SCHIZOPHRENIA - Symptoms and Physiology

Schizophrenia is a severe chronic mental disorder that affects perception, thoughts, emotions, and behavior, often leading to severe impairments in daily functioning. It typically emerges in late adolescence or early adulthood, and while the exact cause is unknown, it is thought to be a multifactorial disorder with genetic, neurobiological, and environmental components.

Schizophrenia’s symptom profile can vary significantly, but is characterized by a wide range of symptoms that can be categorized into positive, negative, and cognitive symptoms. Some people primarily show positive symptoms, while others experience more negative or cognitive ones.

Positive symptoms involve presence of abnormal experiences and behaviors not typically seen in healthy individuals. They are referred to as "positive" because they represent an addition or exaggeration to normal functioning. Positive symptoms can be subdivided into several categories:
Hallucinations are false sensory perceptions that can occur in any sensory modality, although auditory hallucinations are the most common in schizophrenia. Delusions are strongly held false beliefs that are resistant to reason and contradictory evidence. Common delusional themes in schizophrenia include paranoid delusions, like the belief that others are plotting against them, and delusions of grandeur, in which they believe that they have exceptional abilities or importance. Thought disorder refers to disruptions in the normal flow of thought. Individuals with schizophrenia may experience disorganized thinking, characterized by incoherent speech, tangentiality, or loose associations.

Negative symptoms represent a reduction or loss of normal functioning. They include: Affective flattening, which refers to a restricted range of emotional expression. Individuals may appear emotionally unresponsive or exhibit a lack of facial expressions, voice modulation, or gestures. Alogia involves reduced speech output and the inability to engage in meaningful conversation - may respond with brief, monosyllabic answers, or struggle to organize their thoughts into coherent speech. Anhedonia is the inability to experience pleasure or interest in previously enjoyable activities - may lose interest in social interactions, hobbies, and even personal relationships. Avolition refers to a lack of motivation to initiate and sustain goal-directed activities - may struggle with basic self-care tasks, such as personal hygiene or maintaining employment. Social withdrawal involves isolating oneself from social interactions and relationships.

Cognitive symptoms of schizophrenia affect thinking processes and can contribute to functional impairment. These symptoms include an impaired memory - difficulties with short-term and working memory, impacting their ability to remember and process information. Attention deficits can make it challenging to concentrate, leading to distractibility and difficulty in sustaining focus on tasks. Finally, people with schizophrenia may have impaired executive function (encompasses higher-order cognitive processes such as planning, problem-solving, and decision-making).

While mood symptoms are not core features of schizophrenia, some individuals with the disorder may experience co-occurring mood disturbances, such as depression or anxiety.

To be diagnosed with schizophrenia, these symptoms must persist for a long time, typically at least six months, and significantly impair a person's functioning in various areas of life, such as work, relationships, and self-care.

Aberrant neurotransmitter signaling is a central feature of schizophrenia. One of the main theories on the underlying neurobiology of schizophrenia is the dopamine hypothesis. This hypothesis posits that abnormalities in the dopaminergic system play a pivotal role in the development and manifestation of schizophrenia.

The dopamine hypothesis suggests that excessive dopamine activity in certain brain regions, primarily in the mesolimbic pathway, is responsible for the positive symptoms of schizophrenia. In schizophrenia, there is excessive release of dopamine in certain brain regions, particularly the nucleus accumbens, and this can result in heightened neural activity and an altered perception of reality. Conversely, decreased dopamine activity in the mesocortical pathway is thought to underlie the negative symptoms and cognitive deficits seen in schizophrenia. This region connects to the prefrontal cortex, a critical player in executive functions.

Growing evidence also implicates the glutamatergic system in schizophrenia. NMDA receptor hypofunction in particular has gained attention as a potential mechanism.

Structural neuroimaging studies have revealed differences in the brains of individuals with schizophrenia. These include enlarged ventricles, reduced gray matter volume in regions like the prefrontal cortex and hippocampus, and altered white matter connectivity.