People who are depressed usually exhibit symptoms that include changes in mood, sleep, and appetite; they can experience the slowing of motor function, inability to concentrate, impaired decision making, and anxiety. Major depression usually reflects an imbalance in nerve signaling that relies on neurotransmitters such as dopamine and perhaps serotonin. But until recently, few tools existed to identify who suffers from major depression or to predict who will respond to medications targeting these and other pathways. Diagnosing and treating depression becomes even more challenging in patients with movement-related neurological disorders, which can obscure depressive symptoms.

Intersecting pathways

Neurological disorders like Parkinson's disease (PD), Lewy body dementia (LBD), or motor neuron diseases including ALS and dementia of the frontotemporal lobe (FTD) type, are usually not detected until a person exhibits tremors, motor weakness, or cognitive decline. Yet their underlying pathways intersect with those implicated in major depression and anxiety disorders. Recent reports show that among Parkinsonian patients treated for years with levodopa to control tremor, up to 40 percent may experience loss of impulse control, executive dysfunction, and depression. Similarly, an estimated 30 to 50 percent of ALS patients may have cognitive symptoms and depression with or without anxiety. The relationship between dementia and motor neuron disease is evidenced by a single gene mutation that can cause either FTD or ALS in individuals within the same family.

Non-invasive therapy

Understanding these relationships bring hope for more accurate diagnosis and new treatments. Specific rating scales and surveys have emerged to assess depression and cognitive difficulties in ALS and PD patients. Another advance combines use of depression and anxiety rating scales with functional magnetic resonance imaging (fMRI) to identify those who fit one of four subtypes of depression, based on activity and relationships of the different brain regions. This fMRI tool can predict whether a depressed patient will respond well to a new non-invasive therapy called repetitive trancranial magnetic stimulation (rTMS) which can improve mood and cognitive function in patients with major depression, Parkinson’s, and ALS. As researchers continue to make gains in recognizing individual types of depression and brain activity profiles, rTMS tailored to the person may soon become an important treatment option.