Formal thought disorders: from phenomenology to neurobiology

Formal thought disorder (FTD) is present in most psychiatric disorders and in some healthy individuals. In this Review, we present a comprehensive, integrative, and multilevel account of what is known about FTD, covering genetic, cellular, and neurotransmitter effects, environmental influences, experimental psychology and neuropsychology, brain imaging, phenomenology, linguistics, and treatment. FTD is a dimensional, phenomenologically defined construct, which can be clinically subdivided into positive versus negative and objective versus subjective symptom clusters. Because FTDs have been traditionally linked to schizophrenia, studies in other diagnoses are scarce. Aetiologically, FTD is the only symptom under genetic influence in schizophrenia as shown in linkage studies, but familial communication patterns (allusive thinking) have also been associated with the condition. Positive FTDs are related to synaptic rarefication in the glutamate system of the superior and middle lateral temporal cortices. Cortical volume of the left superior temporal gyrus is decreased in patients with schizophrenia who have positive FTD in structural MRI studies and shows reversed hemispheric (right more than left) activation in functional MRI experiments during speech production. Semantic network dysfunction in positive FTD has been demonstrated in experiments of indirect semantic hyperpriming (reaction time). In acute positive FTD, antipsychotics are effective, but a subgroup of patients have treatment-resistant, chronic, positive or negative FTD. Specific psychotherapy as treatment for FTD has not yet been developed. With this solid data on the pathogenesis of FTD, we can now implement clinical studies to treat this condition.