As was the case in 2005, mental health research in 2006 continued its concentration on the role of genes in mental disorders and the effects of the interaction of those genes with environmental factors. However, 2006 brought with it a new focus on clinical and genetic investigations of treatments for those disorders.

Research in schizophrenia examined the clinical effectiveness of newer antipsychotic drugs in comparison with their predecessors. Genetic studies in depression focused on possible predictors of antidepressant treatment outcomes, evidence of whether antidepressant treatment is linked to suicide, and how treatment of depressed mothers affects the likelihood of depressive symptoms and diagnoses in their children.

Schizophrenia

Antipsychotic medications have long been the primary treatment for patients with schizophrenia. Unfortunately, many traditional drugs come with a host of disagreeable side effects related to the inhibition of the neurotransmitter dopamine. As a result many psychiatrists are now prescribing second-generation or “atypical” antipsychotics that are less likely to block dopamine transmission in brain areas not directly affected by the disorder. But is this new class of therapeutic agents more effective and tolerated better by patients than the first-generation therapies?

Most are not, according to work in 2005 and 2006 by Jeffrey Lieberman and colleagues. Research published in 2005 revealed no difference in effectiveness between the first- and second- generation antipsychotics.¹ In terms of tolerability, olanzapine, a second-generation drug, showed a slightly lesser rate of discontinuation by patients of their medication compared to other drugs, but it was associated with unpleasant weight gain and metabolic side effects.

Lieberman’s group continued their work in 2006, publishing two papers in the American Journal of Psychiatry that examined antipsychotic treatment in more detail. The group found that chronic schizophrenic patients were more likely to continue treatment if they were taking olanzapine and risperidone rather than other atypical antipsychotics.² 

1. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, and Hsiao JK for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 2005 353(12):1209–1223.

2. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, Perkins DO, Keefe RS, Davis CE, Severe J, and Hsiao JK for the CATIE Investigators. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. American Journal of Psychiatry 2006 163(4):611–622.

3. McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, and Hsiao JK for the CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Archives of General Psychiatry 2006 63(10):1079–1087.

4. Jones PB, Barnes TRE, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, and Lewis SW. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia. Archives of General Psychiatry 2006 63(10):1079–1087.

5. Georgieva L, Moskvina V, Peirce T, Norton N, Bray NJ, Jones L, Holmans P, Macgregor S, Zammit S, Wilkinson J, Williams H, Nikolov I, Williams N, Ivanov D, Davis KL, Haroutunian V, Buxbaum JD, Craddock N, Kirov G, Owen MJ, and O’Donovan MC. Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proceedings of the National Academy of Sciences USA 2006 103(33):12469–12474.

6. Meyer-Lindenberg A, Buckholtz JW, Kolachana B, R Hariri A, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences USA 2006 103(16):6269–6274.

7. Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, Ellison JA, Schadt EE, Verma IM, Lockhart DJ, and Barlow C. Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 2005 438(7068):662–666.

8. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, and Goldman D. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics 2006 78(5):815–826.

9. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, and Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron 2005 45(5):651–660.

10. McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, Sorant AJ, Papanicolaou GJ, Laje G, Fava M, Trivedi MH, Wisniewski SR, and Manji H. Variation in the gene encoding the serotonin 2a receptor is associated with outcome of antidepressant treatment. American Journal of Human Genetics 2006 78(5):804–814.

11. Weissman MM, Pilowsky DJ, Wickramaratne PJ, Talati A, Wisniewski SR, Fava M, Hughes CW, Garber J, Malloy E, King CA, Cerda G, Sood AB, Alpert JE, Trivedi MH, and Rush AJ for the STAR*D-Child Team. Remissions in maternal depression and child psychopathology: A STAR*D-child report. JAMA 2006 295(12):1389–1398.

12. Olfson M, Marcus SC, and Shaffer D. Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study. Archives of General Psychiatry 2006 63(8):865–872.

13. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, and Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature Neuroscience 2006 9(4):519–525.

14. Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thuemmler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois J-M, Debonnel G, and Lazdunski M. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nature Neuroscience 2006 9(9):1134–1141.

15. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y, and Wong C. Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction. Journal of Neuroscience 2006 26(24):6583–6588.

16. Pu L, Liu Q, and Poo M. BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal. Nature Neuroscience 2006 9(5):605–607.