Comprehensive Study Notes: Schizophrenia and Psychological Disorders

Statistics and Prevalence in the U.S.: * Approximately $25\%$ of adults in the United States suffer from a diagnosable mental illness at any given time. * Over the course of a lifetime, the prevalence of diagnosable mental illness rises to $46\%$ .
Defining Psychological Disorders (The Four Ds): * Deviance: Behavior that departs from the norm. * Distress: Subjective pain or suffering. * Dysfunction: Interference with the ability to perform daily life functions. * Danger: Potential harm to oneself or others.

Etymology: The term Schizophrenia literally translates to "SPLIT MIND."
Core Deficits: * Perceptual deficits: Distortions in how the world is sensed. * Emotional deficits: Challenges in feeling or expressing emotion. * Intellectual deficits: Impairments in cognitive processing and logic.
Clinical Characteristics: * Loss of contact with reality. * Psychosis: A severe state involving disturbances in reality, orientation, and thinking. * Significant inability to function in standard life activities.
Demographic Statistics and Onset: * Prevalence: $1\%$ of both men and women worldwide. * Gender Differences in Onset: * Men generally experience onset in their late teens to early $20s$ . * Women generally experience onset in their late $20s$ to $30s$ .

Recent Findings: A new study suggests Schizophrenia is actually eight distinct genetic disorders.
Concordance for Schizophrenia Among Relatives (Risk Percentages): * Identical Twin: $48\%$ * Offspring of two patients: $46\%$ * Fraternal Twin: $17\%$ * Offspring of one patient: $17\%$ * Sibling: $9\%$ * Nephew or Niece: $4\%$ * Spouse: $2\%$ * Unrelated person in the general population: $1\%$
The Gottesman and Bertelsen (1989) Study on Twin Offspring: * Offspring of a normal fraternal twin of a person with schizophrenia do not show an elevated risk of the disorder. * Offspring of a normal identical twin of a person with schizophrenia are as likely to become schizophrenic as the offspring of the schizophrenic identical twin itself.

Physical Changes in the Brain: * Reduced gray matter volume. * Reduced limbic area volume. * Increased ventricular size, often as a result of reduced surrounding brain tissue.
Adolescent Gray Matter Loss Rates: * Normal Adolescents: Experience an annual loss rate between approximately $0\%$ and $-1\%$ * Subjects with Schizophrenia: Experience a significantly accelerated annual loss rate ranging from $-1\%$ to $-5\%$ .
Epigenetics and Causal Forces: * The development of the illness requires a threshold of causal forces to be exceeded. * Environmental influences act through epigenetic mechanisms, which involve the upregulating and downregulating of gene functioning.
Early Life and Prenatal Risk Factors: * Direct brain damage or injury occurring during early development. * Prenatal complications: Maternal stress, immune responses, and starvation during pregnancy. * Winter birth effect: A statistical increase in schizophrenia for those born in winter months, possibly linked to seasonal viral exposure. * Neuroinflammation: Chronic inflammation in the nervous system.

Prodromal Phase: * Represents the decline in functioning that precedes the first psychotic episode. * Symptoms: Social withdrawal, irritability, physical complaints, and a newfound interest in religion or the occult.
Psychotic Phase (Acute Phase): * Characterized by positive symptoms. * Perceptual disturbances, including auditory hallucinations. * Delusions: These are usually secondary; the "delusion of reference" is a common manifestation. * Disordered thought process and disordered thought content.
Residual Phase (Chronic Phase): * Occurs between episodes of active psychosis. * Characterized by negative symptoms. * Symptoms: Flat affect, social withdrawal, and oddities in thinking and behavior.

Type I (Positive Schizophrenia): * Characteristic Symptoms: Delusions and hallucinations. * Treatment: Good response to antidopaminergic (antipsychotic) drugs. * Outcome: Symptoms are potentially reversible. * Cognitive Impact: Intellectual impairment is typically absent. * Pathological Process: Associated with increased $D_2$ dopamine receptors.
Type II (Negative Schizophrenia): * Characteristic Symptoms: Poverty of speech (alogia) and lack of affect. * Treatment: Poor response to antidopaminergic drugs. * Outcome: Symptoms are often irreversible. * Cognitive Impact: Intellectual impairment is sometimes present. * Pathological Process: Associated with cell loss in the temporal lobes.

The Dopamine Hypothesis: * Derived from observations that amphetamine overdoses (which increase dopamine) mimic schizophrenic symptoms. * First-generation antipsychotics: Their effectiveness is directly related to their ability to block $D_2$ receptors. * Side Effects: Tardive dyskinesia, which involves the basal ganglia. * Aberrant Salience Hypothesis: Proposes that dopamine dysregulation leads to the assignment of significance to irrelevant stimuli. * Limitations: Anti-dopamine drugs are ineffective for $30\%$ to $40\%$ of patients.
Atypical Antipsychotics: * More effective than first-generation drugs because they target $D_2$ receptors less aggressively. * Help treatment-resistant cases by targeting $5HT_2$ serotonin synapses.
The Glutamate Theory: * PCP (Phencyclidine) mimics schizophrenia by inhibiting $NMDA$ receptors. * Unlike pure dopamine models, PCP induced both positive AND negative symptoms. * Pathophysiology: Hypoactive $NMDA$ receptors on $GABA$ neurons lead to excessive glutamate production and subsequent excitotoxicity. * Treatment implication: Glycine can re-regulate $NMDA$ activity, potentially correcting the system and decreasing excess glutamate.

Neural Connectivity: * There is decreased synchrony and connection between disparate brain areas. * Associated with reduced white matter. * Hallucinations are linked to hyper-excitability within small, localized sensory areas rather than global coordination.
Auditory Gating: * Individuals with schizophrenia have a reduced ability to suppress redundant environmental sounds. * This deficiency is measurable as a difference in the $P50$ wave during an EEG.
The Role of Nicotine: * Approximately $80\%$ of people with schizophrenia smoke. * Nicotine normalizes auditory gating and can improve negative symptoms. * A gene for the nicotinic acetylcholine receptor is implicated in both the reduced activity of the receptor and the symptoms of the disorder.

Wisconsin Card Sorting Test ( $WCST$ ): * A diagnostic tool used to assess frontal lobe function. * Results in schizophrenia often show "Hypofrontality," which is decreased activity in the prefrontal cortex during executive tasks like card sorting.