Association between Cognitive Functions, Association between Cognitive Functions, Cortisol Release and Symptoms Severity in Cortisol Release and Symptoms Severity in

Patients with SchizophreniaPatients with Schizophrenia

Prof. Hani Hamed Dessoki, M.D.PsychiatryProf. Psychiatry

Chairman of Psychiatry Department

Beni Suef University

Supervisor of Psychiatry Department

El-Fayoum University

APA memberHanI Hamed and Heba Fathy*, Khadiga Mohamed Ali **

*Assistant Professor of Psychiatry, Cairo University**Professor of Clinical and Chemical Pathology, Benisuef University,

• Schizophrenia is severe mental disorder with

life time prevalence 1-2%.

• Schizophrenia is ranked within the top five causes

of disability and it is considered to be one of the

leading unsolved disorders affecting humans.

Digestive disorder (6%) Musculoskeletal

disorders (4%)

Endocrine (4%)

Neuropsychiatricdisorders (28%)

Cancer (11%)

Cardiovascular disease (22%)

Sense organ impairment (10%)

Other non-communicable diseases (7%)

Respiratory disease (8%)

Schizophrenia

Bipolar disorder

Dementia

Substance-use andalcohol-use disorders

Other mental disorders

Epilepsy

Other neurological disorders

Other neuropsychiatric disorders

MDD

2%

10%

2%

2%

4%

3%

1%

2%

3%

Prince et al. Lancet 2007;370(9590):859–877

Contribution (%) by different non-communicable diseases to disability-adjusted life-years (DALYs) worldwide in 2005

Psychiatric disorders – underestimated and disabling conditions

• Researchers have found higher levels of this 'stress

hormone' in people with schizophrenia.

• The system that is responsible for controlling the

production of cortisol is called the HPA –

hypothalamic-pituitary-adrenal – axis.

• Researchers think higher than normal cortisol levels

might mean the HPA axis isn't working properly.

INTRODUCTION

• The studies indicate a relation between

hypothalamopituitary adrenal axis (HPA) activity and

symptomatology in schizophrenia.

• Cortical secretion was primarily associated with more

severe positive symptoms .

INTRODUCTION

• It has suggested that the relation between

cortisol level and symptoms severity is due to the

augmenting effects of cortisol on dopamine

activity .

• To assess the cortisol level, the cognitive

deficits in schizophrenia.

• To assess the correlation between cognitive

functions, severity of positive & negative

symptoms and cortisol level in patients with

schizophrenia.

• Thirty patients having the diagnosis of

Schizophrenia diagnosed according to DSM-IV

criteria recruited from the Psychiatric outpatient

clinic and inpatient from Kasr El Aini University

hospitals.

• Thirty control subjects (healthy volunteers among

medical and paramedical personnel staff of Kasr

Al-Aini University hospitals.

• All the scales show absence of psychopathology

in the control group.

• They were matched in age and sex.

• The interviews were done over 5 months from July 2012 to November 2012. The interview ranged from one and a half to two hours.

• Semi-structured interview derived from the psychiatric sheet of Kasr Al Aini was done for 60 patients. Then, the diagnosis was confirmed by SCID-I.

• A written informed consent was taken from participants after discussing with them the aim of the study.

• I- Psychiatric examination:

• To assess personal data, positive family history, past

history of neurological or psychiatric condition,

scholastic achievement, duration of illness, ECT,

hospitalization

1. Structured Clinical Interview for DSM IV Axis I

Disorders (SCID I) :It is a diagnostic tool used to

determine the presence of DSM-IV Axis I disorders

(schizophrenia ).

• It is a rating scale scored by the researcher according to

his clinical judgment. PANSS is used to estimate the

severity of psychotic symptoms in patients. The scale has

three parts including:

• positive symptoms scale (P 1-7) which assess delusions,

conceptual disorganization, hallucinations, hyperactivity,

grandiosity, suspiciousness/persecution and hostility.

• Negative symptoms scale (N 1-7) which assess blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking

• General psychopathology scale (G 1-16) which assess Somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation and active social avoidance.

• Figural memory, Visual paired association, Delayed

visual reproduction, and Visual memory span. They are

clinical instruments for appraising major dimensions of

memory functions. In this work, we selected the subtests

which assess the visual memory.

• In this study researchers choose two of the verbal

subtests (Digit span for auditory verbal short-term

(working) memory and Similarities for verbal concept-

formation) and two of the performance subtests (Digit

symbol to assess problem solving abilities, as an indicative

of executive function ,coordination and attention and Block

design to assess visuo-constructive abilities and excutive

planning)

• Salivary samples for cortisol levels assessment were collected and preserved at -20o C in the clinical laboratories of chemical pathology Department.

• Free cortisol levels were assessed by using enzyme-linked immunosorbent assay DRG® Salivary Cortisol ELISA

Results

• In viewing the demographic data of the sample,

there were no statistically significant differences

between the patient groups as regards the

sociodemographic data including age, sex.

• This indicated that the samples were matched

and fit for the study and comparison.

• While regarding educational level, occupation and

marital status, the differences were statistically

significant

Levels of education of patients.

-

Comparison of occupation between both groups.

Comparison of marital status in both groups.

• 2-psychometric tools

• -Wechsler Memory Revised Subtests in both groups:

Wechsler memory Case control P

Mean SD. Mean SD.

Figural memory 6.47 1.776 8.73 1.081 0.003

Visual memory span (forward) 7.77 1.995 9.90 1.807 <0.001

Visual memory span (backward) 5.73 2.303 11.43 1.654 <0.001

Visual paired association 6.83 2.842 13.73 2.815 <0.001

Visual reproduction 20.53 8.274 35.13 3.441 <0.001

• It was reported that Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis.

Tyson P, Laws K and Roberts K, (2005) Tyson P, Laws K and Roberts K, (2005)

Wechsler Case Control P

Mean SD. Mean SD.

Similarities 9.37 4.173 18.67 3.144 <0.001

Digit span 10.30 2.336 14.40 1.773 <0.001

Block.design 14.63 7.271 26.17 6.276 <0.001

Digit symbols 20.78 14.792 44.43 8.675 <0.001

2-Wechsler Adult Intelligence subtests in both groups:

• Dickinson et al., (2007) who found that digit symbol coding task is reliable and easy to administer an information processing inefficiency that is a central feature of the cognitive deficit in schizophrenia.

• There is generalized cognitive decline in patient with schizophrenia and they often have pervasive cognitive deficits ,the cognitive symptoms are a main reason for disability and dysfunction.

Cortisol

level

Case control P

Mean SD. Mean SD.

Cortisol A 29.660 8.2012 5.547 1.8589 <0.001

Cortisol B 17.547 4.8583 2.680 1.0199 <0.001

3-Salivary cortisol level in both groups:

• Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Tyson P, Laws K and Roberts K, (2005) Tyson P, Laws K and Roberts K, (2005)

Wechseler memory Positive Negative Total

Figural memory P R P R P R

0.561 -0.110 0.015 -0.441 0.060 -0.347

Visual memory span forward P R P R P R

0.320 -0.188 0.204 -0.238 0.271 -0.208

Visual memory span backward P R P R P R

0.041 -0.376 0.040 -0.377 0.026 -0.407

Visual paired assossiation P R P R P R

0.073 -0.332 0.002 -0.552 0.008 -0.476

Visual reproduction P R P R P R

0.282 -0.203 0.193 -0.244 0.230 -0.226

Correlation between Positive and Negative Syndrome Scale and Wechseler Memory Revised Scale.

Correlation between Positive and Negative Syndrome

• Krishnadas et al., (2007) found that the forward and backward digit span tasks tap different cognitive abilities that are differentially affected with the diathesis for schizophrenia.

Wechseler intelligence positive negative total

Similarities P R P R P R

0.007 -0.480 0.082 -0.323 0.008 -0.473

Digit span P R P R P R

0.184 -0.249 0.029 -0.398 0.044 -0.370

Block design P R P R P R

0.269 -0.208 0.012 -0.451 0.013 -0.488

digit symbols P R P R P R

0.079 -0.326 0.006 -0.491 0.005 -0.497

Correlation between Wechsler Adult Intelligence Subtests and Positive and Negative Syndrome Scale.

• Reichenberg et al. (2010) reported that patients with schizophrenia had an impaired block design subtest and lower linear slope values than healthy comparison subjects.

• The sample size is small (30 patients), so the results

couldn’t be generalized.

• The inclusion of Kasr Al Ainy patients, who have poor

educational level and low socioeconomic standard,

may limit the results only to those patients.

• The schizophrenic patients have impairment in

cognitive performance.

• The level of cortisol is elevated in patient with

schizophrenia than normal people.

• There is negative correlation between the cognitive

performance and the severity of symptoms

• There is no correlation between cortisol level

and symptoms expression.

• There is no correlation between cortisol level

and cognitive performance

• Further researches are needed to confirm relation between cortisol, psychosis and cognitive performance.

• Cortisol level can be considered a measure of severity and improvement of psychosis.

• More studies using modern technology e.g. MRI and SPECT.