Schizophrenia and Psychotic Disorders

Symptoms and clinical features

Schizophrenia and related psychotic disorders present a wide range of symptoms, which are generally divided into three main categories: positive, negative, and cognitive. Positive symptoms refer to an abnormal exaggeration or distortion of normal functions. In contrast, negative symptoms involve a reduction or loss of typical abilities or behaviors. Positive symptoms include hallucinations, which are sensory experiences without any external stimulus. In schizophrenia, auditory hallucinations, such as hearing voices, are the most common, often involving commentary on the individual's actions, commands, or dialogue. Less common are hallucinations involving sight, touch, smell, or taste. Another hallmark of positive symptoms is delusions—rigid, false beliefs maintained despite evidence to the contrary. These may take several forms, such as persecutory delusions (beliefs of being targeted or harmed), referential delusions (believing unrelated events are personally directed), grandiose delusions (overinflated beliefs about one’s abilities or status), and somatic delusions (false beliefs about bodily health). Disorganized thinking and speech are also key features, with individuals exhibiting tangential or incoherent communication, making it difficult for others to follow conversations, thereby affecting social interactions. Negative symptoms manifest as reduced emotional expression, diminished drive to pursue goals (avolition), poverty of speech (alogia), and the inability to derive pleasure from normally enjoyable activities (anhedonia). Cognitive symptoms include impairments in attention, memory, executive functioning, and processing speed. These deficits can be particularly disabling, as they affect day-to-day tasks, even when other symptoms are under control.

Diagnosis

Diagnosing schizophrenia and psychotic disorders relies on clinical evaluation and established criteria, such as those in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). To be diagnosed with schizophrenia, an individual must exhibit at least two of the following symptoms for a significant portion of a month: delusions, hallucinations, disorganized speech, severely disorganized behavior, or negative symptoms, with delusions, hallucinations, or disorganized speech being mandatory. Additionally, there must be a notable decline in social or occupational functioning, with the disturbance lasting at least six months. It’s critical to exclude other potential causes like drug use, medication side effects, or other medical conditions.

Causes and risk factors

Schizophrenia affects about 1% of the global population, making it a relatively common severe mental illness. Symptoms typically begin in late adolescence or early adulthood, with males often experiencing an earlier onset than females. The lifetime risk of developing schizophrenia is estimated to be around 0.7%. Although incidence rates are similar across different regions and populations, some risk factors such as urban living, migration, and cannabis use, particularly during adolescence, are known to increase susceptibility. The exact cause of schizophrenia remains elusive, though it is widely believed to result from a combination of genetic, environmental, and neurodevelopmental factors. Genetically, schizophrenia has a strong hereditary component, with studies suggesting that 60% to 80% of the risk is genetic. Rather than a single gene, numerous small genetic variations likely contribute to vulnerability. Environmental factors also play a role, with prenatal complications, such as infections, malnutrition, or birth complications, associated with an increased risk. Psychosocial stress, childhood trauma, and cannabis use during critical periods of brain development are additional factors linked to the disorder. The neurodevelopmental hypothesis suggests that genetic predispositions and early environmental stresses disrupt brain development during critical periods, setting the stage for later symptoms.

Biological mechanisms

The biological underpinnings of schizophrenia involve complex changes in brain chemistry and structure. The "dopamine hypothesis" suggests that excessive dopamine activity in certain brain pathways, particularly the mesolimbic pathway, leads to the positive symptoms of schizophrenia, while reduced dopamine activity in the mesocortical pathway may contribute to negative and cognitive symptoms. This theory has driven the development of many antipsychotic drugs. Additionally, glutamate dysfunction, particularly involving NMDA receptors, has been implicated, supported by genetic research and the effects of certain drugs that mimic psychotic symptoms. Structural changes in the brain are another aspect of the disorder’s pathophysiology. Neuroimaging studies frequently show enlarged ventricles, reduced gray matter, and abnormalities in specific regions such as the prefrontal cortex, temporal lobes, and hippocampus. Functional imaging has also revealed decreased activity in areas like the dorsolateral prefrontal cortex, associated with executive function tasks, and increased activity in the medial frontal regions, suggesting disrupted brain circuits.

Treatment strategies

Managing schizophrenia requires a comprehensive approach involving both medication and psychosocial interventions. Antipsychotic drugs are the primary treatment for controlling positive symptoms and preventing relapses. These medications are divided into first-generation (typical) and second-generation (atypical) antipsychotics. While second-generation drugs are often favored due to their lower risk of movement-related side effects, the choice of medication depends on individual needs and the drug’s side effect profile. Psychosocial interventions are vital in improving long-term outcomes. Cognitive-behavioral therapy (CBT), family psychoeducation, social skills training, and supported employment programs all help patients develop coping skills, improve social functioning, and integrate into society.

Test your knowledge

What percentage of the risk of developing schizophrenia is believed to be genetic?

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