On the diagnostic and neurobiological origins of bipolar disorder

Abstract

Psychiatry is constructed around a taxonomy of several hundred diagnoses differentiated by nuances in the timing, co-occurrence, and severity of symptoms. Bipolar disorder (BD) is notable among these diagnoses for manic, depressive, and psychotic symptoms all being core features. Here, we trace current understanding of the neurobiological origins of BD and related diagnoses. To provide context, we begin by exploring the historical origins of psychiatric taxonomy. We then illustrate how key discoveries in pharmacology and neuroscience gave rise to a generation of neurobiological hypotheses about the origins of these disorders that facilitated therapeutic innovation but failed to explain disease pathogenesis. Lastly, we examine the extent to which genetics has succeeded in filling this void and contributing to the construction of an objective classification of psychiatric disturbance.

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

“…The positive symptoms of SCZ overlap with different psychiatric disorders. Indeed, psychosis is also frequent during mood episodes in BD, severe depression, substance use disorder and neurodegenerative disorders ( 16 – 18 ). Intriguingly, some SCZ-like psychopathological abnormalities (i.e., paranoid delusional thinking and auditory hallucinations) are expressed in an attenuated form in 5–8% of the otherwise healthy population, especially in individuals with schizotypal or schizoid personality traits ( 13 , 19 ).…”

Positive moods are all alike? Differential affect amplification effects of ‘elated’ versus ‘calm’ mental imagery in young adults reporting hypomanic-like experiences

“…Positive mood amplification which can, at times, escalate rapidly and be maladaptive is a hallmark of the bipolar disorder spectrum (BPDS). BPDS is characterized by disabling mood states reflected in manic or hypomanic episodes (e.g., elevated, expansive, or irritable mood, and hyperactivity; [1,2]), depressive episodes (e.g., low mood or loss of interest or pleasure), as well as mixed mood episodes [3,4] and/or chronic affective instability [5]. BPDS is associated with high rates of disability [6], medical comorbidities [7][8][9] and suicidality [10].…”

A characteristic cerebellar biosignature for bipolar disorder, identified with fully automatic machine learning

“…It is a highly hereditary disease, running in families, with an early onset, unpredictable course and detrimental impact due to the great risk of fatal self destructive events, long term disability and great financial and social burden, despite existing pharmacological and psychotherapeutic treatment strategies [3]. For these reasons, the neuroanatomy [4] and neurobiology [5] of bipolar disorder are fields of intense research and of paramount importance for 45 million patients globally [6] .…”

“…It is a highly hereditary disease, running in families, with an early onset, unpredictable course and detrimental impact due to the great risk of fatal self-destructive events, long term disability and great financial and social burden, despite existing pharmacological and psychotherapeutic treatment strategies [3]. For these reasons, the neuroanatomy [4], neurogenetics and neurobiology [5] of BD are fields of intense research concerning all brain areas and of paramount importance for 45 million patients globally [6]. In this context, the cerebellum is a relatively recent target of neurogenetics research in BD, with its main functional roles related to modulation of movement, to emotion and to cognition [7].…”