive deficits that suggest they are core features of the illness: stability over time, minimally associated with symptoms, and similarities cross-culturally.Cognition in Schizophrenia Essay. Further, impairments in functional capacity performance meet criteria for an endophenotype, including substantial temporal stability (Light et al., 2012) and low levels of correlation with clinical symptoms (e.g., Bowie et al., 2008). Further, functional capacity scores appear to be minimally related to environmental support (Harvey et al., 2009), suggesting that having more support while performing these skills does not influence the likelihood that people with severe mental illness can perform them with competence. However, as shown recently, limited opportunities for experience in demonstrating skills can contribute to functional skill deficits on these tasks (Holshausen et al., in press).Cognition in Schizophrenia Essay. An important consideration is the suggestion that functional capacity and neurocognitive skills may both reflect a larger common trait that we can call "ability." Several studies with different samples have suggested that there may be one ability trait that cuts across tasks labeled "neurocognitive" and those designated as "functional" (Harvey et al., 2011). Although the types of tasks are quite different, they can be modeled in a way that both connect to one underlying trait in statistical models (Green et al., 2012). Further, cognitive and functional capacity indices were equivalently stable and similarly associated with the single factor over 6-week and 6-month follow-up assessments using sophisticated statistical analyses (Harvey et al., 2013).Cognition in Schizophrenia Essay. 2.6. Phase of illness Previously, there was little need to discriminate the phase of illness of the patients. If schizophrenia developed, it stayed around and it may have actually worsened. Now we can detect risk states earlier, although imprecisely, and are better able to differentiate the effects of treatment, duration of illness, and are early course of illness on cognitive functioning (Cannon et al., 2008). Now we clearly know that the signature of cognitive impairment is not markedly different prior to the onset of diagnosable illness. We also know that, in the absence of the relatively rare phenomenon of nearly complete treatment resistance in older age, there is little consistent evidence of cognitive decline (Harvey et al., 2010). Groups are also working on identifying cognitive predictors of conversion from what looks like a schizophrenia prodrome to a psychotic state. The literature suggests that probably we are looking too late: individuals who are considered to be prodromal and already have cognitive deficits seem more likely to convert to psychosis; those without the deficits seem at lower risk (Seidman et al., 2010). One of our goals in the next decade will be in closing the gap on convergence between clinical and cognitive deficits in cases who are about to convert to psychosis and to "get there earlier" in the cognitive prediction side.Cognition in Schizophrenia Essay. Go to: 3. The future – educated guesses The baseball manager Yogi Berra famously observed that "It's tough to make predictions, especially about the future." Hence, the authors of this article have little to gain, and can only be proved wrong, by sticking our necks out and making predictions, especially about the future. Undaunted, we will make some general guesses at this point. The subsequent trend lines for research in cognition and schizophrenia will be played out in the pages of this new journal, and we will eventually know what we got right and what we got wrong.Cognition in Schizophrenia Essay. One general rule is that research into cognition in schizophrenia follows, often closely in time, developments in basic biological science. Hence, as advances in basic science (e.g., inflammatory markers, optogenetics, epigenetics, pluripotent stem cells, advanced neuroim-aging paradigms, etc.) are applied to schizophrenia, they will also be applied to the cognition of schizophrenia. Once a biomarker is found to be associated with the disease, the next step frequently is to evaluate whether it is related to cognitive impairment. Herein lies one of the advantages of cognition compared with other features of the illness – it is seen as more directly related to known brain circuits. Beyond this general tendency to essentially travel on the coattails of neuroscientific advances, we can identify a few promising directions.Cognition in Schizophrenia Essay. 3.1. Treatment – a 3rd path Treatments for cognition in schizophrenia fall into two categories: training interventions (such as cognitive remediation), and psycho-pharmacology. However, we may soon see a focus on a third approach: neurostimulation. Such approaches include transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) (Minzenberg and Carter, 2012). These approaches attempt to change cognition by directly stimulating the brain. In TMS a strong, transient magnetic field is applied to the scalp from a hand-held coil. That application creates electric current in the brain, which alters the membrane potential and leads to neuronal firing. In tDCS a low-intensity direct current is applied to the scalp, which modulates neuronal excitability (either higher or lower, depending on polarity), but does not cause firing directly. The beneficial effects of these methods sometimes appear to be long lasting, but the results are variable (Guse et al., 2010). The value of these approaches alone, or in combination with other treatment modalities, is likely to be a focus in coming years.Cognition in Schizophrenia Essay. 3.2. The interface of motivation and cognition It is common to view cognition and motivation as separate spheres. Indeed, motivation is much more linked to negative symptoms, such as asociality and avolition. But recent formulations suggest that the two domains may be linked. For example, self-reported intrinsic motivation has an effect on the benefits of cognitive remediation (Medalia and Brekke, 2010). In addition, it is possible that impairments in cognition and social cognition, lead over time to decreases in motivation that we see as negative symptoms, including asociality and anhedonia (Green et al., 2012). Recent developmental models suggest that the two largest unmet treatment needs in schizophrenia, cognition and motivational negative symptoms, are related, and may emerge at different points in development (Beck et al., 2009; Grant and Beck, 2009). That is, long-standing cognitive and social cognitive problems could lead to expectations (dysfunctional beliefs) in which the person learns to not expect to be successful or to enjoy interactions. These beliefs, in turn, lead to motivational negative symptoms. The interaction and overlap between the science of cognition and the science of motivation present wide open areas of exploration for psychopathology.Cognition in Schizophrenia Essay. 3.3. Technology as a problem and a solution Perhaps the most ubiquitous feature of worldwide culture in the 21st century is technology. Television shows for children feature dogs who have blogs and nearly every aspect of life is technology driven. As a result, elderly individuals and people with severe mental illness are expected to perform on-line banking and ATM tasks, and to engage in internet or phone voice menu tasks to schedule appointments and refill predictions (Harvey and Keefe, 2012). In many cases there are no alternatives offered other than internet-based services. This relentless change creates a disadvantage for those with less experience or less ability, but may, paradoxically, offer opportunities. Technology can be less expensive and in an era when health costs are a paramount concern, technology may offer an opportunity for service delivery that would never be possible if in-person interventions were required. For instance, remotely delivered cognitive enhancement interventions have recently been shown to have clinical efficacy (see this issue). Thus, in contrast to the classical model of bricks and mortar clinic, receptionist, therapist, and group interventions, people with severe mental illness could be provided with a low priced device loaded with software and be prompted and cued remotely to self-administer the intervention. This type of intervention has been applied with success for years in aging populations with low levels of experience with technology (Czaja et al., 2006).Cognition in Schizophrenia Essay. 3.4. Applications of animal models It is obvious that animal models of cognition have had a profound impact on our understanding of human cognition. However, they have had a limited impact on the study of cognitive impairment in schizophrenia. To understand the multitude of genetic and molecular mechanisms associated with cognitive impairment in schizophrenia, neural circuit assays (i.e., behavioral tasks known to depend on specific circuits) are needed, and those often come from animal models (Moore et al., 2013). Such models are valuable for neural demonstrations of construct validity (whether the identified cognitive processes are homologous between species), as well as pre-clinical indications of predictive validity (whether a drug is likely to have a therapeutic benefit in human patients) (Keeler and Robbins, 2011). Given an increasing focus on construct validity at the neural level, and increasing examples of successful translation and back-translation, this area could assume a much larger emphasis for the study of cognition in schizophrenia in coming years.Cognition in Schizophrenia Essay. 3.5. Diagnoses An intriguing, though perhaps unsettling, thought about the future of cognition research in schizophrenia is that it might not exist at all. That is, it might not be on schizophrenia per se. One of the implications of the NIMH Research Domains Criteria (RDoC) Project is that specific diagnoses, such as schizophrenia, will not fit into the growing knowledge from neuroscience, and instead the field will move to brain-based constructs that cut across diagnostic boundaries (Cuthbert and Insel, 2010; Insel et al., 2010). A better understanding of these domains might lead to a reorganization of the diagnostic groupings in a way that better carves psychopathology at its neuroscientific joints. In such a reorganization, schizophrenia as a separate disorder could be clumped into a mixed category of psychoses, or split into the meaningful and biologically validated subtypes.Cognition in Schizophrenia Essay. It is easy for this pendulum to swing too far in either direction. A narrow focus on biomarkers or RDoC dimensions risks an overreliance on reductionism that overlooks important higher-order and functional aspects of the disease. In contrast, a narrow focus on clinical syndromes and traditional diagnostic categories risks an overreliance on surface-level clinical features and a continued failure to identify neurobiologically meaningful dimensions or subtypes. Resolving this balancing act will not occur immediately, and schizophrenia is not disappearing as a diagnosis any time soon. Instead, there will be continued efforts to start with existing diagnoses and to revise them incrementally. In this mode, cognition might become a more central part of schizophrenia in diagnostic systems. That very nearly happened for the latest version of the Diagnosis and Statistical Manual (DSM-5) in which cognition was one of several dimensions that was initially slated for inclusion, but ultimately moved out of the main body of the text to Section 3, meaning that it requires additional study (Barch et al., 2013). In contrast to DSM, the proposed revision for the International Classification of Diseases (ICD-11) includes level of cognitive impairment as a specifier (Gaebel, 2012). If that change in ICD-11 is maintained through the field trials and revision process, it will mark the first time that clinicians internationally will be asked to note and record the cognitive status of schizophrenia patients as a routine part of evaluation.Cognition in Schizophrenia Essay. Go to: 4. Conclusions Schizophrenia in the past was a grim diagnosis with a poor prognosis. At the present time, it can probably be better described as a serious condition, with plenty of reasons to be hopeful. The breadth and depth of valuable information on this disease, as in other areas of science, is experiencing rapid, almost exponential, growth. We probably learned more about schizophrenia in the past 10 years than we learned in the previous 100. Like any other area of biomedical science, the sheer volume of the scientific output, as well as the rate of change, is daunting and intimidating. Most of us are conducting research on topics that did not exist, or were not discussed, when we were in training. The future holds both considerable promise and substantial challenge. This new journal will track those developments, help to organize the massive amount of information, and provide a forum for their dissemination and impact.Cognition in Schizophrenia Essay. Schizophrenia is a serious and chronic mental illness that impairs a person's thoughts and behavior, and if untreated, can include psychosis. Schizophrenia is a disabling mental illness that affects more than 1 percent of the world's population. Individuals afflicted with this thought disorder experience hallucinations, disorganized thinking, and are prone to false and paranoid beliefs. These and other symptoms often render the individual fearful, withdrawn, or difficult to interact with.Cognition in Schizophrenia Essay. Schizophrenia takes an enormous toll on afflicted families. Many people with schizophrenia have difficulty maintaining a job or living independently, though it is important to recognize that treatment, especially at the onset of symptoms, allows individuals with a diagnosis of schizophrenia to lead meaningful, productive lives. Schizophrenia afflicts men and women in equal numbers and is found in similar rates in all ethnic groups around the world. The symptom presentation and age of onset do differ between the sexes, however. Men present with more negative symptoms (see below) and become symptomatic at a younger age. The peak age for onset in men is between ages 21 and 25. Women are more likely to be diagnosed between ages 25 and 30, and again after age 45. In women with late onset, hormonal changes associated with perimenopause or menopause are thought to be a contributing factor but the mechanism is unclear and has been a source of debate within the field of psychiatry.Cognition in Schizophrenia Essay. Schizophrenia rarely occurs in children, but awareness of childhood-onset schizophrenia is increasing. It can be difficult to diagnose schizophrenia in teens because the first signs of the illness can include withdrawal from friends, a drop in grades, sleep problems, and irritability—common adolescent behaviors. The period prior to acute onset is known as the prodromal period and often includes withdrawing from others, and an increase in unusual thoughts and suspicions. It is critical to seek a professional opinion if a prodromal period is suspected because early intervention (prior to or just following a first psychotic episode) can greatly minimize symptoms and alter the course of the disease, leading to much higher lifetime functioning.Cognition in Schizophrenia Essay. People with schizophrenia may display hostility or aggression. It should be noted, however, that the vast majority of people with schizophrenia are not aggressive and pose much more danger to themselves than to others.Cognition in Schizophrenia Essay. Schizophrenia is typically a chronic condition and people with this diagnosis cope with symptoms throughout life. However, many people with schizophrenia lead rewarding and meaningful lives in their communities. Can Cognitive Therapy Help People with Schizophrenia? Schizophrenia and Its Treatment Setting the Record Straight on Antipsychotics Anti-Psychotics Lessen Diabetes in Mentally Ill The Importance of Treating a First Psychotic Episode Symptoms The symptoms of schizophrenia are classified by the DSM-5 as positive and negative, each of which includes a suite of behaviors. There may also be cognitive symptoms, which are harder to detect because functioning is already impaired. For a diagnosis to be made, acute symptoms must be present for a one-month period, and continuous signs of a disturbance must be present for at least six months. Despite the severity of their symptoms, many people diagnosed with schizophrenia are unaware that they have an illness.Cognition in Schizophrenia Essay. Positive Symptoms Positive symptoms refer to the presence of psychotic behaviors not seen in healthy people. People with positive symptoms often "lose touch" with reality. Positive symptoms include the following: Hallucinations such as hearing voices are common in schizophrenia. Other types of hallucinations include seeing people or objects that are not there, smelling odors that no one else detects, and feeling things like invisible fingers touching the body.Cognition in Schizophrenia Essay. Delusions are false beliefs that persist even after other people demonstrate that the beliefs are not true or logical. People with schizophrenia can have delusions that seem bizarre, such as believing that neighbors can control their behavior with magnetic waves. Sometimes they believe they are someone else, such as a famous historical figure. They may have paranoid delusions and believe that others are trying to harm them. Thought disorders are unusual or dysfunctional ways of thinking. One form of a thought disorder is called "disorganized thinking." This is when a person has trouble organizing his or her thoughts or connecting them logically. They may talk in a confusing way that is hard to understand. Another form is called "thought blocking." This is when a person stops speaking abruptly in the middle of a thought. When asked why he or she stopped talking, the person may say that it felt as if the thought had been taken out of his or her head. A person with this symptom might make up meaningless words or neologisms.Cognition in Schizophrenia Essay. Movement disorders may appear as agitated body movements. A person with a movement disorder may repeat certain motions over and over. In the other extreme, a person may become catatonic. Catatonia is a state in which a person does not move and does not respond to others. Catatonia is rare today, but it was more common when treatment for schizophrenia was not available. Negative Symptoms Negative symptoms are associated with disruptions to normal emotions and behaviors. These symptoms are harder to recognize as part of the disorder and can be mistaken for depression or other conditions. These symptoms include the following:Cognition in Schizophrenia Essay. Flat affect (a person's face does not move or they talk in a dull or monotonous voice) Lack of pleasure in everyday life Lack of ability to begin and sustain planned activities Speaking little, even when forced to interact People with negative symptoms need help with everyday tasks. They often neglect basic personal hygiene. This may make them seem lazy or unwilling to help themselves, but the problems are symptoms caused by the disorder.Cognition in Schizophrenia Essay. Cognitive Symptoms Cognitive deficits are commonly present in people with schizophrenia, but they may be difficult to recognize as part of the disorder. Often, they are detected only when other tests are performed. Cognitive symptoms include the following: Poor executive functioning (the ability to understand information and use it to make decisions) Trouble focusing or paying attention Problems with working memory (the ability to use information immediately after learning it) Slower processing speed Cognitive symptoms often make it hard to lead a normal life and earn a living. They can cause a great deal of emotional distress. Additionally, the people around an individual with schizophrenia may not realize cognitive deficits are present, so they become easily frustrated when the individual is increasingly confused or forgetful. In previous versions of the DSM, schizophrenia was categorized into the following sub-types: paranoid, disorganized, catatonic, undifferentiated, and residual types. In the DSM-5, schizophrenia is instead evaluated based on severity.Cognition in Schizophrenia Essay. Causes Experts think schizophrenia is caused by several factors. Genes and Environment: Scientists have long known that schizophrenia runs in families. The illness occurs in approximately 1 percent of the general population, but it occurs in 10 percent of people who have a first-degree relative with the disorder, such as a parent, brother, or sister. People who have second-degree relatives (aunts, uncles, grandparents, or cousins) with the disease also develop schizophrenia more often than the general population. The risk is highest for an identical twin of a person with schizophrenia. This individual has about a 50 percent chance of developing the disorder.Cognition in Schizophrenia Essay. Schizophrenia is highly polygenic, meaning it is caused by many different genes, none of which alone is sufficient to produce the outcome. Behavioral geneticists believe that a polygenic risk score (PRS) for schizophrenia is on the horizon, especially for outlier cases, meaning those at the highest risk of developing the disorder. However, environmental factors are also in play, including exposure to viruses or malnutrition before birth, problems during birth, and other not yet known factors.Cognition in Schizophrenia Essay. Drug Use: Research has suggested that using drugs during the teen years and young adulthood can increase the risk of schizophrenia. A growing body of evidence also indicates that smoking marijuana increases the risk of experiencing psychosis, though this may occur only in those already at high risk due to genetic factors. The younger and more frequent the use, the greater the risk of having a psychotic episode.Cognition in Schizophrenia Essay. Treatment Treatment for schizophrenia focuses on eliminating the symptoms of the disease. Treatments include anti-psychotic medications and psychotherapy. It is important to note that people with schizophrenia are at high risk for suicide: 5-6 percent of people with schizophrenia die by suicide and 20 percent attempt suicide at least once. Seeking help for this treatable condition is particularly important to minimize the risk of suicide.Cognition in Schizophrenia Essay. Hospitalization Hospitalization may be necessary during the acute phase of the illness if a person presents a danger to himself or others, or is unable to care for himself. Hospitalization is often recommended to ensure that the person take necessary medication. Medication Antipsychotics have greatly improved the outlook for individual patients as they reduce psychotic symptoms and usually allow the patient to function more effectively and appropriately. Antipsychotic drugs are currently the best treatment available, but they do not cure schizophrenia or ensure that there will be no further psychotic episodes.Cognition in Schizophrenia Essay. People with schizophrenia may be treated with first-generation or second-generation (atypical) antipsychotics. Second-generation medications are generally preferred by clinicians and patients because they have a lower risk of serious side effects.Cognition in Schizophrenia Essay. Anti-psychotic drugs are often very effective in treating the positive symptoms of schizophrenia, particularly hallucinations and delusions. They are typically not as helpful, however, with negative symptoms, such as reduced motivation and emotional expressiveness. Older antipsychotics (neuroleptics) such as haloperidol or chlorpromazine may produce side effects that resemble symptoms that are more difficult to treat, such as dullness and movement disorders. Often, lowering the dose or switching to a different medicine may reduce these side effects. The newer medicines, including olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and paliperidone appear less likely to have this problem. Sometimes when people with the illness become depressed, other symptoms can appear to worsen. The symptoms may improve with the addition of an antidepressant medication.Cognition in Schizophrenia Essay. Response to Medication Anti-psychotics are usually in pill or liquid form. Some anti-psychotics are in an injectable form that is given once or twice a month. Symptoms of schizophrenia, such as feeling agitated and having hallucinations, usually go away within days. Symptoms like delusions usually go away within a few weeks. After about six weeks, many people will see a lot of improvement.Cognition in Schizophrenia Essay. Some people may have a relapse, meaning their symptoms may come back or get worse. Usually, relapses happen when people stop taking their medication, or when they take it inconsistently. Some people stop taking the medication because they feel better or they may feel they don't need it anymore. No one should stop taking an anti-psychotic medication without talking to his or her doctor.Cognition in Schizophrenia Essay. Side Effects of Medication Antipsychotic drugs have many unwanted side effects. Side effects include drowsiness, restlessness, muscle spasms, dry mouth, tremor, blurred vision, rapid heartbeat, sun sensitivity, skin rashes or menstrual problems for women. Atypical antipsychotic medications can cause major weight gain and changes in a person's metabolism. This may increase a person's risk of getting diabetes and high cholesterol. A person's weight, glucose levels, and lipid levels should be monitored regularly by a doctor while taking an atypical anti-psychotic medication. Typical anti-psychotic medications can cause side effects related to physical movement, such as rigidity, persistent muscle spasms, tremors, or restlessness. Most side effects go away after a few days and often can be managed successfully by adjusting the dosage or by using other medications.Cognition in Schizophrenia Essay. One long-term side effect may pose a more serious problem. Tardive dyskinesia (TD) is a disorder characterized by involuntary movements most often affecting the mouth, lips, and tongue, and sometimes other parts of the body. TD is less common among those who use atypical anti-psychotics, but some people may still get TD. People who think that they might have TD should check with their doctor before stopping their medication.Cognition in Schizophrenia Essay. Psychotherapeutic Treatment Therapeutic treatments can help people with schizophrenia who are already stabilized on antipsychotic medication. These treatments help people deal with the everyday challenges of their illness, such as difficulty with communication, self-care, work, and forming and keeping relationships. Learning and using coping mechanisms to address these problems allows people with schizophrenia to socialize and attend school and work.Cognition in Schizophrenia Essay. Patients who receive regular treatment also are more likely to keep taking their medication, and they are less likely to have relapses or be hospitalized. A therapist can help patients better understand and adjust to living with schizophrenia. The therapist can provide education about the disorder, common symptoms or problems patients may experience, and the importance of staying on medications.Cognition in Schizophrenia Essay. Illness Management Skills People with schizophrenia can take an active role in managing their own illness. Once patients learn basic facts about schizophrenia and its treatment, they can make informed decisions about their care. If they know how to watch for the early warning signs of relapse and make a plan to respond, patients can learn to prevent relapses. Patients can also use coping skills to deal with persistent symptoms. Integrated Treatment for Co-Occurring Substance Use Disorder Substance use disorder is the most common co-occurring disorder in people with schizophrenia. Many treatment programs, however, do not address the specific needs of people with schizophrenia.Cognition in Schizophrenia Essay. Rehabilitation Rehabilitation includes a wide array of non-medical interventions emphasizing social and vocational training to help patients and former patients overcome difficulties. Because schizophrenia usually develops in people during the critical career-forming years of life (ages 18 to 35), and because the disease makes normal thinking and functioning difficult, most patients do not receive training in the skills needed for a job. Rehabilitation programs work well when they include both job training and specific therapy designed to improve cognitive or thinking skills. Programs may include vocational counseling, job training, problem-solving, money management skills, use of public transportation, and social skills training. Programs like this help patients hold jobs, remember important details, and improve their functioning.Cognition in Schizophrenia Essay. Individual Psychotherapy Individual psychotherapy involves regularly scheduled talks between the patient and a mental health professional. The sessions may focus on current or past problems, experiences, thoughts, feelings, or relationships. A positive relationship with a therapist gives the patient a reliable source of information, sympathy, encouragement, and hope, all of which are essential for managing the disease. The therapist can help patients better understand and adjust to living with schizophrenia by educating them about the causes, symptoms or problems they may be having. However, psychotherapy is not a substitute for anti-psychotic medication.Cognition in Schizophrenia Essay. Cognitive Behavioral Therapy Cognitive behavioral therapy (CBT) for schizophrenia helps people test the reality of their thoughts and perceptions, including how to "not listen" to their voices, and how to manage their symptoms overall. CBT can help reduce the severity of symptoms and reduce the risk of relapse.Cognition in Schizophrenia Essay. Family Education People with schizophrenia are often discharged from the hospital into the care of their family, so it is important that family members understand the difficulties associated with the illness. With the help of a therapist, they can learn ways to minimize the person's chance of relapse by having an arsenal of coping strategies and problem-solving skills to support their ill relative. In this way, the family can help make sure their loved one sticks with treatment and stays on his or her medication. Additionally, families should learn where to find outpatient and family services.Cognition in Schizophrenia Essay. Self-Help Groups Self-help groups for people with schizophrenia and their families are becoming increasingly common. Although not led by a professional therapist, these groups may be therapeutic because members provide continuing mutual support as well as comfort in knowing that they are not alone. Self-help groups may also serve other important functions. Families working together can more effectively serve as advocates for research and more hospital and community treatment programs. Also, groups may be able to draw public attention to the discrimination many people with mental illnesses face.Cognition in Schizophrenia Essay.

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