What are the differences in neuroanatomy and neurochemistry among various psychiatric disorders with psychosis, such as schizophrenia (SZ) and bipolar disorder (BD)?

From the Guidelines

Psychiatric disorders with psychosis, such as schizophrenia (SZ) and bipolar disorder (BD), exhibit distinct neuroanatomical and neurochemical profiles that underlie their clinical manifestations and guide treatment approaches. The differences in neuroanatomy among these disorders are crucial for understanding their pathophysiology and for developing effective treatment strategies. In schizophrenia, key features include reductions in gray matter volume, particularly in the prefrontal cortex, temporal lobes, and hippocampus, along with enlarged ventricles and dopamine dysregulation, especially in the mesolimbic pathway 1. Bipolar disorder with psychosis, on the other hand, shows less pronounced structural changes but features abnormalities in the amygdala, prefrontal cortex, and anterior cingulate, with disruptions in dopamine, serotonin, and GABA systems. Some of the phases of schizophrenia, such as the prodrome, acute phase, recovery phase, residual phase, and chronic impairment, as outlined in the practice parameter for the assessment and treatment of children and adolescents with schizophrenia 1, highlight the complexity and progression of the disorder, which can inform neuroanatomical and neurochemical studies. However, the provided evidence does not directly compare the neuroanatomy and neurochemistry of various psychiatric disorders with psychosis, making it essential to consider the broader literature to understand these differences fully. The neurobiological distinctions among these disorders are vital for tailoring treatments, such as the use of antipsychotics targeting D2 receptors for schizophrenia, which may need to be combined with mood stabilizers for bipolar disorder, and the use of both antipsychotics and antidepressants for psychotic depression. Understanding these differences is critical for improving morbidity, mortality, and quality of life outcomes in patients with psychiatric disorders characterized by psychosis. Key points to consider in the neuroanatomical and neurochemical differentiation of these disorders include:

• The specific brain regions affected, such as the prefrontal cortex and hippocampus in schizophrenia
• The neurotransmitter systems involved, including dopamine, serotonin, and GABA
• The phases of the disorders, such as those described for schizophrenia, which can impact neuroanatomical and neurochemical findings
• The implications of these differences for treatment, including the choice of pharmacological agents and the need for combined therapies in some cases.

From the Research

Neuroanatomy and Neurochemistry Differences

• The neuroanatomy and neurochemistry of psychiatric disorders with psychosis, such as schizophrenia (SZ) and bipolar disorder (BD), exhibit distinct differences 2.
• Studies have shown that SZ is associated with regionally specific neurotransmitter alterations, including higher glutamate and dopamine measures in the basal ganglia, and lower glutamate, dopamine, and γ-aminobutyric acid (GABA) levels in cortical regions, particularly the frontal cortex, relative to healthy individuals 2.
• The cortico-thalamo-striatal-midbrain circuits are thought to be dysfunctional in SZ, leading to altered brain information processing and underlying psychotic symptoms 2.

Treatment-Related Neurochemical Changes

• Antipsychotic drugs, which are commonly used to treat psychosis, have different receptor-binding profiles and may affect cognition in patients with SZ spectrum disorders (SSDs) 3.
• A systematic review and network meta-analysis found that there were few clear differences between antipsychotics in terms of their effects on cognition, but first-generation dopamine antagonists and clozapine ranked low 3.
• The study suggested that antipsychotics as a group were associated with small superior outcomes compared to placebo, but this may be due to reduced disordered thought patterns rather than improved cognitive function 3.

Effects of Antipsychotic Medication on Brain Structure

• Research has investigated the effects of antipsychotic medication on brain structure, including cortical thickness 4.
• A randomized controlled one-year follow-up study found that low doses of haloperidol, risperidone, and olanzapine had equal effects on gray matter cortical thickness, overall and by lobe, at the medium-term (1 year) 4.
• The study found no significant associations between changes in cortical thickness and clinical and cognitive outcome 4.

Psychotic Symptoms and Treatment

• Electroconvulsive therapy is an established treatment for symptoms of psychosis and is currently recommended for use in patients who are experiencing an acute exacerbation of positive symptoms or who have had catatonia 5.
• Other forms of neuromodulation, such as transcranial magnetic stimulation and transcranial direct current stimulation, have less evidence to support their use and are not formally indicated for the treatment of psychosis 5.
• Positive psychotherapy for psychosis (PPP) is a new approach that focuses on positives rather than problems and has been shown to be effective in strengthening patients' resources, including positive emotions and internal motivation 6.