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Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease.

ABSTRACT: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and add significantly to the burden of disease. These symptoms are most commonly part of the disease spectrum owing to pathological changes within relevant brain regions. Neuropsychiatric problems include disorders of cognition, ranging from mild cognitive impairment to dementia, psychotic symptoms, including, most commonly, well-formed visual hallucinations and paranoid delusions, and mood disorders, such as depression and anxiety. The other common cause of neuropsychiatric problem is secondary to use of dopaminergic drugs. Some PD patients may develop behavioral disorders, including impulse control disorders (ICDs) and addictive symptoms. Psychosis can be due to a mixture of underlying pathology, with triggering or worsening of symptoms with changes to PD medications. Currently, management of these disorders primarily uses therapies developed for general psychiatry and cognitive neurology, rather than specifically for PD. However, significant adverse effects, such as worsening of the motor symptoms of PD, can limit use of some drug therapies. Identification of drug-induced symptoms, such as ICDs, enables withdrawal of the offending drug as the principal management strategy. Research is ongoing in an effort to develop more specific therapies for PD-related neuropsychiatric symptoms.

SUBMITTER: Connolly B

PROVIDER: S-EPMC3899484 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease.

Connolly Barbara B Fox Susan H SH

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20140101 1

Neuropsychiatric symptoms are common in Parkinson's disease (PD) and add significantly to the burden of disease. These symptoms are most commonly part of the disease spectrum owing to pathological changes within relevant brain regions. Neuropsychiatric problems include disorders of cognition, ranging from mild cognitive impairment to dementia, psychotic symptoms, including, most commonly, well-formed visual hallucinations and paranoid delusions, and mood disorders, such as depression and anxiety ...[more]

PMID: 24288035

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Project description:BACKGROUND:Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies. METHODS:Four groups of subjects were recruited from several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear families, 2) unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3) sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4) a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples. RESULTS:In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005). Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. CONCLUSION:Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P < 0.05), whereas 15 would be expected by chance, indicating that many represented false discoveries (Type II errors). Some evidence of replication has been gathered, but more studies are needed to ascertain if circadian gene polymorphisms contribute to susceptibility to affective disorders.

Dataset Information

Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease.

Publications

Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease.

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