Bipolar disorder

Clinical picture (children and adolescents)

• Mania: clearly and persistently elevated or irritable mood, decreased need for sleep, pressured speech, flight of ideas, risky behavior. Onset in adolescence is common; in children the diagnosis must be made carefully. A
• Prevalence: 1.8% for the bipolar spectrum in a meta-analysis of 12 epidemiological studies (16,222 youth) (Van Meter et al., 2011); the rate depends heavily on diagnostic criteria and is uncertain under age 12. B
• Differential diagnosis: ADHD, chronic irritability (disruptive mood dysregulation disorder), depression, substance use. A
• Bipolar disorder in the family is a strong risk factor. A

Circuits and networks

• Amygdala: increased response to emotional stimuli. B
• Broca’s Area (Inferior Frontal Gyrus) (ventrolateral PFC, inferior frontal gyrus) and Orbitofrontal Cortex: emotion regulation; in ENIGMA the greatest thinning is in the left pars opercularis (Hibar et al., 2018). A
• Nucleus Accumbens and Ventral Tegmental Area: reward sensitivity; the hypothesis of an increased reward response in mania. C
• Hippocampus and Thalamus: smaller volumes in ENIGMA (Hibar et al., 2016). A
• Anterior Cingulate Cortex: the intersection of emotion and cognitive control. B

Neurotransmitter systems

• Dopamine (dopamine): increased reward and motivation in mania; antipsychotics block D2 receptors. B
• Serotonin and Noradrenaline: the depressive episode; antidepressants alone can trigger mania. B
• Lithium: acts on intracellular signaling pathways; its exact mechanism of action is unknown. B

Imaging and neurobiological findings

• ENIGMA-BD subcortical (1,710 patients, 2,594 controls): smaller hippocampus (d = −0.23) and thalamus (d = −0.15), larger lateral ventricles; larger thalamus in lithium users (exploratory finding) (Hibar et al., 2016). A
• ENIGMA-BD cortex (1,837 patients, 2,582 controls): thinner frontal, temporal and parietal cortex; the largest effects in the left pars opercularis (d = −0.29), left fusiform gyrus (−0.29) and left rostral middle frontal cortex (−0.28); thinning increases with illness duration. Lithium, antiepileptics and antipsychotics are associated with cortical measures (Hibar et al., 2018). A

Developmental course

• Symptoms often begin in adolescence or young adulthood; the first episode is often depressive. B

Treatment and the systems it targets

• Lithium: FDA approval in 2018 for acute mania and maintenance treatment at ages 7–17 (including a placebo-controlled trial of 81 children). A
• Second-generation antipsychotics (e.g., aripiprazole, risperidone, quetiapine): approved for acute mania in adolescents; weight and metabolic side effects are monitored. A
• Psychoeducation, family-focused therapy, regular sleep and routines. B
• Antidepressants are not used without a mood stabilizer (risk of mania). B

Link to the book (The Green Walnut on the Couch)

• In the book (translated from the Turkish original):
  • SEEKING system, clinical: "anhedonia, depression, addiction, ADHD, mania, and excessive attribution of meaning in psychosis".
  • VTA and accumbens, clinical: "Depression (anhedonia), ADHD, addiction, mania".

In the atlas

Regions

Core structures in bold.

Networks

Neurotransmitter pathways

Panksepp systems

References

1. Hibar DP et al. (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry, 21(12), 1710–1716. Search PubMed
2. Hibar DP et al. (2018). Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Molecular Psychiatry, 23(4), 932–942. Search PubMed
3. Van Meter AR, Moreira AL, Youngstrom EA (2011). Meta-analysis of epidemiologic studies of pediatric bipolar disorder. Journal of Clinical Psychiatry, 72(9), 1250–1256. Search PubMed
4. FDA (2018). Lithium label update (ages 7–17); NICHD summary. Search PubMed