Coping With Stress

Tracking restoration in natural and urban field settingsTerry Hartig (2003) Journal of Environmental Psychology, 23 109–123

Factors That Interact during the Development and Progression of Disease

Diathesis-Stress Model

• Diathesis is vulnerability or susceptibility– Genetic influences

• concordance rate in twin studies• family history of mental disorder• hypothalamic-pituitary-adrenal responsivity

– Developmental

• maternal stressors • childhood maltreatment

• Interaction of Diathesis and Stress– Individuals with more vulnerability are more likely to become ill when

challenged by stresssors

Epidemiology: The scientific study of disease incidence

The term 'incidence' refers to the rate at which new cases occur in a population during a specified period, usually each year.

The term 'prevalence' refers to proportion of a population that are cases.

point prevalence, based on a single examination, at one point in time, tends to underestimate the condition's total frequency.

period prevalence defined as the proportion of a population that are cases at any time within a stated period: 6 months, one year, life-time For example Table 16.1 shows prevalence data at 12 month and life-time periods.

Prevalence and Incidence Statistics

Prevalence of Serious Mental Illness among U.S. Adults

Gender

http://www.nimh.nih.gov/health/statistics/prevalence/serious-mental-illness-smi-among-us-adults.shtml

Disability Adjusted Life Years *, Both Sexes“Established Market Economies”, 1990

(adapted from Global Burden of Disease, 1996)

Group of disorders Proportion of all DALYs

Psychiatric 26.0

Cardiovascular 18.6

Cancer 15.0

Unintentional injuries 8.7

Respiratory 4.8

Gastrointestinal 4.4

Musculoskeletal 4.2

* DALY = years of actual life spent in a disabled state + years of life lost due to premature mortality

Prevalence of Schizophrenia•Schizophrenia affects approximately 1% of the population.(p492)

• Table 16.1 has 0.70% for lifetime

•A new study on worldwide prevalence of schizophrenia.• Bhugra D (2005) The Global Prevalence of Schizophrenia. PLoS Med 2(5):

e151. doi:10.1371/journal.pmed.0020151

• Lifetime prevalence is 4.00 %

• Point prevalence is 0.46 %

• “A total of 1,721 prevalence estimates from 188 studies were identified. These estimates were drawn from 46 countries,”

• “When sites were grouped by economic status, prevalence estimates from ‘‘least developed’’ countries were significantly lower than those from both ‘‘emerging’’ and ‘‘developed’’ sites”

Schizophrenia Is the Major Neurobiological Challenge in Psychiatry

• DSM-5 Diagnosis of Schizophrenia– Characterized by delusions, hallucinations, disorganized speech and

behavior, and other symptoms that cause social or occupational dysfunction.

– For a diagnosis, symptoms must have been present for six months and include at least one month of active symptoms.

– DSM-5 raises the symptom threshold, requiring that an individual exhibit at least two of the specified symptoms. (In the manual’s previous editions, that threshold was one.)

– The diagnostic criteria no longer identify subtypes.

Heritability of Schizophrenia

• The heritability of schizophrenia is a strong indicator of a biological basis for schizophrenia

– Adoption studies• Adult schizophrenics that were adopted as children

are likely to have schizophrenic biological relatives.

– Twin studies• Concordance rates for schizophrenia are higher for

identical than for fraternal twins:

– No single gene has been identified for schizophrenia

• Genes may pass on a susceptibility to develop schizophrenia

The Heritability of Schizophrenia

The Heritability of Schizophrenia

• Genetic influences on Schizophrenia

• Many different genes could be responsible

• A few critical genes have been identified• Neuregulin 1 for regulation of receptors for NMDA, ACh, GABA

• Dysbindin involved in synaptic plasticity

• COMT for the metabolism of dopamine

• G72 involved in glutamate activity

• One gene appearing abnormal in one schizophrenic family is DISC1.

• Transgenic mice with a mutated version of this gene developed enlarged lateral ventricles.

Brain Damage and Schizophrenia

• The negative symptoms of schizophrenia are related to brain damage

– The neurological signs evident in schizophrenia include• Eye tracking problems• Catatonia• Problems with blinking, eye focusing, and visual pursuit

– Schizophrenics exhibit enlarged brain ventricles, which suggests loss of brain cells

– Regions of schizophrenic brain that are abnormal include• Prefrontal cortex• Medial temporal lobes • Medial diencephalon

Eye Tracking in Patients with Schizophrenia versus Control

A Simple Scan for Schizophrenia?

Ventricular Enlargement in Schizophrenia

Identical Genes, Different Fates

Brain Damage and Schizophrenia

The entorhinal cortex, cingulate cortex, parahippocampus, hippocampus and amygdala are smaller in schizophrenics than in most people.

In schizophrenics, pyramidal cells of the hippocampus have a disorganized arrangement.

Abnormal cellular arrangement also found in the entorhinal cortex, cingulate cortex and parahippocampus.

This probably occurs during early cell development.

Cellular Disarray of the Hippocampus in Chronic Schizophrenia

Accelerated Loss of Gray Matter in Adolescents with Schizophrenia

Adolescents with schizophrenia

Hypofrontality in SchizophreniaCortical abnormalities include a thicker corpus callosum and altered function in this structure.Some studies show a loss of gray matter in the frontal lobes, and PET shows less metabolic activity.The hypofrontality hypothesis suggests that schizophrenia may be caused by underactivation of the frontal lobes.

Potential Causes of Brain Damage in Schizophrenia

• The neurological symptoms of schizophrenia may be caused by

– Genetic mutations

– Birth trauma (obstetrical issues)

– Viral infections that impair neural development during the second trimester

• Seasonality effects (schizophrenia is more likely for winter births)

– Nutritional issues (Hunger Winter: female offspring were more likely to exhibit schizophrenia than male offspring)

– Maternal stress may compromise the immune system of the mother and lead to a greater chance of contracting a viral infection

• The “dopamine hypothesis” is that the positive symptoms of schizophrenia involve over-activity of brain dopaminergic synapses

• Dopamine hypothesis is based on – antipsychotic drugs such as chlorpromazine (CPZ) block DA

receptors– amphetamine release DA can reproduce the positive symptoms

of schizophrenia– PET studies indicate greater release of dopamine in the

striatum of schizophrenics to a test dose of amphetamine• Amount of dopamine released was related to the increase in

positive schizophrenia symptoms

Positive Schizophrenia Symptoms: Dopamine

Typical Antipsychotic Drugs Affect Dopamine Receptors

Antipsychotic Drugs That Affect Dopamine Receptors

Typical neuroleptic drugs are all antagonists at dopamine D2 receptors

Cognitive Symptoms

• 15 IQ points below the population mean

• Cognitive decline several years before the onset of other schizophrenia symptoms

• Lower cognitive functions is stable through out the course of the illness

• Cognitive decline should be considered an important part of the etiological hypotheses.

Glutamate Hypothesis

• PCP and ketamine induce positive, negative and cognitive elements of schizophrenia in humans

– PCP and ketamine are antagonists at the NMDA glutamergic receptor

– Glutamate functions as an excitatory amino acid

• NMDA receptor (ionotropic): activation allows Na+ and Ca++ ions to enter membrane (EPSP)

• PCP binding site: PCP binding blocks Ca++ ion entry (antagonist)

The Effects of PCP on the NMDA Receptor

Glutamate and Dopamine

• Schizophrenia may reflect a deficit in glutamate transmission (DA effects are secondary to NMDA)

• Ketamine-induced symptoms are not reversed by DA receptor blockade (e.g. haloperidol)

• Ketamine infusion increases the DA-releasing activity of amphetamine in humans

Recent report on world prevalence of mental disorders

“The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%.”

“Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview.”

Prevalence, Severity, and Unmet Need for Treatment of Mental Disorders in the World Health Organization World Mental Health Surveys JAMA, June 2, 2004—Vol 291, No. 21

Prevalence of Mental Disorders

•Prevalence, Severity, and Unmet Need for Treatment of Mental Disorders. Kessler, JAMA, June 2, 2004—Vol 291, No. 21

One Year Prevalence of Mental Disorders

Living in a City Increases the Risk for Schizophrenia

Childhood Poverty, Cumulative Risk Exposure, and Mental Health in Emerging Adults

• Poverty during early development increases the rate mental health problems for individuals as young adults • more externalizing then internalizing symptoms• early and sustained poverty has the most impact

• Because of elevated cumulative risk exposure• Related to exposure to

• Psychosocial: violence, family turmoil, child separation from family

• Physical: noise, crowding, substandard housing

Coping With Stress

Tracking restoration in natural and urban field settingsTerry Hartig (2003) Journal of Environmental Psychology, 23 109–123

A Model of the Interaction between Stress and Genetic Influences in Schizophrenia